P0640 - Diagnosis of a Combined Immunodeficiency in an Elderly Patient with Recurrent Pneumonia

Introduction:
This case highlights the unusual presentation of a combined immunodeficiency in an elderly patient and demonstrates the importance of considering immunodeficiency in adults with recurrent infections.

Case Description:
A 63-year old man with a history of coronary artery disease and nasopharyngeal squamous cell carcinoma status post surgery, radiation, and chemotherapy was admitted to the ICU with respiratory failure and septic shock secondary to left lower lobe pneumonia. Notably this patient had been admitted with pneumonia four times in the previous five months, with one occurrence complicated by S. pneumoniae bacteremia. CT chest without contrast at time of admission showed left lower lobe pneumonia, multifocal bronchiolitis and mediastinal lymphadenopathy felt to be reactive in the setting of evidence of prior granulomatous disease in the chest (Figure 1). WBC at time of admission was 14.1 K/uL with an ANC of 13.2 K/uL but an ALC of only 100. Serum immunoglobulin levels revealed: IgG 165 (range 600 – 1,560 mg/dL) and IgA 53 (range 90 – 410 mg/dL). Vaccine titers showed poor antibody response — five out of twenty pneumococcal serotypes were within the protective range. Flow cytometry demonstrated an absolute / CD4 helper T cell lymphopenia of 29.9% (32 – 62) and 126 (320 – 2976). HIV was negative. Given his presumed combined immunodeficiency, he received three administrations of 50g IVIG, after which his IgG level rose from 165 to 659. The patient’s clinical course improved and he was discharged. Three weeks after discharge IgG level was 583. He was recommended to continue monthly IVIG infusions and have periodic monitoring of his ALC / CD4-T cell level.

Discussion:
The differential diagnosis for a recurrent pneumonia is broad, including atypical infections, pulmonary obstruction, parenchymal anatomic abnormalities, underlying interstitial lung disease, and immunodeficiency. In this case, the latter was suggested by clinical severity. Secondary immunodeficiency disorders, such as medication side effect, renal disease, and malnutrition are more commonly identified in adults than primary immunodeficiency disorders. Our patient, however, did not have clear evidence of an underlying secondary cause of his immunodeficiency. While cancer therapies may often contribute to secondary immunodeficiency, the monoclonal antibody, cetuximab, our patient received has not been linked to hypogammaglobulinemia or lymphopenia. Primary immunodeficiency disorders tend to escape detection until adulthood, especially those with relatively mild clinical severity, particularly antibody defects, like common variable immunodeficiency (CVID). Due to the variable clinical manifestations of CVID, there is often a diagnostic delay despite its prevalence of 1 in 25,000 people.

Conclusion:
What makes this case presentation unusual and challenging is the detection of not only a humoral immunodeficiency but also a cellular defect seen with the idiopathic CD4 lymphopenia, suggesting the presence of a late-onset combined immunodeficiency.