DOI: 10.1097/01.rhu.0000120897.08819.ac
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PMID: 17043477
Issn Print: 1076-1608
Publication Date: 2004/04/01
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Excerpt
The patient is a 41-year-old woman with a 3-year history of asthma (treated with salmeterol, zafirlukast, and fluticasone therapy). Four weeks after an exacerbation of the chronic sinusitis, despite treatment with gatifloxacin and steroids, the patient developed a disabling, multisystem complex of signs and symptoms. The complex consisted of left episcleritis, erythematous rash of the lower extremities associated with swelling, and painful subcutaneous nodules over the feet and volar aspects of the third and fourth fingers. In addition, there was left elbow and bilateral knee pain and swelling, as well as numbness with paresthesias in the distribution of the right ulnar nerve.
The patient denied any history of arthralgias, rashes, headaches, seizures, or focal weakness. Laboratory evaluation showed increased Westergren sedimentation rate (56 mm/hr), C-reactive protein (CRP; 5.2), white cell count (14,170), and percent eosinophils (40.7%). Biochemical profile, urinalysis, and chest radiographs were normal. The rheumatoid factor was positive (109.8). Antinuclear antibodies were negative. C-ANCA was positive but P-ANCA was negative. Biopsies of the subcutaneous right third finger nodule revealed leukocytoclastic vasculitis and necrobiotic granuloma suggestive of allergic granulomatosis.
Laryngoscopic examination showed an erythematous palate and an epiglottis without polyps or mucosal lesions. Nerve conduction studies and electromyography revealed early bilateral ulnar neuropathy consistent with mononeuritis multiplex.
The patient was treated with high doses of steroids (100 mg prednisone) with subsequent symptomatic and laboratory improvement. Attempts, however, to taper steroids below 60 mg per day resulted in reoccurrence of the subcutaneous nodules, and new mononeuritis multiplex in the left upper and lower extremities. Additionally, there were increases in sedimentation rate, CRP, and eosinophil counts. Because of the intractability, the severity of the neuropathic and cutaneous symptoms, and the potential toxicity of high steroid dosages, 1.5 mg/kg cyclophosphamide was initiated. Three months later, an attempt to maintain the improvement with methotrexate was unsuccessful as a result of the reoccurrence of symptoms. Subsequently, 3 mg/kg infliximab initially, later increased to 6 mg/kg, resulted in remarkable symptomatic and serologic improvement. The treatment enabled reduction of steroids, as early as after the second infusion, to less than 10 mg per day. The patient continues to improve.
The diagnosis of Churg-Strauss granulomatosis was based on the following: a history of asthma, peripheral eosinophilia, extrapulmonary vasculitic lesions with necrotizing granulomas, increased acute-phase proteins, mononeuritis multiplex, arthritis, positive rheumatoid factor, and C-ANCA (possibly reflecting an immunologic epiphenomena).
Tumor necrosis factor (TNF), released by macrophages, is a critical inflammatory mediator leading to activation of vascular endothelium, the inflammatory cascade, and release of other proinflammatory cytokines. Etanercept and infliximab are 2 of the commercially available TNF inhibitors.
The use of infliximab has been reported in similar disorders. Gause et al.1,2 recently described the use of infliximab in combination with immunosuppressive therapy in 6 patients with refractory Wegener granulomatosis (WG). There were pulmonary, renal, and retroorbital granulomas. Infliximab was given at a dosage of 3 mg/kg and 5 mg/kg.
