Lipodermatosclerosis
Overview
|
Clinical 1. Favors the medial aspect of the
lower legs above the malleolus, most commonly on the lower anteromedial calf 2. Indurated
plaques of wood-like consistency on the lower legs, acute and chronic
changes, pain frequent. 3. Acute phase with erythema, warmth
and tenderness, which may be misdiagnosed as infectious cellulitis 4. Chronic phase with indurated
plaques of wood-like consistency and hyperpigmentation 5. Usually develops in the setting of
chronic venous insufficiency 6. Other
associations: higher than normal BMI, female gender, arterial hypertension,
arterial ischemia, episodes of thrombophlebitis. Histopathology 1. Background
of stasis changes; mostly lobular panniculitis without vasculitis. 2. Ischemic
necrosis at the center of fat lobule. 3. Thickened
and fibrotic septa and atrophy of the subcutaneous fat, with marked fibrosis
and sclerosis in late-stage severe cases. 4. lipomembranous changes are common,
particularly in chronic lesions Treatment 1. Compression
stockings, ultrasound therapy, pentoxifylline. 2. Successful
response to anabolic steroids, platelet rich plasma in some cases. |
Introduction
LDS is a form of sclerosing panniculitis
involving the lower legs of middle aged or elderly women and is manifested as a
diffuse sclerosis and pigmentation of the skin and subcutaneous tissue.
Epidemiology
LDS is
the most common form of panniculitis, seen by clinicians far more frequently than
EN, which has the next highest incidence. LDS occurs in association with venous
insufficiency, mostly in overweight women over the age of 40. The female
to male ratio is 4:1. Obesity is common, with 85% of affected patients having a
body mass index (BMI) greater than 30. Comorbidities included
hypertension, thyroid disease, diabetes mellitus, prior history of lower
extremity cellulitis, and deep vein thrombosis. Obstructive sleep apnea and
arthritis (both osteoarthritis and rheumatoid) also are associated with LDS.
Pathogenesis
Most patients with LDS are female
and also have in common venous hypertension and a higher than normal BMI.
Additional associated features that have been sought as pathogenetic factors in
LDS include the following: elevated hydrostatic pressure-induced increased
vascular permeability secondary to down regulation of tight junctions with
extravascular diffusion of fibrin; microthrombi; abnormalities in protein S and
protein C; hypoxia; damage to endothelial
cells by inflammatory cells; up regulation of intercellular adhesion molecule 1
(ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), leukocyte
function-associated antigen 1 (LFA-1), platelet- and endothelial-derived
factors; and inflammation with wound healing and local collagen stimulation leading to fibrosis
and further vascular and lymphatic damage. The fibrosis is accompanied by
increased transforming growth factor-β 1 (TGF-β1) gene and protein expression
as well as an increase in procollagen type 1 gene expression.
Hypoxia in AT induces chronic
inflammation with macrophage infiltration and inflammatory cytokine expression.
The adipocyte plays a significant role in extracellular tissue remodelling. For
this task, the adipocyte produces multiple matrix metalloproteinases (MMPs) as
well as tissue inhibitors of metalloproteinases (TIMPs) and other tissue
proteases needed during tissue remodelling, all of which may significantly
contribute to the tissue remodelling seen in LDS. Studies have linked expansion
of AT (as seen in obesity) to resultant hypoxia, causing an increase in
hypoxia-inducible factor 1α (HIF1α) expression. This stimulates multiple
extracellular factors, including collagen I and III, as well as other
components involved in remodelling the extracellular matrix, leading to
fibrosis as the end result.
Clinical features
LDS has an acute inflammatory
stage and a chronic fibrotic stage with a spectrum
of intermediate and overlapping presentations. In patients presenting
with the acute form, very painful and tender poorly demarcated, cellulitis-like
erythematous plaques persists and evolve to violaceous edematous mildly
indurated plaques or nodules, which are seen on the lower legs above the medial
malleoli, most commonly on the lower anteromedial calf area.
At this point, the changes are relatively diffuse. Unilateral
involvement is seen in 55%, localized plaque in 51%, and ulceration in 13% of
cases.
The pain
can be so intense that patients may not even tolerate a sheet while in bed. In
this stage, patients are frequently misdiagnosed as having EN, cellulitis, or
thrombophlebitis, and compression may not be tolerated. The acute form may last
a few months or even a year. Although patients in this acute phase may present
without obvious signs of venous disease, vascular studies show venous
insufficiency in the majority. In the remaining group of LDS patients with
normal venous studies, most have a high BMI, and given that obesity is usually
associated with inactivity, these patients may not exert enough calf muscle
contraction to maintain normal venous pressure in the lower extremities; also,
obesity is frequently associated with arterial hypertension.
The chronic form of LDS may or
may not be preceded by a clinically obvious acute form. In this phase, there is
marked sclerosis of the dermis and subcutis resulting in sharply demarcated
indurated, depressed, hyper pigmented plaques of wood-like consistency.
These features give the affected leg an “inverted champagne bottle” or a
“bowling pin” appearance.
Diagnostic tests
Diagnostic tests to evaluate
peripheral vascular disease should include ankle brachial index for arterial
evaluation. Also indicated are venous tests: Dopplers to detect thrombi as well
as color duplex sonography to detect direction of flow and severity of venous
reflux. If the clinical findings are characteristic, biopsy of LDS is usually
discouraged, due to poor wound healing and the high incidence of subsequent
development of ulcers at the biopsy site. But if necessary for diagnosis, a
thin elliptical excision from the margin of an erythematous and indurated area,
closed primarily with sutures, is recommended.
Pathology
Histopathologic findings reflect
the evolution of the disease. Dermal stasis changes are present at any stage, including
a proliferation of capillaries and venules, small thick-walled blood vessels, extravasated
erythrocytes, hemosiderin-laden macrophages, superficial and deep
perivascular lymphohistiocytic
infiltrates and fibrosis. Increased melanin along the basal layer of the
epidermis as well as within melanophages in the superficial dermis may also
contribute to the characteristic hyperpigmentation.
In the subcutis, early lesions of
LDS show a sparse infiltrate of lymphocytes in the septa
that rim the fat lobules, accompanied by areas of ischemic fat necrosis in
the center of the fat lobules; the latter is recognized by the presence of
pale-staining, small anucleate adipocytes. Capillary congestion accompanied by
endothelial cell necrosis, thrombosis, red cell extravasation, and hemosiderin
deposition are also observed within fat lobules.
With progression of LDS, the
spectrum of histopathologic changes encompasses increasing degrees of fat
necrosis, septal fibrosis, and thickening; an inflammatory infiltrate
comprising lymphocytes, histiocytes, and foamy macrophages (lipophages); and
partial to extensive atrophy of fat lobules. Advanced lesions show septal
sclerosis most prominently, with marked atrophy of fat lobules secondary to
lipophagic fat necrosis, accompanied by lipomembranous change and a marked
reduction in inflammation. The most severe LDS shows marked fibrosis and
sclerosis in the AT layer with little inflammation.
In late stages, with fibrous thickening
of the lower dermis and replacement of the subcutis by sclerosis, a punch
biopsy of involved skin may not produce any subcutaneous fat.
Lipomembranous or membranocystic
change is a key feature in lipodermatosclerosis. In lipomembranous change, small
pseudocystic spaces are formed within necrotic fat. The spaces are lined by a
hyaline eosinophilic material (lipomembrane) believed to be the residue of disintegrated
adipocytes and their interaction with macrophages. This distinctive membranous
lining is highlighted by periodic acid-Schiff (PAS) staining and may present an
arabesque pattern, with intricate undulating papillary and crenulated projections
into the cystic cavities. However, membranocystic changes are not exclusive to
LDS and may be found in any type of panniculitis.
Short, frayed elastic fibers can be present within the
subcutaneous septa, and these may be calcified, features that resemble
pseudoxanthoma elasticum. By phosphotungstic acid–hematoxylin stain or by
immunofluorescent methods, pericapillary fibrin can also be demonstrated in
lesions of lipodermatosclerosis.
Differential diagnosis
Difficulties
in clinical diagnosis arise most often in early lesions, when the process is
more diffuse and erythematous. At this stage, consideration is often given to
cellulitis, erythema nodosum, or erythema induratum. Persistence of a lesion,
association with stasis changes, and lack of response to antimicrobials suggest
the correct diagnosis, perhaps aided by studies of venous function.
As
induration develops and progresses, differentiation from morphea and
scleromyxedema may be necessary. In morphea, subcutaneous involvement is
predominantly septal, and lipophagic and lipodystrophic changes are not as
prominent as they are in lipodermatosclerosis. Membranocystic changes, when
present, can be of great diagnostic help; however, these findings can occur in
a variety of other conditions, including lupus and dermatomyositis panniculitis,
liposarcoma, erythema nodosum, and diabetic dermopathy.
Leg
elevation and consistent compression therapy are the mainstays of treatment for
lipodermatosclerosis. A patient with arterial compromise should not undergo compression therapy, which is the
first line treatment for LDS. Higher compression gradient (30–40 mm Hg) may be
more effective, but lower pressure (15–20 mm Hg or 20–30 mm Hg) may be
associated with higher rate of compliance, especially in the elderly, and
effectively decreases edema. One mechanism by which compression improves
venous return and decreases edema is via tightening of vascular tight
junctions, and inhibiting permeability of fluid into the perivascular tissue,
thereby preventing progression of venous insufficiency. Stockings must be worn
all day and not removed until bedtime, since even a few days without
compression may lead to recurrence of the edema and inflammation. Because of
the difficulty of wearing stockings, adaptive compression modalities have been
developed, which use sustained or intermittent pneumatic compression.
Traditional anti-inflammatory therapies are usually ineffective in
this condition, although intralesional corticosteroids (e.g. triamcinolone
5–10 mg/cc) may be of benefit when used in conjunction with compression
therapy. Good results are reported with the anabolic steroid stanozolol,
especially in the earlier phases of the disease, but this medication is no
longer commercially available. As a result, danazol has been used
(successfully) as a substitute. Anabolic steroids enhance fibrinolysis, and
they can reduce pain, extent of involvement, and induration of the skin.
However, side effects of sodium retention, lipid profile abnormalities,
hepatotoxicity, and virilization in women do limit their use. Oxandrolone, an
anabolic steroid with less hepatotoxicity and fewer androgenic effects,
represents another therapeutic option.
Pentoxifylline has been successfully used in
LDS cases with and without associated ulceration and is a useful adjunct to
compression for treating venous ulcers and may be effective as monotherapy in
the absence of compression. In fact, in one study hydroxychloroquine and
pentoxifylline combined therapy, without compression, led to a 50% reduction in
pain from baseline.
Ultrasound therapy can reduce and
even resolves induration, tenderness, and erythema. It is a simple and safe
treatment of a painful and refractory condition and may be used along with
Grade-2 compression therapy. Because obesity is a common condition among
affected patients, weight loss is a critical. Capsaicin may alleviate pain
associated with LDS. Finally, refractory disease may respond to intralesional,
autologous, platelet-rich plasma, injected in a grid-like pattern, and repeated
every 2 weeks.
Improvement is also seen in LDS
patients treated with rutin and vitamin C, particularly adjunctive to
compression therapy.
