A 29 year-old male with no past medical or surgical history presented with one year of fevers, a 30 pound weight loss, and fatigue. He had been evaluated by his primary care doctor and a hematologist multiple times throughout the past year without the etiology of his fevers elucidated.
His exam was notable for pallor, bilateral rales, and a distended abdomen. His laboratory values showed leukopenia, thrombocytopenia, transaminitis, as well as elevated LDH and alkaline phosphatase levels. A CT of the chest, abdomen, and pelvis revealed bilateral pleural effusions, hepatosplenomegaly, and diffuse lymphadenopathy. All culture data along with serologies for the viral hepatitides, HIV, CMV and EBV were unrevealing. A lymph node biopsy as well as pleural biopsy were obtained and were non-diagnostic for leukemia/lymphoma but revealed a T-cell predominant infiltrate and complete lack of mature B cells. Immunoglobulin studies revealed hypogammaglobulinemia. He was notably non-immune to the measles, mumps, and HBV. This compilation of findings pointed to the diagnosis of Common Variable Immunodeficiency (CVID). He was treated with intravenous immunoglobulin (IVIG) and was discharged on cyclosporine, antibiotic prophylaxis and periodic IVIG. Following discharge, he continued to have recurrent fevers and pleural effusions. A PET scan revealed increasing lymphadenopathy, prompting an FNA of a retroperitoneal lymph node mass. Pathology confirmed a diagnosis of diffuse large B-cell lymphoma (DLBCL) arising in the background of CVID. He was started on R-CHOP and showed significant clinical improvement.
Discussion:
CVID is a rare disorder affecting roughly 1 in 50,000 people. The cause is unclear, though certain genetic mutations can increase one’s risk of developing it. The disease is characterized by markedly low immunoglobulins, poor or no response to vaccines, as well as impaired memory B-cell formation resulting in recurrent infections (most commonly bacterial sinusoidal infections). These patients are at an increased risk for developing chronic lung disease, gastrointestinal and liver disorders, granulomatous inflammation, and lymphoid hyperplasia. CVID also increases the risk for developing malignancies, most commonly non-Hodgkin’s lymphoma. The cornerstone of treatment is IVIG. Additionally, steroids or immunomodulatory medications can be used to treat any concurrent autoimmune/inflammatory conditions.
Conclusions:
This case highlights the importance of diagnostic persistence when typical etiologies for a particular presentation have not revealed a diagnosis or a patient’s symptoms do not improve with treatment. In our patient, recurrent fevers coupled with negative infectious workup and hypogammaglobulinemia resulted in the discovery of an underlying immune disorder. However, despite appropriate treatment, the patient’s symptoms did not resolve, and the additional diagnosis of DLBCL was made.