Plaques on the lower extremities - Clinical Advisor

Plaques on the lower extremities

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  • Case #1

  • Case #2

Case #1

A woman, aged 55 years, presented with bilateral lower-extremity erythema, edema and pain for two months. She had been treated with two distinct courses of oral antibiotics for presumed cellulitis without improvement.

Further discussion revealed a one-year history of occasional edema in the lower extremities. Medical history was significant for diabetes, hypertension, and heart failure. Vital signs were within normal limits. Erythematous indurated plaques were noted on bilateral lower extremities. Pitting edema and overlying warmth were also appreciated.

Case #2

A woman, aged 40 years, complained of a rash on her bilateral lower extremities. The lesions were first thought to be insect bites, but the areas expanded and changed colors centrally over the course of six months. There was no pain, pruritus, dysesthesia, edema, or warmth, and no prior treatment had been initiated.

History was significant for type 1 diabetes mellitus. On physical exam, atrophic yellow-brown plaques with prominent telangiectasias and a well-defined erythematous indurated border were appreciated on bilateral shins.



HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Arm ulcer on a Latin American immigrant and Discoloration worsens following sun exposure.

CASE #1: Lipodermatosclerosis Lipodermatosclerosis (LDS) is also known as sclerosing panniculitis, hypodermitis sclerodermiformis, or chronic panniculitis with lipomembranous changes. LDS is a disorder of the subcutaneous fat and often occurs in the setting of chronic venous insufficiency (CVI). LDS has...

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CASE #1: Lipodermatosclerosis

Lipodermatosclerosis (LDS) is also known as sclerosing panniculitis, hypodermitis sclerodermiformis, or chronic panniculitis with lipomembranous changes. LDS is a disorder of the subcutaneous fat and often occurs in the setting of chronic venous insufficiency (CVI).

LDS has a relatively short documented history that is directly intertwined with CVI. In the early 1900s, Homans first hypothesized that static venous blood in any part of the body leads to a decreased amount of oxygen in the region and causes the skin in the immediate area to atrophy and ulcerate. In 1953, Piulacks speculated that arteriovenous fistulas in the skin cause hypoxia in the region, leading to detrimental changes in the skin. This was particularly true for the lower extremities. Finally, in 1955, Huriez first described LDS as an indurated lesion he called hypodermitis sclerodermiformis.1

LDS is a disorder that predominantly affects women older than age 40 years. It is believed that LDS is caused by CVI and fibrinolytic abnormalities.2 Patients may also suffer from such comorbidities as diabetes, hypertension, heart failure, kidney failure, peripheral vascular disease, and/or obesity. They may also have a prior history of venous thrombosis.

The damage associated with LDS is triggered by venous hypertension, which leads to increased capillary permeability. Capillary permeability in turn causes the leakage of fibrinogen, which polymerizes to form fibrin cuffs around the vessels. The end result is a significant decrease in oxygen exchange, which ultimately leads to tissue anoxia. It is also believed that deficiencies in proteins C and S, as well as stimulation of collagen in the area, may contribute to the disorder.3

In the acute phase, individuals will often present with erythema, warmth, and pain in the medial portion of the lower extremity, particularly above the malleolus. During the chronic phase, there is marked sclerosis of the subcutis and dermis, which may be accompanied by overlying hemosiderosis. The sclerosis causes the skin to become extremely stiff with clear boundaries from the adjacent normal skin. LDS may also be found in the lower aspect of an abdominal pannus. The classical appearance of LDS is thought to resemble an inverted champagne or wine bottle.

Avoid performing biopsies on lesions of LDS. The lack of clotting factors in the area and poor circulation may lead to poor wound healing. If a sample must be taken, a thin elliptical incision should be made on the margin of the lesion that extends into the deep fat.

Histologically, LDS is a lobular panniculitis with focal macrophage infiltration and fibrosis around shrunken lobules. Within the lobules, fat pseudocysts are lined with a lipomembrane. A lipomembrane is a thin eosinophilic or pale amphoteric layer that has fine, feathery projections into the cavity. Lipomembranous changes are often seen in LDS but are not specific for the disease. There may also be focal areas of fat necrosis, dermal fibrosis, loss of epidermal appendages, and fibrous tissue replacement of the subcutaneous fat. The lipomembrane is positive for periodic acid-Schiff, as well as CD68 and lysozyme, suggesting a contribution of these enzymes from macrophages. Chronic lesions are only weakly positive or negative for CD68 and lysozyme.

Early lesions of LDS are often mistaken for cellulitis, erythema induratum, or erythema nodosum. Signs of venous insufficiency lack of fever or leukocytosis, poor response to antibiotic therapy, and/or a bilateral presentation should help the clinician differentiate LDS from cellulitis. Venous function studies should be considered if available. Other disorders that are often included in the differential diagnoses include necrobiosis lipoidica, morphea, erythema nodosum, erysipelas, diabetic dermopathy, liposarcoma, and traumatic panniculitis.

The mainstays of LDS treatment include leg elevation and compression therapy. Some advocate the use of intralesional corticosteroids in conjunction with compression therapy. Patients should also be advised to optimize the treatment of any medical conditions that may be contributing to their venous insufficiency. Some success has been reported with use of the anabolic steroid stanozolol (Winstrol) (2mg to 5mg b.i.d.).4

Stanozolol must be given early in the disease course and is thought to enhance fibrinolysis, leading to reduced pain, degree of involvement, and cutaneous induration. Patients should be cautioned of the side effects, which include sodium retention, lipid abnormalities, hepatotoxicity, and virilization in women. Oxandrolone (Oxandrin), an alternative anabolic steroid, is thought to have fewer androgenic effects and pose less risk for hepatotoxicity.

Successful treatment with ultrasound, phlebectomy, pentoxifylline (Pentoxil, Trental), hydroxychloroquine (Plaquenil), and fasciotomy has also been reported.4-6 Even with rigorous treatment, LDS tends to run a chronic progressive course.

The woman in this case was treated with leg elevation and compression therapy, resulting in stabilized disease.

CASE #2: Necrobiosis lipoidica

Necrobiosis lipoidica (NL) is classified as a noninfectious palisaded granulomatous dermatitis. In 1929, Oppenheim named the disorder dermatitis atrophicans diabetica. In 1932, Urbach renamed the disease necrobiosis lipoidica diabeticorum (NLD). Up to this point, the disorder was thought to always be associated with diabetes mellitus. In 1935, Goldsmith encountered the first afflicted nondiabetic patient and renamed the disorder necrobiosis lipoidica. While this is the preferred name, NLD remains an ingrained abbreviation in dermatologic literature.

In 1966, Muller and Winkelmann conducted a study to analyze the co-occurrence of NL and diabetes mellitus.7 The results revealed that approximately 65% of patients with NL had type 1 diabetes mellitus. A more recent study revealed that only 11% of patients had a diagnosis of diabetes mellitus at the time of presentation, and an additional 11% were later diagnosed with impaired fasting glucose or frank diabetes mellitus.8

Interestingly, only 0.03% of patients with diabetes mellitus will develop NL, and there is no proven correlation between a patient’s level of glycemic control and the probability of developing the disorder. However, individuals who have both NL and diabetes mellitus have a higher rate of such diabetes-related complications as peripheral neuropathy, limited joint mobility, and retinopathy.9

NL affects women approximately three times more often than it does men, and the disease usually appears between age 20 and 40 years. Unfortunately, the pathogenesis remains largely unknown. Immunoreactants have been found within the vessel walls of lesional and nonlesional skin, leading investigators to believe that NL may be an immunologically mediated vascular disease.10

Others postulate that the microangiopathic vessel changes seen in diabetic patients may result in collagen degeneration and subsequent dermal inflammation. Some believe that anti-collagen antibodies may be the basis of the collagen degeneration; however, no significant increase in antibody level has been appreciated. Elevated platelet adhesion, increased thromboxane A2 production, and increased blood viscosity are additional theories that have not been validated.

Early lesions of NL begin as firm, elevated, red-brown papules. Over time, these lesions expand to develop oval or irregularly round plaques with a well-defined erythematous or violaceous border and a central atrophic yellow portion that may contain numerous telangiectasias and ectatic veins. The lesions are usually symmetric, and 85% of cases occur on the shins. Lesions found elsewhere (e.g., the upper extremities, face, and scalp) are usually annular or serpiginous and tend to be less atrophic. While lesions are typically asymptomatic, some patients complain of pain, pruritus, or dysesthesias. One third of NL cases will ulcerate.

A punch biopsy of NL will often appear rectangular rather than tapered. Histologically, the epidermis tends to be atrophic with loss of the normal rete ridge pattern. A superficial, deep, and interstitial inflammatory process can be appreciated in the reticular dermis, and this inflammation often extends into the subcutaneous fat. The inflammation is composed of lymphocytes, histiocytes, multinucleate giant cells, and plasma cells. Layered palisaded granulomas with pale pink degenerated collagen alternating with histiocytes will appear at low magnification. This pattern is said to look like a layer cake.

Although NL has a distinctive clinical appearance, there are a number of atypical presentations, and early forms can be difficult to recognize.11 The differential diagnosis of NL includes granuloma annulare, necrobiotic xanthogranuloma, sarcoidosis, diabetic dermopathy, stasis dermatitis, and lipodermatosclerosis. An equivalent degree of epidermal atrophy, the presence of telangiectasias, or the yellow-brown discoloration is not normally appreciated in granuloma annulare or sarcoidosis.

Granuloma annulare is also most commonly seen on the distal extremities, including the hands and feet, which may help to differentiate it from NL. The lesions of diabetic dermopathy, stasis dermatitis, and lipodermatosclerosis are also commonly located on the shins, but these dermatoses are usually hyperpigmented rather than yellow. The presence of varicose veins, edema, induration, ulcerations, and eczematous eruptions may also help the clinician to distinguish these disorders from NL. Yellow plaques also characterize necrobiotic xanthogranuloma, but they are most often periocular and associated with a paraproteinemia.

There is no effective treatment for NL. Unfortunately, tight glucose regulation has no effect on the course of the disease. If the patient desires treatment, superpotent topical steroids under occlusion are considered first-line. Some clinicians advocate the use of topical calcineurin inhibitors.12 Topical calcineurin inhibitors may be used when conventional treatment (such as with corticosteroids) is not possible or is unsuccessful. Calcineurin inhibitors are used for short-term treatment of moderate atopic dermatitis. Topical calcineurin inhibitors are relatively new, and long-term side effects are not fully known. The FDA recommends caution when prescribing or using pimecrolimus (Elidel) cream or tacrolimus (Protopic) ointment because of the potential risk of cancer.

In addition, intralesional injections of triamcinolone into the advancing border may be used to halt disease progression. Clinicians must ake care not to inject the central atrophic area, as ulceration may ensue. Systemic corticosteroids may be considered but will elevate the serum glucose.13

Other reported therapies include niacinamide, topical tretinoin, cyclosporine (Gengraf, Neoral, Sandimmune), granulocyte-macrophage colony-stimulating factor, bovine collagen, topical psoralen UVA, UVA1 phototherapy, mycophenolate mofetil (CellCept), etanercept (Enbrel), thalidomide (Thalomid), stanozolol (Winstrol), inositol niacinate, nicofuranose, ticlopidine (Ticlid), pentoxifylline (Pentoxil, Trental), and perilesional heparin. If surgical intervention is necessary because of severe ulceration, excision down to deep fascia or periosteum is peformed to prevent recurrence, followed by split-thickness skin grafting.

NL is usually a chronic disease. In one study, spontaneous remission after an average of eight to 12 years was reported in 17% of patients.7 Areas that ulcerate are prone to infection. Rarely, squamous cell carcinoma has arisen in lesions of NL.

The patient in this case was not bothered by her lesions and did not desire any therapeutic intervention.

Kerri Robbins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.

References

  1. Huriez, Lagache, Desmons, Pelce. [Leg ulcers and trophic disorders of venous origin; data from the study of one thousand hospitalized patients with ulcers]. Rev Prat. 1955;5:2703-2721.
  2. Greenberg AS, Hasan A, Montalvo BM, et al. Acute lipodermatosclerosis is associated with venous insufficiency. J Am Acad Dermatol. 1996;35:566-568.
  3. Falanga V, Bontempo FA, Eaglstein WH. Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration. Arch Dermatol. 1990;126:1195-1197.
  4. Kirsner RS, Pardes JB, Eaglstein WH, Falanga V. The clinical spectrum of lipodermatosclerosis. J Am Acad Dermatol. 1993;28:623-627.
  5. Choonhakarn C, Chaowattanapanit S. Lipodermatosclerosis: improvement noted with hydroxychloroquine and pentoxifylline. J Am Acad Dermatol. 2012;66:1013-1014.
  6. Damian DL, Yiasemides E, Gupta S, Armour K. Ultrasound therapy for lipodermatosclerosis. Arch Dermatol. 2009;145:330-332.
  7. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol. 1966;93:272-282.
  8. O’Toole EA, Kennedy U, Nolan JJ, et al. Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br J Dermatol. 1999;140:283-286.
  9. Boulton AJ, Cutfield RG, Abouganem D, et al. Necrobiosis lipoidica diabeticorum: a clinicopathologic study. J Am Acad Dermatol. 1988;18:530-537.
  10. Quimby SR, Muller SA, Schroeter AL. The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. Arch Dermatol. 1988;124:1364-1371.
  11. Mistry N, Chih-Ho Hong H, Crawford RI. Pretibial angioplasia: a novel entity encompassing the clinical features of necrobiosis lipoidica and the histopathology of venous insufficiency. J Cutan Med Surg. 2011;15:15-20.
  12. Binamer Y, Sowerby L, El-Helou T. Treatment of ulcerative necrobiosis lipoidica with topical calcineurin inhibitor: case report and literature review. J Cutan Med Surg. 2012;16:458-461.
  13. Petzelbauer P, Wolff K, Tappeiner G. Necrobiosis lipoidica: treatment with systemic corticosteroids. Br J Dermatol. 1992;126:542-545.

All electronic documents accessed February 15, 2013.

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