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Thrombotic vasculopathy probably associated with cocaine contaminated with levamisole: report of 2 cases


How to cite this article: Martínez-Velasco MA, Flores-Suárez LF, Toussaint-Caire S, Rodríguez-Carreón A, Díaz-Lozano M, Sánchez-Armendáriz K. Thrombotic vasculopathy probably associated with cocaine contaminated with levamisole: report of 2 cases. Rev Med Inst Mex Seguro Soc. 2015 Jan-Feb;53(1):98-101.

PubMed: http://www.ncbi.nlm.nih.gov/pubmed/25680649


BRIEF REPORTS


Received: April 7th 2014
Accepted: July 10th 2014

Thrombotic vasculopathy probably associated with cocaine contaminated with levamisole: report of 2 cases

María Abril Martínez-Velasco,a Luis Felipe Flores-Suárez,b Sonia Toussaint-Caire,a Angélica Rodríguez-Carreón,a Marisol Díaz-Lozano,a Karen Sánchez-Armendáriza

aDivisión de Dermatología, Hospital General “Dr. Manuel Gea González”, Secretaría de Salud

bClínica de Vasculitis Sistémicas Primarias, Instituto Nacional de Enfermedades Respiratorias


Distrito Federal, México


Communication with: Karen Sánchez Armendáriz
Email: abrilbrug@hotmail.com


The vasculities are complex diseases. Their cutaneous manifestations are very important and often mirror several pathologies. Cocaine use has been related to both, vasculitis and thrombotic vasculopathy and pseudovasculitis. A new syndrome has been described in association with its adulteration with levamisole. It can be very serious, leading patients to death. This is relevant as levamisole-adultered cocaine seems to be increasingly offered to consumers. Our goal is to report the first two cases in Mexico, which faces an important raise in cocaine use, emphasizing that a high suspicion based on certain characteristics allows for early recognition and adequate treatment.

Keywords: Thrombotic vasculopathy; Cocaine; Levamisole; Neutropenia; Vasculitis


Cocaine is a commonly-used drug. In the United States there are five million consumers and in Mexico users have increased from 1.4% in 2002 to 2.5% in 2008.1

As a result of its use neuropsychiatric disorders have been reported, thrombosis of large vessels, and small vessel vasculopathy, which simulates rheumatic autoimmune diseases.2-4 At skin level it produces palpable purpura, digital infarction, necrosis, ulcers, acute generalized exanthematous pustulosis, delusions of parasitosis, and Stevens-Johnson syndrome.5 Since 2006 there have been increased reports of severe leucopenia associated with cocaine,5 which coincide with the use of levamisole to enhance the drug.2 So far only one case has been reported in Latin America,6 to which we add two highly probable cases of this condition, the first in Mexico.

Case reports

Case 1

31-year-old man, consumer of cocaine in the last year; last consumption was 15 days before presenting with purplish spots on pinnae (Figure 1a). A skin biopsy was performed with the diagnostic impression of infectious necrotizing chondritis. Histological examination showed thrombotic vasculopathy and intravascular papillary endothelial hyperplasia (Figure 1a). The blood count was normal; HIV, antinuclear antibodies (ANA), rheumatoid factor, and viral hepatitis panel were negative. He was treated with corticosteroids with complete recovery.


Figure 1a Case 1. Histological sections showed vascular occlusion due to fibrin thrombi in dermis and subcutaneous tissue, with diffuse lymphocytic inflammatory infiltrate and numerous capillary blood vessels


Case 2

38-year-old man, cocaine user for 20 years, with six months of recurring signs of fever, arthralgia, myalgia, and skin lesions associated with drug use. One week after his last inhalation he presented retiform purpura, star-shaped atrophic plaques, sloughing ulcers on cheeks, auricles, and legs (Figure 1b). He underwent skin biopsy with suspected lupus erythematosus and antiphospholipid syndrome; multiple newly formed vessels, fibrosis, and intraluminal thrombi in small vessels without vasculitis were found (Figure 1b). Laboratory studies showed 600 neutrophils/µL, hemoglobin 4.5 g/dL, 450,000 platelets/µL, normal clotting times and complement, ANA and anti-DNA negative. The patient was discharged voluntarily, but 48 hours after he was admitted to another hospital where he died of apparent diffuse alveolar hemorrhage.  


Figure 1b Case 2. Histology showed the beginning of the formation of fibrin thrombi occluding the blood vessels of small gauge in deep reticular dermis and in subcutaneous tissue without inflammatory infiltrate.


Discussion

These two cases are probably the first reports of this condition in Mexico, a country facing a serious problem of drug consumption and trafficking. In both patients, cutaneous manifestations, neutropenia, and histopathological findings, along with recurrence with each consumption, suggest that the cocaine was adulterated with levamisol.7 We recognize limitations in our reports, particularly the lack of complete serological studies; however, clinical and histopathological data reasonably support the diagnosis.

The presence of purpura and star-shaped ulcers on the auricular, nasal tip, and malar region; histopathologic evidence of mixed vascular disease, consisting of occlusive vascular disease, microvascular thrombosis with or without leukocytoclastic vasculitis, reactive endothelial atypia, and newly formed vessels in association with neutropenia; in addition to serological polyreactivity in patients who use cocaine, should lead to suspicion of this ailment.2,6,8,9 So far effect on internal organs has not been reported with alveolar hemorrhage, which in our second case is suggested by the development of pulmonary capillaritis. Table I shows a comparison of the laboratory, serological, and histological characteristics of vasculopathy associated with cocaine adulterated with levamisole.


Table I Comparison of laboratory, serological, and histological characteristics of vascular disease associated with cocaine adulterated with levamisole in several reported cases
Reference Casos
(n)
Neutropenia ANCA ANA dsDNA LAC ACL CRYO C3/C4 low Fibrinoide necrosis Leukocytoclasia Occlusive thrombosis Extravasated erythrocytes Recanalization Neovascularization
Walsh
et al.2
2 1/2 2/2 2/2 NR 0/2 0/2 1/2 NR 1/2 1/2 2/2 0/2 1/2 0/2
Farhat
et al.4
2 NR 2/2 0/2 NR NR 1/2 0/2 0/2 0/2 0/2 2/2 0/2 0/2 0/2
Bradford
et al.9
2 2/2 2/2 NR NR NR 2/2 NR NR 1/2 1/2 2/2 NR NR NR
Jacob
et al.10
2 2/2 2/2 2/2 2/2 1/2 2/2 2/2 0/2 0/2 2/2 2/2 2/2 0/2 1/2
Rongioletti
et al.13
5 0/5 4/5 2/5 1/5 2/5 1/5 0/5 0/5 2/4 2/4 4/4 0/4 0/4 0/4
Powell
et al.14
1 0/1 1/1 0/1 NR 1/1 NR 0/1 NR 0/1 0/1 1/1 0/1 0/1 0/1
Buchanan
et al.15
1 1/1 NR NR NR NR NR NR NR 1/1 1/1 1/1 0/1 0/1 0/1
Waller
et al.16
2 2/2 2/2 0/2 1/2 2/2 1/2 NR NR 1/2 1/2 2/2 1/2 0/2 0/2
Lee
et al.17
1 0/1 1/1 1/1 1/1 0/1 1/1 1/1 NR 0/1 0/1 1/1 0/1 0/1 0/1
Present report 2 2/2 NR 1/2 0/2 0/2 0/2 0/2 0/2 0/2 0/2 2/2 0/2 0/2 1/2
ANCA = anti-neutrophil cytoplasmic antibody; ANA = antinuclear antibodies; dsDNA = double-stranded DNA; LAC =  lupus anticoagulant; ACL = anti-cardiolipin antibodies (IgM or IgG); Cryo = cryoglobulins; NR = not reported

Treatment usually consists of supportive measures and withdrawal of the inducing agent, although in severe cases the use of steroids and immunosuppressive drugs is required, similar to what is done in autoimmune diseases.2-9

Conclusion

It is estimated that about 70% of the cocaine consumed today is contaminated with levamisole, with risk of developing infections or syndromes that mimic rheumatic diseases, so that timely clinical suspicion is essential and requires dissemination in the face of likely growth of the problem. Our cases coincide with existing reports.

References
  1. Sánchez-Zamorano LM, Llerenas AA, Anaya-Ocampo R, Lazcano-Ponce E. Prevalencia del uso de drogas ilegales en funcion del consumo de tabaco en una muestra de estudiantes en México. Salud Pública Mex. 2007;49(Sup 2):s182-93.
  2. Walsh NM, Green PJ, Burlingame RW, Pasternak S, Hanly JG. Cocaine-related retiform purpura: evidence to incriminate the adulterant, levamisole. J Cutan Pathol. 2010;37(12):1212-9.
  3. Muirhead TT, Eide MJ. Images in clinical medicine. Toxic effects of levamisole in a cocaine user. N Engl J Med. 2011;364(24):e52.
  4. Farhat EK, Muirhead TT, Chaffins ML, Douglass MC. Levamisole-induced cutaneous necrosis mimicking coagulopathy. Arch Dermatol. 2010;146(11):1320-1.
  5. Brewer JD, Meves A, Bostwick JM, Hamacher KL, Pittelkow MR. Cocaine abuse: dermatologic manifestations and therapeutic approaches. J Am Acad Dermatol. 2008; 59(3):483-7.
  6. Centers for Disease Control and Prevention (CDC). Agranulocytosis associated with cocaine use-four States, March 2008-November 2009. MMWR Morb Mortal Wkly Rep. 2009;58(49):1381-5.
  7. de la Hera I, Sanz V, Cullen D, Chico R, Petiti G, Villar M, et al. Necrosis of ears after use of cocaine probably adulterated with levamisole. Dermatology. 2011; 223(1):25-8.
  8. Poon SH, Baliog CR Jr, Sams RN, Robinson-Bostom L, Telang GH, Reginato AM. Syndrome of cocaine-levamisole-induced cutaneous vasculitis and immune-mediated leukopenia. Semin Arthritis Rheum. 2011;41(3):434-44.
  9. Bradford M, Rosenberg B, Moreno J, Dumyati G. Bilateral necrosis of earlobes and cheeks: another complication of cocaine contaminated with levamisole. Ann Intern Med. 2010;152(11):758-9.
  10. Jacob RS, Silva CY, Powers JG, Schieke SM, Mendese G, Burlingame RW, et al. Levamisole-induced vasculopathy: a report of 2 cases and a novel histopathologic finding. Am J Dermatopathol. 2012;34(2):208-13.
  11. Chung C, Tumeh PC, Birnbaum R, Tan BH, Sharp L, McCoy E, et al. Characteristic purpura of the ears, vasculitis, and neutropenia-a potential public health epidemic associated with levamisole-adulterated cocaine. J Am Acad Dermatol. 2011;65(4):722-5.
  12. Graf J, Lynch K, Yeh CL, Tarter L, Richman N, Nguyen T, et al. Purpura, cutaneous necrosis and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine. Arthritis Rheum. 2011;63(12):3998-4001.
  13. Rongioletti F, Ghio L, Ginevri F, Bleidl D, Rinaldi S, Edefonti A, et al. Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children. Br J Dermatol. 1999;140(5):948-51.
  14. Powell J, Grech H, Holder J. A boy with cutaneous necrosis occurring during treatment with levamisole. Clinical Exp Dermatol. 2002;27(1):32-3.
  15. Buchanan JA, Vogel JA, Eberhardt AM. Levamisole-induced occlusive necrotizing vasculitis of the ears after use of cocaine contaminated with levamisole. J Med Toxicol. 2011;7(1):83-4.
  16. Waller JM, Feramisco JD, Alberta-Wszolek L, McCalmont TH, Fox LP. Cocaine-associated retiform purpura and neutropenia: is levamisole the culprit? J Am Acad Dermatol. 2010;63(3):530-5.
  17. Lee BL, Stone JH, Gimbel D, Khosroshahi A. A 44-year-old woman with cutaneous bullae and extensive skin necrosis. Arthritis Care Res (Hoboken). 2010;62(12):1805-11.

Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.

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