Primary lymphedema is a form of lymphedema which is not directly attributable to another medical condition.
It can be divided into three forms, depending upon age of onset: congenital lymphedema, lymphedema praecox, and lymphedema tarda.[1]
It can be familial.[2]
Primary Lymphedema
By Joachim Zuther, on July 25th,
2012
While secondary
lymphedema is caused by blockage or damage to a normally functioning lymphatic
system resulting from surgery, radiation, trauma and other known insults, the
formation of primary lymphedema is caused by pathology affecting the lymphatic
system directly in form of a developmental abnormality, most commonly
hypoplasia or hyperplasia involving lymph vessels and/or lymph nodes.
Hypoplasia,
the most common malformation, refers to an incomplete development, that is, the
number of lymph vessels and/or nodes is reduced, or the size of these lymphatic
structures is smaller than normal.
Hyperplasia is
generally associated with a structural malformation of lymph vessels and/or
nodes (lymphangiectasia, or megalymphatics); enlargement (dilation) of lymph
vessels in this case may result in a malfunction of valves located within the
lymph collectors, compromising the flow of lymphatic fluid.
Lymphatic
aplasia is rare and describes the absence of single lymph vessels and/or
nodes, which may be the cause for the onset of primary lymphedema.
The left image depicts normal lymph
collectors, hypoplasia in the middle, hyperplasia on the
right
Primary lymphedema
is far less common than the secondary form; it has been estimated to occur in
one of six thousand individuals (1), predominantly in female patients with a
ratio of one male to three females. In the majority of primary lymphedema
cases, the lower extremities are affected.
The maldevelopment
of the lymphatic system in primary lymphedema is inherited, which means it can
pass from generation to generation.
Several genes can
be involved in the development of the lymphatic system (2) and mutations of any
of these genes may cause lymphedema. However, only one of these genes is
typically responsible for the lymphatic malformation in a particular family.
Inherited lymphedema presents in an autosomal dominant pattern with incomplete
penetrance and variable expression.
What does that
mean?
Except for genes
on the sex chromosomes, both males and females have two copies of each gene.
If only one altered copy of a gene (mutation) causes a malformation, the
condition will be inherited in what is called a dominant pattern, which
essentially means that children of parents with primary lymphedema have a 50%
chance of inheriting the defective gene. This, however, does not explain why
primary lymphedema is more common in female offspring; further studies will
hopefully shed more light on this phenomenon.
In genetics the
strength of a gene is described as penetrance; a strong penetrance is present
if all children who inherit the abnormal gene develop primary lymphedema. If
only a fraction of children who inherit the abnormal gene actually develop the
condition, the penetrance is described as inconsistent or variable. This is
the case with the lymphedema gene; not all children who inherit the mutation
will show evidence of lymphedema. In many cases of primary lymphedema it can be
established that the condition skipped one or more generations.
Variable
expression indicates that the swelling may affect the left leg of one family
member, another family member’s right foot, and yet another family member may
have both legs involved.
In addition,
the age of presentation can also be quite variable. Although the abnormalities
in the development of the lymphatic system are present at birth, lymphedema may
develop at any point later in life, most often during puberty or pregnancy with
a peak in the onset between the ages 10 and 25. However, primary lymphedema
may not visibly develop at all as long as the genetically compromised lymphatic
system is sufficient enough to manage its workload.
Primary lymphedema
can be classified by the age of the patient at the onset of the swelling.
Congenital (pediatric) lymphedema is present at birth or within the first
two years of life and accounts for 10-25% of all cases of primary lymphedema.
Boys typically are affected at birth, and girls most often present with
lymphedema during adolescence (3). A sub-group of patients with congenital
lymphedema has a familial pattern of inheritance, which is known as Milroy’s
disease (4).
The most common
form of primary lymphedema is termed lymphedema praecox, also known as
Meige’s disease; by definition, it becomes clinically evident after birth and
before age 35. This condition accounts for 65-80% of all primary lymphedema
cases and most often arises during puberty or pregnancy.
A relatively rare
form of primary lymphedema is when the first signs of swelling appear after 35
years of age; this condition is called lymphedema tarda.
Regardless of the
cause, there is no cure for lymphedema. However, primary lymphedema can be
very effectively managed, especially if it is diagnosed early. Individuals
affected by lymphedema may encounter a number of problems, which can be either
attributed to other pathologies (comorbidities) that may be present in addition
to existing lymphedema and further exacerbate its symptoms, or secondary
complications which may develop as a result of stagnated
lymphatic fluid. Secondary complications are common to lymphedema, especially
if the swelling is left untreated, and often contribute to the progression of
the swelling.
Both early
diagnosis and intervention of lymphedema are equally crucial for optimal
treatment results. Whether lymphedema is caused by developmental
abnormalities, or surgery/radiation to the lymphatic system, the possible
long-term physical and psychosocial burden resulting from untreated or
mistreated lymphedema can be serious.
Proper treatment
is available, and the classification of lymphedema into primary and secondary
has little significance in determining the method and goal of therapy. The
goal of any treatment is to reduce the swelling and to maintain the reduction –
that is to bring the lymphedema back to a normal, or near-normal size so
affected individuals can continue with the activities of daily living, and to
limit the risk of infection.
The accepted
gold-standard for the treatment of lymphedema is Complete Decongestive Therapy
(CDT). Backed by long standing experience this therapy has shown to be safe and
effective as the standard therapy for lymphedema. Click here to
read more about CDT
Join Lymphedema
Guru, a Facebook page solely dedicated to inform about all
things related to lymphedema – news, support groups, treatment centers, and
much more.
References:
(1) http://jmg.bmj.com/content/22/4/274.full.pdf
(2) http://www.hgen.pitt.edu/projects/lymph/research_update.php
(3) http://www.ncbi.nlm.nih.gov/pubmed/21617474
(4) http://ghr.nlm.nih.gov/condition/milroy-disease
Further Reading:
http://www.lymphnet.org/pdfDocs/nlntreatment.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287178/
http://www.ncbi.nlm.nih.gov/pubmed/9817924
http://adc.bmj.com/content/71/1/44.full.pdf
http://plasticsurgerynotes.net/Lower_Extrimity/lymphatic_disorders.asp
http://www.hgen.pitt.edu/projects/lymph/inheritance.php
http://emedicine.medscape.com/article/191350-overview#a0102
http://www.lymphedemapeople.com/thesite/primary_lymphedema.htm
http://www.medicinenet.com/lymphedema/article.htm
http://www.noblemed.com/primary.htm
http://www.ncbi.nlm.nih.gov/pubmed/18564921y
http://www.ncbi.nlm.nih.gov/pubmed/6843174
It can be divided into three forms, depending upon age of onset: congenital lymphedema, lymphedema praecox, and lymphedema tarda.[1]
It can be familial.[2]
Primary Lymphedema
By Joachim Zuther, on July 25th,
2012
While secondary
lymphedema is caused by blockage or damage to a normally functioning lymphatic
system resulting from surgery, radiation, trauma and other known insults, the
formation of primary lymphedema is caused by pathology affecting the lymphatic
system directly in form of a developmental abnormality, most commonly
hypoplasia or hyperplasia involving lymph vessels and/or lymph nodes.
Hypoplasia,
the most common malformation, refers to an incomplete development, that is, the
number of lymph vessels and/or nodes is reduced, or the size of these lymphatic
structures is smaller than normal.
Hyperplasia is
generally associated with a structural malformation of lymph vessels and/or
nodes (lymphangiectasia, or megalymphatics); enlargement (dilation) of lymph
vessels in this case may result in a malfunction of valves located within the
lymph collectors, compromising the flow of lymphatic fluid.
Lymphatic
aplasia is rare and describes the absence of single lymph vessels and/or
nodes, which may be the cause for the onset of primary lymphedema.
The left image depicts normal lymph
collectors, hypoplasia in the middle, hyperplasia on the
right
Primary lymphedema
is far less common than the secondary form; it has been estimated to occur in
one of six thousand individuals (1), predominantly in female patients with a
ratio of one male to three females. In the majority of primary lymphedema
cases, the lower extremities are affected.
The maldevelopment
of the lymphatic system in primary lymphedema is inherited, which means it can
pass from generation to generation.
Several genes can
be involved in the development of the lymphatic system (2) and mutations of any
of these genes may cause lymphedema. However, only one of these genes is
typically responsible for the lymphatic malformation in a particular family.
Inherited lymphedema presents in an autosomal dominant pattern with incomplete
penetrance and variable expression.
What does that
mean?
Except for genes
on the sex chromosomes, both males and females have two copies of each gene.
If only one altered copy of a gene (mutation) causes a malformation, the
condition will be inherited in what is called a dominant pattern, which
essentially means that children of parents with primary lymphedema have a 50%
chance of inheriting the defective gene. This, however, does not explain why
primary lymphedema is more common in female offspring; further studies will
hopefully shed more light on this phenomenon.
In genetics the
strength of a gene is described as penetrance; a strong penetrance is present
if all children who inherit the abnormal gene develop primary lymphedema. If
only a fraction of children who inherit the abnormal gene actually develop the
condition, the penetrance is described as inconsistent or variable. This is
the case with the lymphedema gene; not all children who inherit the mutation
will show evidence of lymphedema. In many cases of primary lymphedema it can be
established that the condition skipped one or more generations.
Variable
expression indicates that the swelling may affect the left leg of one family
member, another family member’s right foot, and yet another family member may
have both legs involved.
In addition,
the age of presentation can also be quite variable. Although the abnormalities
in the development of the lymphatic system are present at birth, lymphedema may
develop at any point later in life, most often during puberty or pregnancy with
a peak in the onset between the ages 10 and 25. However, primary lymphedema
may not visibly develop at all as long as the genetically compromised lymphatic
system is sufficient enough to manage its workload.
Primary lymphedema
can be classified by the age of the patient at the onset of the swelling.
Congenital (pediatric) lymphedema is present at birth or within the first
two years of life and accounts for 10-25% of all cases of primary lymphedema.
Boys typically are affected at birth, and girls most often present with
lymphedema during adolescence (3). A sub-group of patients with congenital
lymphedema has a familial pattern of inheritance, which is known as Milroy’s
disease (4).
The most common
form of primary lymphedema is termed lymphedema praecox, also known as
Meige’s disease; by definition, it becomes clinically evident after birth and
before age 35. This condition accounts for 65-80% of all primary lymphedema
cases and most often arises during puberty or pregnancy.
A relatively rare
form of primary lymphedema is when the first signs of swelling appear after 35
years of age; this condition is called lymphedema tarda.
Regardless of the
cause, there is no cure for lymphedema. However, primary lymphedema can be
very effectively managed, especially if it is diagnosed early. Individuals
affected by lymphedema may encounter a number of problems, which can be either
attributed to other pathologies (comorbidities) that may be present in addition
to existing lymphedema and further exacerbate its symptoms, or secondary
complications which may develop as a result of stagnated
lymphatic fluid. Secondary complications are common to lymphedema, especially
if the swelling is left untreated, and often contribute to the progression of
the swelling.
Both early
diagnosis and intervention of lymphedema are equally crucial for optimal
treatment results. Whether lymphedema is caused by developmental
abnormalities, or surgery/radiation to the lymphatic system, the possible
long-term physical and psychosocial burden resulting from untreated or
mistreated lymphedema can be serious.
Proper treatment
is available, and the classification of lymphedema into primary and secondary
has little significance in determining the method and goal of therapy. The
goal of any treatment is to reduce the swelling and to maintain the reduction –
that is to bring the lymphedema back to a normal, or near-normal size so
affected individuals can continue with the activities of daily living, and to
limit the risk of infection.
The accepted
gold-standard for the treatment of lymphedema is Complete Decongestive Therapy
(CDT). Backed by long standing experience this therapy has shown to be safe and
effective as the standard therapy for lymphedema. Click here to
read more about CDT
Join Lymphedema
Guru, a Facebook page solely dedicated to inform about all
things related to lymphedema – news, support groups, treatment centers, and
much more.
References:
(1) http://jmg.bmj.com/content/22/4/274.full.pdf
(2) http://www.hgen.pitt.edu/projects/lymph/research_update.php
(3) http://www.ncbi.nlm.nih.gov/pubmed/21617474
(4) http://ghr.nlm.nih.gov/condition/milroy-disease
Further Reading:
http://www.lymphnet.org/pdfDocs/nlntreatment.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287178/
http://www.ncbi.nlm.nih.gov/pubmed/9817924
http://adc.bmj.com/content/71/1/44.full.pdf
http://plasticsurgerynotes.net/Lower_Extrimity/lymphatic_disorders.asp
http://www.hgen.pitt.edu/projects/lymph/inheritance.php
http://emedicine.medscape.com/article/191350-overview#a0102
http://www.lymphedemapeople.com/thesite/primary_lymphedema.htm
http://www.medicinenet.com/lymphedema/article.htm
http://www.noblemed.com/primary.htm
http://www.ncbi.nlm.nih.gov/pubmed/18564921y
http://www.ncbi.nlm.nih.gov/pubmed/6843174