Update on the diagnosis and treatment of Pneumocystis pneumonia

Abstract

Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk.

Figure 1.

(A) Posteroanterior chest radiograph showing diffuse bilateral predominantly interstitial opacities in a 71-year-old male with Pneumocystis pneumonia in the setting of diffuse large B-cell lymphoma on R-CHOP therapy. (B) Selected noncontrast CT axial image revealing bilateral diffuse ground-glass opacities and associated interlobular and intralobular septal thickening. (C) Selected contrast CT axial image revealing diffuse ground-glass pulmonary infiltrates and innumerable cystic changes predominantly in the upper lobes in a 53-year-old male with Pneumocystis pneumonia in the setting of recently diagnosed HIV.

Figure 2.

Calcofluor white staining of Pneumocystis organisms in a bronchoalveolar lavage (BAL) specimen. A human cell on the right has picked up some of the fluorescent stain. Original size×1000, scale bar is 20 μm.

Figure 3.

Histological features of Pneumocystis pneumonia. (A) Pneumocystis pneumonia in a surgical lung biopsy specimen. The characteristic frothy exudates harboring the organisms fills an alveolus (small arrows) lined by reactive type II cells (large arrow). Internal structures of the organisms can be discerned at high magnification (inset). Hematoxylin-Eosin stain; original ×400 and ×1000 (inset), scale bar is 25 μm. (B) Silver stain of Pneumocystis organisms in a surgical lung biopsy. The organisms appear round or cup-shaped, some show intracystic bodies (lower right). Gomori’s Methenamine Silver stain; original size ×400, scale bar is 25 μm. (C) Immunohistochemical stain for Pneumocystis organisms. Surgical lung biopsy; original size ×1000, scale bar is 25 μm. All three images provided courtesy of Dr Frank Schneider, Department of Pathology, Mayo Clinic, Rochester, MN.