Morgellons
disease: Managing a mysterious skin condition
Morgellons disease is
mysterious and controversial. Here you'll find answers to common questions
about
Morgellons disease and suggestions for coping with
it.
Morgellons disease is a mysterious skin disorder characterized by
disfiguring sores and crawling sensations
on and under the skin.
Although Morgellons disease isn't widely recognized as a medical diagnosis,
experts
from the Centers for Disease Control and Prevention (CDC)
are investigating reports of the condition.
If you suspect that you have
Morgellons disease, you may have many questions about the condition. Here's
what you need to know about Morgellons disease, including practical
tips for managing your signs and
symptoms.
What are the signs and
symptoms of Morgellons disease?
According to the Morgellons Research
Foundation, primary signs and symptoms of Morgellons disease
include:
Skin lesions, often accompanied by pain or intense
itching
Fibers which may be white, blue, red or black in and on the
lesions
Crawling sensations on and under the skin, often compared to insects
moving, stinging or biting
Joint and muscle pain
Fatigue significant
enough to interfere with daily activity
Inability to concentrate and
difficulty with short-term memory
Behavioral changes
Other signs and
symptoms may include:
Changes in vision
Stomach pain or other
gastrointestinal symptoms
Changes in skin texture and color
Morgellons
disease shares characteristics with various recognized conditions, including
attention-deficit
disorder, chronic fatigue syndrome, Lyme disease,
obsessive-compulsive disorder and a mental illness
involving false
beliefs about infestation by parasites (delusional parasitosis).
How long
has Morgellons disease been around?
In 1674, English physician and writer
Sir Thomas Browne used the term "Morgellons disease" to describe
"black hairs" emerging from childhood skin lesions. Today, the
Morgellons Research Foundation doesn't
claim that the disorder
described by Browne is the same as Morgellons disease. Rather, the foundation
adopted the term as a convenient label for a set of signs and
symptoms.
How widespread is Morgellons disease?
Reports of Morgellons
disease have been made in every state in the United States and various
countries
around the world. Most reported cases are clustered in
California, Texas and Florida.
What do researchers know about Morgellons
disease?
Beyond anecdotal reports, researchers know little about Morgellons
disease. The Morgellons Research
Foundation reports no known causes
of Morgellons disease and no successful treatment for the condition.
Whether
Morgellons disease is contagious remains a mystery.
How controversial is
Morgellons disease?
Current attitudes toward Morgellons disease fall into
various categories:
Some health professionals believe that Morgellons disease is a specific condition likely to be confirmed by
future research.
Some health professionals believe that signs and
symptoms of Morgellons disease are caused by another
condition,
often mental illness.
Other health professionals don't acknowledge
Morgellons disease or are reserving judgment until more is
known
about the condition.
Some people who suspect Morgellons disease claim
they've been ignored, criticized as delusional or
dismissed as
fakers. In contrast, some doctors say that people who report signs and symptoms
of
Morgellons disease typically resist other explanations for their
condition.
How can you cope with the signs and symptoms of Morgellons
disease?
The signs and symptoms linked to Morgellons disease can be
distressing. Even though health professionals
disagree about the
nature of the condition, you deserve compassionate treatment. While research
continues,
take positive steps to manage your signs and
symptoms.
Establish a caring health care team. Find a doctor who
acknowledges your concerns and does a thorough
examination. Since Morgellons disease often requires frequent follow-up visits, a local health care team may
be most convenient.
Be patient. Your doctor will
likely look for known conditions that point to evidence-based treatments before
considering a diagnosis of Morgellons disease.
Keep an open
mind. Consider various causes for your signs and symptoms, and follow your
doctor's
recommendations for treatment which may include long-term
mental health therapy.
Seek treatment for other conditions. Get treatment for anxiety, depression or any other condition that affects
your
thinking, moods or behavior.
Keep track of the latest news about Morgellons
disease. Supplement the information you find online with
articles
published in peer-reviewed medical journals. Remember that some sources are
more reputable than
are others.
RELATED
Web Resources
http://www.mayoclinic.com/health/morgellons-disease/SN00043
Centers for
Disease Control and
Prevention
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http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?
requestURI=/healthatoz/Atoz/ency/lymphadenitis.jsp
Lymphadenitis
is the inflammation of a lymph node. It is often a complication of a bacterial
infection of a
wound, although it can also be caused by viruses or
other disease agents. Lymphadenitis may be either
generalized,
involving a number of lymph nodes; or limited to a few nodes in the area of a
localized infection.
Lymphadenitis is sometimes accompanied by
lymphangitis, which is the inflammation of the lymphatic vessels
that connect the lymph nodes.
Description
Lymphadenitis
is marked by swollen lymph nodes that are painful, in most cases, when the
doctor touches
them. If the lymphadenitis is related to an infected
wound, the skin over the nodes may be red and warm to
the touch. If
the lymphatic vessels are also infected, there will be red streaks extending
from the wound in
the direction of the lymph nodes. In most cases,
the infectious organisms are hemolytic Streptococci or
Staphylococci. Hemolytic means that the bacteria produce a toxin that
destroys red blood cells.
The extensive network of lymphatic vessels
throughout the body and their relation to the lymph nodes helps
to
explain why bacterial infection of the nodes can spread rapidly to or from
other parts of the body.
Lymphadenitis in children often occurs in
the neck area because these lymph nodes are close to the ears and
throat, which are frequent locations of bacterial infections in
children.
Causes and symptoms
Streptococcal and staphylococcal
bacteria are the most common causes of lymphadenitis, although viruses,
protozoa, rickettsiae, fungi, and the tuberculosis bacillus can also
infect the lymph nodes. Diseases or
disorders that involve lymph
nodes in specific areas of the body include rabbit fever (tularemia),
cat-scratch
disease, lymphogranuloma venereum, chancroid, genital
herpes, infected acne, dental abscesses, and
bubonic plague. In
children, tonsillitis or bacterial sore throats are the most common causes of
lymphadenitis
in the neck area. Diseases that involve lymph nodes
throughout the body include mononucleosis,
cytomegalovirus
infection, toxoplasmosis, and brucellosis.
The early symptoms of
lymphadenitis are swelling of the nodes caused by a buildup of tissue fluid and
an
increased number of white blood cells resulting from the body's
response to the infection. Further
developments include fever, often
as high as 101-102°F (38-39°C) together with chills, loss of
appetite, heavy perspiration, a rapid pulse, and general
weakness.
Diagnosis
Physical examination
The diagnosis of
lymphadenitis is usually based on a combination of the patient's history, the
external
symptoms, and laboratory cultures. The doctor will press
(palpate) the affected lymph nodes to see if they
are sore or
tender. Swollen nodes without soreness are often caused by cat-scratch disease.
In children, the
doctor will need to rule out mumps, tumors in the
neck region, and congenital cysts that resemble swollen
lymph
nodes.
Although lymphadenitis is usually diagnosed in lymph nodes in the
neck, arms, or legs, it can also occur in
lymph nodes in the chest
or abdomen. If the patient has acutely swollen lymph nodes in the groin, the
doctor
will need to rule out a hernia in the groin that has failed
to reduce (incarcerated inguinal hernia). Hernias
occur in 1% of
the general population; 85% of patients with hernias are
male.
Laboratory tests
The most significant tests are a white
blood cell count (WBC) and a blood culture to identify the organism.
A
high proportion of immature white blood cells indicates a bacterial infection.
Blood cultures may be
positive, most often for a species of
staphylococcus or streptococcus. In some cases, the doctor may order
a
biopsy of the lymph node.
Treatment
Medications
The
medications given for lymphadenitis vary according to the bacterium or virus
that is causing it. If the
patient also has lymphangitis, he or she
will be treated with antibiotics, usually penicillin G (Pfizerpen,
Pentids), nafcillin (Nafcil, Unipen), or cephalosporins. Erythromycin
(Eryc, E-Mycin, Erythrocin) is given to
patients who are allergic
to penicillin.
Supportive care
Supportive care of lymphadenitis
includes resting the affected limb and treating the area with hot moist
compresses.
Surgery
Cellulitis associated with
lymphadenitis should not be treated surgically because of the risk of spreading
the
infection. Pus is drained only if there is an abscess and
usually after the patient has been started on antibiotic
treatment.
In some cases, a biopsy of an inflamed lymph node is necessary if no diagnosis
has been made
and no response to treatment has
occurred.
Prognosis
The prognosis for recovery is good if the
patient is treated promptly with antibiotics. In most cases, the
infection can be brought under control in three or four days. Patients
with untreated lymphadenitis may
develop blood poisoning
(septicemia), which is sometimes fatal.
Prevention
Prevention of
lymphadenitis depends on prompt treatment of bacterial and viral
infections.
Key Terms
Hemolytic
Able to break down or
dissolve red blood cells. The bacteria that cause lymphadenitis are
hemolytic.
Hernia
The bulging of a part of the intestine or other
organ through its surrounding wall of tissue. Most hernias are in
the abdominal cavity. An inguinal hernia is located in the groin
area.
Lymph nodes
The glandlike masses of tissue in the lymphatic
system that contain lymphocytes. The lymph nodes also filter
lymph,
which is a clear yellowish tissue fluid that carries lymphocytes and fats
throughout the body.
Lymphangitis
Inflammation of the lymphatic
vessels. It often occurs together with
lymphadenitis.
Septicemia
The presence of bacteria and their
toxins in the bloodstream. Septicemia is sometimes called blood
poisoning.
For Your
Information
McPhee, Stephen, et
al., editors. "Blood Vessels & Lymphatics." In Current Medical Diagnosis
and Treatment,
1998. 37th ed. Stamford: Appleton & Lange,
1997.
------------------------------------------------------
What
Is Sarcoidosis?
Sarcoidosis (sar"koi-do'sis) involves inflammation that
produces tiny lumps of cells in various organs in your
body. The
lumps are called granulomas (gran"u-lo'mahs) because they look like grains of
sugar or sand. They are
very small and can be seen only with a
microscope.
These tiny granulomas can grow and clump together, making
many large and small groups of lumps. If many
granulomas form in an
organ, they can affect how the organ works. This can cause symptoms of
sarcoidosis.
Sarcoidosis can occur in almost any part of your body,
although it usually affects some organs more than others.
It
usually starts in one of two places:
Lungs
Lymph nodes, especially
the lymph nodes in your chest cavity.
Sarcoidosis also often affects
your:
Skin
Eyes
Liver.
Less often, sarcoidosis affects
your:
Spleen
Brain
Nerves
Heart
Tear glands
Salivary
glands
Bones and joints.
Rarely, sarcoidosis affects other organs,
including your:
Thyroid gland
Breasts
Kidneys
Reproductive
organs.
Sarcoidosis almost always occurs in more than one organ at a
time.
Sarcoidosis has an active and a nonactive phase:
In the
active phase, the granulomas form and grow. In this phase, symptoms can
develop, and scar tissue can
form in the organs where the
granulomas occur.
In the nonactive phase, the inflammation goes down, and
the granulomas stay the same size or shrink. But the
scars may
remain and cause symptoms.
The course of the disease varies greatly among
people.
In many people, sarcoidosis is mild. The inflammation that
causes the granulomas may get better on its own. The
granulomas may
stop growing or shrink. Symptoms may go away within a few years.
In some
people, the inflammation remains but doesn't get worse. You may also have
symptoms or flare-ups and
need treatment every now and then.
In
other people, sarcoidosis slowly gets worse over the years and can cause
permanent organ damage. Although
treatment can help, sarcoidosis may
leave scar tissue in the lungs, skin, eyes, or other organs. The scar tissue
can
affect how the organs work. Treatment usually does not affect
scar tissue.
Changes in sarcoidosis usually occur slowly (e.g., over
months). Sarcoidosis does not usually cause sudden
illness. However,
some symptoms may occur suddenly. They include:
Disturbed heart
rhythms
Arthritis in the ankles
Eye symptoms.
In some serious cases in
which vital organs are affected, sarcoidosis can result in
death.
Sarcoidosis is not a form of cancer.
There is no known way
to prevent sarcoidosis.
Sarcoidosis was once thought to be an uncommon
condition. It's now known to affect tens of thousands of
people
throughout the United States. Because many people who have sarcoidosis have no
symptoms, it's hard to
know how many people have the
condition.
Sarcoidosis was identified in the late 1860s. Since then,
scientists have developed better tests to diagnose it and
made
advances in treating it.
The cause of sarcoidosis is not known. And,
there may be more than one thing that causes it.
Scientists think that
sarcoidosis develops when your immune system responds to something in the
environment (e.
g., bacteria, viruses, dust, chemicals) or perhaps
to your own body tissue (autoimmunity).
Normally, your immune system
defends your body against things that it sees as foreign and harmful. It does
this
by sending special cells to the organs that are being affected
by these things. These cells release chemicals that
produce
inflammation around the foreign substance or substances to isolate and destroy
them.
In sarcoidosis, this inflammation remains and leads to the
development of granulomas or lumps.
Scientists have not yet identified
the specific substance or substances that trigger the immune system response in
the first place. They also think that sarcoidosis develops only if
you have inherited a certain combination of genes.
You can't catch
sarcoidosis from someone who has it.
More research is needed to discover
what causes sarcoidosis.
Sarcoidosis affects people of all ages and
races worldwide.
It occurs mostly in:
Adults between the ages of
20 and 40
African Americans (especially women)
People of Asian, German,
Irish, Puerto Rican, and Scandinavian origin.
In the United States,
sarcoidosis affects African Americans somewhat more often and more severely
than
Caucasians.
Studies have shown that sarcoidosis is more
likely to affect certain organs in certain populations. For
example,
Sarcoidosis of the heart and eye appears to be more common in
Japan.
Painful skin lumps on the legs occur more often in people from
Northern Europe.
People who are more likely to get sarcoidosis
include:
Health care workers
Nonsmokers
Elementary and secondary
school teachers
People exposed to agricultural dust, insecticides,
pesticides, or mold
Firefighters.
Brothers and sisters, parents, and
children of people who have sarcoidosis are more likely than others to have
sarcoidosis.
What Are the Signs and Symptoms of Sarcoidosis?
Many
people who have sarcoidosis have no symptoms. Often, the condition is
discovered by accident only
because a person has a chest x ray for
another reason, such as a pre-employment x ray.
Some people have very
few symptoms, but others have many.
Symptoms usually depend on which
organs the disease affects.
Lung Symptoms
Shortness of breath
A
dry cough that doesn't bring up phlegm (flem), or mucus
Wheezing
Pain in
the middle of your chest that gets worse when you breathe deeply or cough
(rare).
Lymph Node Symptoms
Enlarged and sometimes tender lymph
nodes—most often those in your neck and chest but sometimes those under
your chin, in your arm pits, or in your groin.
Skin
Symptoms
Various types of bumps, ulcers, or, rarely, flat areas of
discolored skin, that appear mostly near your nose, eyes,
back,
arms, legs, and scalp. They usually itch but aren't painful. They usually last
a long time.
Painful bumps that usually appear on your ankles and shins and
can be warm, tender, red or purple-to-red in color,
and slightly
raised. This is called erythema nodosum (er"i-the'mah nodo'sum). You may have
fever and swollen
ankles and joint pain along with the bumps. The
bumps often are an early sign of sarcoidosis, but they occur in
other diseases too. The bumps usually go away in weeks to months, even
without treatment.
Disfiguring skin sores that may affect your nose, nasal
passages, cheeks, ears, eyelids, and fingers. This is called
lupus
pernio (loo'pus per'nio). The sores tend to be ongoing and can return after
treatment is over.
Eye Symptoms
Burning, itching, tearing, pain
Red
eye
Sensitivity to light
Dryness
Floaters (i.e., seeing black
spots)
Blurred vision
Reduced color vision
Reduced visual
clearness
Blindness (in rare cases).
Heart Symptoms
Shortness of
breath
Swelling in your legs
Wheezing
Coughing
Irregular heartbeat,
including palpitations (a fluttering feeling of rapid heartbeats) and skipped
beats
Sudden loss of consciousness
Sudden death.
Joint and Muscle
Symptoms
Joint stiffness or swelling—usually in your ankles, feet, and
hands.
Joint pain.
Muscle aches (myalgias).
Muscle pain, a mass in a
muscle, or muscle weakness.
Painful arthritis in your ankles that results
from erythema nodosum. It may need treatment but usually clears up in
several
weeks.
Painless arthritis that can last for months or even years. It should
be treated.
Bone Symptoms
Painless holes in your bones.
Painless
swelling, most often in your fingers.
Anemia that results from granulomas
affecting your bone marrow. This usually should be treated.
Liver
Symptoms
Fever
Fatigue
Itching
Pain in the upper right part of your
abdomen, under the right ribs
Enlarged liver.
Parotid (pah-rot'id) and
Other Salivary Gland Symptoms
Swelling, which makes your cheeks look
puffy
Excessive dryness in your mouth and throat.
Blood, Urinary Tract,
and Kidney Symptoms
Increased calcium in your blood or urine, which can lead
to painful kidney stones
Confusion
Increased urination.
Nervous System
Symptoms
Headaches.
Vision problems.
Weakness or numbness of an arm or
leg.
Coma (rare).
Drooping of one side of your face that results from
sarcoidosis affecting a facial nerve. This can be confused with
Bell's palsy, a disorder that may be caused by a virus.
Paralysis of
your arms or legs that results from sarcoidosis affecting your spinal
cord.
Weakness, pain, or a "stinging needles" sensation in areas where many
nerves are affected by sarcoidosis.
Pituitary (pi-tu'i-tar"e) Gland Symptoms
(Rare)
Headaches
Vision problems
Weakness or numbness of an arm or
leg
Coma (rare).
Other Symptoms
Nasal obstruction or frequent bouts of
sinusitis.
Enlarged spleen, which leads to a decrease in platelets in your
blood and pain in your upper left abdomen. Platelets
are needed to
help your blood clot.
Sarcoidosis may also cause more general symptoms,
including:
Uneasiness, feeling sick (malaise), an overall feeling of ill
health
Tiredness, fatigue, weakness
Loss of appetite or
weight
Fever
Night sweats
Sleep problems
These general symptoms are
often caused by other conditions. If you have these general symptoms but don't
have
symptoms from affected organs, you probably do not have
sarcoidosis.
How Is Sarcoidosis Diagnosed?
Your doctor will find out
if you have sarcoidosis by taking a detailed medical history and conducting a
physical
exam and several diagnostic tests. The purpose is
to:
Identify the presence of granulomas in any of your organs
Rule
out other causes of your symptoms
Determine the amount of damage to any of
your affected organs
Determine whether you need treatment.
Medical
History
Your doctor will ask you for a detailed medical history. He or she
will want to know about any family history of
sarcoidosis and what
jobs you have had that may have increased your chances of getting
sarcoidosis.
Your doctor may also ask whether you have ever been exposed
to inhaled beryllium metal, which is used in
aircraft and weapons
manufacture, or organic dust from birds or hay. These things can produce
granulomas in
your lungs that look like the granulomas that are
caused by sarcoidosis but are actually signs of other
conditions.
Physical Exam
Your doctor will look for symptoms of
sarcoidosis, such as red bumps on your skin; swollen lymph nodes; an
enlarged
liver, spleen, or salivary gland(s); or redness in your eyes. He or she will
also listen for abnormal lung
sounds or heart rhythm. Your doctor
also will check for other likely causes of your symptoms.
Diagnostic
Tests
There is no one specific test for diagnosing sarcoidosis. It is harder
to diagnose sarcoidosis in some organs (e.g.,
heart, nervous
system) than in others. Your doctor will probably conduct a variety of tests
and procedures to help
in the diagnosis.
These
include:
Chest X Ray. A chest x ray takes a picture of your heart and
lungs. It may show granulomas or enlarged lymph
nodes in your chest.
About 95 out of every 100 people who have sarcoidosis have an abnormal chest x
ray.
Doctors usually use a staging system for chest x rays taken to detect
sarcoidosis:
Stage 0: Normal chest x ray
Stage 1: Chest x ray showing
enlarged lymph nodes but otherwise clear lungs
Stage 2: Chest x ray showing
enlarged lymph nodes and shadows in your lungs
Stage 3: Chest x ray showing
shadows in your lungs, but the lymph nodes are not enlarged
Stage 4: Chest x
ray showing scars in the lung tissue.
In general, the higher the stage of the x ray, the worse your symptoms and lung function are. But there are a lot of
differences among people. If your x-ray results show Stages 0,
1, 2, or 3, you may not have symptoms or need
treatment, and you may
get better and have normal chest x rays again over time.
Blood Tests. These
tests can show the number and type of cells in your blood. They also will show
whether there
are increases in your calcium levels or changes in
your liver, kidney, and bone marrow that can occur with
sarcoidosis.
Lung Function Tests. One test uses a spirometer
(spi-rom'e-ter), a device that measures how much and how fast
you
can blow air out of your lungs after taking a deep breath. If there is a lot of
inflammation and/or scarring in
your lungs, you will not be able to
move normal amounts of air in and out.
Another test measures how much air
your lungs can hold. Sarcoidosis can cause your lungs to shrink, and they
will not be able to hold as much air as healthy
lungs.
Electrocardiogram (EKG). This test will help show if your heart is
affected by sarcoidosis.
Pulse Oximetry. A small clip attached to your
finger tip can show how well your heart and lungs are moving
oxygen
into your blood.
Arterial Blood Gas Test. This test is more accurate than
pulse oximetry for checking the level of oxygen in your
bloodstream. Blood is taken from an artery (usually in your wrist). It
is then analyzed for its oxygen and carbon
dioxide
levels.
Fiberoptic Bronchoscopy. In this procedure, your doctor inserts a
long, narrow, flexible tube with a light on the
end through your
nose or mouth into your lungs to look at your airways. This tube is called a
bronchoscope. You
most likely would have this procedure as an
outpatient in a hospital under local anesthesia.
Bronchoalveolar Lavage
(brong"ko-al-ve'o-lar lah-vaje') (BAL). During bronchoscopy, your doctor may
inject a
small amount of salt water (saline) through the
bronchoscope into your lungs. This fluid washes the lungs and
helps
bring up cells and other material from the air sacs deep in your lungs where
the inflammation usually starts
to develop. The cells and fluid are
then examined for signs of inflammation.
Biopsy. Your doctor may take a
small sample of tissue from one of your affected organs. For example, when
breathing tests or chest x rays show signs of sarcoidosis in your
lungs, your doctor may do a fiberoptic
bronchoscopy biopsy. This
will help confirm the diagnosis. Your doctor inserts a tiny forceps through the
bronchoscope to collect tissue that will be examined. Because the
granulomas may be spread out in your lungs, the
bronchoscope may
miss some of them.
Biopsies of your skin and liver are sometimes done to
detect granulomas in these organs.
You may have sarcoidosis in other organs
as well and multiple biopsies may be necessary. However, every organ
involved
does not need to be biopsied for a diagnosis to be made.
Computerized
Tomography (CT) Scan. This test provides a computer-generated image of your
organs that has
more detail than a regular chest x ray. It can
provide more information about how sarcoidosis has affected an
organ.
Your doctor may do a CT scan to:
Obtain more information
about how much of your lung is affected by sarcoidosis.
Detect sarcoidosis
in your liver. A CT scan of your abdomen will show if your liver is enlarged
and if there is a
pattern suggesting granulomas.
Magnetic
Resonance (MR) Scan. This test is also called nuclear magnetic resonance (NMR)
scanning or magnetic
resonance imaging (MRI). This scan uses
powerful magnets and radio waves to make images of some of your
organs that your doctor doesn't want to risk doing a biopsy on. For
example, an MR scan can be used to diagnose
sarcoidosis in your
brain, spinal cord, nerves, or heart.
Thallium and Gallium Scans. These
scans are often done to see if sarcoidosis is affecting your heart. Thallium
and
gallium are radioactive elements. Your doctor injects a small
amount of one of them into a vein in your arm. The
elements collect
at places in your body where there is inflammation. After awhile, your body is
scanned for
radioactivity. Increased radioactivity at any place may
be a sign of inflammation.
This test gives information on the tissue in your
body that has been affected by sarcoidosis and the amount of
damage
to it. But since this test shows all inflammation in your body, even
inflammation caused by conditions
other than sarcoidosis, it does
not give a definite diagnosis of sarcoidosis.
Positron Emission Tomography
(PET) Scan. This test also uses radioactive injections. It may be more
sensitive
than gallium in detecting areas of inflammation. Some
doctors are using it instead of gallium scans.
Your doctor may not need to
find every one of your organs affected by sarcoidosis, only those that cause
symptoms. Often the organs affected by the condition continue to
function well and don't need to be treated.
How Is Sarcoidosis
Treated?
The goals of treatment are to:
Improve how the organs
affected by sarcoidosis work
Relieve symptoms
Shrink the
granulomas.
Treatment may shrink the granulomas and even cause them to
disappear, but this may take many months. If scars
have formed,
treatment may not help, and you may have ongoing symptoms.
Your
treatment depends on:
What symptoms you have
How severe your symptoms
are
Whether any of your vital organs (e.g., your lungs, eyes, heart, or
brain) are affected
How the organ is affected.
Some organs must be
treated, regardless of your symptoms. Others may not need to be treated.
Usually, if you
don't have symptoms, you don't need treatment, and
you probably will recover in time.
Drugs
The main treatment for
sarcoidosis is prednisone. Prednisone is a corticosteroid, or anti-inflammatory
drug.
Sometimes it is used with other drugs. Sometimes other
corticosteroids are used.
Prednisone almost always relieves symptoms of
inflammation. If a symptom doesn't improve with prednisone
treatment within a couple of months, consult your
physician.
Prednisone is usually given for many months, sometimes for a
year or more.
Low doses of prednisone can often relieve symptoms without
causing major side effects.
When used at high doses, prednisone can
cause serious side effects.
Side effects can include:
Weight
gain.
Diabetes.
High blood pressure.
Mood swings
(depression).
Difficulty sleeping at
night.
Heartburn.
Acne.
Thinning of the skin and bones (called
osteoporosis).
Cataracts.
Glaucoma.
Adrenal gland insufficiency, which
occurs when these glands don't make enough of certain hormones. This
requires
treatment by an endocrinologist (en"do-kri-nol'o-jist), a doctor who
specializes in the diagnosis and
treatment of the endocrine glands.
The endocrine glands include your adrenal and pituitary glands.
Aseptic
(a-sep'tik) or avascular (ah-vas'ku-lar) necrosis (ne-kro'sis) of the hip, the
development of cysts and
hardened and dead tissue in the
hip.
Your doctor can usually help you manage these side effects.
When
it is time to stop taking prednisone, you should cut back slowly, with your
doctor's help. This will help
prevent flare-ups of sarcoidosis and
allow your body to adjust to life without the drug.
You may also want to
see an endocrinologist to make sure that your endocrine glands are making
enough
hormones. The endocrinologist may prescribe certain hormones
for you to take until your endocrine glands are
working well
again.
Other Drugs Used To Treat Sarcoidosis
Other drugs are
sometimes used to treat sarcoidosis. Your doctor may prescribe one of them
if:
Your condition gets worse while you are taking prednisone
You
can't stand the side effects of prednisone.
Most of these other drugs are
immune system suppressants. This means that they prevent your immune system
from fighting things like bacteria and viruses. As a result, you may
have a greater chance of getting infections.
Most of these drugs also
can cause serious side effects. Some also could increase your chances of
getting cancer,
especially if you take them at high
doses.
You and your doctor must weigh living with the symptoms of
sarcoidosis against the side effects of the drugs.
Some drugs work
better than others for different people.
You may be given more than one
drug.
Some drugs used to treat sarcoidosis are taken by mouth. Others
are applied locally to an affected area.
Local therapy is the safest way to treat sarcoidosis. The drug is applied directly to the affected area. As a result,
only small amounts of the drug reach other parts of your
body.
Drugs used for local therapy include:
Eye drops
Inhaled
drugs for your lungs
Skin creams.
Drugs can be used locally only if the
affected area is easily reached. For instance, inhaled steroids can ease
coughing and wheezing in the upper airways, but they don't seem to
relieve these symptoms when the affected
lung tissue is deep within
your chest.
Talk with your doctor about these treatments and the side
effects that may occur.
The other drugs used to treat sarcoidosis
include:
Hydroxychloroquine (Plaquenil). This drug can usually help
people who have sarcoidosis in the skin or a high level
of calcium
in their blood. This drug can irritate your stomach.
It also can cause eye
problems. Before starting on this drug, you should see an ophthalmologist
(of"thal-mol'o-
jist), or eye doctor, for some baseline tests. Once
you start taking it, you should have your eyes examined every 6
months.
Methotrexate. This drug is taken once a week by mouth or
injection and usually takes up to 6 months to relieve
symptoms.
This drug may cause side effects, especially if you take
high doses. These include:
Nausea.
Mouth sores.
A decrease in
infection-fighting white blood cells. You then have a greater chance of getting
an infection. If you
take this drug, you should have regular blood
tests to check the levels of your white blood cells.
An allergic reaction in
your lungs that goes away when you stop taking the drug. This is extremely
rare.
Liver damage. This is the most serious side effect. If you take
methotrexate you should be followed regularly by
your
physician.
If you are pregnant, you should not take this drug.
Taking
folic acid can help you reduce your chances of having bad side effects from
methotrexate.
Azathioprine (Imuran). This drug may work in about half of the
people who have sarcoidosis. You usually take it
for at least 6
months. Side effects include:
Nausea
Reduced white blood cell levels,
which increases your chances of getting an infection.
This drug has caused
cancer in some people, especially when they have taken it at high doses.
If
you are pregnant, you should not take this drug.
Cyclophosphamide (Cytoxan).
This is a very toxic drug. It is rarely used to treat sarcoidosis. It is given
only to
people who have serious forms of sarcoidosis, such as
sarcoidosis in their central nervous system
(neurosarcoidosis).
This drug is more likely to cause nausea and
reduce your white blood cell levels than either methotrexate or
azathioprine. Your doctor should check your white blood cell levels
often while you are taking this drug to make
sure you have a high
enough level to fight infection.
Cyclophosphamide can also irritate your
bladder. Some people who have taken it for more than 2 years have
developed bladder cancer.
If you are pregnant, you should not take
this drug.
Cyclophosphamide can be given intravenously (through one of your
veins), which lessens some of its side effects,
but this doesn't
reduce the risk of cancer.
Treatments for Specific Types of
Sarcoidosis
Eyes. Sarcoidosis in your eyes almost always responds well to
treatment. Often, the only treatment you need is
eye drops
containing corticosteroids. You should have yearly eye exams, even if you think
your eyes are doing
well.
Spleen. Sarcoidosis can cause your
spleen to become larger. This can lead to a decrease in your red or white
blood cells or platelets and increase your chances of infection and
blood clotting disorders. Treatment is usually
given to increase
the number of your blood cells and ease your pain. In rare cases, your spleen
may need to be
removed.
Liver. Sarcoidosis rarely causes
permanent liver damage. As a result, your liver usually isn't treated unless
it's
causing major symptoms (e.g., fever). Drug treatment can
usually reduce granulomas in your liver. Liver
transplantation has
been successful in those rare cases in which the condition has become
worse.
Followup care includes regular blood tests to find out how well your
liver is working. You should check with your
doctor to find out how
often you need these tests.
Nervous system. Sarcoidosis in your nervous
system (neurosarcoidosis) usually needs treatment. Nerve tissue
heals slowly, so treatment often takes a long time. You may need to
take several drugs at high doses.
Erythema nodosum. These painful bumps on
your shins often go away in weeks to months without treatment.
Your
doctor probably will not give you medication unless you are very uncomfortable.
Aspirin or ibuprofen, an
anti-inflammatory drug that you can buy
without a prescription, will usually help.
Heart. Sarcoidosis in your heart
is usually treated with steroids. You may also be given heart drugs to improve
your heart's pumping ability or to correct a disturbed heart
rhythm.
If you have a severe heart rhythm disturbance, your doctor may
prescribe one of these devices:
A cardiac pacemaker, a small
battery-operated device, often put under your skin, that regulates your
heartbeat
A defibrillator, an implanted device that shocks your heart into a
normal heartbeat or, if it has stopped, into beating.
If your heart is
severely affected and doesn't respond to treatment, a transplant may be done.
But this is rarely
needed.
Lupus Pernio. This rash on your face,
especially your cheeks and nose, can be distressing because it's in a very
visible area. It often occurs with loss of your sense of smell, nasal
stuffiness, and sinus infections.
Options for treatment include:
Local
treatment with skin creams
Oral drugs (plaquenil or prednisone, for
example)
Local injections of steroid preparations.
Lupus pernio is often
treated by dermatologists, doctors who specialize in skin diseases, working
with a
sarcoidosis specialist.
Because sarcoidosis varies so
much among different people, your doctor may find it hard to tell whether the
treatment is helping.
Other Drugs Being Studied for Possible
Use in Treating Sarcoidosis
Scientists also are studying drugs that are used
for other conditions to see if they can help people who have
sarcoidosis. These drugs include:
Etanercept (Enbrel). This drug
is an immune system suppressant. It's injected under the skin to reduce
symptoms
of rheumatoid arthritis. It may also be used to treat psoriasis (so-ri'ah-sis) or ankylosing spondylitis (ang"ki-lo'sing
spon"di-li'tis), a type of arthritis that affects the joints in the
spine. Early studies suggest that it will not be useful in
treating
sarcoidosis, but research is ongoing.
Infliximab (Remicaide). This drug is
an immune system suppressant. It's injected into a vein in your arm. It's used
to treat Crohn's Disease, rheumatoid arthritis, and ankylosing
spondylitis. Some studies have shown it to help
sarcoidosis
patients who also have lupus pernio, eye disease, or neurosarcoidosis. This
drug has serious side
effects but may improve lung function in some
people who aren't helped by corticosteroids. More research is
needed.
Pentoxifylline. This drug is an immune system suppressant.
Stomach and gastrointestinal side effects are
common. Early studies
show that it has helped some people who have sarcoidosis in their lungs reduce
their doses
of prednisone while taking it. More research is
needed.
Tetracycline. Tetracycline antibiotics are used to treat Lyme
Disease, some types of pneumonia, and acne. A few
small studies
suggest that they may help in treating sarcoidosis in the skin. Research is
ongoing.
Thalidomide. This immune system suppressant can cause bad side
effects. It is effective against other conditions
that involve
granulomas of the skin (e.g., leprosy, tuberculosis). Scientists are studying
this drug to see if it can be
used to treat sarcoidosis in the
skin. More studies are needed.
What Does the Future Hold?
Scientists
worldwide are trying to learn more about sarcoidosis and how to improve its
diagnosis and treatment.
Some recent studies have led to possible
new treatments, which, in turn, are being studied. Current research
includes studies of:
The agent or agents that cause
sarcoidosis
Why sarcoidosis seems to act differently in people of different
races
Why sarcoidosis appears in some families
How genes, passed from one
generation to another, may make some people more likely than others to develop
sarcoidosis
How cells act and communicate with each other to
cause sarcoidosis symptoms.
Living With Sarcoidosis
You should take steps
to stay healthy. This includes:
Don't smoke.
Avoid substances like
dusts and chemicals that can harm your lungs.
Try to follow a healthy eating
plan.
Be as active as you can but don't strain yourself.
Joining a
patient support group may help you adjust to living with sarcoidosis. Talking
to others who have the
same symptoms can help you see how they have
coped with them. To find a local support group, check your
telephone directory or contact one of the sarcoidosis groups listed
under Links.
Your regular doctor may be able to diagnose and treat your
sarcoidosis, but diagnosis and treatment by a doctor
who
specializes in sarcoidosis is recommended. If you prefer to use your regular
doctor, you should see a doctor
who specializes in the organs that
are affected by your sarcoidosis at least once. For example, see an
ophthalmologist if your eyes are affected or a pulmonologist if you
have sarcoidosis in your lungs. These
specialists are often found
at major medical centers. They will work with your regular doctor to help make
a
diagnosis, develop a treatment plan, and schedule periodic exams
and lab tests. .
Pregnancy
Many women give birth to healthy babies
while being treated for sarcoidosis. Pregnancy usually doesn't affect the
course of sarcoidosis, and you can continue corticosteroid treatment
through your pregnancy. None of the other
drugs are recommended for
use during pregnancy.
Sometimes your sarcoidosis may get worse after the
baby is delivered.
Women with severe sarcoidosis, especially if they are
older, may have trouble becoming pregnant.
It's important for you to
discuss this issue with your doctor. If you become pregnant, you should be sure
to get
both good prenatal care and regular sarcoidosis checkups
during and after pregnancy.
Followup Care
Regular followup care is
important, even if you aren't taking medication for your sarcoidosis. New
symptoms can
occur at any time, and your condition can get worse
slowly, without your noticing.
Followup exams usually include:
A
review of your symptoms
A physical exam
A chest x ray and CT
scan
Breathing tests
An eye exam
Blood tests
An electrocardiogram
(EKG).
How often you have your examinations and tests depends on:
How
severe your symptoms are
Which organs were affected at diagnosis
What
treatment you are using
Any complications that may develop during
treatment.
You will probably need routine followup care for several years.
Whether you see your regular doctor or a
sarcoidosis specialist for
this depends on your symptoms during the first year of followup.
Here
are some examples of how your followup care can be managed. They are based on
either your condition
when you were diagnosed with sarcoidosis or
the treatment used.
Followup After Initial Diagnosis
If at
diagnosis, you have no symptoms, a normal breathing test, and an abnormal chest
x ray:
You should plan on having a followup exam every 6 to12 months until
your condition is stable or improving.
Your breathing test may need
to be repeated. The need to repeat it depends on your symptoms and ability to
be
active.
If at your first followup visit, you have no new
symptoms and your chest x ray is normal, you can go to your
regular
doctor for future followup care.
If at diagnosis, you have some
symptoms, an abnormal chest x ray, but you don't need treatment:
You should
plan on having a followup exam in 3 to 6 months.
If at your followup exam,
your condition has gotten worse (i.e., you now have more symptoms, an abnormal
x
ray, or abnormal lab tests) you may need treatment.
If
treatment is started, you may need followup tests more often.
Followup Based
on Your Drug Treatment
If treatment is begun with prednisone:
You
should be checked for the side effects of high blood pressure, too much weight
gain, diabetes, loss of
calcium from your bones, and pain in one or
both hips.
If treatment is begun with hydroxychloroquine:
You should
have an eye exam every 6 months while taking this drug.
If treatment is
begun with methotrexate:
You should have blood tests every month or
every other month to see if you have anemia, low white blood cell or
platelet
levels, or liver inflammation.
Other Followup Tests
Depending on how
serious your condition is and what organs are affected, you may also need to
have certain tests
done regularly.
Eye Tests
Everyone who
is diagnosed with sarcoidosis, even if they don't have eye symptoms, should see
an ophthalmologist
(eye doctor) for eye tests. This is important
because you may have eye damage even if you don't have symptoms.
These
tests may include:
A slit lamp examination. Your doctor uses an
instrument with a high-intensity light source to look at the front of
your
eyes.
A visual fields examination. Your doctor will ask you to you to look
at a light through an instrument.
Inspection of your retina and optic
nerve.
If you develop eye symptoms, your doctor will have you repeat the
tests.
You should also have regular eye exams if you are being treated
with:
Chloroquine or hydroxycholoroquine
(Plaquenil)
Corticosteroids.
Breathing Tests
These tests are used to
check the course of sarcoidosis in your lungs. The results are compared over
time.
Blood Tests
A blood test for calcium should be done. If your
calcium level is high, you probably will need to be treated. You
also should not take vitamin and mineral supplements containing calcium
or vitamin D, and you should avoid too
much exposure to the
sun.
Electrocardiogram
This test is needed to make sure that your
heart is still not affected by sarcoidosis. The heart can be affected at
any time if the sarcoidosis is active.
www.nhlbi.nih.gov/health/dci/Diseases/sarc/sar_whatis.html
---------------------------------------------------------
microlymphatic
hypertension LYMPHOEDEMA
Microlymphatics of human skin.
Int J
Microcirc Clin Exp. 1993; 12(1):1-15 (ISSN: 0167-6865)
Bollinger
A
Department of Internal Medicine, University Hospital, Zurich,
Switzerland.
Microlymphatics of human skin form two superposed networks.
The superficial one located at the level of dermal
papillae may be
visualized by fluorescence microlymphography. Microlymphatics fill from a
subepidermal depot of
minute amounts of FITC-dextran 150,000. In
primary lymphedema with late onset the depicted network with
vessels of normal size is significantly larger than in healthy
controls, whereas in congenital lymphedema (Milroy's
disease)
microlymphatics are aplastic or ectatic (diameter > 90 microns). Lymphatic
microangiopathy with
obliterations of microvessels develops in
chronic venous insufficiency, in lipedema (preliminary results) and after
recurrent erysipelata. In healthy controls microlymphatics are
permeable to FITC-dextran 40,000 and impermeable
to the larger
molecule 150,000. Preserved fragments of the network in chronic venous
insufficiency exhibit
increased permeability to FITC-dextran
150,000. After visualization of the vessels by the fluorescent dye
microlymphatic pressure may be measured by the servo-nulling technique.
First results indicate that
microlymphatic hypertension contributes
to edema formation in patients with primary lymphedema.
PreMedline
Identifier: 8473066
http://www.ewma.org/pdf/fall05/focus_eng.pdf
----------------
Anti-fibrosclerotic
effects of shock wave therapy in lipedema and cellulite.
Biofactors. 2005;
24(1-4):275-82 (ISSN: 0951-6433)
Siems W; Grune T; Voss P; Brenke
R
Loges-School of Physiotherapy, Research Institute of Physiotherapy &
Gerontology, D-38667 Bad Harzburg,
Germany.
[email protected]
In vivo measurements in 26 female patients with
lipedema and cellulite parameters were carried out before and
after
therapy by means of complex physical decongestive therapy (CPDT) including
manual lymph drainage and
compression as main components and/or
shock wave therapy (SWT). Oxidative stress parameters of blood serum
and
biomechanic skin properties/smoothening of dermis and hypodermis surface were
evaluated. Oxidative stress
in lipedema and cellulite was
demonstrated by increased serum concentrations of malondialdehyde (MDA) and
plasma protein carbonyls compared with healthy control persons. Both
MDA and protein carbonyls in blood
plasma decreased after serial
shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA
release from edematous tissue into the plasma. Obviously both therapy
types, SWT and CPDT, mitigate oxidative
stress in lipedema and
cellulite. In parallel SWT improved significantly the biomechanic skin
properties leading to
smoothening of dermis and hypodermis surface.
Significant correlation between MDA depletion of edematous and
lipid enriched dermis and improvement of mechanic skin properties was
demonstrated. From these findings it is
concluded, that a release
of lipid peroxidation (LPO) products from edematous dermis is an important
sclerosis-
preventing effect of SWT and/or CPDT in lipedema and
cellulite. Expression of factors stimulating angiogenesis
and
lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and,
therefore, not involved in
beneficial effects by SWT and/or
CPDT.
PreMedline Identifier:
16403988
-----------------------------
Stewart-Treves
Syndrome
Article Last Updated: Mar 28, 2007
AUTHOR AND EDITOR
INFORMATIONSection 1 of 9 Authors and Editors Introduction Clinical
Differentials
Workup Treatment Follow-up Miscellaneous
References
Author: Geover Fernandez, MD, FAAD, Staff Physician,
Department of Dermatology, University of Medicine and
Dentistry New
Jersey, New Jersey Medical School
Geover Fernandez is a member of the
following medical societies: Alpha Omega Alpha, American Academy of
Dermatology, and American Society for MOHS Surgery
Coauthor(s):
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of
Medicine,
Professor of Pediatrics, Professor of Pathology,
Professor of Preventive Medicine and Community Health,
UMDNJ-New
Jersey Medical School
Editors: Abby S Van Voorhees, MD, Assistant
Professor, Director of Psoriasis Services and Phototherapy Units,
Department of Dermatology, University of Pennsylvania School of
Medicine, Hospital of the University of
Pennsylvania; Michael J
Wells, MD, Associate Professor, Department of Dermatology, Texas Tech
University
Health Sciences Center; Christen M Mowad, MD, Assistant
Professor, Department of Dermatology, Geisinger
Medical Center; Glen
H Crawford, MD, Assistant Clinical Professor, Department of Dermatology,
University of
Pennsylvania School of Medicine; Chief, Division of
Dermatology, The Pennsylvania Hospital; William D James,
MD, Paul R
Gross Professor of Dermatology, University of Pennsylvania School of Medicine;
Vice-Chair,
Program Director, Department of Dermatology, University
of Pennsylvania Health System
Author and Editor
Disclosure
Synonyms and related keywords: cutaneous angiosarcoma,
postmastectomy angiosarcoma, lymphangiosarcoma in
postmastectomy
lymphedema, postlymphedema angiosarcoma, hemangiosarcoma in chronic lymphedema,
hemangiosarcoma in postmastectomy lymphedema, postmastectomy
lymphedema, lymphangiosarcoma, Milroy
disease, Milroy's disease,
idiopathic lymphedema, congenital lymphedema, traumatic lymphedema, filarial
lymphedema
INTRODUCTIONSection 2 of 9 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Follow-up Miscellaneous
References
Background
Stewart-Treves syndrome is a rare, deadly
cutaneous angiosarcoma that develops in long-standing chronic
lymphedema. Most commonly, this tumor is a result of lymphedema induced
by radical mastectomy to treat breast
cancer. Unfortunately,
although the breast cancer may be cured with such radical surgery, this second
primary
cancer may be responsible for the patient's worsening
course. The term Stewart-Treves syndrome is broadly
applied to an
angiosarcoma that arises in a chronically lymphedematous region due to any
cause, including
congenital lymphedema and other causes of secondary
lymphedema unassociated with mastectomy. As reported
by Durr et al
in 2004, this lymphangiosarcoma occurs as a rare complication.
Lymphangiosarcoma is a misnomer
because this malignancy seems to
arise from blood vessels instead of lymphatic vessels. A more appropriate name
is hemangiosarcoma.
In 1906, Lowenstein first described
angiosarcoma in a patient's arm that had been affected by severe
posttraumatic lymphedema for 5 years. In 1948, Stewart and Treves
reported this rare secondary malignancy in 6
cases of angiosarcoma
in postmastectomy lymphedema. They recognized that an edematous arm after
radical
mastectomy for breast cancer may suggest recurrent breast
cancer, but that long-standing chronic edema without
recurrent
cancer may occasionally produce "a heretofore unrecognized and unreported
sequel ... long after the
malignant breast neoplasm has apparently
been arrested ... a new specific tumor." Stewart and Treves suggested
that
these angiosarcomas were probably not observed previously because they were
mistaken for recurrent,
inoperable, cutaneous manifestations of
breast cancer.
Lymphangiosarcoma has been described in Milroy disease
and in idiopathic, congenital, traumatic, or filarial
lymphedema.
A case of lymphangiosarcoma in hereditary lymphedema
of the lower extremity has been reported in a 36-year-old
woman.
Despite of chemotherapy, local hyperthermia, and later amputation of the
extremity, the patient died of
progressive disease due to pulmonary
metastasis. In respect to this case, the different therapeutic concepts, as
reported in the literature, and their results are presented and
discussed.
Pathophysiology
The pathogenic mechanism by which
lymphedema may induce angiosarcoma has been the subject of controversy.
Stewart and Treves found a high incidence of third malignancies in
patients with postmastectomy angiosarcoma.
Thus, they speculated
that a systemic carcinogenic factor was the main causative factor in the
pathogenesis of
lymphangiosarcomas.
In 1979, Schreiber and
others postulated the concept of local immunodeficiency in the presence of
lymphedema.
This theory is supported by experimental evidence. In
1960, Stark and associates demonstrated that homograft
skin
transplanted to lymphedematous arms survive much longer than those transplanted
to healthy arms.
Therefore, lymphedema may cause some degree of
local immunodeficiency and lead to oncogenesis.
The possibility that
radiation therapy has an important role in the induction of lymphangiosarcoma
is also
postulated. Sternby et al reported that, in their study,
the patient with the shortest interval between radical
mastectomy
and the onset of the tumor (8 mo) received both preoperative radiation therapy
of the breast and
involved axillary lymph nodes followed by
fractionated radiation. Others suggest that irradiation is not an essential
factor in the pathogenesis of this tumor. Finally, irradiation may be
an indirect cause of lymphangiosarcomas
because it may cause
axillary node sclerosis and thereby accelerate and aggravate the
edema.
Frequency
International
Currently, approximately 400 cases
are reported in the world literature. In 1962, Schirger calculated that the
incidence of this disease is 0.45% in patients who survive at least 5
years after radical mastectomy. Others have
noted a much lower
incidence of 0.07% in patients after
mastectomy.
Mortality/Morbidity
Lymphangiosarcomas are extremely
aggressive tumors with a high local recurrence rate and a tendency to
metastasize
early to many areas. Long-term survivors are the
exceptions.
Metastatic angiosarcoma to the lungs and chest wall are
the most common cause of death in patients with Stewart-
Treves
syndrome.
Metastases to the liver and bones can also occur.
Lymphangiomas
are associated with a high rate of local recurrence and metastasis, even after
aggressive surgical
treatment.
Race
No racial
predominance exists.
Sex
Most patients with Stewart-Treves syndrome
are women with a history of breast cancer that has been treated
with radical mastectomy, which causes chronic
lymphedema.
Age
Stewart-Treves syndrome usually occurs in middle-aged
or elderly women, a few years or many years after
mastectomy.
In 1981, Sordillo and associates reported a peak
incidence in persons aged 65-70 years.
In 1972, Woodward et al described a
series of 23 patients in a review of 163 cases of Stewart-Treves syndrome
from the literature. They recorded an average patient age of 68.8 years
at the onset of lymphangiosarcoma; the
youngest patient was aged 44
years and the oldest, 84 years.
CLINICALSection 3 of 9
Authors and Editors Introduction Clinical Differentials Workup Treatment
Follow-up
Miscellaneous References
History
This tumor
typically develops in patients many years after mastectomy, more commonly 5-15
years after surgery.
In their original series, Stewart and Treves
reported that the earliest angiosarcoma appeared 6 years after radical
mastectomy, the longest interval being 24 years (average, 12.5 y).
In
1988, Tomita and associates demonstrated that the most common interval between
radical mastectomy and the
onset of lymphangiosarcoma was 5-14
years.
In 1981, Yap et al reported a series of 22 patients in whom the
median interval from mastectomy to the onset of
angiosarcoma was 11
years (range, 5-16 y).
Physical
As Stewart and Treves described,
edema occurs first.
Severe chronic edema of an upper extremity usually
occurs in patients with Stewart-Treves syndrome.
In patients who undergo
radical mastectomy, edema first appears on the arm on the side operated
on.
The occurrence of edema is not associated with complications such as
postoperative infection or thrombosis.
The edematous area gradually extends
from arm to forearm and dorsal aspect of the hand and fingers.
Initially,
pain is absent, although skin distention may produce local discomfort.
In
the areas of long-standing chronic edema, recurrent erysipelas may occur, just
as they do in patients with
congenital lymphedema.
The skin
tends to become atrophic and eventually pachydermatous, with prominent wrinkle
lines. At times,
hyperkeratoses and telangiectasias can be
observed.
After an interval of 1-30 years, a purplish patch appears that
then develops into a plaque or nodule in the area of
chronic
lymphedema.
Other initial lesions may include a palpable subcutaneous mass
or a poorly healing eschar with recurrent bleeding
and
oozing.
The lesions of Stewart-Treves syndrome typically appear as multiple
reddish blue macules or nodules that may
become
polypoid.
Around these nodules, small satellite areas can develop and
become confluent, forming an enlarging lesion.
Sometimes, a bullous
component may be seen.
As the angiosarcoma continues to grow and expand, the
overlying atrophic epidermis may ulcerate, producing
recurrent
episodes of bleeding and infection.
Necrosis may be evident in advanced
cutaneous tumors.
Ultimately, extensive cutaneous nodules and systemic
metastases appear. These nodules most commonly occur in
the lungs
and cause the patient's death.
Not every tumor in an area of lymphedema is
an angiosarcoma.
Causes
The most important single causative agent
in Stewart-Treves syndrome is prolonged chronic lymphedema.
Although
Stewart-Treves syndrome develops after radical mastectomy in most patients,
lymphangiosarcoma also
develops in other forms of acquired
lymphedema and in congenital lymphedema.
Causes for such secondary
lymphedema may include trauma, surgical invasion of the groin for the treatment
of
penile or cervical cancer, filariasis, idiopathic acquired
lymphedema, vascular stasis, and morbid obesity.
Edema secondary to cardiac
or renal disease is not associated with this malignancy. Thus, edema alone is
not
sufficient to cause lymphangiosarcoma. Perhaps additional
factors such as a genetic predisposition are
required.
DIFFERENTIALSSection 4 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment
Follow-up
Miscellaneous References
Angioedema, Acquired
Angioedema,
Hereditary
Angioendotheliomatosis
Angiolymphoid Hyperplasia with
Eosinophilia
Kaposi
Sarcoma
Lymphangiectasia
Lymphangioma
Lymphocytoma Cutis
Malignant
Melanoma
Metastatic Carcinoma of the Skin
Other Problems to be
Considered
Telangiectatic metastatic breast disease to the
skin
Hemangioendotheliomas
Hemangiopericytomas
WORKUPSection
5 of 9 Authors and Editors Introduction Clinical Differentials Workup
Treatment Follow-up
Miscellaneous References
Lab
Studies
Although Stewart-Treves syndrome is also known as
lymphangiosarcoma, ultrastructural and immunohistologic
studies
show that this malignancy arises from blood vessels rather than lymphatic
vessels.
The following immunohistologic and ultrastructural findings can be
used to confirm that the tumor originates from
blood
vessels.
Antibodies against factor VIII–related antigen are markers for
endothelial cells. Although malignant endothelial cells
may not
always show positive staining with this marker, a more sensitive endothelial
marker, lectin Ulex europaeus-
I, is more likely to react with
hemangiosarcoma tumor cells. However, the specificity of this marker is reduced
in
people with blood group O because normal epithelial cells and
carcinomas also bind this lectin in these individuals.
CD34 antigen is a
marker of vascular endothelial cells and does not react with the lymphatic
endothelium.
Antikeratin antibodies show no evidence of keratin in this
malignancy; this finding confirms that the tumor cells
are
nonepithelial in origin.
Positive staining for laminin, CD31, collagen IV,
and vimentin can aid in diagnosing the tumors as angiosarcomas.
Imaging
Studies
MRI is recommended to evaluate the local extent of
angiosarcomas. However, its true value is in question because
of
poor results in delineating the margin of the tumor. It may be low in signal
intensity on T2-weighting and short-
tau inversion recovery (STIR)
imaging, reflecting the densely cellular, fibrous stroma and sparsely
vascularized
tumor histology (Schindera, 2005). Additional
administration of intravenous contrast medium may reveal
significant enhancement of the tumorous lesions.
Chest CT should be
performed to rule out metastatic disease to the lungs before the patient
undergoes extensive
surgery.
Chest radiography can help in
identifying pulmonary metastases and pleural
effusion.
Procedures
Analysis of a biopsy specimen is essential
to the diagnosis of lymphangiosarcoma.
Fine needle aspiration is inadequate
for diagnosis.
Histologic Findings
Histologically, angiosarcomas in
Stewart-Treves syndrome are indistinguishable from angiosarcomas in
nonlymphedematous sites. Postlymphedema angiosarcomas are characterized
by proliferating vascular channels,
which dissect the dermal
collagen and, often, the obliterate appendages. Tumor endothelial cells lining
these
channels show marked hyperchromatism and pleomorphism. Mitoses
are commonly seen in these tumor cells.
The vascular endothelial
cells appear round or oval, and they are protuberant and often project into the
lumen.
Erythrocytes can be seen inside these vascular channels. The
overlying epidermis may be hyperkeratotic and
acanthotic, or it may
be atrophic. Prominent proliferation of reticular fibers can be seen in
association with this
malignancy.
At electron microscopic
examination, lymphangiosarcoma cells are surrounded by a complete basal lamina.
In
some tumor cells, pinocytosis, intercellular junctions, and
cytoplasmic intermediate filaments are observed. In
addition,
Weibel-Palade bodies and erythrophagocytosis are often present. These
ultrastructural findings suggest a
vascular endothelial origin
rather than a lymphatic endothelial origin.
Staging
In 1959,
McConnell and Haslam divided the course of development of lymphangiosarcoma
into 3 stages. This
staging system lacks universal
application.
Stage 1 - Prolonged lymphedema
This stage is
characterized by extensive edema that causes the degeneration of fat and
collagen mainly in the deep
part of the dermis.
Edema separates
the collagen bands, creating a misperception of an increased amount of fibrous
tissue in the area.
Stage 2 - Premalignant angiomatosis
This stage
involves multiple foci of small, proliferating channels in the dermis and
subdermis. These vessels are
lined by hyperplastic endothelial
cells, as well as normal, flattened cells.
The areas of angiomatosis vary in
size, ranging from 100 µm to a couple of centimeters in
diameter.
Superficial areas can be seen as bruises or vesicles, whereas
deeper areas are seen as areas of induration and
hemorrhage.
Early lesions show little evidence of malignancy, but
more advanced lesions reveal early malignant transformation
with an
increased number of mitotic figures and pleomorphic cells.
Stage 3 - Frankly
malignant angiosarcoma
These aggressive tumors develop from areas of
premalignant angiomatosis.
The histologic features of this malignancy are
described above in stage 2.
TREATMENTSection 6 of 9 Authors
and Editors Introduction Clinical Differentials Workup Treatment Follow-
up Miscellaneous References
Medical
Care
Chemotherapy and irradiation continue to be evaluated as
adjuvants to surgery.
Currently, these treatment options offer little
benefit.
In 2000, Grobmyer and associates found no statistical significant
difference in the survival rates of patients treated
with
chemotherapy compared with those treated with irradiation.
Although
long-term survivors after either radiation therapy or systemic chemotherapy
have been reported, the
overall results have been
discouraging.
As a result of these findings, these treatment options are
reserved for patients with inoperable, advanced disease or
those
who refuse surgery.
In 1994, Furue et al demonstrated that immunotherapy may
be beneficial as palliative treatment for pleural
effusions caused
by metastatic angiosarcoma.
Surgical Care
Early amputation or
wide local excision provides the best chance of long-term survival in patients
with Stewart-
Treves syndrome. Some authorities favor radical
ablative surgery with an early diagnosis, in order to confer a
reasonable prognosis with this rare but aggressive disease (Roy, 2005).
A nihilistic approach is undesirable.
The most common approach in
patients with lymphangiosarcoma is amputation of the limb or forequarter rather
than wide local surgical excision.
Even in cases with early
surgical treatment, the prognosis is disappointing, with a high rate of local
recurrence and
metastasis.
Metastatic disease should exclude
surgical treatment unless surgery is useful for symptomatic
improvement.
Chemotherapy, immunotherapy, and/or radiation therapy can be
used as adjuvants to surgery (see Medical
Care).
FOLLOW-UPSection 7 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment Follow-
up
Miscellaneous References
Further Inpatient Care
Complications
from metastatic disease, such as pleural effusions, may require hospitalization
of the patient.
The patient may need further inpatient care for pain
control.
Deterrence/Prevention
The most efficient way to avoid
this highly lethal disease is by preventing or treating long-standing
lymphedema,
which predisposes individuals to this lymphangiosarcoma
years later.
Other complications commonly associated with chronic
lymphedema, such as erysipelas and deep venous
thromboses, must be
prevented by regularly examining these areas and then treating them.
Early
biopsy of any suggestive lesion should be performed because early diagnosis and
surgical treatment offers
the highest rate of long-term
survival.
Complications
Patients can present with recurrent
episodes of erysipelas and deep venous thromboses in areas of chronic
lymphedema.
Other
complications include recurrent infections and
malignancies.
Prognosis
The prognosis is dismal.
The
5-year survival rate reported by Sordillo et al in 1981 is 13.6%, and it is
8.5% in the series by Woodward et al.
In 1987, Hultberg found that patients
with Stewart-Treves syndrome had a mean survival of 20 months after
tumor onset.
Untreated patients have an average survival of 5-8
months.
Patient Education
Patients should be informed about the
significance of prolonged chronic lymphedema and about how to reduce
and
control it.
Patients should be encouraged to seek early medical attention if
they notice unexplained skin changes or
unresolved
lymphedema.
Patients should be educated about complications, such as
recurrent infections, deep venous thrombosis, and
malignancies,
that can occur with lymphedema.
For excellent patient education resources,
visit eMedicine's Women's Health Center and Cancer and Tumors
Center. Also, see eMedicine's patient education articles Mastectomy and
Breast Cancer.
MISCELLANEOUSSection 8 of 9 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Follow-up Miscellaneous References
Medical/Legal
Pitfalls
Failure to perform biopsy to evaluate suspicious skin lesions
in patients with long-standing lymphedema is a
pitfall.
REFERENCESSection 9 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment Follow-
up
Miscellaneous References
Breidenbach M, Rein D, Schmidt T, et al.
Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-
Treves
syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity
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Cozen W, Bernstein L, Wang
F, et al. The risk of angiosarcoma following primary breast cancer. Br J
Cancer. Oct
1999;81(3):532-6. [Medline].
Dürr HR, Pellengahr C,
Nerlich A, et al. Stewart-Treves syndrome as a rare complication of a
hereditary
lymphedema. Vasa. Feb 2004;33(1):42-5.
[Medline].
Furue M, Yamada N, Takahashi T, et al. Immunotherapy for
Stewart-Treves syndrome. Usefulness of intrapleural
administration
of tumor-infiltrating lymphocytes against massive pleural effusion caused by
metastatic
angiosarcoma. J Am Acad Dermatol. May 1994;30(5 Pt
2):899-903. [Medline].
Goetze S, Schmook T, Audring H. [Successful treatment
of Stewart-Treves syndrome with liposomal
doxorubicin]. J Dtsch
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Grobmyer SR, Daly JM,
Glotzbach RE, Grobmyer AJ 3rd. Role of surgery in the management of
postmastectomy
extremity angiosarcoma (Stewart-Treves syndrome). J
Surg Oncol. Mar 2000;73(3):182-8. [Medline].
Hallel-Halevy D, Yerushalmi J,
Grunwald MH, et al. Stewart-Treves syndrome in a patient with elephantiasis. J
Am
Acad Dermatol. Aug 1999;41(2 Pt 2):349-50.
[Medline].
Heitmann C, Ingianni G. Stewart-Treves syndrome:
lymphangiosarcoma following mastectomy. Ann Plast Surg.
Jan
2000;44(1):72-5. [Medline].
Hultberg BM. Angiosarcomas in chronically
lymphedematous extremities. Two cases of Stewart-Treves
syndrome. Am
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Krause KI, Hebert AA,
Sanchez RL, Solomon AR Jr. Anterior abdominal wall angiosarcoma in a morbidly
obese
woman. J Am Acad Dermatol. Aug 1986;15(2 Pt 2):327-30.
[Medline].
Laguerre B, Lefeuvre C, Kerbrat P, Hassel M. [Stewart-Treves
syndrome arising in post-traumatic lymphedema].
Bull Cancer. Mar
1999;86(3):279-82. [Medline].
Lowenstein S. Der atiologische zusammenhang
zwischen akutem ein-maligem trauma und sarkon. Beitr Z klin Clir.
1906;48:780.
McConnell AH, Haslam P. Angiosarcoma in post-mastectomy
lymphedema: report of five cases and review of the
literature. Br J
Surg. 1959;46:322-32.
Muller R, Hajdu SI, Brennan MF. Lymphangiosarcoma
associated with chronic filarial lymphedema. Cancer. Jan 1
1987;59(1):179-83. [Medline].
Nakazono T, Kudo S, Matsuo Y, et al.
Angiosarcoma associated with chronic lymphedema (Stewart-Treves
syndrome) of the leg: MR imaging. Skeletal Radiol. Jul 2000;29(7):413-6.
[Medline].
Offori TW, Platt CC, Stephens M, Hopkinson GB. Angiosarcoma in
congenital hereditary lymphoedema (Milroy''s
disease)-- diagnostic
beacons and a review of the literature. Clin Exp Dermatol. Mar
1993;18(2):174-7. [Medline].
Roy P, Clark MA, Thomas JM. Stewart-Treves
syndrome--treatment and outcome in six patients from a single
centre. Eur J Surg Oncol. Nov 2004;30(9):982-6. [Medline].
Ruocco V,
Schwartz RA, Ruocco E. Lymphedema: an immunologically vulnerable site for
development of
neoplasms. J Am Acad Dermatol. Jul 2002;47(1):124-7.
[Medline].
Schindera ST, Streit M, Kaelin U, et al. Stewart-Treves syndrome:
MR imaging of a postmastectomy upper-limb
chronic lymphedema with
angiosarcoma. Skeletal Radiol. Mar 2005;34(3):156-60. [Medline].
Schirger A.
Postoperative lymphedema: etiologic and diagnostic factors. Med Clin North Am.
Jul 1962;46:1045-
50. [Medline].
Schreiber H, Barry FM, Russell
WC, et al. Stewart-Treves syndrome. A lethal complication of postmastectomy
lymphedema and regional immune deficiency. Arch Surg. Jan
1979;114(1):82-5. [Medline].
Schwartz RA, Kardashian JF, McNutt NS, et al.
Cutaneous angiosarcoma resembling anaplastic Kaposi''s sarcoma
in a
homosexual man. Cancer. Feb 15 1983;51(4):721-6. [Medline].
Schwartz RA.
Kaposi's sarcoma. In: Schwartz RA, ed. Skin Cancer: Recognition and Management.
1988:80-8.
Sinclair SA, Sviland L, Natarajan S. Angiosarcoma arising in a
chronically lymphoedematous leg. Br J Dermatol.
Apr
1998;138(4):692-4. [Medline].
Sordillo PP, Chapman R, Hajdu SI, et al.
Lymphangiosarcoma. Cancer. Oct 1 1981;48(7):1674-9. [Medline].
Stark RB,
Dwyer EM, De Forest M. Effect of surgical ablation of regional lymph nodes on
survival of
homografts. Ann NY Acad Sci.
1960;87:140-148.
Sternby NH, Gynning I, Hogeman KE. Postmastectomy
angiosarcoma. Acta Chir Scand. 1961;121:420-432.
Stewart FW, Treves N.
Lymphangiosarcoma in postmastectomy lymphedema: A report of six cases in
elephantiasis chirurgica. Cancer. 1948;1:64-81.
Tomita K, Yokogawa
A, Oda Y, Terahata S. Lymphangiosarcoma in postmastectomy lymphedema
(Stewart-
Treves syndrome): ultrastructural and immunohistologic
characteristics. J Surg Oncol. Aug 1988;38(4):275-82.
[Medline].
Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising
in chronic lymphedematous extremities. Cancer.
Aug
1972;30(2):562-72. [Medline].
Yap BS, Yap HY, McBride CM, Bodey GP.
Chemotherapy for postmastectomy lymphangiosarcoma. Cancer. Mar
1
1981;47(5):853-6. [Medline].
Stewart-Treves Syndrome
excerpt
Article Last Updated: Mar 28,
2007
------------------------------------
HYPERKERITOSIS
In
long standing lymphedemas hyperkeritosis can be a problem. This is an
overabundant skin thickening with
callous formation and possibly
wart-like papillomas. It is gray-brown in color and can occur anywhere on the
involved area. This is not often seen in upper extremity
involvement. Sometimes hyperkeritosis can be mistaken
for dried
lymph fluid. Hyperkeritosis is a skin change, a scarring, and should never be
removed through
debridement. Surgical excision is the only
treatment, however effective skin care treatment can substantially
reduce the severity.
FUNGAL INFECTIONS
Fungal infections
occur frequently in lower extremity lymphedema patients. The stagnant protein
rich fluid is a
breeding ground for bacteria and feet enclosed in a
dark, moist environment are prime targets for infections.
Fungal
infections manifest themselves through itching between the toes, small
blisters, a gray or whitish film on
the skin, and foul odor.
Sometimes the skin peels off between the toes. Initially only slight scale may
be noted but
soon it spreads and nail changes can take place. It
can be a problem in only one foot or it can be bilateral.
Patients with
foot fungus need to be careful not to contaminate other household members. The
infected patient
can shed tiny fragments of skin and fungus.
Similar sources of infection exist in discarded bandages or clothes on
any surface. The tub or shower should be cleaned thoroughly immediately
after use. Patients should not go
barefoot in the bathroom but lay
a towel down on the floor. That towel needs to be removed and placed in the
wash immediately after use. All towels and washcloths should be used
only once before washing. Going barefoot
generally is not
recommended unless the patient has been instructed to air feet at regular
intervals.
These patients should not go barefoot in the therapy clinic.
Make sure you place a towel on the floor for the
patient to step
onto after removing shoes. Do not have the patient drop socks or stockings onto
the floor. They
should be placed inside the patient’s
shoes.
In the beginning stages of foot fungus, over the counter foot
fungal medications can be used. Sometimes a
prescription drug is
required. Patients with repeated problems of foot fungus need to be followed by
a physician.
The therapist may chose to include treating the foot
fungus as a part of the therapy session. Gloves should be
worn.LYMPHATIC CYSTS
These are abnormally widened initial lymph
vessel visible as tiny vesicles or blisters. When they burst there is
danger
of infection. These need to be monitored daily. During manual lymph drainage be
careful of over-pulling
the skin around these areas. There should be
no stimulation directly over the area itself. With increasing
decongestion of the lymphedemetous area, the lymphatic cysts usually
dry up.
The skin needs to be kept supple and moist. Lymphedema is a very
drying condition. Cracks in the skin,
particularly on the feet and
around the toe and fingernails, need to be avoided. A good low pH lotion or
cream is
recommended. Lotions or creams that have fragrances, dyes
or lanolin should not be considered. There are many
products on the
market that advertise "low pH" or "pH balanced" and these are
preferred.
The best time to apply moisturizer is after bathing. It is
not recommended it be applied just prior to donning
medical
compression garments. Lotions/creams can get "caught" up in the garment fabric.
If the patient doesn’t
wash the garment daily, this can hasten the
deterioration of the garment fabric. Some patients can develop itching
or a rash if applied prior to bandaging, particularly in the hot summer
weather.
Maintaining a good fluid intake will assist with skin
moisturization. Sometimes patients mistakenly think if they
limit
the fluid intake, the swelling in the involved limb will be reduced. Good skin
integrity can only be maintained
if oral fluids are
adequate
Hyperkeratosis and Papillomatosis
By Jenny Veitch,
Lymphoedema Specialist
Hyperkeratosis Papillomatosis
What are
hyperkeratosis and papillomatosis?
These are changes which can take place
within the skin and present as thickening and solidness (described as
fibrosis*)
of the tissues.
The cause of these characteristic changes is the result of
untreated lymphoedema and are generally found on lower
limbs.
How can they be recognised?
Hyperkeratosis is a warty
scaly change in the skin due to an increased production of keratin, a surface
protein.
Papillomatosis is a cobblestone change in the skin surface due to
dilated surface lymphatic vessels or focal
accumulations of lymph;
they are non-compressible due to thickening and fibrosis of surrounding
tissues. Warty
hyperkeratosis and papillomatosis often coexist in
which case the skin resembles elephant skin (known as
elephantiasis).
How can they be prevented?
As already stated,
these changes generally appear as a result of oedema being untreated. The
fitting of good quality
compression hosiery and meticulous daily
skin care, including the use of moisturising cream, should help to
prevent changes occurring within the skin and tissues.
How can
these changes be treated?
It is important to moisturise the affected area
twice daily with 50% white soft paraffin and 50% liquid paraffin
mixed, until the skin improves. In more severe cases, salicylic acid 5%
in an ointment base may be used, this will
help to lift the scales
from the skin surface. This must be discussed with the health care professional
responsible
for your care.
When the skin condition has improved,
daily application of aqueous cream can be applied at night in order to keep
the skin well hydrated and supple. Appropriate class and size of
compression hosiery must be worn daily to
maintain the improved
skin condition.
If the limb is very swollen and distorted in shape it will
be essential to receive an intensive course of treatment
known as
decongestive lymphatic therapy (DLT) from a qualified lymphoedema
specialist.
NB * Fibrosis is an increase in the thickness and amount of
collagen in the skin. It conveys a harder consistency
to the
tissues concerned.
Lymphorrhoea
By LSN Trustee and Nursing Advisor,
Denise Hardy
Lymphorrhoea is the leakage, or weeping, of lymph fluid
through the skin surface. Large beads of fluid appear on
the skin
and trickle from the affected areas.
Causes of Lymphorrhoea
May be the
result of lacerations, abrasions, or trauma of the altered dry skin of
longstanding oedema e.g. graze/cut
It may result from the rupture (bursting)
of lymphangiomas (described more fully below)
It may also occur in a sudden
or acute oedema (swelling) where the shiny, taut skin has stretched so rapidly
that it
splits, forming a leak.
Lymphorrhoea - the problems it
causes
The skin feels very cold, wet and uncomfortable
The fluid can soak
through dressings which may need changing many times a day to cope with the
large amounts
of leakage
The fluid can collect in shoes/slippers
clothing and bed linen can become soaked and require frequent
changes
Lymphorroea will increase the risk of cellulitis - the break in the
skin acts as an entry for bacteria. Infection will
cause further
problems (pain/inflammation/flu-like symptoms and increased amounts of fluid
leakage)
If left to leak and dressings are not regularly changed the lymph
(being an excellent culture medium) may grow
bacteria causing odour
and discolouration
Lymphorrhoea may cause social difficulties and
embarassement. Lymphorrhoea not uncommonly affects the
genital area
and may be difficult to distinguish from urinary incontinence.
Treatment of
Lymphorrhoea
In order to stop the fluid leaking, a series of steps are
essential.
Your Lymphoedema nurse/therapist or other nurse involved in your
care should be able to help you with these
steps following a full
assessment of the cause of the leakage:
The area around the 'leak' needs to
be cleaned carefully to ensure the risk of infection is reduced.
An
emollient (moisturising cream/lotion) should be applied to the skin to improve
the condition and protect it (by
acting as a barrier) against
further skin breakdown.
A non-adherent (non sticky), absorbent, (e.g.
Allevyn/Cutinova/lyofoam) sterile dressing should be applied to the
leaking area to prevent further trauma to the skin - and to absorb the
leakage.
Pressure should be applied. For example a limb should be supported
with appropriate bandaging e.g. Multi Layer
Lymphoedema Bandaging
(MLLB) with short stretch compression bandages. This normally stops the flow of
leakage within 24-48 hours. Bandages may have to be replaced
frequently during this period of time to remove wet
bandages/
dressings and to prevent further skin breakdown. MLLB should continue until the
skin condition has
improved enough to wear your stockings/sleeve
again.
At rest, the affected limb should be elevated to reduce the effects
of gravity.
Once the leakage has stopped, and the skin condition has
improved, your usual compression garment should once
again be
applied. The garment will keep the swelling to a minimum and prevent any
further 'leaks' appearing.
Lymphangiomas
Lymphangiomas are often referred
to as 'lymph blisters'.
They consist of enlarged, or bulging lymphatic
vessels just under the surface of the skin, which give the
appearance of a blister.
Lymphangiomas can occur as a result of
damage to the deep lymphatic vessels e.g. following radiotherapy, or
surgery
and they generally contain clear lymph fluid (though sometimes it can be blood
stained).
If Lymphangiomas burst, they result in wetness around the area or
even profuse leakage which is a risk of
potential
infection.
Treatment involves strict skin hygiene and the usual lymphoedema
cornerstones of treatment - especially
compression.
If left
untreated, the lymph blisters may become harder and firmer and begin to look
like firm skin nodules.
Lymphangiomas are not
cancerous.
Information updated on this page 1/08 by the Lymphland
Editorial Board
Please note that lymphedema specialists are those
specifically trained. Information about Jenny Vietch is not
known
so treat her article as if it came from a non-professional
view.
---------------------------------
Incontinentia
Pigmenti
Article Last Updated: Feb 18, 2008
AUTHOR AND EDITOR
INFORMATIONSection 1 of 11 Authors and Editors Introduction Clinical
Differentials Workup Treatment Medication Follow-up Miscellaneous
Multimedia References
Author: Kara N Shah, MD, PhD, Assistant Professor,
Department of Pediatrics, Section of Dermatology,
Children's
Hospital of Philadelphia
Kara N Shah is a member of the following
medical societies: American Academy of Dermatology, American
Academy of Pediatrics, and Society for Pediatric
Dermatology
Editors: Bernice R Krafchik, MBChB, FRCPC, Professor
Emeritus, Department of Pediatrics, Section of
Dermatology,
University of Toronto; David F Butler, MD, Professor of Dermatology, Texas
A&M University
College of Medicine; Director, Division of
Dermatology, Scott and White Clinic; Director Dermatology Residency
Training Program, Scott and White Clinic; Robert A Schwartz, MD, MPH,
Professor and Head of Dermatology,
Professor of Medicine, Professor
of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and
Community Health, UMDNJ-New Jersey Medical School; Glen H Crawford, MD,
Assistant Clinical Professor,
Department of Dermatology, University
of Pennsylvania School of Medicine; Chief, Division of Dermatology, The
Pennsylvania Hospital; Dirk M Elston, MD, Director, Department of
Dermatology, Geisinger Medical Center
Author and Editor
Disclosure
Synonyms and related keywords: IP, Bloch-Sulzberger syndrome,
ectodermal dysplasia, neurocutaneous syndrome
INTRODUCTIONSection 2
of 11 Authors and Editors Introduction Clinical Differentials Workup
Treatment
Medication Follow-up Miscellaneous Multimedia
References
Background
Incontinentia pigmenti (IP) is an X-linked
dominant neurocutaneous syndrome with cutaneous, neurologic,
ophthalmologic, and dental manifestations. Garrod reported the first
probable case of IP in 1906 and described it
as a peculiar
pigmentation of the skin in an infant. Subsequently, Bloch and Sulzberger
further defined the
condition in 1926 and 1928, respectively, as a
clinical syndrome with a constellation of unique features that
includes typical cutaneous manifestations.
Pathophysiology
IP
is an X-linked dominant genodermatosis characterized by abnormalities of the
tissues and organs derived from
the ectoderm and neuroectoderm and
represents a type of ectodermal dysplasia. Involvement of the skin, hair,
teeth, and nails is seen in conjunction with neurologic and
ophthalmologic anomalies. In female IP patients,
lyonization results
in functional mosaicism of X-linked genes, which is manifested by the
blaschkoid distribution of
cutaneous lesions.1 Cells expressing the
mutated X chromosomes selectively eliminate around the time of birth;
therefore,
females with IP have an extremely skewed X-inactivation pattern. Normal X
chromosomes are active in
unaffected skin, and mutated X
chromosomes are active in skin affected with IP.
Frequency
United
States
No incidence or prevalence data are available on IP in the US
population.
International
IP is an uncommon disease. Up until 1987,
only 700 cases had been reported in the literature. The disease is
probably underreported because many mild or uncomplicated cases are
likely unrecognized.
Mortality/Morbidity
The prognosis depends on the
presence and severity of associated extracutaneous manifestations. Morbidity
and
mortality primarily result from neurologic and ophthalmologic
complications, including mental retardation,
seizures, and vision
loss.
Race
IP has a worldwide distribution. IP appears to be more
common among white patients, but it has also been
reported in blacks
and Asians.
Sex
IP is an X-linked dominant, male lethal syndrome.
More than 95% of reported cases of IP occur in females. IP
may
rarely occur in males with Klinefelter syndrome (XXY syndrome) or as a result
of somatic mosaicism or
hypomorphic (less deleterious) mutations in
the NEMO gene.2, 3
Age
Characteristic skin lesions compatible with
the early, vesicular and/or verrucous stages of IP are present at birth or
develop in the first few weeks of life in approximately 90% of
patients. The cutaneous manifestations of the
hyperpigmented stage
develop during infancy and persist during childhood. The hyperpigmented lesions
usually
fade during adolescence. The cutaneous manifestations of
the atrophic/hypopigmented stage develop during
adolescence and
early adulthood and persist indefinitely. Hair, nail, and dental anomalies
often first manifest during
infancy and are permanent. Late-onset
IP is occasionally reported in older infants. Neurologic and ophthalmologic
sequelae often manifest during early
infancy.
CLINICALSection 3 of 11 Authors and Editors
Introduction Clinical Differentials Workup Treatment
Medication
Follow-up Miscellaneous Multimedia References
History
In most
patients, cutaneous manifestations are present at birth or occur within the
first 2 weeks of life. The
cutaneous manifestations usually appear
in a characteristic, chronologic sequence. Other systemic manifestations,
including ocular defects, CNS abnormalities, and dental abnormalities,
may not be recognized until infancy or early
childhood.
A
family history of IP in the mother is reported to occur in 28% of patients. In
most patients (62%), the syndrome
occurs sporadically. Germline
mutations inherited from the father have been reported in over 80% of cases of
sporadic IP. Male patients with IP generally appear to have a
sporadic form. The development of postzygotic
mutation and
resulting somatic mosaicism is the likely mechanism in most male patients. In a
study of 42 boys
with IP, only 5 had evidence of NEMO gene mutation.
The male phenotype is similar to that of the female
phenotype,
although unilateral presentation is a more common occurrence in boys
(15%).
The proposed diagnostic criteria for IP are as
follows:
In the absence of a family history, the presence of at
least 1 major criterion is necessary. The presence of minor
criteria supports the diagnosis of IP.
Major
criteria
Typical neonatal vesicular rash with eosinophilia
Typical
blaschkoid hyperpigmentation on the trunk, fading in adolescence
Linear,
atrophic hairless lesions
Minor criteria
Dental
anomalies
Alopecia
Wooly hair
Abnormal nails
With a definitive
family history, the presence of any major criterion strongly supports the
diagnosis of IP.
Other characteristic features include the
following:
Suggestive history or evidence of typical rash,
hyperpigmentation, or atrophic hairless lesions
Vertex alopecia
Dental
anomalies
Retinal disease
Multiple male
miscarriages
Physical
Significant clinical heterogeneity exists in IP
with regard to ectodermal, ophthalmologic, and neurologic
abnormalities, even within families. The cutaneous findings generally
progress through 4 distinct characteristic
stages, although some
stages may overlap temporally and some may not occur at all in individual
patients. Affected
males often have limited involvement of 1 or 2
limbs.
Ectodermal changes
Skin features occur in 4
stages.
Stage 1 (vesicular) is characterized by the development of red
papules and vesicles on an erythematous base that
follow Blaschko
lines. Lesions are seen predominantly on the extremities but may also occur on
the trunk or on the
head and neck. The vesicular stage has been
reported to occur in 90-95% of patients. In most patients (>90%),
lesions
are present at birth or develop within the first 2 weeks of life. They resolve
within several months. Rarely,
self-limiting episodes of
recrudescence of vesicular lesions have been reported to occur in older infants
and
children with IP in association with an intercurrent febrile
illness.
Stage 2 (verrucous) is characterized by thickened, warty-appearing
linear and whorled plaques on an erythematous
base that follow
Blaschko lines. In general, lesions develop on the extremities and trunk but
may also be seen on
the head and neck. Verrucous lesions have been
reported to occur in 70-80% of IP patients. In most patients,
verrucous lesions develop in the first few weeks to months of life and
subsequently resolve over weeks to months.
Stage 3 (hyperpigmented) is
characterized by the development of streaks and whorls of brown or slate-gray
pigmentation along Blaschko lines; this occurs in 90-98% of IP
patients. Hyperpigmented lesions usually involve
the trunk but may
also involve the extremities, the skin folds, or the head and neck. The
location of the
hyperpigmented lesions does not appear to correlate
with areas of prior skin involvement during the earlier
vesicular
and verrucous stages. Hyperpigmented lesions generally develop within the first
few months of life and
resolve slowly by adolescence.
Stage 4
(atrophic/hypopigmented) is characterized by hypopigmented, atrophic, and
reticulate or linear patches
observed on the lower extremities,
usually involving the calves. Atrophic lesions usually develop during
adolescence
and persist into adulthood. Atrophic lesions have been reported to occur in
30-75% of IP patients.
Abnormal dermatoglyphic patterns have also been
reported.
Hair changes include scarring alopecia and are seen in 28-38% of
patients. An absence or hypoplasia of the
eyebrows and eyelashes has
also been reported. Finally, hair is sparse in early childhood; later, it has a
lusterless,
wiry, and coarse appearance.
Nail features4 include
nail dystrophy, which ranges from mild pitting or ridging of the nail plate to
hyperkeratosis
and onycholysis. This is observed in 7-40% of IP
patients, and usually multiple fingernails and toenails are
affected. Nail dystrophy may improve with age. Subungual and periungual
keratotic tumors associated with pain,
bony deformities, and lytic
lesions involving the underlying phalanges also may be seen, usually in older
children
and adults.5, 6, 7 The fingers are most commonly
affected.
Dental abnormalities8, 9 are seen in 80% of patients and can
involve both deciduous and permanent teeth. Dental
anomalies are
permanent and thus serve as a very useful diagnostic finding in older patients.
Delayed dentition,
partial anodontia, and conical or pegged teeth
are the most common dental findings. Poor enamel quality leading to
an increased incidence of dental caries has been reported historically,
but this association has been questioned.
Ophthalmologic findings10,
11
Ophthalmologic findings occur in 20-35% of patients, and asymmetric
involvement is common. Loss of visual
acuity and blindness are
significant complications. Blindness has been reported to develop in 7% of IP
patients.
Ophthalmologic manifestations may become evident within the first
few weeks to months of life and may progress
rapidly to permanent
visual deficits.
Retinal vaso-occlusive events with resultant ischemia are
believed to be the primary mechanism underlying ocular
pathology.
Retinal manifestations include retinal detachment,
proliferative retinopathy, fibrovascular retrolental membranes,
foveal hypoplasia, vitreous hemorrhages, and atrophy of the ciliary
body.
Nonretinal manifestations include strabismus, optic nerve atrophy,
conjunctival pigmentation, microphthalmia,
keratitis, cataracts,
iris hypoplasia, nystagmus, and uveitis.
Neurologic
abnormalities
Neurologic complications occur in 30% of IP patients and
often manifest within the neonatal period.
Seizures are the most common
neurologic complication and usually develop within the first few weeks of
life.
Neurologic complications may result in part from microvascular
vaso-occlusive ischemic events involving the
CNS. Involvement of the
cerebral hemispheres, cerebellum, and corpus callosum may occur.12 Progressive
periventricular hemorrhagic infarcts have been reported.
Other
neurodevelopmental manifestations include developmental delay, mental
retardation, ataxia, spastic paralysis,
microcephaly, cerebral
atrophy, porencephaly, hypoplasia of the corpus callosum, and periventricular
cerebral
edema.
Other anomalies that have been reported to occur
with increased frequency in patients with IP include
supernumerary
nipples, nipple hypoplasia, and breast hypoplasia.
Causes
IP is
caused by mutations in the NEMO/IKK-gamma gene, which is located on chromosome
Xq28. NEMO/IKK-
gamma is the regulatory subunit of the inhibitor
kappa kinase (IKK) complex and is required for the activation of
the transcription factor NF-kappaB (NF-kB). NF-kB is central to many
immune, inflammatory, and apoptotic
pathways.
Activation of
NF-kB prevents apoptosis in response to the tumor necrosis factor family of
cytokines. NF-kB
activity is normally regulated via the inhibitor
kB protein. Tumor necrosis factor receptor activation results in
phosphorylation and inactivation of inhibitor kB by IKK, thus resulting
in activation of NF-kB. Loss of IKK activity
results in deficient
NF-kB activity and increased susceptibility to apoptosis.
Cells that
retain IKK activity may produce additional cytokines that trigger apoptosis in
neighboring IKK-deficient
cells, thus creating an amplification
loop that eventually results in the death of all of the IKK-deficient cells.
This
mechanism is believed to produce the cutaneous manifestations
of the vesicular stage of IP. The proliferation of
surviving
IKK-positive cells may result in the production of the verrucous lesions seen
in stage 2 of IP. The
pathophysiology of the hyperpigmented
cutaneous findings seen in stage 3 and the atrophic/hypopigmented
manifestations of stage 4 remains unknown. Inflammation and subsequent
postinflammatory changes may play a
role.
The peripheral
eosinophilia seen in the early stages of IP may result from the production of
eotaxin, an eosinophil-
selective cytokine, during the inflammatory
cascade that results from a loss of NEMO/IKK-gamma activity.
Activation of eosinophils with subsequent release of cellular proteases
may trigger the development of the vesicular
stage of IP.13
The
pathophysiology underlying the CNS manifestations in IP are unknown, but
inflammation resulting from loss
of NEMO/IKK-gamma activity may
contribute to the development of vascular occlusive events.
Females with
hypomorphic mutations in NEMO/IKK-gamma may have few clinical manifestations of
IP.
A single mutation in NEMO/IKK-gamma involving the deletion of exons 4
through 10 accounts for most (80%) IP
mutations.
Hypomorphic
mutations in the zinc-finger domain of NEMO/IKK-gamma result in X-linked
recessive ectodermal
dysplasia and immunodeficiency. A family
history of IP may be elicited. Such mutations result in decreased but
not
absent IKK activity and thus allow for low-level NF-kB
activation.
Hypomorphic mutations in the stop codon of NEMO/IKK-gamma result
in the X-linked dominant ectodermal
dysplasia osteopetrosis
lymphedema syndrome.
Confirmation of NEMO/IKK-gamma mutations in males is
difficult due to the high rate of post-zygotic mosaicism.
NEMO/IKK-gamma
knockout mice manifest a cutaneous phenotype similar to female IP patients and
develop
neurologic sequelae, although they do not develop dental or
ocular abnormalities. They also develop diffuse
apoptosis of
splenic and thymic lymphocytes, which does not occur in human IP patients.14,
15
Genetic testing for NEMO/IKK-gamma mutations is available through the
Baylor College of Medicine Medical
Genetics
Laboratories.
DIFFERENTIALSSection 4 of 11 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Acropustulosis of Infancy
Bullous
Pemphigoid
Dermatopathia Pigmentosa Reticularis
Epidermolysis
Bullosa
Focal Dermal Hypoplasia Syndrome
Herpes Simplex
Herpes
Zoster
Hypomelanosis of Ito
Impetigo
Insect Bites
Langerhans Cell
Histiocytosis
Lichen
Striatus
Mastocytosis
Milia
Miliaria
Naegeli-Franceschetti-Jadassohn
Syndrome
Other Problems to be Considered
Stage 1 -
Vesicular
Bullous impetigo
Herpes simplex
Varicella (herpes)
zoster
Epidermolysis bullosa
Bullous mastocytosis
Bullous congenital
ichthyosiform erythroderma (epidermolytic hyperkeratosis)
Congenital bullous
pemphigoid
Linear IgA bullous disease of childhood
Langerhans cell
histiocytosis
Erythema toxicum
Miliaria
Acropustulosis of
infancy
Arthropod assault
Stage 2 - Verrucous
Linear epidermal
nevus
Lichen striatus
X-linked dominant chondrodysplasia
punctata
Verruca vulgaris
Stage 3 - Pigmented
Linear and
whorled nevoid hypermelanosis
Pigmentary mosaicism
Dermatopathia
pigmentosa reticularis
Naegeli-Franceschetti-Jadassohn syndrome
X-linked
dominant chondrodysplasia punctata
Stage 4 -
Depigmented
Hypomelanosis of Ito (IP achromians)
Focal dermal
hypoplasia syndrome (Goltz syndrome)
X-linked dominant chondrodysplasia
punctata
WORKUPSection 5 of 11 Authors and Editors
Introduction Clinical Differentials Workup Treatment Medication
Follow-up Miscellaneous Multimedia References
Lab
Studies
Leukocytosis and eosinophilia may be noted.
When acute
inflammatory skin changes are present, eosinophilia (=80%) may be seen in the
peripheral blood.
Evidence of neutrophil dysfunction (defects in
chemotaxis), lymphocyte dysfunction (decreased proliferation in
response to mitogen stimulation), and altered immunologic reactivity
has been reported in some patients.
Quantitative immunoglobulin
levels and lymphocyte subpopulation counts are normal.
Imaging
Studies
Head CT scanning and brain MRI16 may demonstrate cerebral edema,
hydrocephalus, structural brain
abnormalities, cerebral infarctions,
and hypointense areas or hypoattenuation.
Magnetic resonance spectroscopy
and angiography have demonstrated reduced cerebral blood flow and elevated
cerebrospinal fluid lactate levels, consistent with cerebral ischemia
secondary to cerebrovascular occlusive events.
17
Single-photon
emission CT scanning may show decreased cerebral blood flow.18
EEG is
helpful for localizing CNS lesions and epileptogenic foci in patients with
seizures.
Other Tests
Karyotype analysis is recommended in male
infants with IP in order to detect Klinefelter syndrome (XXY
syndrome).
Genetic testing for NEMO/IKK-gamma mutations is available
through the Baylor College of Medicine Medical
Genetics
Laboratories.
Procedures
Skin biopsy may be diagnostic if
performed during the early vesicular and verrucous stages of IP (stages
1-2).
Histologic Findings
Stage 1 (vesicular)
Spongiotic
dermatitis with eosinophil-filled intraepidermal vesicles and an eosinophilic
epidermal and dermal
infiltrate are seen. The epidermis often
contains dyskeratotic cells, either singly or in small clusters.
Stage 2
(verrucous)
Acanthosis, papillomatosis, and hyperkeratosis with
increased numbers of dyskeratotic cells, which sometimes
form
whorled collections,19 are seen. Basal cells show vacuolization and a decrease
in melanin content.
Eosinophils can persist in the epidermis and
dermis, and melanophages are often present in the papillary
dermis.
Stage 3 (hyperpigmented)
Melanin deposition in
melanophages within a thickened papillary dermis is seen. Colloid bodies in the
papillary
dermis, dyskeratotic cells in the epidermis, and basal
cell layer vacuolar changes may be seen. The histologic
findings
are often suggestive of IP but are not specific.
Stage 4
atrophic/hypopigmented)
Atrophic epidermis with loss of the normal rete
ridge pattern and dermal eccrine structures with a reduction in
basal melanocytes are seen. Colloid bodies may be seen. The histologic
findings are nonspecific.
TREATMENTSection 6 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Medical Care
Treatment is not usually required for
the cutaneous lesions. The vesicles of the inflammatory stage should be left
intact, and the skin should be monitored for the development of
secondary bacterial infections. Emollients and
topical antibiotics
may be used as needed.
Oral hygiene and regular dental care is necessary,
and dental restoration may be indicated.
Seizures should be treated with
anticonvulsants.
Routine neurodevelopmental assessments should be made, with
referral to occupational and physical therapists as
warranted.
Frequent ophthalmologic evaluations are required,
especially during the first year of life, in order to diagnose and
treat potential ophthalmologic complications.
Surgical
Care
Abnormal retinal fibrovascular proliferation can be treated with
xenon laser photocoagulation or cryosurgery.20
Retinal detachments may be
treated using vitreoretinal surgery.
Consultations
Dermatologists
may help in the initial evaluation and can perform a skin biopsy to aid in
diagnosis.
Ophthalmologists can perform regular ophthalmologic examinations
and manage any ophthalmologic sequelae.
Neurologists can perform a complete
initial neurologic examination (including imaging studies and EEG), initiate
and monitor anticonvulsant therapy in patients with seizures, and
facilitate neurodevelopmental evaluation and
intervention.
General dentists can provide regular dental care,
screening for dental complications, and restorative dental care.
Geneticists
can provide appropriate genetic counseling and genetic testing for the patient
and his or her family.
MEDICATIONSection 7 of 11 Authors
and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia References
In
patients with seizures, anticonvulsant drugs are used. These agents have
central and peripheral anticholinergic
effects and sedative
effects. They also block the active reuptake of norepinephrine and serotonin. A
variety of
anticonvulsants are available, and they should be
selected at the discretion of the neurologist.
FOLLOW-UPSection
8 of 11 Authors and Editors Introduction Clinical Differentials Workup
Treatment
Medication Follow-up Miscellaneous Multimedia
References
Further Outpatient Care
The presence of variable
disease expression in an affected family makes monitoring for potential
complications
important. Regular follow-up with a neurologist,
ophthalmologist, dentist, and dermatologist should be coordinated
as needed.
Complications
Secondary bacterial infection
can develop during the vesicular stage, but this is rare.
Seizures and
mental retardation are common in patients with structural brain malformations
or evidence of
ischemic brain injury.
Ophthalmologic
complications can lead to reduced visual acuity and
blindness.
Prognosis
The prognosis of IP is generally
good.
Morbidity and mortality are related to neurologic and ophthalmologic
sequelae, including seizures, visual
impairment, and mental
retardation.
Patients with structural brain abnormalities and neonatal
seizures are at greater risk for motor and intellectual
impairment.
Patient Education
Inform parents that delayed
eruption of both deciduous and permanent teeth is common.
Reassure parents
that if no evidence of CNS involvement or seizures is seen in their infant, the
neurodevelopmental
prognosis is excellent.
Genetic counseling
should be offered to the family.
Counsel parents on the expected course of
cutaneous manifestations.
MISCELLANEOUSSection 9 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Medical/Legal Pitfalls
Failure to make a correct
diagnosis based on cutaneous findings and ocular, CNS, and dental
abnormalities
Failure to perform skin biopsy of vesicular or verrucous
lesions to confirm a diagnosis of IP
Failure to refer patients to
neurologists and ophthalmologists for evaluation and treatment
Failure to
provide appropriate genetic counseling
Special Concerns
Examine
the mother and all female relatives of a child with IP for clinical features of
IP. Carefully look for dental
abnormalities and stage 4 cutaneous
changes (eg, atrophic/hypopigmented lesions involving the lower
legs).
MULTIMEDIASection 10 of 11 Authors and Editors
Introduction Clinical Differentials Workup Treatment
Medication
Follow-up Miscellaneous Multimedia References
REFERENCESSection
11 of 11 Authors and Editors Introduction Clinical Differentials Workup
Treatment
Medication Follow-up Miscellaneous Multimedia
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1153-60.
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Incontinentia Pigmenti excerpt
Article Last
Updated: Feb 18, 2008
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disease: Managing a mysterious skin condition
Morgellons disease is
mysterious and controversial. Here you'll find answers to common questions
about
Morgellons disease and suggestions for coping with
it.
Morgellons disease is a mysterious skin disorder characterized by
disfiguring sores and crawling sensations
on and under the skin.
Although Morgellons disease isn't widely recognized as a medical diagnosis,
experts
from the Centers for Disease Control and Prevention (CDC)
are investigating reports of the condition.
If you suspect that you have
Morgellons disease, you may have many questions about the condition. Here's
what you need to know about Morgellons disease, including practical
tips for managing your signs and
symptoms.
What are the signs and
symptoms of Morgellons disease?
According to the Morgellons Research
Foundation, primary signs and symptoms of Morgellons disease
include:
Skin lesions, often accompanied by pain or intense
itching
Fibers which may be white, blue, red or black in and on the
lesions
Crawling sensations on and under the skin, often compared to insects
moving, stinging or biting
Joint and muscle pain
Fatigue significant
enough to interfere with daily activity
Inability to concentrate and
difficulty with short-term memory
Behavioral changes
Other signs and
symptoms may include:
Changes in vision
Stomach pain or other
gastrointestinal symptoms
Changes in skin texture and color
Morgellons
disease shares characteristics with various recognized conditions, including
attention-deficit
disorder, chronic fatigue syndrome, Lyme disease,
obsessive-compulsive disorder and a mental illness
involving false
beliefs about infestation by parasites (delusional parasitosis).
How long
has Morgellons disease been around?
In 1674, English physician and writer
Sir Thomas Browne used the term "Morgellons disease" to describe
"black hairs" emerging from childhood skin lesions. Today, the
Morgellons Research Foundation doesn't
claim that the disorder
described by Browne is the same as Morgellons disease. Rather, the foundation
adopted the term as a convenient label for a set of signs and
symptoms.
How widespread is Morgellons disease?
Reports of Morgellons
disease have been made in every state in the United States and various
countries
around the world. Most reported cases are clustered in
California, Texas and Florida.
What do researchers know about Morgellons
disease?
Beyond anecdotal reports, researchers know little about Morgellons
disease. The Morgellons Research
Foundation reports no known causes
of Morgellons disease and no successful treatment for the condition.
Whether
Morgellons disease is contagious remains a mystery.
How controversial is
Morgellons disease?
Current attitudes toward Morgellons disease fall into
various categories:
Some health professionals believe that Morgellons disease is a specific condition likely to be confirmed by
future research.
Some health professionals believe that signs and
symptoms of Morgellons disease are caused by another
condition,
often mental illness.
Other health professionals don't acknowledge
Morgellons disease or are reserving judgment until more is
known
about the condition.
Some people who suspect Morgellons disease claim
they've been ignored, criticized as delusional or
dismissed as
fakers. In contrast, some doctors say that people who report signs and symptoms
of
Morgellons disease typically resist other explanations for their
condition.
How can you cope with the signs and symptoms of Morgellons
disease?
The signs and symptoms linked to Morgellons disease can be
distressing. Even though health professionals
disagree about the
nature of the condition, you deserve compassionate treatment. While research
continues,
take positive steps to manage your signs and
symptoms.
Establish a caring health care team. Find a doctor who
acknowledges your concerns and does a thorough
examination. Since Morgellons disease often requires frequent follow-up visits, a local health care team may
be most convenient.
Be patient. Your doctor will
likely look for known conditions that point to evidence-based treatments before
considering a diagnosis of Morgellons disease.
Keep an open
mind. Consider various causes for your signs and symptoms, and follow your
doctor's
recommendations for treatment which may include long-term
mental health therapy.
Seek treatment for other conditions. Get treatment for anxiety, depression or any other condition that affects
your
thinking, moods or behavior.
Keep track of the latest news about Morgellons
disease. Supplement the information you find online with
articles
published in peer-reviewed medical journals. Remember that some sources are
more reputable than
are others.
RELATED
Web Resources
http://www.mayoclinic.com/health/morgellons-disease/SN00043
Centers for
Disease Control and
Prevention
--------------------------------------------
http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?
requestURI=/healthatoz/Atoz/ency/lymphadenitis.jsp
Lymphadenitis
is the inflammation of a lymph node. It is often a complication of a bacterial
infection of a
wound, although it can also be caused by viruses or
other disease agents. Lymphadenitis may be either
generalized,
involving a number of lymph nodes; or limited to a few nodes in the area of a
localized infection.
Lymphadenitis is sometimes accompanied by
lymphangitis, which is the inflammation of the lymphatic vessels
that connect the lymph nodes.
Description
Lymphadenitis
is marked by swollen lymph nodes that are painful, in most cases, when the
doctor touches
them. If the lymphadenitis is related to an infected
wound, the skin over the nodes may be red and warm to
the touch. If
the lymphatic vessels are also infected, there will be red streaks extending
from the wound in
the direction of the lymph nodes. In most cases,
the infectious organisms are hemolytic Streptococci or
Staphylococci. Hemolytic means that the bacteria produce a toxin that
destroys red blood cells.
The extensive network of lymphatic vessels
throughout the body and their relation to the lymph nodes helps
to
explain why bacterial infection of the nodes can spread rapidly to or from
other parts of the body.
Lymphadenitis in children often occurs in
the neck area because these lymph nodes are close to the ears and
throat, which are frequent locations of bacterial infections in
children.
Causes and symptoms
Streptococcal and staphylococcal
bacteria are the most common causes of lymphadenitis, although viruses,
protozoa, rickettsiae, fungi, and the tuberculosis bacillus can also
infect the lymph nodes. Diseases or
disorders that involve lymph
nodes in specific areas of the body include rabbit fever (tularemia),
cat-scratch
disease, lymphogranuloma venereum, chancroid, genital
herpes, infected acne, dental abscesses, and
bubonic plague. In
children, tonsillitis or bacterial sore throats are the most common causes of
lymphadenitis
in the neck area. Diseases that involve lymph nodes
throughout the body include mononucleosis,
cytomegalovirus
infection, toxoplasmosis, and brucellosis.
The early symptoms of
lymphadenitis are swelling of the nodes caused by a buildup of tissue fluid and
an
increased number of white blood cells resulting from the body's
response to the infection. Further
developments include fever, often
as high as 101-102°F (38-39°C) together with chills, loss of
appetite, heavy perspiration, a rapid pulse, and general
weakness.
Diagnosis
Physical examination
The diagnosis of
lymphadenitis is usually based on a combination of the patient's history, the
external
symptoms, and laboratory cultures. The doctor will press
(palpate) the affected lymph nodes to see if they
are sore or
tender. Swollen nodes without soreness are often caused by cat-scratch disease.
In children, the
doctor will need to rule out mumps, tumors in the
neck region, and congenital cysts that resemble swollen
lymph
nodes.
Although lymphadenitis is usually diagnosed in lymph nodes in the
neck, arms, or legs, it can also occur in
lymph nodes in the chest
or abdomen. If the patient has acutely swollen lymph nodes in the groin, the
doctor
will need to rule out a hernia in the groin that has failed
to reduce (incarcerated inguinal hernia). Hernias
occur in 1% of
the general population; 85% of patients with hernias are
male.
Laboratory tests
The most significant tests are a white
blood cell count (WBC) and a blood culture to identify the organism.
A
high proportion of immature white blood cells indicates a bacterial infection.
Blood cultures may be
positive, most often for a species of
staphylococcus or streptococcus. In some cases, the doctor may order
a
biopsy of the lymph node.
Treatment
Medications
The
medications given for lymphadenitis vary according to the bacterium or virus
that is causing it. If the
patient also has lymphangitis, he or she
will be treated with antibiotics, usually penicillin G (Pfizerpen,
Pentids), nafcillin (Nafcil, Unipen), or cephalosporins. Erythromycin
(Eryc, E-Mycin, Erythrocin) is given to
patients who are allergic
to penicillin.
Supportive care
Supportive care of lymphadenitis
includes resting the affected limb and treating the area with hot moist
compresses.
Surgery
Cellulitis associated with
lymphadenitis should not be treated surgically because of the risk of spreading
the
infection. Pus is drained only if there is an abscess and
usually after the patient has been started on antibiotic
treatment.
In some cases, a biopsy of an inflamed lymph node is necessary if no diagnosis
has been made
and no response to treatment has
occurred.
Prognosis
The prognosis for recovery is good if the
patient is treated promptly with antibiotics. In most cases, the
infection can be brought under control in three or four days. Patients
with untreated lymphadenitis may
develop blood poisoning
(septicemia), which is sometimes fatal.
Prevention
Prevention of
lymphadenitis depends on prompt treatment of bacterial and viral
infections.
Key Terms
Hemolytic
Able to break down or
dissolve red blood cells. The bacteria that cause lymphadenitis are
hemolytic.
Hernia
The bulging of a part of the intestine or other
organ through its surrounding wall of tissue. Most hernias are in
the abdominal cavity. An inguinal hernia is located in the groin
area.
Lymph nodes
The glandlike masses of tissue in the lymphatic
system that contain lymphocytes. The lymph nodes also filter
lymph,
which is a clear yellowish tissue fluid that carries lymphocytes and fats
throughout the body.
Lymphangitis
Inflammation of the lymphatic
vessels. It often occurs together with
lymphadenitis.
Septicemia
The presence of bacteria and their
toxins in the bloodstream. Septicemia is sometimes called blood
poisoning.
For Your
Information
McPhee, Stephen, et
al., editors. "Blood Vessels & Lymphatics." In Current Medical Diagnosis
and Treatment,
1998. 37th ed. Stamford: Appleton & Lange,
1997.
------------------------------------------------------
What
Is Sarcoidosis?
Sarcoidosis (sar"koi-do'sis) involves inflammation that
produces tiny lumps of cells in various organs in your
body. The
lumps are called granulomas (gran"u-lo'mahs) because they look like grains of
sugar or sand. They are
very small and can be seen only with a
microscope.
These tiny granulomas can grow and clump together, making
many large and small groups of lumps. If many
granulomas form in an
organ, they can affect how the organ works. This can cause symptoms of
sarcoidosis.
Sarcoidosis can occur in almost any part of your body,
although it usually affects some organs more than others.
It
usually starts in one of two places:
Lungs
Lymph nodes, especially
the lymph nodes in your chest cavity.
Sarcoidosis also often affects
your:
Skin
Eyes
Liver.
Less often, sarcoidosis affects
your:
Spleen
Brain
Nerves
Heart
Tear glands
Salivary
glands
Bones and joints.
Rarely, sarcoidosis affects other organs,
including your:
Thyroid gland
Breasts
Kidneys
Reproductive
organs.
Sarcoidosis almost always occurs in more than one organ at a
time.
Sarcoidosis has an active and a nonactive phase:
In the
active phase, the granulomas form and grow. In this phase, symptoms can
develop, and scar tissue can
form in the organs where the
granulomas occur.
In the nonactive phase, the inflammation goes down, and
the granulomas stay the same size or shrink. But the
scars may
remain and cause symptoms.
The course of the disease varies greatly among
people.
In many people, sarcoidosis is mild. The inflammation that
causes the granulomas may get better on its own. The
granulomas may
stop growing or shrink. Symptoms may go away within a few years.
In some
people, the inflammation remains but doesn't get worse. You may also have
symptoms or flare-ups and
need treatment every now and then.
In
other people, sarcoidosis slowly gets worse over the years and can cause
permanent organ damage. Although
treatment can help, sarcoidosis may
leave scar tissue in the lungs, skin, eyes, or other organs. The scar tissue
can
affect how the organs work. Treatment usually does not affect
scar tissue.
Changes in sarcoidosis usually occur slowly (e.g., over
months). Sarcoidosis does not usually cause sudden
illness. However,
some symptoms may occur suddenly. They include:
Disturbed heart
rhythms
Arthritis in the ankles
Eye symptoms.
In some serious cases in
which vital organs are affected, sarcoidosis can result in
death.
Sarcoidosis is not a form of cancer.
There is no known way
to prevent sarcoidosis.
Sarcoidosis was once thought to be an uncommon
condition. It's now known to affect tens of thousands of
people
throughout the United States. Because many people who have sarcoidosis have no
symptoms, it's hard to
know how many people have the
condition.
Sarcoidosis was identified in the late 1860s. Since then,
scientists have developed better tests to diagnose it and
made
advances in treating it.
The cause of sarcoidosis is not known. And,
there may be more than one thing that causes it.
Scientists think that
sarcoidosis develops when your immune system responds to something in the
environment (e.
g., bacteria, viruses, dust, chemicals) or perhaps
to your own body tissue (autoimmunity).
Normally, your immune system
defends your body against things that it sees as foreign and harmful. It does
this
by sending special cells to the organs that are being affected
by these things. These cells release chemicals that
produce
inflammation around the foreign substance or substances to isolate and destroy
them.
In sarcoidosis, this inflammation remains and leads to the
development of granulomas or lumps.
Scientists have not yet identified
the specific substance or substances that trigger the immune system response in
the first place. They also think that sarcoidosis develops only if
you have inherited a certain combination of genes.
You can't catch
sarcoidosis from someone who has it.
More research is needed to discover
what causes sarcoidosis.
Sarcoidosis affects people of all ages and
races worldwide.
It occurs mostly in:
Adults between the ages of
20 and 40
African Americans (especially women)
People of Asian, German,
Irish, Puerto Rican, and Scandinavian origin.
In the United States,
sarcoidosis affects African Americans somewhat more often and more severely
than
Caucasians.
Studies have shown that sarcoidosis is more
likely to affect certain organs in certain populations. For
example,
Sarcoidosis of the heart and eye appears to be more common in
Japan.
Painful skin lumps on the legs occur more often in people from
Northern Europe.
People who are more likely to get sarcoidosis
include:
Health care workers
Nonsmokers
Elementary and secondary
school teachers
People exposed to agricultural dust, insecticides,
pesticides, or mold
Firefighters.
Brothers and sisters, parents, and
children of people who have sarcoidosis are more likely than others to have
sarcoidosis.
What Are the Signs and Symptoms of Sarcoidosis?
Many
people who have sarcoidosis have no symptoms. Often, the condition is
discovered by accident only
because a person has a chest x ray for
another reason, such as a pre-employment x ray.
Some people have very
few symptoms, but others have many.
Symptoms usually depend on which
organs the disease affects.
Lung Symptoms
Shortness of breath
A
dry cough that doesn't bring up phlegm (flem), or mucus
Wheezing
Pain in
the middle of your chest that gets worse when you breathe deeply or cough
(rare).
Lymph Node Symptoms
Enlarged and sometimes tender lymph
nodes—most often those in your neck and chest but sometimes those under
your chin, in your arm pits, or in your groin.
Skin
Symptoms
Various types of bumps, ulcers, or, rarely, flat areas of
discolored skin, that appear mostly near your nose, eyes,
back,
arms, legs, and scalp. They usually itch but aren't painful. They usually last
a long time.
Painful bumps that usually appear on your ankles and shins and
can be warm, tender, red or purple-to-red in color,
and slightly
raised. This is called erythema nodosum (er"i-the'mah nodo'sum). You may have
fever and swollen
ankles and joint pain along with the bumps. The
bumps often are an early sign of sarcoidosis, but they occur in
other diseases too. The bumps usually go away in weeks to months, even
without treatment.
Disfiguring skin sores that may affect your nose, nasal
passages, cheeks, ears, eyelids, and fingers. This is called
lupus
pernio (loo'pus per'nio). The sores tend to be ongoing and can return after
treatment is over.
Eye Symptoms
Burning, itching, tearing, pain
Red
eye
Sensitivity to light
Dryness
Floaters (i.e., seeing black
spots)
Blurred vision
Reduced color vision
Reduced visual
clearness
Blindness (in rare cases).
Heart Symptoms
Shortness of
breath
Swelling in your legs
Wheezing
Coughing
Irregular heartbeat,
including palpitations (a fluttering feeling of rapid heartbeats) and skipped
beats
Sudden loss of consciousness
Sudden death.
Joint and Muscle
Symptoms
Joint stiffness or swelling—usually in your ankles, feet, and
hands.
Joint pain.
Muscle aches (myalgias).
Muscle pain, a mass in a
muscle, or muscle weakness.
Painful arthritis in your ankles that results
from erythema nodosum. It may need treatment but usually clears up in
several
weeks.
Painless arthritis that can last for months or even years. It should
be treated.
Bone Symptoms
Painless holes in your bones.
Painless
swelling, most often in your fingers.
Anemia that results from granulomas
affecting your bone marrow. This usually should be treated.
Liver
Symptoms
Fever
Fatigue
Itching
Pain in the upper right part of your
abdomen, under the right ribs
Enlarged liver.
Parotid (pah-rot'id) and
Other Salivary Gland Symptoms
Swelling, which makes your cheeks look
puffy
Excessive dryness in your mouth and throat.
Blood, Urinary Tract,
and Kidney Symptoms
Increased calcium in your blood or urine, which can lead
to painful kidney stones
Confusion
Increased urination.
Nervous System
Symptoms
Headaches.
Vision problems.
Weakness or numbness of an arm or
leg.
Coma (rare).
Drooping of one side of your face that results from
sarcoidosis affecting a facial nerve. This can be confused with
Bell's palsy, a disorder that may be caused by a virus.
Paralysis of
your arms or legs that results from sarcoidosis affecting your spinal
cord.
Weakness, pain, or a "stinging needles" sensation in areas where many
nerves are affected by sarcoidosis.
Pituitary (pi-tu'i-tar"e) Gland Symptoms
(Rare)
Headaches
Vision problems
Weakness or numbness of an arm or
leg
Coma (rare).
Other Symptoms
Nasal obstruction or frequent bouts of
sinusitis.
Enlarged spleen, which leads to a decrease in platelets in your
blood and pain in your upper left abdomen. Platelets
are needed to
help your blood clot.
Sarcoidosis may also cause more general symptoms,
including:
Uneasiness, feeling sick (malaise), an overall feeling of ill
health
Tiredness, fatigue, weakness
Loss of appetite or
weight
Fever
Night sweats
Sleep problems
These general symptoms are
often caused by other conditions. If you have these general symptoms but don't
have
symptoms from affected organs, you probably do not have
sarcoidosis.
How Is Sarcoidosis Diagnosed?
Your doctor will find out
if you have sarcoidosis by taking a detailed medical history and conducting a
physical
exam and several diagnostic tests. The purpose is
to:
Identify the presence of granulomas in any of your organs
Rule
out other causes of your symptoms
Determine the amount of damage to any of
your affected organs
Determine whether you need treatment.
Medical
History
Your doctor will ask you for a detailed medical history. He or she
will want to know about any family history of
sarcoidosis and what
jobs you have had that may have increased your chances of getting
sarcoidosis.
Your doctor may also ask whether you have ever been exposed
to inhaled beryllium metal, which is used in
aircraft and weapons
manufacture, or organic dust from birds or hay. These things can produce
granulomas in
your lungs that look like the granulomas that are
caused by sarcoidosis but are actually signs of other
conditions.
Physical Exam
Your doctor will look for symptoms of
sarcoidosis, such as red bumps on your skin; swollen lymph nodes; an
enlarged
liver, spleen, or salivary gland(s); or redness in your eyes. He or she will
also listen for abnormal lung
sounds or heart rhythm. Your doctor
also will check for other likely causes of your symptoms.
Diagnostic
Tests
There is no one specific test for diagnosing sarcoidosis. It is harder
to diagnose sarcoidosis in some organs (e.g.,
heart, nervous
system) than in others. Your doctor will probably conduct a variety of tests
and procedures to help
in the diagnosis.
These
include:
Chest X Ray. A chest x ray takes a picture of your heart and
lungs. It may show granulomas or enlarged lymph
nodes in your chest.
About 95 out of every 100 people who have sarcoidosis have an abnormal chest x
ray.
Doctors usually use a staging system for chest x rays taken to detect
sarcoidosis:
Stage 0: Normal chest x ray
Stage 1: Chest x ray showing
enlarged lymph nodes but otherwise clear lungs
Stage 2: Chest x ray showing
enlarged lymph nodes and shadows in your lungs
Stage 3: Chest x ray showing
shadows in your lungs, but the lymph nodes are not enlarged
Stage 4: Chest x
ray showing scars in the lung tissue.
In general, the higher the stage of the x ray, the worse your symptoms and lung function are. But there are a lot of
differences among people. If your x-ray results show Stages 0,
1, 2, or 3, you may not have symptoms or need
treatment, and you may
get better and have normal chest x rays again over time.
Blood Tests. These
tests can show the number and type of cells in your blood. They also will show
whether there
are increases in your calcium levels or changes in
your liver, kidney, and bone marrow that can occur with
sarcoidosis.
Lung Function Tests. One test uses a spirometer
(spi-rom'e-ter), a device that measures how much and how fast
you
can blow air out of your lungs after taking a deep breath. If there is a lot of
inflammation and/or scarring in
your lungs, you will not be able to
move normal amounts of air in and out.
Another test measures how much air
your lungs can hold. Sarcoidosis can cause your lungs to shrink, and they
will not be able to hold as much air as healthy
lungs.
Electrocardiogram (EKG). This test will help show if your heart is
affected by sarcoidosis.
Pulse Oximetry. A small clip attached to your
finger tip can show how well your heart and lungs are moving
oxygen
into your blood.
Arterial Blood Gas Test. This test is more accurate than
pulse oximetry for checking the level of oxygen in your
bloodstream. Blood is taken from an artery (usually in your wrist). It
is then analyzed for its oxygen and carbon
dioxide
levels.
Fiberoptic Bronchoscopy. In this procedure, your doctor inserts a
long, narrow, flexible tube with a light on the
end through your
nose or mouth into your lungs to look at your airways. This tube is called a
bronchoscope. You
most likely would have this procedure as an
outpatient in a hospital under local anesthesia.
Bronchoalveolar Lavage
(brong"ko-al-ve'o-lar lah-vaje') (BAL). During bronchoscopy, your doctor may
inject a
small amount of salt water (saline) through the
bronchoscope into your lungs. This fluid washes the lungs and
helps
bring up cells and other material from the air sacs deep in your lungs where
the inflammation usually starts
to develop. The cells and fluid are
then examined for signs of inflammation.
Biopsy. Your doctor may take a
small sample of tissue from one of your affected organs. For example, when
breathing tests or chest x rays show signs of sarcoidosis in your
lungs, your doctor may do a fiberoptic
bronchoscopy biopsy. This
will help confirm the diagnosis. Your doctor inserts a tiny forceps through the
bronchoscope to collect tissue that will be examined. Because the
granulomas may be spread out in your lungs, the
bronchoscope may
miss some of them.
Biopsies of your skin and liver are sometimes done to
detect granulomas in these organs.
You may have sarcoidosis in other organs
as well and multiple biopsies may be necessary. However, every organ
involved
does not need to be biopsied for a diagnosis to be made.
Computerized
Tomography (CT) Scan. This test provides a computer-generated image of your
organs that has
more detail than a regular chest x ray. It can
provide more information about how sarcoidosis has affected an
organ.
Your doctor may do a CT scan to:
Obtain more information
about how much of your lung is affected by sarcoidosis.
Detect sarcoidosis
in your liver. A CT scan of your abdomen will show if your liver is enlarged
and if there is a
pattern suggesting granulomas.
Magnetic
Resonance (MR) Scan. This test is also called nuclear magnetic resonance (NMR)
scanning or magnetic
resonance imaging (MRI). This scan uses
powerful magnets and radio waves to make images of some of your
organs that your doctor doesn't want to risk doing a biopsy on. For
example, an MR scan can be used to diagnose
sarcoidosis in your
brain, spinal cord, nerves, or heart.
Thallium and Gallium Scans. These
scans are often done to see if sarcoidosis is affecting your heart. Thallium
and
gallium are radioactive elements. Your doctor injects a small
amount of one of them into a vein in your arm. The
elements collect
at places in your body where there is inflammation. After awhile, your body is
scanned for
radioactivity. Increased radioactivity at any place may
be a sign of inflammation.
This test gives information on the tissue in your
body that has been affected by sarcoidosis and the amount of
damage
to it. But since this test shows all inflammation in your body, even
inflammation caused by conditions
other than sarcoidosis, it does
not give a definite diagnosis of sarcoidosis.
Positron Emission Tomography
(PET) Scan. This test also uses radioactive injections. It may be more
sensitive
than gallium in detecting areas of inflammation. Some
doctors are using it instead of gallium scans.
Your doctor may not need to
find every one of your organs affected by sarcoidosis, only those that cause
symptoms. Often the organs affected by the condition continue to
function well and don't need to be treated.
How Is Sarcoidosis
Treated?
The goals of treatment are to:
Improve how the organs
affected by sarcoidosis work
Relieve symptoms
Shrink the
granulomas.
Treatment may shrink the granulomas and even cause them to
disappear, but this may take many months. If scars
have formed,
treatment may not help, and you may have ongoing symptoms.
Your
treatment depends on:
What symptoms you have
How severe your symptoms
are
Whether any of your vital organs (e.g., your lungs, eyes, heart, or
brain) are affected
How the organ is affected.
Some organs must be
treated, regardless of your symptoms. Others may not need to be treated.
Usually, if you
don't have symptoms, you don't need treatment, and
you probably will recover in time.
Drugs
The main treatment for
sarcoidosis is prednisone. Prednisone is a corticosteroid, or anti-inflammatory
drug.
Sometimes it is used with other drugs. Sometimes other
corticosteroids are used.
Prednisone almost always relieves symptoms of
inflammation. If a symptom doesn't improve with prednisone
treatment within a couple of months, consult your
physician.
Prednisone is usually given for many months, sometimes for a
year or more.
Low doses of prednisone can often relieve symptoms without
causing major side effects.
When used at high doses, prednisone can
cause serious side effects.
Side effects can include:
Weight
gain.
Diabetes.
High blood pressure.
Mood swings
(depression).
Difficulty sleeping at
night.
Heartburn.
Acne.
Thinning of the skin and bones (called
osteoporosis).
Cataracts.
Glaucoma.
Adrenal gland insufficiency, which
occurs when these glands don't make enough of certain hormones. This
requires
treatment by an endocrinologist (en"do-kri-nol'o-jist), a doctor who
specializes in the diagnosis and
treatment of the endocrine glands.
The endocrine glands include your adrenal and pituitary glands.
Aseptic
(a-sep'tik) or avascular (ah-vas'ku-lar) necrosis (ne-kro'sis) of the hip, the
development of cysts and
hardened and dead tissue in the
hip.
Your doctor can usually help you manage these side effects.
When
it is time to stop taking prednisone, you should cut back slowly, with your
doctor's help. This will help
prevent flare-ups of sarcoidosis and
allow your body to adjust to life without the drug.
You may also want to
see an endocrinologist to make sure that your endocrine glands are making
enough
hormones. The endocrinologist may prescribe certain hormones
for you to take until your endocrine glands are
working well
again.
Other Drugs Used To Treat Sarcoidosis
Other drugs are
sometimes used to treat sarcoidosis. Your doctor may prescribe one of them
if:
Your condition gets worse while you are taking prednisone
You
can't stand the side effects of prednisone.
Most of these other drugs are
immune system suppressants. This means that they prevent your immune system
from fighting things like bacteria and viruses. As a result, you may
have a greater chance of getting infections.
Most of these drugs also
can cause serious side effects. Some also could increase your chances of
getting cancer,
especially if you take them at high
doses.
You and your doctor must weigh living with the symptoms of
sarcoidosis against the side effects of the drugs.
Some drugs work
better than others for different people.
You may be given more than one
drug.
Some drugs used to treat sarcoidosis are taken by mouth. Others
are applied locally to an affected area.
Local therapy is the safest way to treat sarcoidosis. The drug is applied directly to the affected area. As a result,
only small amounts of the drug reach other parts of your
body.
Drugs used for local therapy include:
Eye drops
Inhaled
drugs for your lungs
Skin creams.
Drugs can be used locally only if the
affected area is easily reached. For instance, inhaled steroids can ease
coughing and wheezing in the upper airways, but they don't seem to
relieve these symptoms when the affected
lung tissue is deep within
your chest.
Talk with your doctor about these treatments and the side
effects that may occur.
The other drugs used to treat sarcoidosis
include:
Hydroxychloroquine (Plaquenil). This drug can usually help
people who have sarcoidosis in the skin or a high level
of calcium
in their blood. This drug can irritate your stomach.
It also can cause eye
problems. Before starting on this drug, you should see an ophthalmologist
(of"thal-mol'o-
jist), or eye doctor, for some baseline tests. Once
you start taking it, you should have your eyes examined every 6
months.
Methotrexate. This drug is taken once a week by mouth or
injection and usually takes up to 6 months to relieve
symptoms.
This drug may cause side effects, especially if you take
high doses. These include:
Nausea.
Mouth sores.
A decrease in
infection-fighting white blood cells. You then have a greater chance of getting
an infection. If you
take this drug, you should have regular blood
tests to check the levels of your white blood cells.
An allergic reaction in
your lungs that goes away when you stop taking the drug. This is extremely
rare.
Liver damage. This is the most serious side effect. If you take
methotrexate you should be followed regularly by
your
physician.
If you are pregnant, you should not take this drug.
Taking
folic acid can help you reduce your chances of having bad side effects from
methotrexate.
Azathioprine (Imuran). This drug may work in about half of the
people who have sarcoidosis. You usually take it
for at least 6
months. Side effects include:
Nausea
Reduced white blood cell levels,
which increases your chances of getting an infection.
This drug has caused
cancer in some people, especially when they have taken it at high doses.
If
you are pregnant, you should not take this drug.
Cyclophosphamide (Cytoxan).
This is a very toxic drug. It is rarely used to treat sarcoidosis. It is given
only to
people who have serious forms of sarcoidosis, such as
sarcoidosis in their central nervous system
(neurosarcoidosis).
This drug is more likely to cause nausea and
reduce your white blood cell levels than either methotrexate or
azathioprine. Your doctor should check your white blood cell levels
often while you are taking this drug to make
sure you have a high
enough level to fight infection.
Cyclophosphamide can also irritate your
bladder. Some people who have taken it for more than 2 years have
developed bladder cancer.
If you are pregnant, you should not take
this drug.
Cyclophosphamide can be given intravenously (through one of your
veins), which lessens some of its side effects,
but this doesn't
reduce the risk of cancer.
Treatments for Specific Types of
Sarcoidosis
Eyes. Sarcoidosis in your eyes almost always responds well to
treatment. Often, the only treatment you need is
eye drops
containing corticosteroids. You should have yearly eye exams, even if you think
your eyes are doing
well.
Spleen. Sarcoidosis can cause your
spleen to become larger. This can lead to a decrease in your red or white
blood cells or platelets and increase your chances of infection and
blood clotting disorders. Treatment is usually
given to increase
the number of your blood cells and ease your pain. In rare cases, your spleen
may need to be
removed.
Liver. Sarcoidosis rarely causes
permanent liver damage. As a result, your liver usually isn't treated unless
it's
causing major symptoms (e.g., fever). Drug treatment can
usually reduce granulomas in your liver. Liver
transplantation has
been successful in those rare cases in which the condition has become
worse.
Followup care includes regular blood tests to find out how well your
liver is working. You should check with your
doctor to find out how
often you need these tests.
Nervous system. Sarcoidosis in your nervous
system (neurosarcoidosis) usually needs treatment. Nerve tissue
heals slowly, so treatment often takes a long time. You may need to
take several drugs at high doses.
Erythema nodosum. These painful bumps on
your shins often go away in weeks to months without treatment.
Your
doctor probably will not give you medication unless you are very uncomfortable.
Aspirin or ibuprofen, an
anti-inflammatory drug that you can buy
without a prescription, will usually help.
Heart. Sarcoidosis in your heart
is usually treated with steroids. You may also be given heart drugs to improve
your heart's pumping ability or to correct a disturbed heart
rhythm.
If you have a severe heart rhythm disturbance, your doctor may
prescribe one of these devices:
A cardiac pacemaker, a small
battery-operated device, often put under your skin, that regulates your
heartbeat
A defibrillator, an implanted device that shocks your heart into a
normal heartbeat or, if it has stopped, into beating.
If your heart is
severely affected and doesn't respond to treatment, a transplant may be done.
But this is rarely
needed.
Lupus Pernio. This rash on your face,
especially your cheeks and nose, can be distressing because it's in a very
visible area. It often occurs with loss of your sense of smell, nasal
stuffiness, and sinus infections.
Options for treatment include:
Local
treatment with skin creams
Oral drugs (plaquenil or prednisone, for
example)
Local injections of steroid preparations.
Lupus pernio is often
treated by dermatologists, doctors who specialize in skin diseases, working
with a
sarcoidosis specialist.
Because sarcoidosis varies so
much among different people, your doctor may find it hard to tell whether the
treatment is helping.
Other Drugs Being Studied for Possible
Use in Treating Sarcoidosis
Scientists also are studying drugs that are used
for other conditions to see if they can help people who have
sarcoidosis. These drugs include:
Etanercept (Enbrel). This drug
is an immune system suppressant. It's injected under the skin to reduce
symptoms
of rheumatoid arthritis. It may also be used to treat psoriasis (so-ri'ah-sis) or ankylosing spondylitis (ang"ki-lo'sing
spon"di-li'tis), a type of arthritis that affects the joints in the
spine. Early studies suggest that it will not be useful in
treating
sarcoidosis, but research is ongoing.
Infliximab (Remicaide). This drug is
an immune system suppressant. It's injected into a vein in your arm. It's used
to treat Crohn's Disease, rheumatoid arthritis, and ankylosing
spondylitis. Some studies have shown it to help
sarcoidosis
patients who also have lupus pernio, eye disease, or neurosarcoidosis. This
drug has serious side
effects but may improve lung function in some
people who aren't helped by corticosteroids. More research is
needed.
Pentoxifylline. This drug is an immune system suppressant.
Stomach and gastrointestinal side effects are
common. Early studies
show that it has helped some people who have sarcoidosis in their lungs reduce
their doses
of prednisone while taking it. More research is
needed.
Tetracycline. Tetracycline antibiotics are used to treat Lyme
Disease, some types of pneumonia, and acne. A few
small studies
suggest that they may help in treating sarcoidosis in the skin. Research is
ongoing.
Thalidomide. This immune system suppressant can cause bad side
effects. It is effective against other conditions
that involve
granulomas of the skin (e.g., leprosy, tuberculosis). Scientists are studying
this drug to see if it can be
used to treat sarcoidosis in the
skin. More studies are needed.
What Does the Future Hold?
Scientists
worldwide are trying to learn more about sarcoidosis and how to improve its
diagnosis and treatment.
Some recent studies have led to possible
new treatments, which, in turn, are being studied. Current research
includes studies of:
The agent or agents that cause
sarcoidosis
Why sarcoidosis seems to act differently in people of different
races
Why sarcoidosis appears in some families
How genes, passed from one
generation to another, may make some people more likely than others to develop
sarcoidosis
How cells act and communicate with each other to
cause sarcoidosis symptoms.
Living With Sarcoidosis
You should take steps
to stay healthy. This includes:
Don't smoke.
Avoid substances like
dusts and chemicals that can harm your lungs.
Try to follow a healthy eating
plan.
Be as active as you can but don't strain yourself.
Joining a
patient support group may help you adjust to living with sarcoidosis. Talking
to others who have the
same symptoms can help you see how they have
coped with them. To find a local support group, check your
telephone directory or contact one of the sarcoidosis groups listed
under Links.
Your regular doctor may be able to diagnose and treat your
sarcoidosis, but diagnosis and treatment by a doctor
who
specializes in sarcoidosis is recommended. If you prefer to use your regular
doctor, you should see a doctor
who specializes in the organs that
are affected by your sarcoidosis at least once. For example, see an
ophthalmologist if your eyes are affected or a pulmonologist if you
have sarcoidosis in your lungs. These
specialists are often found
at major medical centers. They will work with your regular doctor to help make
a
diagnosis, develop a treatment plan, and schedule periodic exams
and lab tests. .
Pregnancy
Many women give birth to healthy babies
while being treated for sarcoidosis. Pregnancy usually doesn't affect the
course of sarcoidosis, and you can continue corticosteroid treatment
through your pregnancy. None of the other
drugs are recommended for
use during pregnancy.
Sometimes your sarcoidosis may get worse after the
baby is delivered.
Women with severe sarcoidosis, especially if they are
older, may have trouble becoming pregnant.
It's important for you to
discuss this issue with your doctor. If you become pregnant, you should be sure
to get
both good prenatal care and regular sarcoidosis checkups
during and after pregnancy.
Followup Care
Regular followup care is
important, even if you aren't taking medication for your sarcoidosis. New
symptoms can
occur at any time, and your condition can get worse
slowly, without your noticing.
Followup exams usually include:
A
review of your symptoms
A physical exam
A chest x ray and CT
scan
Breathing tests
An eye exam
Blood tests
An electrocardiogram
(EKG).
How often you have your examinations and tests depends on:
How
severe your symptoms are
Which organs were affected at diagnosis
What
treatment you are using
Any complications that may develop during
treatment.
You will probably need routine followup care for several years.
Whether you see your regular doctor or a
sarcoidosis specialist for
this depends on your symptoms during the first year of followup.
Here
are some examples of how your followup care can be managed. They are based on
either your condition
when you were diagnosed with sarcoidosis or
the treatment used.
Followup After Initial Diagnosis
If at
diagnosis, you have no symptoms, a normal breathing test, and an abnormal chest
x ray:
You should plan on having a followup exam every 6 to12 months until
your condition is stable or improving.
Your breathing test may need
to be repeated. The need to repeat it depends on your symptoms and ability to
be
active.
If at your first followup visit, you have no new
symptoms and your chest x ray is normal, you can go to your
regular
doctor for future followup care.
If at diagnosis, you have some
symptoms, an abnormal chest x ray, but you don't need treatment:
You should
plan on having a followup exam in 3 to 6 months.
If at your followup exam,
your condition has gotten worse (i.e., you now have more symptoms, an abnormal
x
ray, or abnormal lab tests) you may need treatment.
If
treatment is started, you may need followup tests more often.
Followup Based
on Your Drug Treatment
If treatment is begun with prednisone:
You
should be checked for the side effects of high blood pressure, too much weight
gain, diabetes, loss of
calcium from your bones, and pain in one or
both hips.
If treatment is begun with hydroxychloroquine:
You should
have an eye exam every 6 months while taking this drug.
If treatment is
begun with methotrexate:
You should have blood tests every month or
every other month to see if you have anemia, low white blood cell or
platelet
levels, or liver inflammation.
Other Followup Tests
Depending on how
serious your condition is and what organs are affected, you may also need to
have certain tests
done regularly.
Eye Tests
Everyone who
is diagnosed with sarcoidosis, even if they don't have eye symptoms, should see
an ophthalmologist
(eye doctor) for eye tests. This is important
because you may have eye damage even if you don't have symptoms.
These
tests may include:
A slit lamp examination. Your doctor uses an
instrument with a high-intensity light source to look at the front of
your
eyes.
A visual fields examination. Your doctor will ask you to you to look
at a light through an instrument.
Inspection of your retina and optic
nerve.
If you develop eye symptoms, your doctor will have you repeat the
tests.
You should also have regular eye exams if you are being treated
with:
Chloroquine or hydroxycholoroquine
(Plaquenil)
Corticosteroids.
Breathing Tests
These tests are used to
check the course of sarcoidosis in your lungs. The results are compared over
time.
Blood Tests
A blood test for calcium should be done. If your
calcium level is high, you probably will need to be treated. You
also should not take vitamin and mineral supplements containing calcium
or vitamin D, and you should avoid too
much exposure to the
sun.
Electrocardiogram
This test is needed to make sure that your
heart is still not affected by sarcoidosis. The heart can be affected at
any time if the sarcoidosis is active.
www.nhlbi.nih.gov/health/dci/Diseases/sarc/sar_whatis.html
---------------------------------------------------------
microlymphatic
hypertension LYMPHOEDEMA
Microlymphatics of human skin.
Int J
Microcirc Clin Exp. 1993; 12(1):1-15 (ISSN: 0167-6865)
Bollinger
A
Department of Internal Medicine, University Hospital, Zurich,
Switzerland.
Microlymphatics of human skin form two superposed networks.
The superficial one located at the level of dermal
papillae may be
visualized by fluorescence microlymphography. Microlymphatics fill from a
subepidermal depot of
minute amounts of FITC-dextran 150,000. In
primary lymphedema with late onset the depicted network with
vessels of normal size is significantly larger than in healthy
controls, whereas in congenital lymphedema (Milroy's
disease)
microlymphatics are aplastic or ectatic (diameter > 90 microns). Lymphatic
microangiopathy with
obliterations of microvessels develops in
chronic venous insufficiency, in lipedema (preliminary results) and after
recurrent erysipelata. In healthy controls microlymphatics are
permeable to FITC-dextran 40,000 and impermeable
to the larger
molecule 150,000. Preserved fragments of the network in chronic venous
insufficiency exhibit
increased permeability to FITC-dextran
150,000. After visualization of the vessels by the fluorescent dye
microlymphatic pressure may be measured by the servo-nulling technique.
First results indicate that
microlymphatic hypertension contributes
to edema formation in patients with primary lymphedema.
PreMedline
Identifier: 8473066
http://www.ewma.org/pdf/fall05/focus_eng.pdf
----------------
Anti-fibrosclerotic
effects of shock wave therapy in lipedema and cellulite.
Biofactors. 2005;
24(1-4):275-82 (ISSN: 0951-6433)
Siems W; Grune T; Voss P; Brenke
R
Loges-School of Physiotherapy, Research Institute of Physiotherapy &
Gerontology, D-38667 Bad Harzburg,
Germany.
[email protected]
In vivo measurements in 26 female patients with
lipedema and cellulite parameters were carried out before and
after
therapy by means of complex physical decongestive therapy (CPDT) including
manual lymph drainage and
compression as main components and/or
shock wave therapy (SWT). Oxidative stress parameters of blood serum
and
biomechanic skin properties/smoothening of dermis and hypodermis surface were
evaluated. Oxidative stress
in lipedema and cellulite was
demonstrated by increased serum concentrations of malondialdehyde (MDA) and
plasma protein carbonyls compared with healthy control persons. Both
MDA and protein carbonyls in blood
plasma decreased after serial
shock wave application and CPDT. The SWT itself and CPDT itself lead to MDA
release from edematous tissue into the plasma. Obviously both therapy
types, SWT and CPDT, mitigate oxidative
stress in lipedema and
cellulite. In parallel SWT improved significantly the biomechanic skin
properties leading to
smoothening of dermis and hypodermis surface.
Significant correlation between MDA depletion of edematous and
lipid enriched dermis and improvement of mechanic skin properties was
demonstrated. From these findings it is
concluded, that a release
of lipid peroxidation (LPO) products from edematous dermis is an important
sclerosis-
preventing effect of SWT and/or CPDT in lipedema and
cellulite. Expression of factors stimulating angiogenesis
and
lymphangiogenesis such as VEGF was not induced by SWT and/or CPDT and,
therefore, not involved in
beneficial effects by SWT and/or
CPDT.
PreMedline Identifier:
16403988
-----------------------------
Stewart-Treves
Syndrome
Article Last Updated: Mar 28, 2007
AUTHOR AND EDITOR
INFORMATIONSection 1 of 9 Authors and Editors Introduction Clinical
Differentials
Workup Treatment Follow-up Miscellaneous
References
Author: Geover Fernandez, MD, FAAD, Staff Physician,
Department of Dermatology, University of Medicine and
Dentistry New
Jersey, New Jersey Medical School
Geover Fernandez is a member of the
following medical societies: Alpha Omega Alpha, American Academy of
Dermatology, and American Society for MOHS Surgery
Coauthor(s):
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of
Medicine,
Professor of Pediatrics, Professor of Pathology,
Professor of Preventive Medicine and Community Health,
UMDNJ-New
Jersey Medical School
Editors: Abby S Van Voorhees, MD, Assistant
Professor, Director of Psoriasis Services and Phototherapy Units,
Department of Dermatology, University of Pennsylvania School of
Medicine, Hospital of the University of
Pennsylvania; Michael J
Wells, MD, Associate Professor, Department of Dermatology, Texas Tech
University
Health Sciences Center; Christen M Mowad, MD, Assistant
Professor, Department of Dermatology, Geisinger
Medical Center; Glen
H Crawford, MD, Assistant Clinical Professor, Department of Dermatology,
University of
Pennsylvania School of Medicine; Chief, Division of
Dermatology, The Pennsylvania Hospital; William D James,
MD, Paul R
Gross Professor of Dermatology, University of Pennsylvania School of Medicine;
Vice-Chair,
Program Director, Department of Dermatology, University
of Pennsylvania Health System
Author and Editor
Disclosure
Synonyms and related keywords: cutaneous angiosarcoma,
postmastectomy angiosarcoma, lymphangiosarcoma in
postmastectomy
lymphedema, postlymphedema angiosarcoma, hemangiosarcoma in chronic lymphedema,
hemangiosarcoma in postmastectomy lymphedema, postmastectomy
lymphedema, lymphangiosarcoma, Milroy
disease, Milroy's disease,
idiopathic lymphedema, congenital lymphedema, traumatic lymphedema, filarial
lymphedema
INTRODUCTIONSection 2 of 9 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Follow-up Miscellaneous
References
Background
Stewart-Treves syndrome is a rare, deadly
cutaneous angiosarcoma that develops in long-standing chronic
lymphedema. Most commonly, this tumor is a result of lymphedema induced
by radical mastectomy to treat breast
cancer. Unfortunately,
although the breast cancer may be cured with such radical surgery, this second
primary
cancer may be responsible for the patient's worsening
course. The term Stewart-Treves syndrome is broadly
applied to an
angiosarcoma that arises in a chronically lymphedematous region due to any
cause, including
congenital lymphedema and other causes of secondary
lymphedema unassociated with mastectomy. As reported
by Durr et al
in 2004, this lymphangiosarcoma occurs as a rare complication.
Lymphangiosarcoma is a misnomer
because this malignancy seems to
arise from blood vessels instead of lymphatic vessels. A more appropriate name
is hemangiosarcoma.
In 1906, Lowenstein first described
angiosarcoma in a patient's arm that had been affected by severe
posttraumatic lymphedema for 5 years. In 1948, Stewart and Treves
reported this rare secondary malignancy in 6
cases of angiosarcoma
in postmastectomy lymphedema. They recognized that an edematous arm after
radical
mastectomy for breast cancer may suggest recurrent breast
cancer, but that long-standing chronic edema without
recurrent
cancer may occasionally produce "a heretofore unrecognized and unreported
sequel ... long after the
malignant breast neoplasm has apparently
been arrested ... a new specific tumor." Stewart and Treves suggested
that
these angiosarcomas were probably not observed previously because they were
mistaken for recurrent,
inoperable, cutaneous manifestations of
breast cancer.
Lymphangiosarcoma has been described in Milroy disease
and in idiopathic, congenital, traumatic, or filarial
lymphedema.
A case of lymphangiosarcoma in hereditary lymphedema
of the lower extremity has been reported in a 36-year-old
woman.
Despite of chemotherapy, local hyperthermia, and later amputation of the
extremity, the patient died of
progressive disease due to pulmonary
metastasis. In respect to this case, the different therapeutic concepts, as
reported in the literature, and their results are presented and
discussed.
Pathophysiology
The pathogenic mechanism by which
lymphedema may induce angiosarcoma has been the subject of controversy.
Stewart and Treves found a high incidence of third malignancies in
patients with postmastectomy angiosarcoma.
Thus, they speculated
that a systemic carcinogenic factor was the main causative factor in the
pathogenesis of
lymphangiosarcomas.
In 1979, Schreiber and
others postulated the concept of local immunodeficiency in the presence of
lymphedema.
This theory is supported by experimental evidence. In
1960, Stark and associates demonstrated that homograft
skin
transplanted to lymphedematous arms survive much longer than those transplanted
to healthy arms.
Therefore, lymphedema may cause some degree of
local immunodeficiency and lead to oncogenesis.
The possibility that
radiation therapy has an important role in the induction of lymphangiosarcoma
is also
postulated. Sternby et al reported that, in their study,
the patient with the shortest interval between radical
mastectomy
and the onset of the tumor (8 mo) received both preoperative radiation therapy
of the breast and
involved axillary lymph nodes followed by
fractionated radiation. Others suggest that irradiation is not an essential
factor in the pathogenesis of this tumor. Finally, irradiation may be
an indirect cause of lymphangiosarcomas
because it may cause
axillary node sclerosis and thereby accelerate and aggravate the
edema.
Frequency
International
Currently, approximately 400 cases
are reported in the world literature. In 1962, Schirger calculated that the
incidence of this disease is 0.45% in patients who survive at least 5
years after radical mastectomy. Others have
noted a much lower
incidence of 0.07% in patients after
mastectomy.
Mortality/Morbidity
Lymphangiosarcomas are extremely
aggressive tumors with a high local recurrence rate and a tendency to
metastasize
early to many areas. Long-term survivors are the
exceptions.
Metastatic angiosarcoma to the lungs and chest wall are
the most common cause of death in patients with Stewart-
Treves
syndrome.
Metastases to the liver and bones can also occur.
Lymphangiomas
are associated with a high rate of local recurrence and metastasis, even after
aggressive surgical
treatment.
Race
No racial
predominance exists.
Sex
Most patients with Stewart-Treves syndrome
are women with a history of breast cancer that has been treated
with radical mastectomy, which causes chronic
lymphedema.
Age
Stewart-Treves syndrome usually occurs in middle-aged
or elderly women, a few years or many years after
mastectomy.
In 1981, Sordillo and associates reported a peak
incidence in persons aged 65-70 years.
In 1972, Woodward et al described a
series of 23 patients in a review of 163 cases of Stewart-Treves syndrome
from the literature. They recorded an average patient age of 68.8 years
at the onset of lymphangiosarcoma; the
youngest patient was aged 44
years and the oldest, 84 years.
CLINICALSection 3 of 9
Authors and Editors Introduction Clinical Differentials Workup Treatment
Follow-up
Miscellaneous References
History
This tumor
typically develops in patients many years after mastectomy, more commonly 5-15
years after surgery.
In their original series, Stewart and Treves
reported that the earliest angiosarcoma appeared 6 years after radical
mastectomy, the longest interval being 24 years (average, 12.5 y).
In
1988, Tomita and associates demonstrated that the most common interval between
radical mastectomy and the
onset of lymphangiosarcoma was 5-14
years.
In 1981, Yap et al reported a series of 22 patients in whom the
median interval from mastectomy to the onset of
angiosarcoma was 11
years (range, 5-16 y).
Physical
As Stewart and Treves described,
edema occurs first.
Severe chronic edema of an upper extremity usually
occurs in patients with Stewart-Treves syndrome.
In patients who undergo
radical mastectomy, edema first appears on the arm on the side operated
on.
The occurrence of edema is not associated with complications such as
postoperative infection or thrombosis.
The edematous area gradually extends
from arm to forearm and dorsal aspect of the hand and fingers.
Initially,
pain is absent, although skin distention may produce local discomfort.
In
the areas of long-standing chronic edema, recurrent erysipelas may occur, just
as they do in patients with
congenital lymphedema.
The skin
tends to become atrophic and eventually pachydermatous, with prominent wrinkle
lines. At times,
hyperkeratoses and telangiectasias can be
observed.
After an interval of 1-30 years, a purplish patch appears that
then develops into a plaque or nodule in the area of
chronic
lymphedema.
Other initial lesions may include a palpable subcutaneous mass
or a poorly healing eschar with recurrent bleeding
and
oozing.
The lesions of Stewart-Treves syndrome typically appear as multiple
reddish blue macules or nodules that may
become
polypoid.
Around these nodules, small satellite areas can develop and
become confluent, forming an enlarging lesion.
Sometimes, a bullous
component may be seen.
As the angiosarcoma continues to grow and expand, the
overlying atrophic epidermis may ulcerate, producing
recurrent
episodes of bleeding and infection.
Necrosis may be evident in advanced
cutaneous tumors.
Ultimately, extensive cutaneous nodules and systemic
metastases appear. These nodules most commonly occur in
the lungs
and cause the patient's death.
Not every tumor in an area of lymphedema is
an angiosarcoma.
Causes
The most important single causative agent
in Stewart-Treves syndrome is prolonged chronic lymphedema.
Although
Stewart-Treves syndrome develops after radical mastectomy in most patients,
lymphangiosarcoma also
develops in other forms of acquired
lymphedema and in congenital lymphedema.
Causes for such secondary
lymphedema may include trauma, surgical invasion of the groin for the treatment
of
penile or cervical cancer, filariasis, idiopathic acquired
lymphedema, vascular stasis, and morbid obesity.
Edema secondary to cardiac
or renal disease is not associated with this malignancy. Thus, edema alone is
not
sufficient to cause lymphangiosarcoma. Perhaps additional
factors such as a genetic predisposition are
required.
DIFFERENTIALSSection 4 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment
Follow-up
Miscellaneous References
Angioedema, Acquired
Angioedema,
Hereditary
Angioendotheliomatosis
Angiolymphoid Hyperplasia with
Eosinophilia
Kaposi
Sarcoma
Lymphangiectasia
Lymphangioma
Lymphocytoma Cutis
Malignant
Melanoma
Metastatic Carcinoma of the Skin
Other Problems to be
Considered
Telangiectatic metastatic breast disease to the
skin
Hemangioendotheliomas
Hemangiopericytomas
WORKUPSection
5 of 9 Authors and Editors Introduction Clinical Differentials Workup
Treatment Follow-up
Miscellaneous References
Lab
Studies
Although Stewart-Treves syndrome is also known as
lymphangiosarcoma, ultrastructural and immunohistologic
studies
show that this malignancy arises from blood vessels rather than lymphatic
vessels.
The following immunohistologic and ultrastructural findings can be
used to confirm that the tumor originates from
blood
vessels.
Antibodies against factor VIII–related antigen are markers for
endothelial cells. Although malignant endothelial cells
may not
always show positive staining with this marker, a more sensitive endothelial
marker, lectin Ulex europaeus-
I, is more likely to react with
hemangiosarcoma tumor cells. However, the specificity of this marker is reduced
in
people with blood group O because normal epithelial cells and
carcinomas also bind this lectin in these individuals.
CD34 antigen is a
marker of vascular endothelial cells and does not react with the lymphatic
endothelium.
Antikeratin antibodies show no evidence of keratin in this
malignancy; this finding confirms that the tumor cells
are
nonepithelial in origin.
Positive staining for laminin, CD31, collagen IV,
and vimentin can aid in diagnosing the tumors as angiosarcomas.
Imaging
Studies
MRI is recommended to evaluate the local extent of
angiosarcomas. However, its true value is in question because
of
poor results in delineating the margin of the tumor. It may be low in signal
intensity on T2-weighting and short-
tau inversion recovery (STIR)
imaging, reflecting the densely cellular, fibrous stroma and sparsely
vascularized
tumor histology (Schindera, 2005). Additional
administration of intravenous contrast medium may reveal
significant enhancement of the tumorous lesions.
Chest CT should be
performed to rule out metastatic disease to the lungs before the patient
undergoes extensive
surgery.
Chest radiography can help in
identifying pulmonary metastases and pleural
effusion.
Procedures
Analysis of a biopsy specimen is essential
to the diagnosis of lymphangiosarcoma.
Fine needle aspiration is inadequate
for diagnosis.
Histologic Findings
Histologically, angiosarcomas in
Stewart-Treves syndrome are indistinguishable from angiosarcomas in
nonlymphedematous sites. Postlymphedema angiosarcomas are characterized
by proliferating vascular channels,
which dissect the dermal
collagen and, often, the obliterate appendages. Tumor endothelial cells lining
these
channels show marked hyperchromatism and pleomorphism. Mitoses
are commonly seen in these tumor cells.
The vascular endothelial
cells appear round or oval, and they are protuberant and often project into the
lumen.
Erythrocytes can be seen inside these vascular channels. The
overlying epidermis may be hyperkeratotic and
acanthotic, or it may
be atrophic. Prominent proliferation of reticular fibers can be seen in
association with this
malignancy.
At electron microscopic
examination, lymphangiosarcoma cells are surrounded by a complete basal lamina.
In
some tumor cells, pinocytosis, intercellular junctions, and
cytoplasmic intermediate filaments are observed. In
addition,
Weibel-Palade bodies and erythrophagocytosis are often present. These
ultrastructural findings suggest a
vascular endothelial origin
rather than a lymphatic endothelial origin.
Staging
In 1959,
McConnell and Haslam divided the course of development of lymphangiosarcoma
into 3 stages. This
staging system lacks universal
application.
Stage 1 - Prolonged lymphedema
This stage is
characterized by extensive edema that causes the degeneration of fat and
collagen mainly in the deep
part of the dermis.
Edema separates
the collagen bands, creating a misperception of an increased amount of fibrous
tissue in the area.
Stage 2 - Premalignant angiomatosis
This stage
involves multiple foci of small, proliferating channels in the dermis and
subdermis. These vessels are
lined by hyperplastic endothelial
cells, as well as normal, flattened cells.
The areas of angiomatosis vary in
size, ranging from 100 µm to a couple of centimeters in
diameter.
Superficial areas can be seen as bruises or vesicles, whereas
deeper areas are seen as areas of induration and
hemorrhage.
Early lesions show little evidence of malignancy, but
more advanced lesions reveal early malignant transformation
with an
increased number of mitotic figures and pleomorphic cells.
Stage 3 - Frankly
malignant angiosarcoma
These aggressive tumors develop from areas of
premalignant angiomatosis.
The histologic features of this malignancy are
described above in stage 2.
TREATMENTSection 6 of 9 Authors
and Editors Introduction Clinical Differentials Workup Treatment Follow-
up Miscellaneous References
Medical
Care
Chemotherapy and irradiation continue to be evaluated as
adjuvants to surgery.
Currently, these treatment options offer little
benefit.
In 2000, Grobmyer and associates found no statistical significant
difference in the survival rates of patients treated
with
chemotherapy compared with those treated with irradiation.
Although
long-term survivors after either radiation therapy or systemic chemotherapy
have been reported, the
overall results have been
discouraging.
As a result of these findings, these treatment options are
reserved for patients with inoperable, advanced disease or
those
who refuse surgery.
In 1994, Furue et al demonstrated that immunotherapy may
be beneficial as palliative treatment for pleural
effusions caused
by metastatic angiosarcoma.
Surgical Care
Early amputation or
wide local excision provides the best chance of long-term survival in patients
with Stewart-
Treves syndrome. Some authorities favor radical
ablative surgery with an early diagnosis, in order to confer a
reasonable prognosis with this rare but aggressive disease (Roy, 2005).
A nihilistic approach is undesirable.
The most common approach in
patients with lymphangiosarcoma is amputation of the limb or forequarter rather
than wide local surgical excision.
Even in cases with early
surgical treatment, the prognosis is disappointing, with a high rate of local
recurrence and
metastasis.
Metastatic disease should exclude
surgical treatment unless surgery is useful for symptomatic
improvement.
Chemotherapy, immunotherapy, and/or radiation therapy can be
used as adjuvants to surgery (see Medical
Care).
FOLLOW-UPSection 7 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment Follow-
up
Miscellaneous References
Further Inpatient Care
Complications
from metastatic disease, such as pleural effusions, may require hospitalization
of the patient.
The patient may need further inpatient care for pain
control.
Deterrence/Prevention
The most efficient way to avoid
this highly lethal disease is by preventing or treating long-standing
lymphedema,
which predisposes individuals to this lymphangiosarcoma
years later.
Other complications commonly associated with chronic
lymphedema, such as erysipelas and deep venous
thromboses, must be
prevented by regularly examining these areas and then treating them.
Early
biopsy of any suggestive lesion should be performed because early diagnosis and
surgical treatment offers
the highest rate of long-term
survival.
Complications
Patients can present with recurrent
episodes of erysipelas and deep venous thromboses in areas of chronic
lymphedema.
Other
complications include recurrent infections and
malignancies.
Prognosis
The prognosis is dismal.
The
5-year survival rate reported by Sordillo et al in 1981 is 13.6%, and it is
8.5% in the series by Woodward et al.
In 1987, Hultberg found that patients
with Stewart-Treves syndrome had a mean survival of 20 months after
tumor onset.
Untreated patients have an average survival of 5-8
months.
Patient Education
Patients should be informed about the
significance of prolonged chronic lymphedema and about how to reduce
and
control it.
Patients should be encouraged to seek early medical attention if
they notice unexplained skin changes or
unresolved
lymphedema.
Patients should be educated about complications, such as
recurrent infections, deep venous thrombosis, and
malignancies,
that can occur with lymphedema.
For excellent patient education resources,
visit eMedicine's Women's Health Center and Cancer and Tumors
Center. Also, see eMedicine's patient education articles Mastectomy and
Breast Cancer.
MISCELLANEOUSSection 8 of 9 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Follow-up Miscellaneous References
Medical/Legal
Pitfalls
Failure to perform biopsy to evaluate suspicious skin lesions
in patients with long-standing lymphedema is a
pitfall.
REFERENCESSection 9 of 9 Authors and Editors
Introduction Clinical Differentials Workup Treatment Follow-
up
Miscellaneous References
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Stewart-Treves Syndrome
excerpt
Article Last Updated: Mar 28,
2007
------------------------------------
HYPERKERITOSIS
In
long standing lymphedemas hyperkeritosis can be a problem. This is an
overabundant skin thickening with
callous formation and possibly
wart-like papillomas. It is gray-brown in color and can occur anywhere on the
involved area. This is not often seen in upper extremity
involvement. Sometimes hyperkeritosis can be mistaken
for dried
lymph fluid. Hyperkeritosis is a skin change, a scarring, and should never be
removed through
debridement. Surgical excision is the only
treatment, however effective skin care treatment can substantially
reduce the severity.
FUNGAL INFECTIONS
Fungal infections
occur frequently in lower extremity lymphedema patients. The stagnant protein
rich fluid is a
breeding ground for bacteria and feet enclosed in a
dark, moist environment are prime targets for infections.
Fungal
infections manifest themselves through itching between the toes, small
blisters, a gray or whitish film on
the skin, and foul odor.
Sometimes the skin peels off between the toes. Initially only slight scale may
be noted but
soon it spreads and nail changes can take place. It
can be a problem in only one foot or it can be bilateral.
Patients with
foot fungus need to be careful not to contaminate other household members. The
infected patient
can shed tiny fragments of skin and fungus.
Similar sources of infection exist in discarded bandages or clothes on
any surface. The tub or shower should be cleaned thoroughly immediately
after use. Patients should not go
barefoot in the bathroom but lay
a towel down on the floor. That towel needs to be removed and placed in the
wash immediately after use. All towels and washcloths should be used
only once before washing. Going barefoot
generally is not
recommended unless the patient has been instructed to air feet at regular
intervals.
These patients should not go barefoot in the therapy clinic.
Make sure you place a towel on the floor for the
patient to step
onto after removing shoes. Do not have the patient drop socks or stockings onto
the floor. They
should be placed inside the patient’s
shoes.
In the beginning stages of foot fungus, over the counter foot
fungal medications can be used. Sometimes a
prescription drug is
required. Patients with repeated problems of foot fungus need to be followed by
a physician.
The therapist may chose to include treating the foot
fungus as a part of the therapy session. Gloves should be
worn.LYMPHATIC CYSTS
These are abnormally widened initial lymph
vessel visible as tiny vesicles or blisters. When they burst there is
danger
of infection. These need to be monitored daily. During manual lymph drainage be
careful of over-pulling
the skin around these areas. There should be
no stimulation directly over the area itself. With increasing
decongestion of the lymphedemetous area, the lymphatic cysts usually
dry up.
The skin needs to be kept supple and moist. Lymphedema is a very
drying condition. Cracks in the skin,
particularly on the feet and
around the toe and fingernails, need to be avoided. A good low pH lotion or
cream is
recommended. Lotions or creams that have fragrances, dyes
or lanolin should not be considered. There are many
products on the
market that advertise "low pH" or "pH balanced" and these are
preferred.
The best time to apply moisturizer is after bathing. It is
not recommended it be applied just prior to donning
medical
compression garments. Lotions/creams can get "caught" up in the garment fabric.
If the patient doesn’t
wash the garment daily, this can hasten the
deterioration of the garment fabric. Some patients can develop itching
or a rash if applied prior to bandaging, particularly in the hot summer
weather.
Maintaining a good fluid intake will assist with skin
moisturization. Sometimes patients mistakenly think if they
limit
the fluid intake, the swelling in the involved limb will be reduced. Good skin
integrity can only be maintained
if oral fluids are
adequate
Hyperkeratosis and Papillomatosis
By Jenny Veitch,
Lymphoedema Specialist
Hyperkeratosis Papillomatosis
What are
hyperkeratosis and papillomatosis?
These are changes which can take place
within the skin and present as thickening and solidness (described as
fibrosis*)
of the tissues.
The cause of these characteristic changes is the result of
untreated lymphoedema and are generally found on lower
limbs.
How can they be recognised?
Hyperkeratosis is a warty
scaly change in the skin due to an increased production of keratin, a surface
protein.
Papillomatosis is a cobblestone change in the skin surface due to
dilated surface lymphatic vessels or focal
accumulations of lymph;
they are non-compressible due to thickening and fibrosis of surrounding
tissues. Warty
hyperkeratosis and papillomatosis often coexist in
which case the skin resembles elephant skin (known as
elephantiasis).
How can they be prevented?
As already stated,
these changes generally appear as a result of oedema being untreated. The
fitting of good quality
compression hosiery and meticulous daily
skin care, including the use of moisturising cream, should help to
prevent changes occurring within the skin and tissues.
How can
these changes be treated?
It is important to moisturise the affected area
twice daily with 50% white soft paraffin and 50% liquid paraffin
mixed, until the skin improves. In more severe cases, salicylic acid 5%
in an ointment base may be used, this will
help to lift the scales
from the skin surface. This must be discussed with the health care professional
responsible
for your care.
When the skin condition has improved,
daily application of aqueous cream can be applied at night in order to keep
the skin well hydrated and supple. Appropriate class and size of
compression hosiery must be worn daily to
maintain the improved
skin condition.
If the limb is very swollen and distorted in shape it will
be essential to receive an intensive course of treatment
known as
decongestive lymphatic therapy (DLT) from a qualified lymphoedema
specialist.
NB * Fibrosis is an increase in the thickness and amount of
collagen in the skin. It conveys a harder consistency
to the
tissues concerned.
Lymphorrhoea
By LSN Trustee and Nursing Advisor,
Denise Hardy
Lymphorrhoea is the leakage, or weeping, of lymph fluid
through the skin surface. Large beads of fluid appear on
the skin
and trickle from the affected areas.
Causes of Lymphorrhoea
May be the
result of lacerations, abrasions, or trauma of the altered dry skin of
longstanding oedema e.g. graze/cut
It may result from the rupture (bursting)
of lymphangiomas (described more fully below)
It may also occur in a sudden
or acute oedema (swelling) where the shiny, taut skin has stretched so rapidly
that it
splits, forming a leak.
Lymphorrhoea - the problems it
causes
The skin feels very cold, wet and uncomfortable
The fluid can soak
through dressings which may need changing many times a day to cope with the
large amounts
of leakage
The fluid can collect in shoes/slippers
clothing and bed linen can become soaked and require frequent
changes
Lymphorroea will increase the risk of cellulitis - the break in the
skin acts as an entry for bacteria. Infection will
cause further
problems (pain/inflammation/flu-like symptoms and increased amounts of fluid
leakage)
If left to leak and dressings are not regularly changed the lymph
(being an excellent culture medium) may grow
bacteria causing odour
and discolouration
Lymphorrhoea may cause social difficulties and
embarassement. Lymphorrhoea not uncommonly affects the
genital area
and may be difficult to distinguish from urinary incontinence.
Treatment of
Lymphorrhoea
In order to stop the fluid leaking, a series of steps are
essential.
Your Lymphoedema nurse/therapist or other nurse involved in your
care should be able to help you with these
steps following a full
assessment of the cause of the leakage:
The area around the 'leak' needs to
be cleaned carefully to ensure the risk of infection is reduced.
An
emollient (moisturising cream/lotion) should be applied to the skin to improve
the condition and protect it (by
acting as a barrier) against
further skin breakdown.
A non-adherent (non sticky), absorbent, (e.g.
Allevyn/Cutinova/lyofoam) sterile dressing should be applied to the
leaking area to prevent further trauma to the skin - and to absorb the
leakage.
Pressure should be applied. For example a limb should be supported
with appropriate bandaging e.g. Multi Layer
Lymphoedema Bandaging
(MLLB) with short stretch compression bandages. This normally stops the flow of
leakage within 24-48 hours. Bandages may have to be replaced
frequently during this period of time to remove wet
bandages/
dressings and to prevent further skin breakdown. MLLB should continue until the
skin condition has
improved enough to wear your stockings/sleeve
again.
At rest, the affected limb should be elevated to reduce the effects
of gravity.
Once the leakage has stopped, and the skin condition has
improved, your usual compression garment should once
again be
applied. The garment will keep the swelling to a minimum and prevent any
further 'leaks' appearing.
Lymphangiomas
Lymphangiomas are often referred
to as 'lymph blisters'.
They consist of enlarged, or bulging lymphatic
vessels just under the surface of the skin, which give the
appearance of a blister.
Lymphangiomas can occur as a result of
damage to the deep lymphatic vessels e.g. following radiotherapy, or
surgery
and they generally contain clear lymph fluid (though sometimes it can be blood
stained).
If Lymphangiomas burst, they result in wetness around the area or
even profuse leakage which is a risk of
potential
infection.
Treatment involves strict skin hygiene and the usual lymphoedema
cornerstones of treatment - especially
compression.
If left
untreated, the lymph blisters may become harder and firmer and begin to look
like firm skin nodules.
Lymphangiomas are not
cancerous.
Information updated on this page 1/08 by the Lymphland
Editorial Board
Please note that lymphedema specialists are those
specifically trained. Information about Jenny Vietch is not
known
so treat her article as if it came from a non-professional
view.
---------------------------------
Incontinentia
Pigmenti
Article Last Updated: Feb 18, 2008
AUTHOR AND EDITOR
INFORMATIONSection 1 of 11 Authors and Editors Introduction Clinical
Differentials Workup Treatment Medication Follow-up Miscellaneous
Multimedia References
Author: Kara N Shah, MD, PhD, Assistant Professor,
Department of Pediatrics, Section of Dermatology,
Children's
Hospital of Philadelphia
Kara N Shah is a member of the following
medical societies: American Academy of Dermatology, American
Academy of Pediatrics, and Society for Pediatric
Dermatology
Editors: Bernice R Krafchik, MBChB, FRCPC, Professor
Emeritus, Department of Pediatrics, Section of
Dermatology,
University of Toronto; David F Butler, MD, Professor of Dermatology, Texas
A&M University
College of Medicine; Director, Division of
Dermatology, Scott and White Clinic; Director Dermatology Residency
Training Program, Scott and White Clinic; Robert A Schwartz, MD, MPH,
Professor and Head of Dermatology,
Professor of Medicine, Professor
of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and
Community Health, UMDNJ-New Jersey Medical School; Glen H Crawford, MD,
Assistant Clinical Professor,
Department of Dermatology, University
of Pennsylvania School of Medicine; Chief, Division of Dermatology, The
Pennsylvania Hospital; Dirk M Elston, MD, Director, Department of
Dermatology, Geisinger Medical Center
Author and Editor
Disclosure
Synonyms and related keywords: IP, Bloch-Sulzberger syndrome,
ectodermal dysplasia, neurocutaneous syndrome
INTRODUCTIONSection 2
of 11 Authors and Editors Introduction Clinical Differentials Workup
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Medication Follow-up Miscellaneous Multimedia
References
Background
Incontinentia pigmenti (IP) is an X-linked
dominant neurocutaneous syndrome with cutaneous, neurologic,
ophthalmologic, and dental manifestations. Garrod reported the first
probable case of IP in 1906 and described it
as a peculiar
pigmentation of the skin in an infant. Subsequently, Bloch and Sulzberger
further defined the
condition in 1926 and 1928, respectively, as a
clinical syndrome with a constellation of unique features that
includes typical cutaneous manifestations.
Pathophysiology
IP
is an X-linked dominant genodermatosis characterized by abnormalities of the
tissues and organs derived from
the ectoderm and neuroectoderm and
represents a type of ectodermal dysplasia. Involvement of the skin, hair,
teeth, and nails is seen in conjunction with neurologic and
ophthalmologic anomalies. In female IP patients,
lyonization results
in functional mosaicism of X-linked genes, which is manifested by the
blaschkoid distribution of
cutaneous lesions.1 Cells expressing the
mutated X chromosomes selectively eliminate around the time of birth;
therefore,
females with IP have an extremely skewed X-inactivation pattern. Normal X
chromosomes are active in
unaffected skin, and mutated X
chromosomes are active in skin affected with IP.
Frequency
United
States
No incidence or prevalence data are available on IP in the US
population.
International
IP is an uncommon disease. Up until 1987,
only 700 cases had been reported in the literature. The disease is
probably underreported because many mild or uncomplicated cases are
likely unrecognized.
Mortality/Morbidity
The prognosis depends on the
presence and severity of associated extracutaneous manifestations. Morbidity
and
mortality primarily result from neurologic and ophthalmologic
complications, including mental retardation,
seizures, and vision
loss.
Race
IP has a worldwide distribution. IP appears to be more
common among white patients, but it has also been
reported in blacks
and Asians.
Sex
IP is an X-linked dominant, male lethal syndrome.
More than 95% of reported cases of IP occur in females. IP
may
rarely occur in males with Klinefelter syndrome (XXY syndrome) or as a result
of somatic mosaicism or
hypomorphic (less deleterious) mutations in
the NEMO gene.2, 3
Age
Characteristic skin lesions compatible with
the early, vesicular and/or verrucous stages of IP are present at birth or
develop in the first few weeks of life in approximately 90% of
patients. The cutaneous manifestations of the
hyperpigmented stage
develop during infancy and persist during childhood. The hyperpigmented lesions
usually
fade during adolescence. The cutaneous manifestations of
the atrophic/hypopigmented stage develop during
adolescence and
early adulthood and persist indefinitely. Hair, nail, and dental anomalies
often first manifest during
infancy and are permanent. Late-onset
IP is occasionally reported in older infants. Neurologic and ophthalmologic
sequelae often manifest during early
infancy.
CLINICALSection 3 of 11 Authors and Editors
Introduction Clinical Differentials Workup Treatment
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History
In most
patients, cutaneous manifestations are present at birth or occur within the
first 2 weeks of life. The
cutaneous manifestations usually appear
in a characteristic, chronologic sequence. Other systemic manifestations,
including ocular defects, CNS abnormalities, and dental abnormalities,
may not be recognized until infancy or early
childhood.
A
family history of IP in the mother is reported to occur in 28% of patients. In
most patients (62%), the syndrome
occurs sporadically. Germline
mutations inherited from the father have been reported in over 80% of cases of
sporadic IP. Male patients with IP generally appear to have a
sporadic form. The development of postzygotic
mutation and
resulting somatic mosaicism is the likely mechanism in most male patients. In a
study of 42 boys
with IP, only 5 had evidence of NEMO gene mutation.
The male phenotype is similar to that of the female
phenotype,
although unilateral presentation is a more common occurrence in boys
(15%).
The proposed diagnostic criteria for IP are as
follows:
In the absence of a family history, the presence of at
least 1 major criterion is necessary. The presence of minor
criteria supports the diagnosis of IP.
Major
criteria
Typical neonatal vesicular rash with eosinophilia
Typical
blaschkoid hyperpigmentation on the trunk, fading in adolescence
Linear,
atrophic hairless lesions
Minor criteria
Dental
anomalies
Alopecia
Wooly hair
Abnormal nails
With a definitive
family history, the presence of any major criterion strongly supports the
diagnosis of IP.
Other characteristic features include the
following:
Suggestive history or evidence of typical rash,
hyperpigmentation, or atrophic hairless lesions
Vertex alopecia
Dental
anomalies
Retinal disease
Multiple male
miscarriages
Physical
Significant clinical heterogeneity exists in IP
with regard to ectodermal, ophthalmologic, and neurologic
abnormalities, even within families. The cutaneous findings generally
progress through 4 distinct characteristic
stages, although some
stages may overlap temporally and some may not occur at all in individual
patients. Affected
males often have limited involvement of 1 or 2
limbs.
Ectodermal changes
Skin features occur in 4
stages.
Stage 1 (vesicular) is characterized by the development of red
papules and vesicles on an erythematous base that
follow Blaschko
lines. Lesions are seen predominantly on the extremities but may also occur on
the trunk or on the
head and neck. The vesicular stage has been
reported to occur in 90-95% of patients. In most patients (>90%),
lesions
are present at birth or develop within the first 2 weeks of life. They resolve
within several months. Rarely,
self-limiting episodes of
recrudescence of vesicular lesions have been reported to occur in older infants
and
children with IP in association with an intercurrent febrile
illness.
Stage 2 (verrucous) is characterized by thickened, warty-appearing
linear and whorled plaques on an erythematous
base that follow
Blaschko lines. In general, lesions develop on the extremities and trunk but
may also be seen on
the head and neck. Verrucous lesions have been
reported to occur in 70-80% of IP patients. In most patients,
verrucous lesions develop in the first few weeks to months of life and
subsequently resolve over weeks to months.
Stage 3 (hyperpigmented) is
characterized by the development of streaks and whorls of brown or slate-gray
pigmentation along Blaschko lines; this occurs in 90-98% of IP
patients. Hyperpigmented lesions usually involve
the trunk but may
also involve the extremities, the skin folds, or the head and neck. The
location of the
hyperpigmented lesions does not appear to correlate
with areas of prior skin involvement during the earlier
vesicular
and verrucous stages. Hyperpigmented lesions generally develop within the first
few months of life and
resolve slowly by adolescence.
Stage 4
(atrophic/hypopigmented) is characterized by hypopigmented, atrophic, and
reticulate or linear patches
observed on the lower extremities,
usually involving the calves. Atrophic lesions usually develop during
adolescence
and persist into adulthood. Atrophic lesions have been reported to occur in
30-75% of IP patients.
Abnormal dermatoglyphic patterns have also been
reported.
Hair changes include scarring alopecia and are seen in 28-38% of
patients. An absence or hypoplasia of the
eyebrows and eyelashes has
also been reported. Finally, hair is sparse in early childhood; later, it has a
lusterless,
wiry, and coarse appearance.
Nail features4 include
nail dystrophy, which ranges from mild pitting or ridging of the nail plate to
hyperkeratosis
and onycholysis. This is observed in 7-40% of IP
patients, and usually multiple fingernails and toenails are
affected. Nail dystrophy may improve with age. Subungual and periungual
keratotic tumors associated with pain,
bony deformities, and lytic
lesions involving the underlying phalanges also may be seen, usually in older
children
and adults.5, 6, 7 The fingers are most commonly
affected.
Dental abnormalities8, 9 are seen in 80% of patients and can
involve both deciduous and permanent teeth. Dental
anomalies are
permanent and thus serve as a very useful diagnostic finding in older patients.
Delayed dentition,
partial anodontia, and conical or pegged teeth
are the most common dental findings. Poor enamel quality leading to
an increased incidence of dental caries has been reported historically,
but this association has been questioned.
Ophthalmologic findings10,
11
Ophthalmologic findings occur in 20-35% of patients, and asymmetric
involvement is common. Loss of visual
acuity and blindness are
significant complications. Blindness has been reported to develop in 7% of IP
patients.
Ophthalmologic manifestations may become evident within the first
few weeks to months of life and may progress
rapidly to permanent
visual deficits.
Retinal vaso-occlusive events with resultant ischemia are
believed to be the primary mechanism underlying ocular
pathology.
Retinal manifestations include retinal detachment,
proliferative retinopathy, fibrovascular retrolental membranes,
foveal hypoplasia, vitreous hemorrhages, and atrophy of the ciliary
body.
Nonretinal manifestations include strabismus, optic nerve atrophy,
conjunctival pigmentation, microphthalmia,
keratitis, cataracts,
iris hypoplasia, nystagmus, and uveitis.
Neurologic
abnormalities
Neurologic complications occur in 30% of IP patients and
often manifest within the neonatal period.
Seizures are the most common
neurologic complication and usually develop within the first few weeks of
life.
Neurologic complications may result in part from microvascular
vaso-occlusive ischemic events involving the
CNS. Involvement of the
cerebral hemispheres, cerebellum, and corpus callosum may occur.12 Progressive
periventricular hemorrhagic infarcts have been reported.
Other
neurodevelopmental manifestations include developmental delay, mental
retardation, ataxia, spastic paralysis,
microcephaly, cerebral
atrophy, porencephaly, hypoplasia of the corpus callosum, and periventricular
cerebral
edema.
Other anomalies that have been reported to occur
with increased frequency in patients with IP include
supernumerary
nipples, nipple hypoplasia, and breast hypoplasia.
Causes
IP is
caused by mutations in the NEMO/IKK-gamma gene, which is located on chromosome
Xq28. NEMO/IKK-
gamma is the regulatory subunit of the inhibitor
kappa kinase (IKK) complex and is required for the activation of
the transcription factor NF-kappaB (NF-kB). NF-kB is central to many
immune, inflammatory, and apoptotic
pathways.
Activation of
NF-kB prevents apoptosis in response to the tumor necrosis factor family of
cytokines. NF-kB
activity is normally regulated via the inhibitor
kB protein. Tumor necrosis factor receptor activation results in
phosphorylation and inactivation of inhibitor kB by IKK, thus resulting
in activation of NF-kB. Loss of IKK activity
results in deficient
NF-kB activity and increased susceptibility to apoptosis.
Cells that
retain IKK activity may produce additional cytokines that trigger apoptosis in
neighboring IKK-deficient
cells, thus creating an amplification
loop that eventually results in the death of all of the IKK-deficient cells.
This
mechanism is believed to produce the cutaneous manifestations
of the vesicular stage of IP. The proliferation of
surviving
IKK-positive cells may result in the production of the verrucous lesions seen
in stage 2 of IP. The
pathophysiology of the hyperpigmented
cutaneous findings seen in stage 3 and the atrophic/hypopigmented
manifestations of stage 4 remains unknown. Inflammation and subsequent
postinflammatory changes may play a
role.
The peripheral
eosinophilia seen in the early stages of IP may result from the production of
eotaxin, an eosinophil-
selective cytokine, during the inflammatory
cascade that results from a loss of NEMO/IKK-gamma activity.
Activation of eosinophils with subsequent release of cellular proteases
may trigger the development of the vesicular
stage of IP.13
The
pathophysiology underlying the CNS manifestations in IP are unknown, but
inflammation resulting from loss
of NEMO/IKK-gamma activity may
contribute to the development of vascular occlusive events.
Females with
hypomorphic mutations in NEMO/IKK-gamma may have few clinical manifestations of
IP.
A single mutation in NEMO/IKK-gamma involving the deletion of exons 4
through 10 accounts for most (80%) IP
mutations.
Hypomorphic
mutations in the zinc-finger domain of NEMO/IKK-gamma result in X-linked
recessive ectodermal
dysplasia and immunodeficiency. A family
history of IP may be elicited. Such mutations result in decreased but
not
absent IKK activity and thus allow for low-level NF-kB
activation.
Hypomorphic mutations in the stop codon of NEMO/IKK-gamma result
in the X-linked dominant ectodermal
dysplasia osteopetrosis
lymphedema syndrome.
Confirmation of NEMO/IKK-gamma mutations in males is
difficult due to the high rate of post-zygotic mosaicism.
NEMO/IKK-gamma
knockout mice manifest a cutaneous phenotype similar to female IP patients and
develop
neurologic sequelae, although they do not develop dental or
ocular abnormalities. They also develop diffuse
apoptosis of
splenic and thymic lymphocytes, which does not occur in human IP patients.14,
15
Genetic testing for NEMO/IKK-gamma mutations is available through the
Baylor College of Medicine Medical
Genetics
Laboratories.
DIFFERENTIALSSection 4 of 11 Authors and
Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Acropustulosis of Infancy
Bullous
Pemphigoid
Dermatopathia Pigmentosa Reticularis
Epidermolysis
Bullosa
Focal Dermal Hypoplasia Syndrome
Herpes Simplex
Herpes
Zoster
Hypomelanosis of Ito
Impetigo
Insect Bites
Langerhans Cell
Histiocytosis
Lichen
Striatus
Mastocytosis
Milia
Miliaria
Naegeli-Franceschetti-Jadassohn
Syndrome
Other Problems to be Considered
Stage 1 -
Vesicular
Bullous impetigo
Herpes simplex
Varicella (herpes)
zoster
Epidermolysis bullosa
Bullous mastocytosis
Bullous congenital
ichthyosiform erythroderma (epidermolytic hyperkeratosis)
Congenital bullous
pemphigoid
Linear IgA bullous disease of childhood
Langerhans cell
histiocytosis
Erythema toxicum
Miliaria
Acropustulosis of
infancy
Arthropod assault
Stage 2 - Verrucous
Linear epidermal
nevus
Lichen striatus
X-linked dominant chondrodysplasia
punctata
Verruca vulgaris
Stage 3 - Pigmented
Linear and
whorled nevoid hypermelanosis
Pigmentary mosaicism
Dermatopathia
pigmentosa reticularis
Naegeli-Franceschetti-Jadassohn syndrome
X-linked
dominant chondrodysplasia punctata
Stage 4 -
Depigmented
Hypomelanosis of Ito (IP achromians)
Focal dermal
hypoplasia syndrome (Goltz syndrome)
X-linked dominant chondrodysplasia
punctata
WORKUPSection 5 of 11 Authors and Editors
Introduction Clinical Differentials Workup Treatment Medication
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Lab
Studies
Leukocytosis and eosinophilia may be noted.
When acute
inflammatory skin changes are present, eosinophilia (=80%) may be seen in the
peripheral blood.
Evidence of neutrophil dysfunction (defects in
chemotaxis), lymphocyte dysfunction (decreased proliferation in
response to mitogen stimulation), and altered immunologic reactivity
has been reported in some patients.
Quantitative immunoglobulin
levels and lymphocyte subpopulation counts are normal.
Imaging
Studies
Head CT scanning and brain MRI16 may demonstrate cerebral edema,
hydrocephalus, structural brain
abnormalities, cerebral infarctions,
and hypointense areas or hypoattenuation.
Magnetic resonance spectroscopy
and angiography have demonstrated reduced cerebral blood flow and elevated
cerebrospinal fluid lactate levels, consistent with cerebral ischemia
secondary to cerebrovascular occlusive events.
17
Single-photon
emission CT scanning may show decreased cerebral blood flow.18
EEG is
helpful for localizing CNS lesions and epileptogenic foci in patients with
seizures.
Other Tests
Karyotype analysis is recommended in male
infants with IP in order to detect Klinefelter syndrome (XXY
syndrome).
Genetic testing for NEMO/IKK-gamma mutations is available
through the Baylor College of Medicine Medical
Genetics
Laboratories.
Procedures
Skin biopsy may be diagnostic if
performed during the early vesicular and verrucous stages of IP (stages
1-2).
Histologic Findings
Stage 1 (vesicular)
Spongiotic
dermatitis with eosinophil-filled intraepidermal vesicles and an eosinophilic
epidermal and dermal
infiltrate are seen. The epidermis often
contains dyskeratotic cells, either singly or in small clusters.
Stage 2
(verrucous)
Acanthosis, papillomatosis, and hyperkeratosis with
increased numbers of dyskeratotic cells, which sometimes
form
whorled collections,19 are seen. Basal cells show vacuolization and a decrease
in melanin content.
Eosinophils can persist in the epidermis and
dermis, and melanophages are often present in the papillary
dermis.
Stage 3 (hyperpigmented)
Melanin deposition in
melanophages within a thickened papillary dermis is seen. Colloid bodies in the
papillary
dermis, dyskeratotic cells in the epidermis, and basal
cell layer vacuolar changes may be seen. The histologic
findings
are often suggestive of IP but are not specific.
Stage 4
atrophic/hypopigmented)
Atrophic epidermis with loss of the normal rete
ridge pattern and dermal eccrine structures with a reduction in
basal melanocytes are seen. Colloid bodies may be seen. The histologic
findings are nonspecific.
TREATMENTSection 6 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Medical Care
Treatment is not usually required for
the cutaneous lesions. The vesicles of the inflammatory stage should be left
intact, and the skin should be monitored for the development of
secondary bacterial infections. Emollients and
topical antibiotics
may be used as needed.
Oral hygiene and regular dental care is necessary,
and dental restoration may be indicated.
Seizures should be treated with
anticonvulsants.
Routine neurodevelopmental assessments should be made, with
referral to occupational and physical therapists as
warranted.
Frequent ophthalmologic evaluations are required,
especially during the first year of life, in order to diagnose and
treat potential ophthalmologic complications.
Surgical
Care
Abnormal retinal fibrovascular proliferation can be treated with
xenon laser photocoagulation or cryosurgery.20
Retinal detachments may be
treated using vitreoretinal surgery.
Consultations
Dermatologists
may help in the initial evaluation and can perform a skin biopsy to aid in
diagnosis.
Ophthalmologists can perform regular ophthalmologic examinations
and manage any ophthalmologic sequelae.
Neurologists can perform a complete
initial neurologic examination (including imaging studies and EEG), initiate
and monitor anticonvulsant therapy in patients with seizures, and
facilitate neurodevelopmental evaluation and
intervention.
General dentists can provide regular dental care,
screening for dental complications, and restorative dental care.
Geneticists
can provide appropriate genetic counseling and genetic testing for the patient
and his or her family.
MEDICATIONSection 7 of 11 Authors
and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia References
In
patients with seizures, anticonvulsant drugs are used. These agents have
central and peripheral anticholinergic
effects and sedative
effects. They also block the active reuptake of norepinephrine and serotonin. A
variety of
anticonvulsants are available, and they should be
selected at the discretion of the neurologist.
FOLLOW-UPSection
8 of 11 Authors and Editors Introduction Clinical Differentials Workup
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Medication Follow-up Miscellaneous Multimedia
References
Further Outpatient Care
The presence of variable
disease expression in an affected family makes monitoring for potential
complications
important. Regular follow-up with a neurologist,
ophthalmologist, dentist, and dermatologist should be coordinated
as needed.
Complications
Secondary bacterial infection
can develop during the vesicular stage, but this is rare.
Seizures and
mental retardation are common in patients with structural brain malformations
or evidence of
ischemic brain injury.
Ophthalmologic
complications can lead to reduced visual acuity and
blindness.
Prognosis
The prognosis of IP is generally
good.
Morbidity and mortality are related to neurologic and ophthalmologic
sequelae, including seizures, visual
impairment, and mental
retardation.
Patients with structural brain abnormalities and neonatal
seizures are at greater risk for motor and intellectual
impairment.
Patient Education
Inform parents that delayed
eruption of both deciduous and permanent teeth is common.
Reassure parents
that if no evidence of CNS involvement or seizures is seen in their infant, the
neurodevelopmental
prognosis is excellent.
Genetic counseling
should be offered to the family.
Counsel parents on the expected course of
cutaneous manifestations.
MISCELLANEOUSSection 9 of 11
Authors and Editors Introduction Clinical Differentials Workup Treatment
Medication Follow-up Miscellaneous Multimedia
References
Medical/Legal Pitfalls
Failure to make a correct
diagnosis based on cutaneous findings and ocular, CNS, and dental
abnormalities
Failure to perform skin biopsy of vesicular or verrucous
lesions to confirm a diagnosis of IP
Failure to refer patients to
neurologists and ophthalmologists for evaluation and treatment
Failure to
provide appropriate genetic counseling
Special Concerns
Examine
the mother and all female relatives of a child with IP for clinical features of
IP. Carefully look for dental
abnormalities and stage 4 cutaneous
changes (eg, atrophic/hypopigmented lesions involving the lower
legs).
MULTIMEDIASection 10 of 11 Authors and Editors
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REFERENCESSection
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Medication Follow-up Miscellaneous Multimedia
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Incontinentia Pigmenti excerpt
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