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We and others have proposed that desensitisation, vaccination, or inhalation of antigens by asthmatic patients may trigger Churg-Strauss syndrome (CSS).1-4 Few observations of vasculitis occurring immediately after massive inhalation of a presumed antigen have been published.2 We describe here four patients who experienced acute onset of systemic vasculitis after massive antigen inhalation.
Case 1: Several hours after massively inhaling dark diesel fumes, a 55 year old man developed rapid onset dyspnoea, sinusitis, and high fever, which regressed with short term steroid treatment. After three months he complained of bilateral foot drop, which was found to be due to mononeuritis multiplex in the left peroneal nerve upon clinical examination. The erythrocyte sedimentation rate was 72 mm/1st h, white blood cell count was 16.12×109/l,3 with 1870 eosinophils, serum creatinine 170 μmol/l; proteinuria 0.7 g/day, and microscopic haematuria. Specific anti-myeloperoxidase perinuclear labelling antineutrophil cytoplasmic antibodies (ANCA) were detected (30 IU). A neuromuscular biopsy showed necrotising vasculitis of the vasa nervorum and small sized muscle vessels, together with granulomas. Renal biopsy showed patchy necrotising glomerulonephritis. We retained the diagnosis of Wegener's granulomatosis. Despite corticosteroids and intravenous cyclophosphamide, the patient developed left orchitis and underwent plasma exchanges and received oral cyclophosphamide. Clinical and biological signs improved, except serum creatinine which persisted at 150 μmol/l. After three years, receiving daily prednisone and cyclophosphamide, the patient remains in clinical remission.
Case 2: A 38 year old woman presented in August 1990 with acute dyspnoea and purpura. While in the countryside during the harvest season, she had inhaled grain dust and developed dyspnoea within a few hours and red spots on her legs in the following days. In December 1990, digital vasculitis occurred in all the fingers of both hands. Supra-aortic angiography showed bilateral occlusion in the radial and ulnar arteries; microaneurysms were seen in digital arterioles. A skin biopsy detected vasculitis at the dermal-hypodermal junction with mononuclear cell and eosinophil infiltrates in the artery walls without leucocytoclastic or necrotising vasculitis. Ulnar artery biopsy showed complete occlusion of the artery lumen without evidence of vasculitis. CSS was diagnosed and prednisone was prescribed, which was progressively tapered over 18 months. Eight years later, the patient remains well.
Case 3: A 53 year old woman who worked in a bakery for 30 years had had asthma for 20 years, with skin tests positive for flour antigens. In March 1988, 10 days after massively inhaling flour dust (a flour sack broke), she experienced acute fever and mild tenderness in her arms and right foot, with motor and sensory mononeuritis multiplex in the left peroneal nerve upon clinical examination. ANCA were not tested. Neuromuscular biopsy showed microvasculitis with perivenular lymphoplasmacytic infiltrates. CSS was diagnosed and prednisone was prescribed, which was tapered within 18 months and maintained at 5 mg/day to control asthma. The patient remains asymptomatic nine years later.
Case 4: A 27 year old man was admitted in September 1980 for acute dyspnoea and high fever that occurred a few hours after massively inhaling cereal dust in a store that raised and sold pigeons. These signs regressed after oral prednisone treatment, but one month later he developed vascular purpura on his legs. A bilateral basal opacity was seen on chest xray examination. ANCA were not tested. Skin biopsy showed leucocytoclastic vasculitis in small and medium sized vessels, without fibrinoid necrosis. Prednisone (1 mg/kg/day) was prescribed, then tapered and discontinued when all symptoms resolved. After one month, the same symptoms reappeared after another exposure to pigeons. A chest roentgenogram showed extensive bilateral basal nodules, and pulmonary biopsy disclosed vasculitic lesions, with fibrinoid necrosis of arteriole and venule walls. Despite treatment with prednisone the patient developed multiple cranial nerve disease. He received oral cyclophosphamide, but no improvement occurred and the patient underwent 13 plasma exchanges. The cranial nerve disease and chest nodules were regressive. Cyclophosphamide was discontinued after 12 months and the patient remains disease-free 18 years later.
Causative and precipitating agents of CSS have rarely been identified; we have noted that onset is sometimes associated with desensitisation, vaccination, exposure to various drugs or environmental substances, or too rapid steroid tapering.4 In case 4 (previously published2), the abundance of actinomycetes in pneumocytes might suggest that they caused the vasculitis.
Stephens et al described bronchoallergic aspergillosis evolving to CSS,4 and Orridset al reported a case of CSS induced by free base cocaine.5 Some drugs have been associated with the occurrence of CSS, particularly recently zafirlukast.6Rapid onset of microscopic polyangiitis within a few hours or days after massive antigen inhalation has not been described previously. Small vessel vasculitis mechanisms implicate ANCA, neutrophils and proinflammatory cytokines, and their interactions with external antigens.7 8 In our patients, the occurrence of vasculitis may reflect hypersensitivity to the inhaled antigen, because they had daily professional exposure or contact with diesel fumes (case 1), harvest grain dust (case 2), flour (case 3), or pigeons and/or cereal dust (case 4) and because massive antigen inhalation was the only potential triggering event identified before the onset of systemic vasculitis. Such overwhelming antigen exposure probably contributes, in these patients, to systemic dissemination and the acute onset of systemic vasculitis progressive immune complex formation and deposition.