INCREASED RISK OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH WEGENERS GRANULOMATOSIS

Combining cyclophosphamide (Cy) and corticosteroids has dramatically i mproved the prognosis of Wegener's granulomatosis (WG). But this treat ment carries the risks of severe infectious complications and drug tox icity. During a 10-month period, we observed 6 cases of Pneumocystis c arinii pneumonia (PCP) in 23 patients with biopsy-proven WG and renal involvement. These 23 patients were enrolled in a multicenter controll ed clinical trial designed to evaluate the efficacy and safety of eith er intermittent high-dose pulse Cy or daily oral low-dose Cy in combin ation with oral prednisone. Mean delay of onset of PCP was 2.5 months after the beginning of the immunosuppressive therapy. In all cases, th e diagnosis of PCP was established by cytological examination of bronc hoalveolar lavage fluid. None of the patients experienced severe leuko penia at the time of diagnosis, but the mean lymphocyte count decrease d to 495/mm3 (range 100 to 830/mm3) and 2 patients had inverted CD4/CD 8 T-cell ratios. Renal function was significantly impaired (creatinine mia = 493.5 vs 195.4 micromol/l; p = 0.03) in the 6 patients presentin g PCP vs those without. High-dose co-trimoxazole therapy was successfu l in 3 patients, but 3 others who required mechanical ventilation died Treatment of WG with daily prednisone and either pulse or oral Cy may have contributed to higher rates of PCP in the past than previously t hought and, therefore, patients currently receiving such a regimen may be at greater risk for PCP. For these patients, this opportunistic in fection must remain highly suspect in order to reach a diagnosis earli er and rapidly initiate treatment. In addition, recommendations for pr ophylactic therapy are needed.