174 Journal of the European Academy of Dermatology & Venereology, 3 (1994) 174-177© 1994 Elsevier Science B.V. All rights reserved 0926-9959/94/507.00

DERVEN 118

Case Report

Leg uleeration due to the antiphospholipid syndrome:suecessful treatment with intralesional corticosteroids

and failure of prolonged stanozolol therapy

Vincetit Falanga ''•̂ , Harvey Brown ,̂ Jeffrey Pardes '' and Robert S. KirsnerUniversity of Miami School of Medicine Departments of " Dermatology and ^ Medicine, Miami, FL, USA

Abstract

The clinical manifestations of the antiphospholipid antibody syndrome (APLA) include throm-bosis, thrombocytopenia and recurrent fetal loss. Livedo reticularis and leg uleeration mayoccur as the result of vascular occlusion, and are difficult to treat. We report a patient with apainful leg uleeration and livedo reticularis secondary to APLA in whom intralesional triamci-nolone injections induced rapid and complete healing of the uleeration. A year later, the ulcerhas not recurred. Initial and prolonged treatment with stanozolol, an androgenic steroid withfibrinolytic properties that has been proposed as a treatment for this condition, seemed to helpat first but failed to cause persistent healing. We suggest that intralesional injection ofcorticosteroids should be the initial treatment of choice in ulcers due to APLA.

Key words: Ulcer; Antiphospholipid syndrome; Corticosteroid; Stanozolol

The chnical manifestations of the an-tiphospholipid antibody syndrome (APLA)include vascular thrombosis (arterial and ve-nous), thrombocytopenia and recurrent fetalloss. Antiphospholipid antibodies are proba-bly involved in the pathogenesis of thrombo-sis in APLA; their presence can be detected

Correspondence to; Vincent Falanga M.D., Univer-sity of Miami School Of Medicine, P.O. Box 016250,Miami, FL 33126, USA. Tel. (305) 547-5975; Fax (305)547-6191.

SSDI 0926-9959(93)E0043-K

by testing for biologically false positiveVDRL (venereal disease research labora-tory), lupus anti-coagulant and anti-cardioli-pin antibodies [1]. The APLA is not re-stricted to patients with systemic lupus ery-thematosus, but can occur in the setting ofother collagen vascular diseases as well as inotherwise normal individuals. Cutaneous ul-eeration and livedo reticularis are unusualcomplications of the APLA and are the re-sult of thrombosis and vascular occlusion. Ithas been hypothesized that fibrinolytic ther-apy, such as with stanozolol, may help these

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ulcerations [2], In this report, we presentevidence that stanozolol failed to cause per-sistent healing of the ulceration, while in-tralesional injections of corticosteroids maybe a highly effective therapy for cutaneousulcers due to this syndrome.

Case report

A 36-year-old woman originally from Chilewas referred to us because of a painful ulcer-ation of 6 months duration on her left lowerextremity. She had systemic lupus erythe-matosus, hypertension and a history of twospontaneous abortions. Previous testing in-cluded a positive lupus anticoagulant and thepresence of anticardiolipin antibodies. Hermedications were phenobarbital, colchicine,lisinoprii, nifedipine, cimetidine and pred-nisone (20 mg/day). On physical examina-tion, a 1,8 X 1.8 cm ulcer with a necrotic basewas present over her left medial malleolus(Fig, 1), and she had bilateral reticulatederythema around her ankles. Normal or neg-ative laboratory studies included a completeblood count, chemistry profile, prothrombintime, urinalysis, liver function tests, C3, C4,cryoglobulin, cryofibrinogen and FTA {freetreponemal antibody). The patient had a pos-itive antinuclear antibody at a titer of 1 :2560in a speckled pattern, positive double-stranded DNA antibodies at a titer of 1:40,and a positive anti-cardiolipin IgG antibodyof 21 IU (normal 0-7.5) 2. In addition, alupus anticoagulant was detectable, with herpartial thromboplastin time (PTT) of 52(normal up to 45 s) uncorrected with theaddition of normal plasma. A 4-mm punchbiopsy from the edge of the ulcer showed amoderate polymorphous inflammatory infil-trate throughout the upper dermis withoutvasculitis but with evidence of intravascularthrombi in the superficial dermal vessels, Amild inflammatory infiltrate was presentaround the thrombosed blood vessels.

Because it has been hypothesized that the

cutaneous manifestations of the APLA mayrespond to fibrinolytic therapy, the patientwas started on stanozolol, 2 mg orally twicedaily [3,4]. She had immediate relief of herpain but after 2 months without healing ofher ulcer, stanozolol was increased to 4 mgtwice daily. Within 2 weeks, her ulcer beganto re-epithelialize and was completely healedafter 2 months. In addition, there was almostcomplete disappearance of the reticulate ery-thema (Fig. 2). She remained pain-free. Af-ter healing of her ulceration, anticardiolipinIgG antibodies were no longer detectable.She was told to continue stanozolol at thesame dosage. The dosage of prednisonethroughout her course was maintained at10-20 mg a day. Her ulcer remained healedfor one month, at which time she returned asthe painful ulceration recurred in the samelocation. The dosage of stanozolol was in-creased to 6 mg twice daily which, in 2 weeks,resulted once again in prompt resolution ofher pain and healing of the ulcer. However,she kept experiencing episodes of recurrentulceration despite continued treatment withstanozolol at doses up to 6 mg twice daily, atwhich time she developed dysmenorrhea,acne and hirsutism. The dosage of stanozololwas decreased to 2 mg a day with resultantresolution of the dysmenorrhea and acne.The increased facial hair began to subside.At this point, a total of 1.5 ml of a triamci-nolone acetonide :lidocaine (1:1) mixturewas injected in the edges of the ulceration.This resulted in decreased pain and re-epi-thelization over a 2-week period. After thatsingle injection, she has remained asymp-tomatic and ulcer free after a one year fol-low-up. Stanozolol was stopped altogether 3months after the use of intralesional corti-costeroids.

Discussion

The cutaneous manifestations of the an-tiphospholipid antibody syndrome (APLA)described in this report, leg ulceration and

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Fig. 1. Sharply defined uleeration of the medial aspect ol the ankle. The ulcer b.isc is necrotic, and the surroundingskin shows a reticulate pattern of erythema.

livedo reticularis., have already been associ-ated with APLA [5]. Their treatment hasproved difficult, but it has been suggested

that fibrinolytic therapy may help these com-plications. Our case indicates that stanozolol,after an initial improvement manifested by

Fig. 2. Healed uleeration with scar formation. The surrounding skin shows less reticulated erythema, but subtlelivedo reticularis may still be seen on the foot.

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decreased pain, temporary healing of the ul-eeration, and systemic serological improve-ment, did not result in persistent pain reliefand healing of the uleeration. We proposethat the improvement observed initially withstanozolol may have been coincidental with ageneral systemic improvement of her condi-tion, or that this therapy is only partiallysuccessful in the treatment of ulcerationsdue to the APLA. A single intralesional in-jection of triamcinolone acetonide resultedin pain relief and healing of the uicerationthat has now persisted for a year.

The histological findings of the cutaneousmanifestations of APLA are characterized byintravascular thrombi within superficial der-mal vessels [6], as well as a varying degree ofperivascular inflammation [7]. It is possiblethat this inflammatory component is indeedplaying an important role in the pathogenesisof these cutaneous manifestations of APLA,and that the intralesional injection of triam-cinoione in our patient altered this aspect ofthe pathogenesis.

References

1 Bowles CA. Vasculopathy assoeiated with antiphos-pholipid antibody syndrome. Rheum Dis Clin N Amiy9();16:471-490.

2 Stephens CJM. The antiphospholipid syndrome.Clinical correlations, cutaneous features, mecha-nisms of thrombosis and treatment of patients withthe lupus anticoagulant and anticardiolipin antibod-ies. BrJ Dermato! 1991;I25:199-206.

3 Kluft C, Preston FE, Malia RG, Wyngaardt G,Greaves IM. Vcrheijen JH, Dooijewaard G.Stanozolol induced changes in fibrinolysis and coag-ulation in healthy adults. Thromb. Haemostas1984;5I:157-164.

4 Falanga V. Kirsner RS. Eagistcin WH, Katz MH,Kerdei FA. Stanozolol in the treatment of leg ulcerdue to cryofibrinogenemia. Lancet 199l;i:347-348.

5 Alareon-Scgovia D. Sanchez-Guerrero J. Primaryantiphospholipid syndrome. J Rheum. 1989;I6:482-488.

6 Grob JJ, San Marco M, Aillaud MF, Andrac L,Gabriel B, Juhan-Vaque I, Mercicr C, Bonerandi JJ.Unfading acral microlivcdo. J Am Acad Dermatol1991:24:53-58.

7 Grob JJ, Bonerandi JJ. Thrombotic skin disease as amarker of the anticardiolipin syndrome. J Am AcadDermatoi 1989;6:I()63-IO69.