An Unusual Case of Hypercalcemia Due to Graft-Versus-Host Disease

Hypercalcemia is a common disorder with a wide differential and is most commonly related to malignancy and hyperparathyroidism. Hypercalcemia is a rarely reported consequence of graft-versus-host disease (GVHD) and may be related to a granulomatous manifestation of the common stem cell transplantation procedure.

A 67-year-old woman with a history of allogenic stem cell transplantation due to myelodysplastic syndrome presented to the bone marrow transplant clinic with dysphagia, muscle aches, and rash. She was found to have an extremely increased calcium and 1,25-dihydroxyvitamin D levels, which were ultimately corrected with administration of steroids and zoledronic acid.

While uncommon, granulomatous disease can lead to hypercalcemia via the activation of 1α-hydroxylase within macrophages, which, in turn, activates 1,25-dihydroxyvitamin D leading to an increased serum calcium level. GVHD is a common, variably presenting complication of bone marrow transplantation. Granulomatous processes related to GVHD may mediate hypercalcemia in patients with both increased calcium and 1,25-dihydroxyvitamin D levels.

This is a rare cause of calcitriol-mediated hypercalcemia associated with GVHD. There have been cases of granulomas associated with GVHD, and this could potentially lead to ectopic production of calcitriol. We deemed GVHD to be a likely cause of the patient's calcitriol-mediated hypercalcemia because we did not find another etiology that fit the clinical findings. Physician awareness of this complication and the appropriate workup will allow future researchers to properly elucidate the etiology of this rare complication.