Hypercalcemia Secondary to Immune Reconstitution Inflammatory Syndrome in an HIV-Infected Individual With Mycobacterium avium Complex

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon cause of hypercalcemia in HIV-infected patients recently started on highly active antiretroviral therapy (HAART). It is hypothesized that increased granulomatous formation due to IRIS leads to an overproduction of calcitriol. High levels of calcitriol, then, can lead to significant hypercalcemia. We present the case of a 63-year-old male with HIV off HAART presented to the emergency room for confusion, frequent falls, and cough. His CD-4 count was noted to be below 35 cells/µL (255-2,496). Over the course of the hospitalization, the patient was found to have disseminated Mycobacterium avium complex (MAC) infection and was initiated on HAART. Initiation of HAART was followed by an increase in calcium up to 14.1 mg/dL. The hypercalcemia did not respond to either Calcitonin or Pamidronate. Consideration was then given to IRIS in the setting of MAC infection leading to increased granulomatous formation. Calcium levels normalized within three days of therapy after initiation of prednisone for the treatment of IRIS. It is thought that an increase in CD-4 counts leads to the recovery of an immune response. This can lead to granulomatous inflammation. An increase in granuloma formation can cause hypercalcemia due to overproduction of calcitriol via increased 1𝛼-hydroxylase activity from macrophages. Our case report describes IRIS-mediated hypercalcemia in an HIV-infected individual with MAC infection. This unusual cause of severe hypercalcemia should be considered in differential diagnoses for immunocompromised patients in the appropriate setting. Prompt treatment of IRIS with glucocorticoids can lead to the resolution of hypercalcemia.