Pulmonary Wegener's granulomatosis.

The clinical course, radiographic features and pathology of 18 cases of Wegeners granulomatosis with pulmonary involvement are presented. Glomerulitis and generalized vasculitis were not features of this series. Nodular pulmonary densities characterized the chest radiographs. Five cases showed improvement in one lung with progression in another, thus dif­ ferentiating the disease from neoplasia. Vasculitis, rarely with fibrinoid necrosis, characterized the pathology. Cytotoxic drugs caused sustained clinical improvement in six patients and appear to be the treatment of choice. In troduction This report presents additional data on the clinical and pathological features of Wegener’s granulomatosis as seen in a series of 18 patients with pulmonary in­ volvement. Twelve patients of this group have already been described.8 The thera­ peutic efficacy of cytotoxic or immunosup­ pressive drugs is evidenced by the con­ tinued control of the disease in the majority of our patients receiving these agents. H istorical Background Klinger,9 in 1931, first described two pa­ tients with necrotizing granulomatous in­ flammation and angiitis which he regarded as a variant of polyarteritis nodosa. Wegener, in 1936 and 1939,12 recorded several cases and recognized the clinical and pathological features of the syn­ drome which now bears his name. Fahey et al4 and Godman and Churg6 further de­ fined the disease as consisting of (1) necrotizing granulomas of the respiratory tract, (2) generalized angiitis, (3) necrotiz­ ing glomerulitis and (4 ) disseminated granulomas. Waltons report of 56 cases illustrated the dismal outlook for most cases; the average survival in that series being five months.11 The majority of cases succumbed to progressive renal failure. Hood et al, in 1956, recorded five cases of pulmonary Wegeners granuloma, which did not develop systemic illness and whose course was relatively benign compared with the disseminated disease.7 While two or three of these cases were probably cases of eosinophilic granuloma, several appear to represent examples of the localized pulmo­ nary form of necrotizing granulomatosis. Carrington and Liebow, in 1966, firmly established the localized pulmonary form of Wegeners granulomatosis as a distinct entity, often separable on clinical grounds from the systemic variety by the relatively indolent evolution and absence of severe renal involvement.3 2 4 9 250 P A T C H E FSK Y AND ISR A E L C linical F indings The ages of the patients ranged from 27 to 72 years, being comprised of 12 men and 6 women. No unusual environmental or occupational features could be elicited. No patients showed evidence of rheumatoid arthritis or other “collagen disease.” The onset of clinical symptoms was most often slow and insidious, but in five pa­ tients (cases 1, 3, 6, 8 and 16) the onset was explosive, one patient expiring of res­ piratory failure after a brief illness with the diagnosis being made only at autopsy. Six patients were asymptomatic at the time of diagnosis, their disease having been de­ tected by routine chest X-ray examination. Cough and dyspnea were major manifesta­ tions in seven patients and three patients presented with an acute febrile illness. One patient’s presenting symptom was a subcutaneous nodule; this feature was an early manifestation in another. Pharyngitis was the presenting symptom in one patient, while upper respiratory tract involvement developed subsequent to the pulmonary lesions in three cases. No patient exhibited signs of renal disease. Hemolytic anemia with thrombocytopenia developed in one patient. The tuberculin test was positive in seven patients and negative in five patients. Cul­ ture of sputum specimens in six cases for acid fast and fungi were negative. The characteristic radiological features in these cases were nodular pulmonary densi­ ties. These were unilateral in six cases and bilateral in five cases. In five patients, there was cavitation of the mass lesions; three cases showed diffuse bilateral infiltration. In five patients, the masses enlarged in one lung while improving in the other. Pathology The most complete account of the patho­ logic findings in pulmonary Wegeners granulomatosis is that of Carrington and Liebow.3 Material from our studies closely conforms with their description. The gross lung specimens were person­ ally examined in five cases: one lobectomy, two excision biopsies and two autopsies. The lesions in the lung parenchyma ap­ peared as tan-white nodules of varying sizes, with discrete but not encapsulated margins. Cavitation and necrosis was pres­ ent in two cases. Most often the lesions re­ sembled rounded “white infarcts,” or had a consistency much like that of lymphoid tissue. Microscopically, the hallmark of the lesion was a necrotizing inflammatory pro­ cess with vasculitis. In most cases, there was also superimposed infarct-like necrosis. This was especially prominent in the cavitating lesions. The dominant cell popu­ lation was made up of lymphocytes and plasma cells. In several cases there was a distinctly nodular, germinal center-like con­ figuration of the inflammatory infiltrate. However, this was only a superficial re­ semblance as these nodules were composed of relatively mature plasma cells and lymphocytes, without actively dividing, or phagocytic reticulum cells. In one case, plasma cells were so numerous that the initial diagnosis was erroneously thought to be plasma cell granuloma (case 4 ), while in another, prominence of lympho­ cytic cells prompted an initial pathologic diagnosis of malignant lymphoma (case 7). Eosinophils and polymorphonuclear leuko­ cytes were present in all cases in varying amounts, with eosinophils being prominent in one case (case 2). Young, plump fibroblasts and reticulum cells were present throughout several cases. Discrete sarcoid-like granulomas were rare, but scattered giant cells were seen in several instances. Typical caseous necrosis with prominent giant cell reaction was not seen. The periphery of the lesions usually showed a granulation tissue-like response;