Chapter 174

Cutaneous Changes
in Peripheral Venous
and Lymphatic
Insufficiency
Craig N. Burkhart, Chris Adigun,
& Claude S. Burton

CHRONIC VENOUS DISEASE

Anatomy
Veins are thin-walled, distensible, and collapsible
structures that function to transport blood toward
the heart and act as a reservoir for preventing intravascular volume overload. Microscopically, veins
consist of an intima, media, and outer collagenous
adventitia. All peripheral veins contain endothelium
lined, semilunar, venous valves, which promote
unidirectional blood flow toward the heart. Vascular
endothelium is described in detail in Chapter 165
and the anatomy of the venous system of the lower
extremities is described in Chapter 249.

OTHER VENOUS DISEASES

EPIDEMIOLOGY.
Obese women at a mean age of approximately 60
years seem to be especially affected by superficial
venous thrombosis (SVT) with triggering risk factors proposed, including malignancy, pregnancy,
conditions promoting venous stasis, and intravenous drug abuse. The 3-month overall mortality
for SVT is very low with estimates ranging from 0%
to 1% (http://www.accessmedicine.com/iedetect.
aspx#2994656).
The most worrisome feature of SVT is that DVTs
may occur concurrently, with an incidence varying
from 5.6% to 36.0% depending on the study.
ETIOLOGY AND PATHOGENESIS.
In addition to thrombi, inflammation of the veins
(phlebitis) may be caused by chemicals (drugs), infections, and as part of inflammatory diseases. Common drugs include potassium chloride, diazepam,

antibiotics, and hypotonic or hypertonic solutions.

When infectious agents on the skin or intravenous
fluid track down catheters, they may cause a septic
(suppurative) phlebitis.
CLINICAL FINDINGS.
Superficial phlebitis is the clinical finding of pain,
tenderness, induration, and/or erythema in a superficial vein often associated with a palpable cord.
These signs may be due to inflammation, infection,
and/or thrombosis. Various eponyms are used for
phlebitis in certain locations. For example, Mondor
disease (sclerosing lymphangitis) refers to superficial phlebitis of the breast or dorsal penile vein, and
superficial thrombophlebitis usually refers to superficial phlebitis of a lower extremity vein. Clinically, a
thrombus is suggested by superficial phlebitis with
a palpable cord that persists after a limb is raised.
Migratory thrombophlebitis (Trousseau sign) is a
form of SVT, which develops, resolves, and recurs
in normal veins of the body at various times (http://
www.accessmedicine.com/iedetect.aspx#2994657,
http://www.accessmedicine.com/iedetect.
aspx#2994658). When migratory thrombophlebitis
is associated with cancer (especially adenocarcinoma), the eponym Trousseau syndrome is used. Migratory superficial thrombophlebitis may be seen
in Behet disease, thromboangiitis obliterans with
trauma, intravenous drug abuse, and secondary
syphilis. Thrombophlebitis in patients with syphilis
is rare and should be distinguished from patients
with lupus anticoagulants causing biologically
false-positive serologic reactions.
LABORATORY TESTS.
Due to the possibility of coexisting occult DVT in
patients with superficial venous thrombosis, some
experts recommend compression ultrasound for
all patients with lower extremity superficial venous
thrombosis. However, this recommendation has not
been explicitly tested in any trial and clinical judgment should guide further testing.
Additionally, thromboembolism (DVT or SVT) is
often the presenting symptom of cancer and some
physicians obtain high diagnostic yield through extensive screening for occult malignancy, especially
when the thrombosis is idiopathic (http://www.
accessmedicine.com/iedetect.aspx#2994659).

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260 Chapter 174: Cutaneous Changes in Peripheral Venous and Lymphatic Insufficiency

TREATMENT.
As SVT has a much lesser risk of pulmonary embolism than DVT and the clinical importance of preventing SVT recurrence is unclear, less aggressive
anticoagulation and treatment are recommended
and these patients should be managed in conjunction with an appropriate specialist.

LYMPHEDEMA
Lymphedema-Related Genetic
Diseases
Lymphedema in children is almost always primary,
with a sex ratio of one male to three females. Primary lymphedema is customarily classified based on
age of onset: congenital lymphedemapresents
at birth or soon thereafter, lymphedema praecox
presents between age 1 and 35, or lymphedema
tardapresents after age 35. Approximately 77%
94% of the various types of lymphedema occur as
lymphedema praecox.18 Disease-causing mutations
of primary lymphedema have been determined
for Milroy, lymphedema-distichiasis, and hypotrichosislymphedematelangiectasia syndromes. A
genetic defect has not been discovered in the other
forms of primary lymphedema, including Meige
syndrome, and thus require phenotypic classification for a diagnosis.
In lymphedema tardum, where the lymphedema
does not become clinically evident until after age
35, the pathologic mechanism is usually due to a
developmental abnormality in the lymphatic system that does not present until after it is precipitated by trauma, illness, or physical immobility.
In the diagnosis of lymphedema in children, clinical signs of lymphedema may be subtle. A complete
family history is mandatory, and clinical investigation of relatives may be necessary if a hereditary
form of lymphedema is suspected. Physical examination of the entire body should be performed
to assess the extent of the lymphedema, whether
there is limb overgrowth, and if there is associated
systemic involvement. In primary lymphedema,
facial, conjunctival, and genital lymphedema is
typically seen in association with the limbs involved.
Another potential clue that primary lymphedema
is present is if a child has had more than one attack
of erysipelas.19 There is a cohort of patients with
primary lymphedema that have associated systemic
lymphatic abnormalities, with the most common

systemic involvement being the intestine. Therefore,

imaging may be reasonable based on findings of
the history and physical examination to rule out
systemic involvement.
In the initial evaluation of a child with suspected
primary lymphedema, qualitative lymphoscintigraphy can be considered in the radiologic evaluation.
This modality is not without its limitations, but it
can help determine whether persistent swelling in
a child is lymphatic in origin. However, it does not
assist in the diagnosis or treatment of lymphedema.
HYPOTRICHOSISLYMPHEDEMA
TELANGIECTASIA
Etiology and Pathogenesis.
This rare form of primary lymphedema is caused by
a mutation in the transcription factor gene SOX18.
Both autosomal dominant and recessive inheritance have been reported. Mouse models have
shown that SOX18 plays a critical role in the activation of the Prox1 gene and the induction of differentiation of the lymphatic vasculature from precursors
during development. This mutation leads to the
characteristic phenotype of lymphedema, alopecia,
and telangiectasia.28
Clinical and Radiologic Findings.
Lymphedema presents in puberty, most commonly
in the lower extremities, although lymphedema
of the eyelids has been reported. Hair is normal at
birth, but then is lost in infancy. By early childhood,
scalp hair is sparse, and eyebrows and eyelashes
are often absent. Skin may be thin and transparent,
but may have a cutis marmorata-like appearance.
Telangiectasias have a predilection for the palms
and soles, but may also be found on the scalp, legs,
and genitalia.29
MEIGE SYNDROME
Etiology and Pathogenesis.
The genetic basis of Meige syndrome has yet to be
been determined, though current studies suggest
that mutations in the hepatocyte growth factor
(HGF) and receptor (MET) pathway.30,31 However, as
Meige syndrome manifests a nonspecific phenotype, it is possible that it arises from a number of
congenital lymphatic defects.

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Chapter 174:

Cutaneous Changes in Peripheral Venous and Lymphatic Insufficiency 261

Clinical and Radiologic Findings.

Lymphedema typically develops during puberty.
Facial puffiness with deep creases and wrinkling
may occur. It characteristically presents with unilateral lower extremity edema, although involvement
of upper extremities has been reported. The delay
in onset is theorized to be due to an underlying defect in the lymphatic circulation that is subsequently unmasked by a secondary insult such as trauma,
infection, or hormonal factors. There is a female
predominance, approximately 1:3, which supports
the theory for a hormonal role. It tends to follow an
autosomal dominant pattern of inheritance.18,30
There are other inherited syndromes that have
lymphedema as a clinical feature. These include
Hennekam lymphangiectasia-lymphedema, Aagenaes lymphedema-cholestasis, microcephalychorioretinopathylymphedema, IronsBianchi syndrome,
and the Turners, Noonans, and PraderWilli
syndromes.

smooth dermalsubcutaneous interface whereas in

women superficial fat lobules protrude into the dermis, giving irregular contours (http://www.accessmedicine.com/iedetect.aspx#2994671). A variety
of cosmetic procedures and light-based therapies
are purported to reduce these lesions; some are US
Food and Drug Administration approved, and are
popular for the beauty conscience and in specialized spas. Few have been shown to long-term benefit, and noninvasive approaches to this condition
have been advised (http://www.accessmedicine.
com/iedetect.aspx#2994672). Idiopathic cyclic
edema is described in young women and may have
a relationship to the menstrual cycle.

LOCALIZED AREAS OF
LYMPHEDEMA
Lipemia (Fat Leg Syndrome,
Lipohyperplasia Dolorosa)
Lipedema is an infrequently made diagnosis but
can be distinguished from lymphedema by the
characteristics that are summarized in eBox 1744.1 (http://www.accessmedicine.com/iedetect.
aspx#2994670). Allen and Hines described this
condition in the 1940s and noted its bilaterality,
progression, and accentuation by warm weather
and activity. Particularly vexing is the aching and
pain below the knee in the patients who are generally overweight. Strong familial history is present.
Feet swelling and the absence of the KaposiStemmer sign is characteristic. Edematous hyperplastic
fat cells characterize the histology. If compression
fails, lipectomy has been used.

Cellulite (Orange-Peel Skin,

Gynoid Lipodystrophy)
Cellulite is a dimpled appearance of the skin, especially in the upper thighs in overweight women,
even those who are slightly overweight. It is distinct
from lipemia and lymphedema and is more a cosmetic concern than a health concern. Males have a

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