Lymphocyte surge as a marker for immunorestitution disease due to Pneumocystis jiroveci pneumonia in HIV-negative immunosuppressed hosts

Pneumocystis jiroveci (previously known as Pneumocystis carinii f. sp. hominis) pneumonia (PcP) [1] is a wellknown opportunistic infection affecting immunocompromised hosts, especially patients infected with HIV. However, with the rising number of patients receiving immunosuppressive therapy, PcP is being increasingly recognised in immunosuppressed hosts who are not infected with HIV [2]. For instance, one previous study found PcP in 3.4–43% of solid organ transplant recipients not infected with HIV, with an especially high incidence among patients on long-term steroid therapy [3]. Though the exact pathogenesis of PcP remains obscure, it has been suggested that immunorestitution disease (IRD) contributes to the manifestation of PcP [4]. Reported here are seven cases of PcP manifesting as IRD in HIV-negative immunosuppressed hosts. Between July 1995 and June 2003, 35 patients were diagnosed with PcP at the Queen Mary and United Christian Hospitals in Hong Kong based on the presence of radiologically proven pulmonary infiltrations, the presence of P. jiroveci in bronchoalveolar lavage fluid, and symptoms consistent with the clinical picture of PcP infection, such as fever, cough, and dyspnoea. Twenty-five of the patients were HIV positive; 19 of these patients were newly diagnosed and had not begun highly active antiretroviral therapy (HAART) at the time of presentation. The remaining 10 patients were HIV-negative immunosuppressed subjects with renal diseases (glomerulonephritis in 2, renal transplantation in 1), haematological conditions (immune thrombocytopenic purpura in 2), autoimmune diseases (bullous pemphigoid in 1, pemphigus vulgaris in 1, juvenile rheumatoid arthritis in 1), and solid organ tumour (thymoma in 1). The case of one patient with Cushing’s disease was reported previously [4]. The immunosuppressive therapy administered to these patients consisted of an endogenous steroid in one, steroid therapy in three, and a combination of steroids and cytotoxic treatment in five. Altogether there were 22 male and 13 female patients, and their ages ranged from 7 to 75 years (mean ± SD, 43.3 ±13.9 years). Thirty of them were ethnic Chinese, four were Thai and one was Filipino. The most common clinical presentations of PcP were dyspnoea (80%), fever (80%), non-productive cough (54.3%), and productive cough with clear sputum (31.4%). A minority of the patients presented with chest pain (8.6%), general malaise (8.6%), anorexia (8.6%), dizziness (5.7%), sore throat (5.7%), and diarrhoea (5.7%). Oxygen desaturation with SaO2 <90% while on ambient air occurred in three of the patients. Chest radiographs revealed bilateral lesions in 30 patients, whereas five patients had unilateral involvement. An alveolar pattern of radiographic lesions was shown in 19 patients, whereas interstitial radiographic lesions were found in the remaining 16 patients. Unilateral pleural effusion was noted in one patient upon admission. Pneumothorax was not observed in any of our patients on presentation. None of the 35 patients had received prior chemoprophylaxis for PcP. High-dose intravenous cotrimoxazole was given to 30 patients, and intravenous pentamidine was initiated in the remaining five patients. We defined IRD as an acute symptomatic presentation of PcP temporally related to the recovery of the immune system (as evidenced by an increase in the absolute lymphocyte count), which resulted in immunopathological V. C. C. Cheng . I. F. N. Hung . B. S. F. Tang . K. Y. Yuen (*) Division of Infectious Diseases, Centre of Infection, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China e-mail: kyyuen@hkucc.hku.hk Tel.: +852-28554892 Fax: +852-28551241