Common variable immunodeficiency in a patient with recurrent bronchitis presenting with pneumococcal sepsis

LEARNING OBJECTIVE 1: Consider immunodeficiency in a patient with a history of recurrent infections LEARNING OBJECTIVE 2: Distinguish common variable immunodeficiency (CVID) from other immunodeficiencies using history and laboratory testing CASE: A 29 year-old male presented with a 2-day history of fever, dyspnea, and pleuritic chest pain. On admission, he was febrile, diaphoretic, and tachycardic; CBC showed leukocytosis (WBC 33,000/ μL) and chest X-ray showed left lower lobe opacity. Blood cultures were positive for Streptococcus pneumonia. Labs revealed he was in acute kidney injury (AKI) with a creatinine of 1.6 mg/dL (baseline 0.7); his urinalysis showed proteinuria and hematuria. He denied cough, meningismus, or gastrointestinal and urinary symptoms. Further questioning revealed a 16-year history of 1-2 bronchitis episodes a year. He clinically improved and blood cultures cleared within 48 hours of hydration and treatment with intravenous (IV) antibiotics. Given his history of recurrent bronchitis, current sepsis, and AKI with proteinuria and hematuria, an extensive lab work-up was performed, including HIV, Hepatitis B and C, ANA, p-ANCA, c-ANCA, anti-GBM, complements, and immunoglobulins. This was remarkable for an IgA level of <6.67 mg/dL (normal 53- 334), IgG of 36.1 mg/dL (normal 53-334), and IgM <4.17 mg/dL (normal 53-334). Titers for diphtheria, pertussis, tetanus, hemophilus influenza B, and streptococcus pneumonia showed absent response. Based on his markedly reduced immunoglobulin levels, deficient response to immunization, and absence of any other identifiable immunodeficiency, a tentative diagnosis of CVID was made. Repeat immunoglobulin titers showed persistently low IgA and IgM but an increase in IgG from 31.6 to 519. Because of the IgG increase, he was given Tdap and pneumococcal vaccines and post-vaccination titers will be sent shortly to gauge response and confirm diagnosis. If the diagnosis is confirmed, he will receive his first dose of IVIG. DISCUSSION: CVID is a rare entity, affecting 1 in 50,000 patients. It is a primary antibody deficiency that can lead to a host of pathologies, including recurrent infections, chronic lung disease, gastrointestinal issues, autoimmune disorders, and malignancy. It is defined as low serum levels of IgG, IgA, and IgM with poor or absent antibody production and exclusion of other causes of immunoglobulin deficiency. Sinopulmonary infections (like otitis media, sinusitis, bronchitis, and pneumonia) are the most common presentations of patients with CVID, occurring in up to 73% of patients. Pneumonia in CVID can be severe and frequently requires IV antibiotics. Complications of pneumonia include sepsis, pleurisy, bronchiectasis, and empyema. When considering immunodeficiency, it is vital to distinguish between CVID and other immunodeficiencies. Age of onset is important as patients over 15 years rarely present with X-linked (Bruton's) agammaglobulinemia (characterized as decreased serum immunoglobulins and absent B cells) or X-linked hyper-IgMsyndrome. Serum immunoglobulin levels are essential to distinguish CVID from hyper-IgM syndromes and selective IgA deficiency. Medication history is important as certain drugs can induce hypogammaglobulinemia such as anti-malarials, steroids, and sulfasalazine. This case illustrates a severe complication as the presentation of a rare medical problem. It is essential to consider a broader differential in a patient with recurrent infections, and to differentiate CVID from other immunodeficiency syndromes.