Macrophage Activation in Lupus Nephritis: An Unknown Cause of Severe Hypercalcemia

A Hispanic male in his 20s presented to the hospital with altered mental status and severe hypercalcemia. During his hospitalization, he developed clinical deterioration requiring intubation and ICU transfer. Initial work-up revealed low PTH and PTHrP levels, along with elevated vitamin D 25-OH and 1,25-OH levels. He developed progressive acute kidney injury, and a kidney biopsy later confirmed macrophage activation syndrome (MAS) in a background of type III lupus nephritis. His hypercalcemia resolved following pulse methylprednisolone therapy. Once clinically improved, the patient reported recent use of vitamin D supplementation. After excluding other causes of non-PTH-dependent hypercalcemia with elevated 1,25-OH vitamin D, MAS was determined to be the driver of increased 1-alpha hydroxylase activity, exacerbated by exogenous vitamin D. This is the first reported case of severe hypercalcemia due to MAS from lupus nephritis, compounded by vitamin D supplementation.