Active Crohn Disease and Hypercalcemia Treated with Infliximab
Objective: To report a case of 1,25-dihydroxyvitamin D–mediated hypercalcemia caused by active Crohn disease that improved with infliximab therapy.
Methods: We present the clinical and laboratory findings and describe the clinical course of a patient who had hypercalcemia during Crohn disease exacerbations. The literature is reviewed regarding 1,25-dihydroxyvitamin D production in Crohn disease, and the 3 cases of hypercalcemia in individuals with Crohn disease reported in the literature are described.
Results: A 50-year-old man with long-standing Crohn disease treated with multiple bowel resections presented for take-down ileostomy. He was hypercalcemic and had suppressed parathyroid hormone and parathyroid hormone–related peptide levels. Histopathology of the resected ileostomy site and adjacent small bowel indicated active Crohn disease. Hypercalcemia promptly resolved after a few days of treatment with intravenous glucocorticoids. One month later, hypercalcemia recurred in the presence of an inappropriately high 1,25-dihydroxyvitamin D level and increased urinary calcium and serum angiotensin-converting enzyme levels. The serum and urinary calcium levels became normal with infliximab therapy. Three previous reports of hypercalcemia caused by active Crohn disease describe effective treatment with glucocorticoids. This is the first report of successful response to infliximab in this setting.
Conclusion: Hypercalcemia mediated by 1,25-dihydroxyvitamin D in the setting of Crohn disease may respond to glucocorticoid-sparing immunomodulators.

Vitamin D–mediated hypercalcemia from activated macrophages within granuloma is a well-recognized complication of sarcoidosis and mycobacterial infections. A similar mechanism of hypercalcemia has been described in lymphoma. Hypercalcemia has also been reported in other granulomatous diseases including Wegener granulomatosis, eosinophilic granuloma, coccidioidomycosis, candidiasis, and histoplasmosis.

Crohn disease is a granulomatous disease associated with multiple perturbations of calcium metabolism. Many affected individuals exhibit 25-hydroxyvitamin D deficiency and secondary hyperparathyroidism. Decreased bone mineral density and increased bone turnover have also been demonstrated in patients with Crohn disease, the mechanism of which is only partially related to chronic glucocorticoid use.

To our knowledge, hypercalcemia secondary to active Crohn disease has only been reported in 3 cases. In these cases, the 1,25-dihydroxyvitamin D level paralleled the clinical activity of Crohn disease and rapidly responded to relatively high doses of systemic or enteral glucocorticoids.

We present a case of long-standing Crohn disease in a man with 1,25-dihydroxyvitamin D–induced hypercalcemia that responded to infliximab monotherapy.