Disseminated Histoplasmosis with Secondary Hemophagocytic Lymphohistiocytosis in a Renal Transplant Recipient on Belatacept-based Immunosuppression

Abstract

Effective post-transplant immunosuppression is essential to induce tolerance to allogeneic tissues and promote long-term graft survival. However, suppression of the immune system significantly increases the risk of opportunistic infections. In addition to the ongoing challenge of balancing graft survival and preventing infections, previous gold-standard calcineurin inhibitor-based immunosuppression also posed an increased risk of nephrotoxicity, cardiac disease, and diabetes. Belatacept is approved as an alternative to calcineurin inhibitor-based regimens. Although belatacept has improved cardiovascular and metabolic adverse events in renal transplant patients’ but it carries a notably higher risk of long-term graft survival and renal toxicity, similar to calcineurin inhibitor-based regimens. However, there may be an increased risk of infections with its mechanism of action. We present a case of a 62-year-old female who developed disseminated histoplasmosis 18 months after being on belatacept-based immunosuppression after a deceased donor renal transplant for end-stage renal disease secondary to focal segmental glomerulosclerosis. Grocott Methenamine Stain (GMS) of peripheral blood smear showed intracellular yeast in neutrophils, consistent with histoplasmosis. Disseminated histoplasmosis was confirmed with positive bronchoalveolar lavage (BAL) and urine culture. The patient later developed hemophagocytic lymphohistiocytosis (HLH) secondary to immunosuppression and disseminated histoplasmosis. The patient succumbed to the disease despite maximal medical therapy. To our knowledge, there is one other published report of disseminated histoplasmosis in a patient with belatacept-based immunosuppression. The unique feature of this case is the development of HLH secondary to disseminated histoplasmosis while on belatacept. Further research is needed to evaluate the need for antifungal prophylaxis in patients on belatacept therapy.