Seasonal variation in Swedish sarcoidosis patients with severe hypercalcemia

Sarcoidosis associated hypercalcemia (SAHC) is a challenging clinical problem as it can result in severe morbidity. Sunlight exposure and conversion of vitamin D to its active form by macrophages in granulomas have been suggested as possible causes. We aimed to disentangle mechanisms behind SAHC by investigating any associations with season, granuloma burden and lung macrophages. Patients with SAHC were identified from a local cohort. The patients were divided in two groups: mild and severe SAHC. Data on when SAHC occurred, HLA-DRB1 alleles, bronchoalveolar lavage fluid (BALF) macrophages, extrapulmonary manifestations (EPM) and serum angiotensin-converting enzyme (s-ACE) as a marker for granuloma burden were retrieved from medical records. Out of 83 patients with SAHC, severe hypercalcemia was found in 36 patients, 75% of whom presented between May and October (p < 0.001). No seasonal variation was observed for patients with mild hypercalcemia. Elevated s-ACE was more common in patients with severe hypercalcemia (84% of patients), compared to 46% in the group with mild hypercalcemia (p < 0.001). HLA-DRB1*04 was more frequent in the group with severe hypercalcemia, compared to the mild group (67% vs. 32%, p < 0.01). Results support SAHC being associated with sun exposure. Risk factors to be observant of are elevated s-ACE and HLA-DRB1*04.