Old drug new trick: levamisole-adulterated cocaine causing acute kidney injury
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American Journal of Emergency Medicine
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Old drug new trick: levamisole-adulterated cocaine causing acute kidney injury?
Abstract
Levamisole is an agent previously used in humans and later withdrawn from the US drug market due to concerns of agranulocy- tosis. It is currently used as an adulterating agent in cocaine, bringing to light toxicities typically manifested by vasculitis and Skin necrosis. We report a case of a 36-year-old crack cocaine user who presented with a purpuric rash on her face and limbs. Levamisole-induced vasculitis was suspected, and she therefore underwent an extensive work-up. In addition to these findings, she also presented with acute kidney injury of unknown etiology, which was later attributed to levamisoleadulterated cocaine.
Levamisole (Ergamisol) is an agent previously used in humans as an immunomodulator and chemotherapy adjuvant and later with- drawn from the US drug market due to concerns of agranulocytosis. Recently, it has been found in up to 77% of seized cocaine samples imported into the United States [1-3].
Many adverse effects have been reported with the use of levamisole-adulterated cocaine, including agranulocytosis; pro- gressive cutaneous purpura affecting the ears, face, and extremi- ties; serologic autoantibodies; and thrombotic vasculopathy with or without vasculitis [2-5]. However, the finding of acute kidney injury is rarely reported.
A 36-year-old woman with a history of sarcoidosis presented to the emergency department with purple lesions over her face and limbs present for 3 days. She admitted to smoking cocaine on a regular basis but denied intravenous drug abuse. Her temperature was 101.4?F, heart rate of 119 beats per minute, respiratory rate of 20 breaths per minute, and blood pressure of 120/65 mm Hg. Her skin was noted to be warm and dry, with violaceous lesions in a malar distribution over her face, hands, wrists, and a patchy distribution over her legs. She had significant perioral swelling and mucosal breakdown with serosanguinous drainage. Laboratories were signif- icant for sodium of 131 mEq/L, potassium of 3.1 mEq/L, bicarbonate of 13 mmol/L, creatinine of 2.8 mg/dL, glomerular filtration rate (GFR) of 24 mL/min/1.73 m2, venous pH of 7.23, and lactate of 1.8 mmol/L. Complete blood cell count and liver function tests were within normal limits. Urine toxicology screen was positive for cocaine metabolites. She was admitted to the intensive care unit for intravenous fluids, antimicrobials, and further evaluation of her acute renal failure.
Testing for syphilis, human immunodeficiency virus, hepatitis panel, and complement were negative. Immunologic panel was negative for antinuclear antibody, centromere antibodies, Rheumatoid factor, immunoglobulin M cardiolipin antibodies, ?-2 glycoprotein,
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perinuclear antineutrophil cytoplasmic antibodies, and cytoplasmic antineutrophil cytoplasmic antibodies. Quantitative titers for perinuclear- antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibodies were less than 1:10. Haptoglobin was found to be 320 mg/dL. Blood and urine cultures were all negative.
Over the course of 3 days, she received 7 L of fluid, a sodium bicarbonate infusion, and her serum creatinine improved to 1.5 mg/dL (GFR, 48 mL/min/1.73 m2). The patient’s bicarbonate improved to 30 mmol/L. Nephrology and other consultants involved in her care concluded that levamisole was the culprit. By day 18, her serum creatinine improved to a level of 0.8 mg/dL (GFR, 98 mL/min/1.73 m2). Patients with levamisole exposure typically present with cutane- ous manifestations [6]. A unique finding in this case includes acute
kidney injury.
Levamisole-induced vasculopathy is a diagnosis of exclusion and should be strongly considered with clinical findings, the most classic being cutaneous manifestations such as purpura or bullae [7]. Confirmatory tests with gas chromatography-mass spectrometry are not possible in most cases because the test is not routinely done [8]. This case is important because of her acute renal failure and a nongap metabolic acidosis. After aggressive fluid hydration, her serum creatinine normalized over the course of her stay, and her renal ultrasound was normal. Therefore, her renal injury was thought to be intrinsic injury secondary to levamisole-induced vasculitis. The nongap metabolic acidosis was believed to be due to renal tubular necrosis secondary to acute kidney injury. This resolved with the administration of a sodium bicarbonate infusion. Although rare, levamisole has only been associated with renal failure in one other case. The prevalence of renal injury may be more common but underrecognized [7].
Interestingly, our patient presented with classic raised purpura
that became necrotic over the course of her stay in addition to acute kidney injury and without positive antibodies described in previous literature of levamisole. However, positive antibodies are not specific nor are they required to make the diagnosis, which is done by exclusion. After exclusion of other potential diagnoses by consultants of various specialties including clinical pharmacy, dermatology, nephrology, toxicology, infectious diseases, and intensivists, levamisole-induced vasculitis was deemed to be the most likely culprit of these clinical findings. Acute kidney injury appears to be another clinical complication that needs to be considered in patients given the diagnosis of levamisole-induced vasculopathy through a multiteam approach of patient care.
We report a case of levamisole-associated renal injury, after urine
toxicology confirmed presence of cocaine metabolites. Further studies are needed to link levamisole-adulterated cocaine to acute kidney injury. A multidisciplinary approach is vital to quickly recognize and treat this syndrome without further work-up.
John H. Stroger, Jr. Hospital of Cook County, Department of Pharmacy
Chicago, Illinois, USA E-mail address: abeer.ammar1@gmail.com
Mark Livak, MD
John H. Stroger, Jr. Hospital of Cook County, Department of Emergency
Medicine, Chicago, Illinois, USA E-mail address: mlivak@cookcountyhhs.org
Joanne C. Witsil, PharmD, RN*
John H. Stroger, Jr. Hospital of Cook County, Department of Pharmacy
Chicago, Illinois, USA John H. Stroger, Jr. Hospital of Cook County, Department of Emergency
Medicine, Chicago, Illinois, USA
*Corresponding author. John H. Stroger, Jr. Hospital of Cook County Department of Pharmacy 1901 West Harrison Street
LL-170, Chicago, IL 60612 Tel.: +1 312 864 5826: fax: +1 312 864 9393.
E-mail address: jwitsil@cookcountyhhs.org
http://dx.doi.org/10.1016/j.ajem.2014.08.015
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