Plasmapheresis and Steroid Treatment of Levamisole-Induced Vasculopathy and Associated Skin Necrosis in Crack/Cocaine Users

Abstract

French

Background:

Levamisole was removed from the market due to complications of agranulocytosis and skin necrosis. Levamisole has been reported in a high proportion of seized cocaine in North America and has been associated with multiple cases of skin necrosis.

Objective:

We report three cases of levamisole/cocaine-induced skin necrosis who responded to treatment with plasmapheresis and immunosuppression.

Results:

Three patients presented with painful necrotic skin lesions on the ears, cheeks, breasts, and buttocks. The extremities were involved in two patients and the upper respiratory tract mucosa in one patient. All had markers of immune activation, with elevated C-reactive protein, antinuclear antibody, and perinuclear antineutrophil cytoplasmic antibody. Skin biopsy in all cases revealed a mixed pattern of thrombosis and vasculitis within dermal vessels, with overlying ischemic ulceration of skin and soft tissues. One patient required extensive debridement of the skin and soft tissue of the calves and also had respiratory involvement. All patients were treated with plasmapheresis and immunosuppression with rapid stabilization and/or improvement of the lesions.

Conclusion:

Levamisole is frequently added to crack/cocaine; we report three patients who developed vascular lesions and skin necrosis after using cocaine/levamisole. These improved with plasmapheresis and immunosuppression as well as abstention from the drugs; one patient with severe disease required debridement and skin grafting.

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References

Barbano

Ginevri

Ghiggeri

. Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome. Pediatr Nephrol 1999;13:602–3, doi:10.1007/s004670050753.

Drew

Carter

Nathanson

. Levamisole-associated neutropenia and autoimmune granulocytotoxins. Ann Rheum Dis 1980;39:59–63, doi:10.1136/ard.39.1.59.

Scheinberg

Bezerra

Almeida

. Cutaneous necrotising vasculitis induced by levamisole. Br Med J 1978;1: 408, doi:10.1136/bmj.1.6110.408.

Menni

Pistritto

Gianotti

. Ear lobe bilateral necrosis by levamisole-induced occlusive vasculitis in a pediatric patient. Pediatr Dermatol 1997;14:477–9, doi:10.1111/j.1525-1470.1997.tb00695.x.

Raymon

Isenschmid

. Letter to the editor: The possible role of levamisole in illicit cocaine preparations. J Anal Toxicol 2009;33: 620–2.

Chang

Osterloh

Thomas

. Levamisole: A dangerous new cocaine adulterant. Clin Pharmacol Ther 2010;88:408–11, doi:10.1038/clpt.2010.156.

Bradford

Rosenberg

Moreno

. Bilateral necrosis of earlobes and cheeks: Another complication of cocaine contaminated with levamisole. Ann Intern Med 2010;152:758–9.

Buchanan

Vogel

Eberhardt

. Levamisole-induced occlusive necrotizing vasculitis of the ears after use of cocaine contaminated with levamisole. J Med Toxicol 2011;7:83–4.

Ching

Smith

Jr . Levamisole-induced necrosis of skin, soft tissue, and bone: Case report and review of literature. J Burn Care Res 2012;33:e1–5, doi:10.1097/BCR.0b013e318233fc64.

10.

Farhat

Muirhead

Chaffins

. Levamisole-induced cutaneous necrosis mimicking coagulopathy. Arch Dermatol 2010; 146:1320–1, doi:10.1001/archdermatol.2010.335.

11.

Farmer

Malhotra

Mays

. Necrotizing peripheral vasculitis/vasculopathy following the use of cocaine laced with levamisole. J Burn Care Res 2012;33:e6–11, doi:10.1097/BCR. 0b013e318235615a.

12.

Graf

Lynch

Yeh

. Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine. Arthritis Rheum 2011;63:3998–4001, doi:10.1002/art.30590.

13.

Gross

Brucker

Bahce-Altuntas

. A novel cutaneous vasculitis syndrome induced by levamisole-contaminated cocaine. Clin Rheumatol 2011;30:1385–92.

14.

Jacob

Silva

Powers

. Levamisole-induced vasculopathy: A report of 2 cases and a novel histopathologic finding. Am J Dermatopathol 2012;34:208–13.

15.

Jenkins

Babu

Hsu-Hung

. ANCA-positive necrotizing vasculitis and thrombotic vasculopathy induced by levamisole-adulterated cocaine: A distinctive clinicopathologic presentation. J Am Acad Dermatol 2011;65:e14–6, doi:10.1016/j.jaad.2010.09.778.

16.

Khan

Cuchacovich

Espinoza

. Vasculopathy, hematological, and immune abnormalities associated with levamisole-contaminated cocaine use. Semin Arthritis Rheum 2011;41: 445–54, doi:10.1016/j.semarthrit.2011.04.010.

17.

McGrath

Isakova

Rennke

. Contaminated cocaine and antineutrophil cytoplasmic antibody-associated disease. Clin J Am Soc Nephrol 2011;6:2799–805, doi:10.2215/CJN.03440411.

18.

Mouzakis

Somboonwit

Lakshmi

. Levamisole induced necrosis of the skin and neutropenia following intranasal cocaine use: A newly recognized syndrome. J Drugs Dermatol 2011;10: 1204–7.

19.

Poon

Baliog

Jr Sams

. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leukopenia. Semin Arthritis Rheum 2011;41:434–44, doi:10.1016/j.semarthrit.2011.05.009.

20.

Waller

Feramisco

Alberta-Wszolek

. Cocaine-associated retiform purpura and neutropenia: Is levamisole the culprit? J Am Acad Dermatol 2010;63:530–5, doi:10.1016/j.jaad.2010.01.055.

21.

Walsh

Green

Burlingame

. Cocaine-related retiform purpura: Evidence to incriminate the adulterant, levamisole. J Cutan Pathol 2010;37:1212–9, doi:10.1111/j.1600-0560. 2010.01613.x.

22.

Zwang

Van Wagner

Rose

. A case of levamisole-induced systemic vasculitis and cocaine-induced midline destructive lesion: A case report. J Clin Rheumatol 2011;17:197–200.

23.

Czuchlewski

Brackney

Ewers

. Clinicopathologic features of agranulocytosis in the setting of levamisole-tainted cocaine. Am J Clin Pathol 2010;133:466–72, doi:10.1309/AJCPOPQNBP5THKP1.

24.

Drew

Carter

. Granulocytotoxic autoantibodies in HLA-B27 neutropenic patients. Transplantation 1979;27:436–7.

25.

Symoens

Veys

Mielants

. Adverse reactions to levamisole. Cancer Treat Rep 1978;62:1721–30.

26.

Auzerie

Chiali

Bussel

. Leg ulcers associated with cryoglobulinemia: Clinical study of 15 patients and response to treatment. Arch Dermatol 2003;139:391–3, doi:10.1001/archderm.139.3.391.

27.

Aydin

Gursu

Karadag

. Role of plasmapheresis performed in hemodialysis units for the treatment of anti-neutrophilic cytoplasmic antibody-associated systemic vasculitides. Ther Apher Dial 2011;15:493–8, doi:10.1111/j.1744-9987.2011. 00960.x.

28.

Berkman

Orlin

. Use of plasmapheresis and partial plasma exchange in the management of patients with cryoglobulinemia. Transfusion 1980;20:171–8, doi:10.1046/j.1537-2995.1980.20280169957.x.