INTRODUCTION: Pneumocystis jiroveci pneumonia (PJP) is a common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Granulomatous PJP, often associated with pulmonary nodules, is an unusual manifestation of this infection. We describe a case of granulomatous PJP associated with a CD4+ lymphocyte count over 200 cells/mm3, developing in the context of immune reconstitution with highly active antiretroviral therapy (HAART).
CASE PRESENTATION: A 40-year old male presented to hospital in March 2006 with progressive cough, dyspnea, and 20 kg weight loss over several weeks. Chest imaging revealed diffuse bilateral ground glass infiltrates, and PJP was confirmed by bronchoalveolar lavage (BAL). The patient was subsequently found to be HIV positive, with a CD4+ count of 22 cells/mm3, HIV viral load greater than 5 million copies/mL, and evidence of HIV dementia. A 21-day course of trimethoprim-sulfamethoxazole and prednisone resulted in a good clinical response. He was also started on HAART shortly before completing treatment for PJP. Two months after initiating HAART, his CD4+ count had risen to 359 cells/mm3 and viral load was 31,000 copies/mL. Due to an allergic reaction to sulfamethoxazole, PJP prophylaxis was discontinued. In July 2006, Routine chest radiography was performed at a university HIV clinic, revealing multiple bilateral pulmonary nodules. Subsequent chest computed tomography (CT) confirmed the presence of multiple discrete pulmonary nodules, most prominent in the apices (See Figure). The patient was asymptomatic, compliant with therapy, and his CD4+ count was 266 cells/mm3. The patient developed malaise, night sweats, and progressive cough over the next year, prompting a pulmonary referral in July 2007. CD4+ counts had been consistently above 200 cells/mm3 for the previous seven months, with undetectable viral loads. Chest CT revealed progression of the nodules. BAL, transbronchial biopsies and transthoracic biopsy were negative. However, his symptoms progressed, with drenching night sweats and worsening cough, wheeze, and dyspnea. Thoracoscopic lung biopsy was performed in November 2007. Pathology confirmed the presence of hyalinized necrotizing granulomas containing Pneumocystis organisms. Despite a CD4+ count of 266 cells/mm3, ongoing symptoms prompted treatment with atovaquone, with subsequent clinical but not radiographic improvement.
DISCUSSIONS: Granulomatous PJP is an uncommon presentation of Pneumocystis infection, occurring in 3–5% of HIV cases (1). Respiratory and systemic symptoms are common. BAL and transbronchial biopsy, sensitive for PJP in HIV-infected patients, are often negative, and diagnosis is usually made by open lung biopsy or autopsy (1). Reports of granulomatous PJP have consistently demonstrated CD4+ counts below 200 cells/mm3. Immune reconstitution inflammatory syndrome (IRIS) is a clinical deterioration after the initiation of HAART, despite improvement in markers of HIV infection. Seen in 10–25%, IRIS typically occurs within eight weeks of therapy, in patients with a brisk CD4+ response from a pre-treatment value below 50 cells/mm3. The pathogenesis relates to unmasked infection or an inflammatory response to nonreplicating antigens; granuloma formation is common due to T-lymphocyte activation (2). IRIS due to PJP has been rarely reported, occurring two weeks to seven months after initiation of HAART.
CONCLUSION: Granulomatous PJP mimics other nodular lung diseases seen in HIV-infected patients. Our patient developed pulmonary nodules after CD4+ recovery with HAART, suggesting Pneumocystis-associated IRIS. Our case is unique in that there was a significant delay in symptoms after the radiographic demonstration of pulmonary nodules, without a clear inciting factor for the development of symptoms and in the setting of an adequate CD4+ count. Finally, the clinical improvement with directed PJP therapy is evidence for active infection, either alone or in association with IRIS.
DISCLOSURE: Sachin Pendharkar, No Financial Disclosure Information; No Product/Research Disclosure Information