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Wegener's Granulomatosis With Peripheral Eosinophilia

1993; Elsevier BV; Volume: 104; Issue: 4 Linguagem: Inglês

10.1378/chest.104.4.1290

1931-3543

Meir Krupsky, Zvi Landau, Beatriz Lifschitz‐Mercer, P Resnitzky,

Vascular Anomalies and Treatments

A patient with Wegener's granulomatosis (WC) diagnosed by ultrasound-guided transthoracic biopsy of a pulmonary nodule is reported. The case is atypical because of marked eosinophilia in the peripheral blood and the pleural effusion. The granulomatous infiltrate of the lung showed the classic picture of WG without eosinophils. The patient responded dramatically to treatment with steroids and cyclophosphamide. This variant form of WG poses problems in its distinction from Churg-Strauss syndrome, and the differential diagnosis between these two entities is discussed. A patient with Wegener's granulomatosis (WC) diagnosed by ultrasound-guided transthoracic biopsy of a pulmonary nodule is reported. The case is atypical because of marked eosinophilia in the peripheral blood and the pleural effusion. The granulomatous infiltrate of the lung showed the classic picture of WG without eosinophils. The patient responded dramatically to treatment with steroids and cyclophosphamide. This variant form of WG poses problems in its distinction from Churg-Strauss syndrome, and the differential diagnosis between these two entities is discussed. Churg-Strauss syndrome; Wegener's granulomatosis Wegener's granulomatosis (WG) is a distinct clinicopathologic entity characterized by vasculitis and necrotizing granulomas capable of involving all organs. The disease primarily affects the upper and lower respiratory tracts and causes a glomerulonephritis with various degrees of disseminated vasculitis involving both small arteries and veins.1Fauci AS Haynes BF Kats E The spectrum of vasculitis: clinical, pathologic immunologic and therapeutic considerations.Ann Intern Med. 1978; 89: 660-676Crossref PubMed Scopus (1030) Google Scholar, 2Cupps TR Fauci AS The vasculitides. WB Saunders, Philadelphia1981: 1-211Google Scholar, 3Fauci As Haynes BF Katz P Wolff SM Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years.Ann Intern Med. 1983; 98: 76-85Crossref PubMed Scopus (1702) Google Scholar By contrast, Churg-Strauss syndrome (CSS) is characterized by the presence of asthma, a history of atopy, and eosinophilia in conjunction with a systemic necrotizing vasculitis.4Chumbley LC Harrison EG DeRemee RA Allergic granulomatosis and angiitis (Churg-Strauss syndrome): report and analysis of 30 cases.Mayo Clin Proc. 1977; 52: 477-484PubMed Google Scholar We report a case that clinically and morphologically falls within the spectrum of WG. However, this case was characterized by significant peripheral blood eosinophilia and pleural involvement in the form of a pleural effusion with high eosinophil count in the absence of parenchymal eosinophilic infiltration. A 43-year-old man was admitted to the hospital because of ankle arthritis. He had been well until four weeks earlier, when pain and swelling developed in the ankle joints. The patient smoked one pack of cigarettes daily for 20 years and lost 16 kg in weight during the year before hospitalization. On admission, his temperature was 36.6°C. Examination of the lung revealed a right pleural effusion. The left ankle was swollen, warm, and tender. Moderate effusion and a few petechial lesions were present. A small vesicle was noted on the malleolar aspect of the ankle. Pain and mild swelling also were noted in the right ankle. Because of the patient's complaints of severe burning heel sensations, an electromyographic examination was performed, showing a pattern consistent with mononeuritis multiplex. The chest x-ray films and a computed tomography scan of the lungs (Fig 1) showed bilateral multiple nodules with well-defined margins and a right pleural effusion in association with a cavitary subpleural mass. Sinus x-ray films showed mucosal thickening of the right maxillary sinus. The erythrocyte sedimentation rate was 117 mm. The leukocyte count was 9.5 × 109/L, and the total eosinophil count was 1.04 × 109/L. Urinalysis gave a + + test for protein; the sediment contained 5 white cells per high power field, more than 100 red blood cells per high power field, 5 to 10 granular casts per high power field, and occasional red blood cell casts. Serum C-reactive protein concentration was 119 mg/L. Concentrations of polyclonal IgG were 1,290 mg/dl and of IgE were 320 IU/ml (normal, 100 IU/ml). Rheumatoid factor and antinuclear antibody were not present and complement levels were normal. Antineutrophil cytoplasmatic autoantibodies were present in low titer. Pulmonary function studies showed very mild nonreversible, obstructive airflow dysfunction without evidence of restriction. The diffusion capacity for carbon monoxide was normal. An arterial blood gas level determination (with the patient breathing room air) revealed normal Po2 and Pco2 values. Pleural fluid analysis showed an exudate with 15.1 × 109/L cells, 61 percent of which were eosinophils; no tumor cells were seen. Coincidental parasitic infestations and infectious fungal processes were excluded by special stains and cultures. Transthoracic, trephine needle biopsy of the right subpleural excavated mass lesion was performed under ultrasound guidance. The histologic results of the biopsy (Fig 2) showed regions of necrosis traversing consolidated pulmonary parenchyma, a necrotizing granulomatous process, and adjacent microangiitis without tissue eosinophilia (Fig 3).FIGURE 3Fibroblastic proliferation with inflammatory infiltrates and many multinucleated giant cells at the periphery of necrotic areas in WG.View Large Image Figure ViewerDownload (PPT) On the third day after admission, large hemorrhagic blisters developed on the left ankle area which progressed to destructive punched-out ulcers. Skin biopsy specimens showed nonspecific leukocytoclastic vasculitis. An oral regimen consisting of 2 mg/kg/d of cyclophosphamide and 1 mg/kg/d of prednisone was given as initial therapy. Using this combination of immunosuppressive therapy, a prolonged remission without serious side-effects resulted. Serial chest x-ray film studies demonstrated clearing of the pulmonary nodules and disappearance of the pleural effusion. During induction of remission, the leukocyte count as well as the eosinophils returned to normal values. After eight weeks of treatment, antineutrophil cytoplasmatic autoantibody titers were negative, and the erythrocyte sedimentation rate as well as the serum C-reactive protein returned to normal values. The treatment was gradually tapered and finally discontinued after 14 months. While not receiving treatment for six months, the patient remains free of any symptoms or signs of disease. The diagnosis of WG in our case was based on the finding of upper and lower respiratory tract involvement, renal disease, variable degrees of disseminated vasculitis involving joints, skin, and nervous system, and a classic pathologic picture by lung biopsy. The patient had no history of allergy, asthma or bronchospastic disorder. The pulmonary findings in the case presented include subpleural cavitary mass and marked eosinophilic pleural effusion. Pleural involvement in the form of a pleural effusion can be seen in about 10 percent of patients with WG, whereas pleural masses caused by inflammatory pseudotumors have been reported only rarely.5England DM Unger JM Pleural-based mass in an elderly man with arthralgia.Chest. 1987; 91: 603-604Crossref Scopus (3) Google Scholar The major differential diagnosis in this case is allergic granulomatosis and angiitis, CSS. Frequently these two enties share clinical and histopathological features. Clinical definition of CSS requires the presentation of allergic history, asthmatic bronchitis, peripheral blood eosinophilia in excess of 1.5 × 109/L, and systemic vasculitis involving two or more extrapulmonary organs.4Chumbley LC Harrison EG DeRemee RA Allergic granulomatosis and angiitis (Churg-Strauss syndrome): report and analysis of 30 cases.Mayo Clin Proc. 1977; 52: 477-484PubMed Google Scholar Churg-Strauss syndrome is associated with transient patchy infiltrates and does not form nodules. Renal involvement in CSS appears to be less frequent and less prominent, whereas death from CSS occurs due to cardiac involvement.6Lanham JG Elkon KB Pusey CD Hughes GR Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome.Medicine. 1984; 63: 65-81Crossref PubMed Scopus (1071) Google Scholar In contrast, an allergic background is no more frequent in WG than in the general population, and asthma is rare. Single or multiple nodules or masses, with or without cavitation, are the most frequent manifestations, whereas diffuse or patchy infiltrates are rather rare and should alert the physician to the possibility of an alveolar hemorrhage. The positive antineutrophil cytoplasmatic autoantibody test in our patient, which decreased after treatment, is frequent in WG and unusual in CSS.7Case Records of the Massachusetts General Hospital (case 17 1976). N Engl J Med 1976; 294:944-51Google Scholar8Jennette JC Falc RJ Anti neutrophil cytoplasmatic autoantibodies and associated disease: a review.Am J Kidney Dis. 1990; 15: 517-529Abstract Full Text PDF PubMed Scopus (283) Google Scholar Peripheral blood eosinophilia is only an occasional and only minimal finding in WG. Yousem and Lombard9Yousem SA Lombard CM The eosinophilic variant of Wegener's granulomatosis.Hum Pathol. 1988; 19: 682-688Abstract Full Text PDF PubMed Scopus (65) Google Scholar reported four cases of an unusual histologic variant of WG characterized by prominent tissue infiltrates of eosinophils in the absence of peripheral blood eosinophilia. In contrast, almost all patients with CSS have, at some point in their clinical course, the distinguishing characteristics of a profound peripheral blood eosinophilia as well as intense tissue eosinophilia. In these diseases, eosinophilia may be a result of a hypersensitivity reaction to exogenous antigens. The respiratory tract may be the portal of entry of some as yet unknown provocative agent or agents. In CSS, IgE levels range between 500 to 1,000 IU/ml4Chumbley LC Harrison EG DeRemee RA Allergic granulomatosis and angiitis (Churg-Strauss syndrome): report and analysis of 30 cases.Mayo Clin Proc. 1977; 52: 477-484PubMed Google Scholar and are probably a response to some unrecognized extrinsic allergen. In WG, IgE levels are within normal levels or slightly elevated. The significance of increased IgE levels is unknown. It may reflect a reaction towards an extrinsic allergen or may reflect a response toward material released by injured lung or other tissue affected by the granulomatous reaction.10Wolf SM Fauci AS Horn RG Dale DC Wegener's granulomatosis.Ann Intern Med. 1984; 83: 513-521Google Scholar We conclude that WG with peripheral blood eosinophilia, but with no parenchymal eosinophilia, is a distinct variant of the disease and is differentiated from CSS on the basis of clinical and morphologic findings, as well as on the basis of the patient's response to specific immunosuppressive therapy.