Gibong Lee, BSc(Pharm), MD, Daniel Negash, MSc, MD, Richard Arseneau, MD, FRCPC

Chronic levamisole-induced vasculitis: A case report

After exposure to cocaine adulterated with the immunomodulator levasimole, a 48-year-old patient developed acute inflammation and ulcers that were expected to require long-term home nursing care.

ABSTRACT: In the case reported here, Case data presented as purpuric macules that cocaine abuse led to levasimole- A 48-year-old female presented with a coalesced into patches on the right hip, induced vasculitis and chronic ul- 2-day history of severe pain. Exami- then rapidly spread distally and bilat- cers. Levamisole is an old immuno- nation revealed redness and heat on erally, evolving into painful bullae and modulator that is no longer approved her left thigh, with multiple new bul- necrotic plaques. With subsequent epi - for human use in North America, but lous formations and ulcerations. The sodes of cocaine abuse, these lesions is used to dilute or “cut” cocaine. patient reported inhaling cocaine be- recurred and progressed to become Studies report that 46% of cocaine fore symptom onset. Central necrotic chronic ulcers. in circulation in Canada contains lev- tissues were present in some of the In the immediately preceding ad- amisole. Although the role of levam- ulcers examined (Figure 1 ). Purpura mission, wound culture had shown isole as a cutting agent is unclear, in the pinna and the lobes of the ears Methicillin-resistant Staphylococcus its adverse effect is apparent. Many were also noted. Chronic ulcers in the aureus (MRSA) and pseudomonas, case reports describe vasculitis anterior tibial area were also noted and skin biopsy confirmed vasculitis and neutropenia, both of which are (Figure 2 ). Her history included mul- with immune deposits of IgM, IgG, transient and often resolve sponta- tiple previous admissions over the and C3. Pathology did not indicate neously once exposure to the sub- years with the same symptoms. Since thrombosis. The urine test was posi- stance ends. This case and others her most recent previous admission, tive for levamisole. At this time, an reviewed suggest that early recogni- the patient had been taking a mainte- attempt to perform a skin graft was tion of levasimole-induced vasculitis nance dose of prednisone. She was made by plastic surgery and failed due is needed to prevent ulcers from also taking part in a methadone main- to graft tissue infection and possible developing and becoming chronic. tenance program for past heroin necrosis, as well as because of im- addiction and current cocaine abuse. paired wound healing secondary to Because of the overt signs of in- cocaine use. flammation, vasculitis and bacterial The patient’s condition during the super-infection were suspected. The admission described in this case report patient was started on piperacillin and was further complicated by develop- tazobactem and soon switched to van- ment of mild leukopenia. The immune comycin and ceftazidime because of an allergic reaction. Clinical diagno- Mr Lee is an MD candidate at the Universi- sis of levamisole-induced vasculitis ty of British Columbia. Dr Negash is in year was made and antibiotics were dis- 3 of an internal medicine residency at UBC. continued. Acute inflammatory lesions Dr Arseneau is a staff internist at St. Paul’s improved over the next 24 hours. Hospital and a clinical assistant professor Records from past admissions in - in the Division of General Internal Medicine This article has been peer reviewed. dicated that her lesions had initially at UBC.

302 BC MEDICAL JOURNAL VOL. 54 NO. 6, JULY/AUGUST 2012 www.bcmj.org Chronic levamisole-induced vasculitis: A case report

workup included testing for levels of isolated in 30% to 71% of cocaine reports,7 and while high doses help- C-reactive protein, antineutrophil cy- samples circulating in the US2,3 and ed our patient’s acute inflammatory toplasmic antibody (ANCA), and anti- up to 46% of cocaine samples in Cana- symptoms, prednisone was ineffec- nuclear antibody (ANA). Test results da.4 It is thought that levamisole is a tive in resolving her more chronic, revealed the following: normal CRP preferred adulterant because it en- ulcerated lesions. of 8.7, equivocal levels of ANCA hances the cocaine effect.5 Levamisole All other levamisole-related case (myeloperoxidase of 39.3 and pro- was used in the past as an immuno - reports we reviewed described rapid- teinase 3 of 30.2) with atypical peri- modulator, a steroid-sparing agent for ly resolving lesions as the patients nuclear pattern, ANA of 1:80, normal conditions such as nephritic syndrome.6 avoided further cocaine exposure.7-9 complements levels, and no cryoglob- Since the 1970s it has fallen out of As in these cases, our patient pre- ulins. favor because of numerous reports of sented with familiar symptoms of By day 4 of admission, the patient vasculitis and agranulocytosis/neutro- levamisole-related vasculitis with ear- had improved clinically. Her only penia, and because other safe agents lobe8 and leg involvement, as well as treatment at that time was prophylac- are now available. Current use is lim- neutropenia.4,10,11 Where our case dif- tic subcutaneous heparin for deep vein ited to veterinary practice, where lev- fered from others was in the chronici- thrombosis. Subsequently, a trial of amisole serves as an anthelmintic.3 ty of the patient’s ulcers. Although the IV heparin was initiated and found to Despite increasing recognition of acute inflammation of levamisole- provide no additional improvement. levamisole-induced adverse effects, induced vasculitis improves once co- The acute inflammation was resolved, no effective treatment has been delin- caine use ends, the lesions can pro- but her chronic ulcers were expected eated. Anticoagulation is suggested, gress to a chronic state and may not be to cause further debilitating pain and but the effectiveness of this is uncer- as readily reversible. This poses a require long-term home nursing care. tain. Recent case series by Han and notable impact on public health given colleagues describe a patient with the prevalence of cocaine abuse. Discussion recurrent levamisole-related purpura Cocaine abuse is common in North despite a trial of warfarin within ther- Summary America, with an estimated 2 million apeutic INR levels and a trial of dal- In the case reported here, the patient’s people identified as current (past teparin anticoagulation.7 While pred- cocaine abuse led to levamisole- month) users.1 Levamisole has been nisone showed promise in many case induced vasculitis and chronic leg

Figure 1. Central necrotic tissues on patient’s thigh. Figure 2. Chronic ulcers in anterior tibial area.

www.bcmj.org VOL. 54 NO. 6, JULY/AUGUST 2012 BC MEDICAL JOURNAL 303 Chronic levamisole-induced vasculitis: A case report

ulcers. This case and others suggest that early recognition of vasculitis is needed to prevent chronic ulcers. Cli- nicians should note that patients pre- senting with levamisol-induced vas- Levamisole has been isolated in culitis may appear to have cellulitis 30% to 71% of cocaine samples and that IV antibiotics will often have been initiated in the ER. It is impor- circulating in the US and up to 46% tant to make the correct diagnosis and of cocaine samples in Canada. discontinue unnecessary antibiotics. Clinicians should inquire about recent cocaine use and the route of adminis- tration, as well as previous similar reactions. It is reasonable to suspect a reac- tion to levamisole in the following clinical situations: • New-onset vasculitis in patients sus- Use and Health. Accessed 2 May 2012. 7. Han C, Sreeenivasan G, Dutz JP. Re- pected of using cocaine. http://oas.samhsa.gov/NSDUH/2k7NSD versible retiform purpura: A sign of co - • Vasculitis involving the earlobes. UH/2k7results.cfm#Ch2. caine use. CMAJ 2011;183:E597-600. • Recurrent vasculitis that rapidly re- 2. Casale JF, Corbeil EM, Hays PA. Identifi- 8. Bradford M, Rosenberg B, Moreno J, et solves spontaneously. cation of levamisole impurities found in al. Bilateral necrosis of earlobes and • Vasculitis that persists despite treat- illicit cocaine exhibits. Microgram J 2008; cheeks: Another complication of cocaine ment. 6:82-89. contaminated with levamisole. Ann Intern • Unexplained leukopenia in patients 3. US Department of Justice National Drug Med 2010;152:758-759. suspected of using cocaine. Intelligence Center. National Drug Threat 9. MacFarlane DG, Bacon PA. Levamisole- An initial diagnosis can be con- Assessment 2010. Accessed 2 May induced vasculitis due to circulating im - firmed by urine levamisole screening 2012. www.justice.gov/ndic/pubs38/ mune complexes. BMJ 1978;i:407-408. and a skin biopsy. 38661/drugImpact.htm. 10. Van Wieren A, Kapoor M, Rao P, et al. A 4. Wiens MO, Son WK, Ross C, et al. Cases: new low for an old high: Neutropenia Competing interests Cocaine adulterant linked to neutrope- induced by levamisole-adulterated co - None declared. nia. CMAJ 2010;182:57-59. caine. Med Health R I 2010;93:320-321. 5. Morley SR, Forrest ARW, Galloway JH. 11. Zhu NY, LeGatt DF, Turner AR. Agranulo- References Levamisole as a contaminant of illicit cytosis after consumption of cocaine 1. Department of Health and Human Serv- cocaine. Int Assoc Forensic Toxicol 2006; adulterated with levamisole. Ann Intern ices: Substance Abuse and Mental Health 44:6. Med 2009;150:287-289. Services Administration (SAMHSA) & 6. Bagga A, Hari P. Levamisole-induced vas- Office of Applied Studies (OAS). Results culitis. Pedatri Nephrol 2000;14:1057- from the 2007 National Survey on Drug 1058.

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