Hypercalcemia in Necrobiotic Xanthogranuloma: First Reported Case and Insight Into Treatment

Abstract

Necrobiotic xanthogranuloma (NXG) is a rare systemic and progressive granulomatous disease first described in 1980. Given no established first-line therapy, treatment focuses on the control of skin lesions and associated complications. Despite it being a granulomatous disease, NXG has not been associated with hypercalcemia. About 140 cases of NXG have been reported to date but, to our knowledge, this is the first case to be complicated by hypercalcemia. Our case confirms a granulomatous disease-mediated production of 1α-hydroxylase leading to increased synthesis of 1,25-dihydroxyvitamin D and subsequent hypercalcemia. Based on this pathophysiology, we elected to start systemic glucocorticoids, titrated to clinical and metabolic response. Steroid-sparing agents need to be considered to avoid long-term complications but continue controlling this granulomatous disease. © 2017 American Society for Bone and Mineral Research.

A Multicenter Cross-Sectional Study and Systematic Review of Necrobiotic Xanthogranuloma With Proposed Diagnostic Criteria

“…Of the patients tested in our cohort, 61% had low C4 levels, and 23% had cryoglobulinemia. Finally, we identified a pattern of low 25-hydroxyvitamin D with normal or high 1,25-dihydroxyvitamin D. Granuloma-mediated production of 1α-hydroxylase, a well-documented phenomenon in patients with sarcoidosis, may lead to increased synthesis of 1,25-dihydroxyvitamin D and subsequent hypercalcemia . Given small sample sizes, the associations between these abnormal results of laboratory tests and NXG merit further investigations.…”

“…In the systematic review, the initial search yielded 1199 records, 151 of which were included (Figure). These reports described 201 patients with NXG, with demographics, comorbidities, and clinical features (detailed in the eTable in the Supplement).…”