The Uncommon Combination of Common Variable Immunodeficiency, Macrophage Activation Syndrome, and Cytomegalovirus Retinitis Asghar Aghamohammadi, 1 Hassan Abolhassani, 1 Armin Hirbod-Mobarakeh, 1 Fariba Ghassemi, 2 Shervin Shahinpour, 1 Nasrin Behniafard, 1 Ghazal Naghibzadeh, 1 Amir Imanzadeh, 1 and Nima Rezaei 1,3 Abstract Common variable immunodeficiency (CVID) is a heterogeneous group of disorders with varied immunologic phenotypes and clinical manifestations. Patients with CVID are mainly characterized by decreased serum im- munoglobulin levels, and increased susceptibility to recurrent bacterial infections, autoimmune disorders, and malignancies. Here we present a CVID patient who has developed a clinical polyclonal lymphocytic infiltration phenotype associated with severe and irreversible pancytopenia with unknown etiology. Progressive unilateral loss of vision and cytomegalovirus retinitis indicated the cause of patient’s pancytopenia. Introduction C ommon variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by a lack of immunoglobulin production, antibody decreases, and in some cases T-lymphocyte dysfunction (1,2). In CVID patients, a number of conditions occur with increased fre- quency, and the main categories are: recurrent bacterial in- fections, autoimmune diseases, polyclonal lymphocytic infiltrations, enteropathy, and cancers (3–7). Despite several studies in the field of CVID showing the pathophysiology and genetic defects of the disease, its fundamental cause still re- mains unknown for the majority of patients (2,8–13). The management of CVID has improved with immuno- globulin replacement therapy, and prophylactic antibiotics have increased survival of patients in recent decades (14,15). However, this treatment resulted in a higher frequency of non-infectious clinical complications in these patients (16). The main causes of these complications are immune dysre- gulation, T-cell deficiency, and a breakdown in central and peripheral mechanisms of tolerance induction or mainte- nance (17,18). Cytomegalovirus (CMV) is a ubiquitous DNA virus and a member of the Herpesviridae family that frequently causes life-threatening infections in immunocompromised patients (19,20). Although the presence of severe viral in- fections such as varicella (21), herpes simplex virus (HSV), measles (22), and other chronic enteroviral infections (23) in CVID have been reported, severe CMV disease is an infre- quent complication in CVID patients (24). Isolated CMV lymphadenitis, pneumonia, and gastrointestinal involve- ment have been reported in these patients (24). Here we describe a patient with CVID that presented with CMV infection leading to rhegmatogenous retinal detachment and pancytopenia. Case Report The patient is a male with a history of gynecomastia, umbilical hernia, and a lack of tonsils at birth. He is the first child of related parents, with no family history of immuno- deficiency. He was fully vaccinated without any complica- tion and was quite healthy until the age of 2 y, when he presented with severe recurrent diarrhea. He experienced recurrent episodes of upper and lower respiratory tract in- fections such as pneumonia, sinusitis, and otitis media, which required antibiotic therapy and hospitalization. At the age of 4 y, he was referred to the departments of infectious disease and clinical immunology of the Children’s Medical Center Hospital for further evaluation. He was diagnosed with CVID based on panhypogammaglobulinemia (low IgG, IgA, and IgM; Table 1), poor responses to vaccines (anti- tetanus antibody = 0.1, anti-diphtheria antibody = 0.1, and anti-pneumococcal antibody = 100 to 120), and after the ex- clusion of other antibody deficiencies associated with well- defined single gene defects. He received regular intravenous 1 Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, 2 Eye Research Center, Farabi Hospital, and 3 Molecular Immunology Research Center, and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. VIRAL IMMUNOLOGY Volume 25, Number 2, 2012 ª Mary Ann Liebert, Inc. Pp. 161–165 DOI: 10.1089/vim.2011.0060 161