JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
drug use in the United States has been steadily increasing and in 2013 up to 24.6 million Americans reported the use of an illicit drug in the past month. 1 Cocaine abuse is widespread in our society with over 5 million Americans using some form of the drug. 2
Levamisole is an immunomodulatory drug, developed in the 1960s, that was initially used as an adjuvant agent in the treatment of colorectal cancer and rheumatoid arthritis. 3,6 The first case of cutaneous necrotizing vasculitis caused by levamisole was described in 1978. 4 It was subsequently banned due its severe side-effect profile which included agranulocytosis and vasculitis. 5,6 It is now currently used as an anthelmintic agent in veterinary medicine. 6 In recent years, levamisole has been used as a bulking agent in cocaine due to its physical similarities and its ability to potentiate the effects of cocaine. It has been thought to potentiate the stimulatory effects of cocaine by increasing the amount of dopamine in the brain and having cholinergic effects. According to U.S. Drug Enforcement Agency (DEA) estimates, up to 69% of cocaine imported into the United States is contaminated with levamisole. 7 In 2009 the Centers for Disease Control and Prevention (CDC) first reported the link between agranulocytosis and cocaine abuse 5 , and in 2010, the first case of levamisole-induced vasculitis in a cocaine abuser was reported. 8 Over the following years, a rise in the number of cases of levamisole-induced vasculitis has been reported. According to previous reports, levamisole-induced cutaneous vasculitis is more commonly seen in women with amedian age of 45 years. 9 The pathogenesis of levamisole-induced necrotizing vasculitis is still unknown, but some postulate that immune complexes are formed. A common theory is that the induced autoantibodies stimulate immune cells to release cytotoxic agents causing cellular destruction. 10 With the widespread use of levamisole-adulterated cocaine, early recognition of levamisole-induced vasculitis is important in order to prevent recurrent episodes in the future that can lead to significant complications.
Figure 1: Right Arm: Large, retiform, centrally necrotic, purpuric plaque on the right upper extremity with surrounding background of inflammation and erythema.
CLINICAL PRESENTATION AND DIAGNOSIS
Levamisole-induced Vasculitis (LIV) presents with a unique clinical picture that is characterized by reticulated purpuric lesions and hemorrhagic bullae with concurrent central necrosis occurring most commonly on the lower extremities and ears. 9 The predilection for the ears is a specific finding for LIV and is thought to possibly arise due to the lower temperature and smaller vessels favoring the deposition of immune complexes. 10 These necrotizing vasculitic lesions with an erythematous base arealso foundon theupper extremities, trunk, face, nose, andoral region. 11 Arthralgias of the large joints are commonly reported clinical manifestations. Many patients also have constitutional symptoms including fever, weight loss, night sweats, myalgia, and malaise. 12 Rhinorrhea and recurrent sinusitis have also been reported, most likely related to the nasal inhalation of cocaine. Levamisole has immunomodulatory effects that lead to the increase of multiple autoantibodies. Elevated Perinuclear ANCA (p-ANCA) has the strongest association in LIV, with cytoplasmic ANCA (c-ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase-3 (anti-PR3) and human neutrophil elastase antibodies also elevated in some patients. Studies have also shown elevated titers of lupus anticoagulant, antinuclear,
Figure 2: Hemorrhagic, purpuric plaque with surrounding rim of inflammatory erythema involving the right helix and lobule.
Figure 3:
Numerous, faintly hyperpigmented to violaceous macules
scattered over mid and upper back.
J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017 141
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