Case Presentation: A 50 year-old non-smoking Hispanic man with history of interstitial lung disease and recurrent pulmonary infections including recent Pneumocystis jiroveci pneumonia (PJP) presented with 2 weeks history of fever, productive cough, and worsening of dyspnea. The patient reported dyspepsia with oral thrush. During his childhood in Mexico, the patient experienced multiple upper and lower respiratory illnesses. Upon admission, the patient was febrile and hypoxic with SpO2 in the low 80s. CXR showed multifocal pneumonia and chest CT revealed diffuse ground-glass opacities and bilateral bronchiectasis. HIV and acute hepatitis panel were negative, ANA, c-ANCA, p-ANCA also negative. Further hematological studies revealed low immunoglobulins (IgG 368 mg/dl, IgA 24 mg/dl, IgM <20 mg/dl) and severe lymphopenia (CD4+ < 20 cells/mm3). Bone marrow biopsy showed normocellular non-aberrant myeloid dominant bone marrow. Lymphocytes were significantly decreased but included polyclonal mature B cells, NK cells, T-large granular lymphocytes and immunophenotypically normal CD4+ and CD8+ T cells (CD4/CD8 ratio 0.2). During the hospitalization, patient initially improved with antibiotic therapy for community-acquired pneumonia, nystatin for oral candidiasis, and trimethoprim/sulfamethoxazole for PJP prophylaxis. But two weeks from admission he developed fever again. One dose of intravenous immunoglobulins was given. Therapy with cefepime was extended. Cultures remained negative. Lung wedge biopsy showed cytomegalovirus (CMV) pneumonitis, chronic inflammation, and treated PJP. Ganciclovir was started and after one week of treatment, serum CMV DNA decreased from 300K to 105K copies/ml. Patient was discharged with valgancyclovir and PJP prophylaxis in a stable condition to pursue further immunological work-up.
Discussion: We presented a case of an adult male with history of frequent pulmonary infections and PJP who was hospitalized with acute hypoxic respiratory failure due to multifocal pneumonia. The patient was found to have cytomegalovirus pneumonitis and his work up revealed hypogammaglobulinemia, very low CD4 count, and repeated negative HIV test. We have reviewed the literature and found similar clinical presentations of immunodeficiency. Late-onset combined immunodeficiency (LOCID) is a rare recently described condition which represents a subset of common variable immunodeficiency (CVID). LOCID should be considered in patients presenting with opportunistic infection(s) and CD4+ count less than 200/mm3. The infections associated with this condition include CMV colitis, CMV retinitis, toxoplasmosis, cryptosporidiosis, and PJP. Higher prevalence of autoimmune or lymphoproliferative complications with significantly higher morbidity and mortality was also reported in LOCID patients compared to those with CVID without T-cell defects.
Conclusions: The diagnosis and treatment of late-onset combined immunodeficiency represents several challenges and requires multidisciplinary approach. Early diagnosis, genetic studies, specific T-cell immunophenotyping, and close follow-up will help us to understand this condition better and likely benefit patients suspected to have LOCID.