Silica can trigger autoimmune diseases via production of autoantibodies (1). We describe a case of pulmonary silicosis complicated by microscopic polyangiitis.
A 42-year-old Caucasian male was admitted to the hospital with hematuria associated with fevers, night sweats and fifteen pounds weight loss of three months duration. Simultaneously, he had a non-productive cough. Past medical history was only significant for cigarette smoking. He was not on any medications. He worked as a stonecutter, cutting blue sandstone in his backyard for 15 years without using any protective equipment. He was afebrile, normotensive and non-distressed. Oxygen saturation was 96% on room air. Chest auscultation revealed crackles diffusely. Digital clubbing was present. Urinalysis showed red blood cells and red blood cell casts. Serum creatinine was 3.5 mg/dL and hemoglobin was 8.6 g/dL. Erythrocyte sedimentation rate was 146 mm/h and antinuclear antibodies titer was 1:320. Anti double-stranded DNA antibodies, anti-glomerular basement membrane antibodies and antistreptolysin-O antibodies were all negative. Antineutrophil cytoplasmic antibodies against myeloperoxidase (P-ANCA) titer was positive at 1:640. Chest radiograph showed diffuse micronodular infiltrates along with calcified hilar and mediastinal lymphadenopathy (figures 1 and 2). Transbronchial biopsies revealed fibro-inflammatory changes involving the alveolar septae. Examination under polarized light demonstrated refractile material (figure 3). Energy Dispersive X-ray Analysis indicated the presence of silica. A percutaneous kidney biopsy demonstrated necrotizing crescentic glomerulonephritis, a renal form of microscopic polyangiitis (figure 4). Diagnosis: pulmonary silicosis with P-ANCA associated microscopic polyangiitis. The patient was treated with prednisone and cyclophosphamide with resolution of his hematuria and stabilization of his renal function.
Silicosis is a disease produced by inhalation of crystalline silica, most commonly quartz. Blue sandstone contains 50% quartz (2). Silica containing compounds have an adjuvant effect on immune responses and are potent stimulators of lymphocytes and monocytes or macrophages. Silicosis has been associated with different connective tissue diseases. Branwell in 1914 reported a relation between scleroderma and silica exposure. Caplan in 1953 described an association between rheumatoid arthritis and silicosis. Silica exposure has been associated with a high prevalence of autoantibodies such as antinuclear antibodies, rheumatoid factor and antineutrophil cytoplasmic antibodies (ANCA) (1,3). The antigens targeted by ANCA have been identified as either myeloperoxidase (P-ANCA) or proteinase-3 (C-ANCA). Patients with ANCA-associated vasculitis have 4.4 times greater odds ratio for silica exposure compared with control subjects (4). Six cases of suspected microscopic polyangiitis have been described in patients with pulmonary silicosis before 1990 with unknown ANCA titers (5). Three cases of P-ANCA associated microscopic polyangiitis have been reported in patients with pulmonary silicosis since 1994 (5,6,7).
We report a case of pulmonary silicosis with P-ANCA associated microscopic polyangiitis. Our case is unique in that both diagnoses are definitively proven histologically. Exposure to silica should be considered in the history of patients with autoimmune diseases. Furthermore patients with pulmonary silicosis may develop ANCA-associated vasculitis in extrapulmonary sites.
Theodossis Zacharis, None.