Blau syndrome initially presenting with hypercalcemia: a case report and literature review

Blau syndrome is a rare granulomatous autoinflammatory disease typically characterized by a triad of polyarthritis, uveitis, and dermatitis. It is caused by either an inherited autosomal dominant pathogenic variant or a de novo pathogenic variant in NOD2. In this report, we present an 11-month-old boy with Blau syndrome who initially presented with calcitriol-mediated hypercalcemia. Severe hypercalcemia was controlled with intravenous fluids, diuretics, calcitonin, and a short course of corticosteroids. Following resolution of the hypercalcemic episode, the patient gradually developed the full clinical spectrum of Blau syndrome, including the classic triad, along with hepatosplenomegaly, lymphadenopathy, and bone marrow involvement. Trio genome sequencing identified a de novo heterozygous pathogenic variant in NOD2. Following the genetic diagnosis, corticosteroids and methotrexate were initiated to control the disease. This is the first reported case of Blau syndrome presenting with hypercalcemia as an initial manifestation, preceding the development of the classic triad. This case underscores the importance of considering Blau syndrome in the differential diagnosis of early-onset hypercalcemia of unknown etiology. Molecular genetic testing should be pursued in such cases to facilitate an accurate and timely diagnosis and appropriate management.