Dermatology Online Journal

Anetoderma secondary to antiphospholipid antibodies
John Eungdamrong MD PhD, Max Fischer MD, Rishi Patel MD, Shane Meehan MD, Miguel Sanchez MD
Dermatology Online Journal 18 (12): 26

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York

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Abstract

Anetoderma is an elastolytic disorder that is associated with a number of infectious and autoimmune disorders. We present a case of a patient with generalized anetoderma, who was later found to have positive antinuclear antibodies and antiphospholipid antibodies (APAs). Numerous other cases have been reported in literature and some authors have suggested that anetoderma is a highly specific sign of APAs, with or without other manifestations of systemic lupus erythematosus or antiphospholipid syndrome. Thus, work up for connective-tissue disorders should be considered in any patients who present with this skin finding.

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History

A 60-year-old man presented to the Dermatology Clinic at Bellevue Hospital Center with a ten-year history of pruritus. He has had itchy skin since young adulthood but over the past ten years, the pruritus has intensified and is now localized mainly to his back. One month prior to the initial presentation, he was admitted to Bellevue Hospital Center for chest pain. At that time, an eruption was noted during routine physical examination and he was subsequently referred to the dermatology service for further evaluation. The patient feels that the eruption has been there for at least ten years but is unsure about the exact duration.

Past medical history included type 2 diabetes mellitus, hypertension, and anemia of unclear etiology. Review of systems was notable for fatigue, lower extremities edema, and chest discomfort at rest. He denied fever, chills, joint pain, oral ulcers, shortness of breath, and difficulty swallowing. He has never been diagnosed with deep vein thrombosis and there is no family history of autoimmune diseases.

Physical examination

Figure 1	Figure 2

Numerous flesh-colored, saccular papules and plaques are present on the back, chest, and proximal aspects of the extremities. The lesions on the back follow a Christmas tree distribution. Newer lesions have erythematous borders, whereas older ones are atrophic with overlying wrinkled skin. On palpation, the papules are softer than the surrounding normal skin, producing a positive button hole sign.

Erythematous, scaly plaques are present on scalp and elbows. Erythematous patches with greasy scale on the face and a rubbery subcutaneous nodule is present on the left lateral neck.

Laboratory data

Hemoglobin was 11.9 g/dL and platelet count of 103 x 10⁹/L. Glucose was of 196 mg/dL. Thyroid stimulating hormone level was normal. Borrelia burgdorferi western blot, Treponemal antibody, quantiferon gold, HIV, and hepatitis A, B and C serologies were negative. Antinuclear antibody was positive with a titer of 1:640 with a nucleolar pattern. Anti-Ro/SSA and anti-La/SSB antibodies were negative. Antiphospholipid syndrome panel was notable for partial thromboplastin time (PTT) of 92.2 seconds, anti-cardiolipin IgG titer of 331, and anti-beta-2-GP1 IgG titer of 134.6.

Histopathology

Figure 3	Figure 4

There is a superficial perivascular mixed-cell infiltrate comprised predominantly of lymphocytes. An elastic Van Gieson stain reveals diminished elastic fibers within the superficial dermis.

Discussion

Anetoderma is a rare elastolytic disorder that results in atrophic macules or saccular herniations of subcutaneous tissue. Primary anetoderma can be classified into the Jadassohn-Pellizzari type, in which there are preceding inflammatory lesions, or the Schweninger-Buzzi type, in which there are no preceding inflammatory lesions. Secondary anetoderma is associated with a number of systemic diseases, which include infections (e.g., Lyme borrelosis, human immunodeficiency virus infection (HIV)), medications (e.g., penicillamine), and malignant disorders (e.g., cutaneous B-cell lymphoma) [1, 2, 3, 4]. However, the best-characterized association is with autoimmune findings, in particular antiphospholipid antibodies (APAs) with or without evidence of antiphospholipid syndrome (APS) [5].

The observation of anetoderma and its association with various autoimmune disorders has led to the hypothesis that anetoderma has an immunologic basis [6]. The initial description of anetoderma in five patients with a false-positive rapid plasma reagin (RPR) test was reported in 1995 [7]. Three out of these five patients fulfilled criteria for APSs, whereas the remaining two fulfilled criteria for systemic lupus erythematosus (SLE). This association was further supported by a case series of nine patients with anetoderma in which six of the nine had positive APAs. In four of these patients, anetoderma was the first manifestation of the underlying autoimmune disorders [8]. A case series further divided anetoderma in association with APAs into two sub-groups [9]. In one group (n=14), the patients were comprised mostly of young women with atrophic lesions on the upper trunk and arms. Nearly 65% of the patients in this group experienced thrombotic complications, which included miscarriage, stroke, and deep vein thrombosis. The thrombotic complications were predominantly in the non-HIV positive group. These included spontaneous abortion (four of 14), stroke (two of 14), and phlebitis or venous thrombosis (four of 14). In the HIV positive cases, there was only a single case (out of n = 7) with a history of “thrombotic episode.”

The mechanism by which APAs may cause focal loss of elastic fiber is not clear. Histopathologic examination of anetoderma in patients with APAs often showed some perivascular and peri-adnexal inflammatory infiltrates as well as microthrombi [7]. Some authors believe that these microthrombi could lead to localized ischemia at the recruitment of inflammatory cells and altered matrix metalloproteinase (MMPs) expression [10, 11]. Another hypothesis considers shared epitopes between b2-glycoprotein 1 and the elastin fiber. This hypothesis was put forth after immune deposits, which surrounded the elastic fibers, were noted in some specimens [12]. Previous attempts to treat anetoderma have focused on addressing these mechanisms, which include the uses of anti-fibrinolytics, such as topical epsilon-aminocaproic and oral colchicine [13, 14]. To our knowledge, medications with anti-MMP activity, such as doxycycline have never been used. Further investigation of the pathogenic mechanisms underlying formation of new lesions may lead to novel therapies in the future.

References

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14. Braun RP, et al. Treatment of primary anetoderma with colchicine. J Am Acad Dermatol 1998; 38:1002 [PubMed]

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