Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis

Abstract

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5–10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13–1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30–100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient’s hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Calcinosis Cutis and Calciphylaxis in Autoimmune Connective Tissue Diseases

“…The rationale for administering these drugs in these types of patients is the inhibition of macrophage proinflammatory cytokine production and reducing calcium turnover [ 4 ]. The human monoclonal antibody targeting the key bone resorption mediator RANKL, denosumab, has been reported to be effective in a patient with multiple sclerosis and metastatic calcinosis cutis due to refractory hypercalcaemia [ 150 ], but its efficacy remains to be explored in patients with calcinosis secondary to connective tissue disease Other drugs, such as warfarin, are currently not recommended [ 143 ].…”

Management of hypercalcaemia due to hypervitaminosis D

“…Denosumab has proven efficacy in treatment of malignant hypercalcaemia, but there is limited evidence for its use in hypercalcaemia in other settings. 5,6 It inhibits bone resorption, one of the mechanisms through which hypervitaminosis D leads to hypercalcaemia. Furthermore, the long half-life of denosumab complements the lengthy anticipated action of vitamin D due to its lipid solubility, potentially preventing rebound hypercalcaemia until normalisation of the vitamin D level.…”