Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to compare the efficacy of thiabendazole (TBZ) with that of levamisole in the treatment of murine lupus. Both drugs were given in the presence of the T-dependent antigen dinitrofluorobenzene (DNFB). Female NZB/NZW F1 mice 2 months of age were treated with TBZ + DNFB, levamisole + DNFB, and drug solvents, once a week, from 2 through 9 months of age. All mice were then left without further treatment for an additional 2 months. TBZ/DNFB treatment has significantly reduced proteinuria, glomerular deposition of immunoglobulins and complement components, and development of the proliferative glomerulonephritis characteristic of untreated NZB/NZW mice. Levamisole/DNFB treatment, on the other hand, had little to no effect on the course of the disease when compared with untreated NZB/NZW mice. These studies clearly demonstrate the effectiveness of the TBZ/antigen therapy in maintaining renal function in autoimmune diseased mice.
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PMID:Thiabendazole-induced suppression of renal damage in a murine model of autoimmune disease. 623 53

The United States Public Health Service Administration is alerting medical professionals that a substantial percentage of cocaine imported into the United States is adulterated with levamisole, a veterinary pharmaceutical that can cause blood cell disorders such as severe neutropenia and agranulocytosis. Levamisole was previously approved in combination with fluorouracil for the treatment of colon cancer; however, the drug was withdrawn from the U.S. market in 2000 because of the frequent occurrence of agranulocytosis. The detection of autoantibodies such as antithrombin (lupus anticoagulant) and an increased risk of agranulocytosis in patients carrying the human leukocyte antigen B27 genotype suggest that toxicity is immune-mediated. In this perspective, we provide an historical account of the levamisole/cocaine story as it first surfaced in 2008, including a succinct review of levamisole pharmacology, pharmacokinetics, and preclinical/clinical evidence for levamisole-induced agranulocytosis. Based on the available information on levamisole metabolism in humans, we propose that reactive metabolite formation is the rate-limiting step in the etiology of agranulocytosis associated with levamisole, in a manner similar to other drugs (e.g., propylthiouracil, methimazole, captopril, etc.) associated with blood dyscrasias. Finally, considering the toxicity associated with levamisole, we propose that the 2,3,5,6-tetrahydroimidazo[2,1-b]thiazole scaffold found in levamisole be categorized as a new structural alert, which is to be avoided in drug design.
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PMID:Immune-mediated agranulocytosis caused by the cocaine adulterant levamisole: a case for reactive metabolite(s) involvement. 2239 19

Levamisole-induced vasculitis is a relatively new entity in people who use cocaine. We describe a 44-year-old woman with a history of cocaine use who presented with a complaint of a painful rash of 2-3 month's duration on her extremities, cheeks, nose, and earlobes. She had not experienced fever, weight loss, alopecia, dry eyes, oral ulcers, photosensitivity, or arthralgia. Examination revealed tender purpuric eruptions with central necrosis on her nose, cheeks, earlobes, and extremities. Laboratory investigations revealed neutropenia, an elevated erythrocyte sedimentation rate (ESR), presence of lupus anticoagulant, low complement component 3 (C3), and presence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). A urine toxicology screen was positive for cocaine, and gas chromatography-mass spectrometry was positive for levamisole. Skin biopsy showed leukocytoclastic vasculitis and small vessel thrombosis. Necrotic lesions of the nose led to its self-amputation. Large bullae on the lower extremities ruptured, leading to wound infection and extensive necrosis that required multiple surgical debridements. When necrosis progressed despite debridement, bilateral above-knee amputation of the legs was performed. Once new lesions stopped appearing, the patient was discharged home. Two months later, she had a recurrence related to cocaine use. To the best of our knowledge, this is only the second reported case of levamisole-induced vasculitis that required above-knee amputation.
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PMID:Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: an extensive case with necrosis of skin, soft tissue, and cartilage. 2318 90

Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically present with a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis involving the extremities, trunk, nasal tip, digits, cheeks, and/or ears. A history of cocaine abuse can be elicited. Histologic features include microvascular thrombi and/or leukocytoclastic vasculitis involving small vessels of the superficial and deep dermis. Epidermal involvement is variably seen. Laboratory findings include leukopenia, neutropenia (including agranulocytosis), elevated erythrocyte sedimentation rate, normal coagulation studies, and positive autoantibodies including perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibody, and lupus anticoagulant. Differential diagnosis includes other microscopic vasculitides, and clinical and laboratory correlation with histologic findings is essential. Lesions typically resolve with the cessation of cocaine use. Because of the treatment implications and rising incidence of this entity, rapid and accurate diagnosis is essential.
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PMID:Levamisole-Induced Vasculitis: A Characteristic Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine. 2623 Jun

Cocaine-induced vasculitis is a rare complication found in drug abusers. It occurs due to cocaine adulterated with levamisole. Levamisole was once used as a chemotherapy and immunomodulator for different conditions. One of the side effects of this medication is necrotizing vasculitis which has been reported in the US and Puerto Rico. Here we present another case of cocaine induced vasculitis in Puerto Rico. We describe a 43-year-old female with past medical history of bronchial asthma, migraine, and crack smoking who presented to the emergency room due to blood in her urine for 5 days. She also reported fever, chills, and fatigue. At the physical exam she had a right knee ulcer with swelling erythema, warmth, and pain. Also, she had retiform purpuric plaque lesions in her ears, bilaterally. Eroded plaques with elevated borders at left foot and finger dorsum were also present. Laboratory workup was positive for cocaine. The patient showed leucopenia and microcytic anemia with a normal absolute neutrophil count in her cell blood count. Blood cultures, urine cultures, and ulcer cultures were negative. Urinalysis was positive for proteinuria and hematuria. Also, the patient had positive perinuclear anti-neutrophil cytoplasmic antibody, cytoplasmic anti-neutrophil cytoplasmic antibody, and antinuclear antibody tests and elastase specificity. She showed negative anticardiolipin and lupus anticoagulant antibodies. Her complement levels were decreased. The punch biopsy of her ear showed superficial thrombosis of superficial vascular plexus with perivascular lymphocytic infiltrates and deeper sections showed epidermal necrosis and necrotizing vasculitis. She was started on a high dose of steroids, but could not complete the treatment because she escaped from the hospital before finishing her treatment.
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PMID:Cocaine-induced vasculitis: is this a new trend? 2779 26