Introduction: Immune checkpoint inhibitors (ICIs) have recently become a crucial component of cancer therapy, subsequently triggering a range of immunotherapy-related adverse effects (IRAEs), including hypercalcaemia due to drug-induced sarcoid-like reactions (DISRs). DISRs are defined as systemic granulomatous reactions that occur in relation to the initiation of offending agents. Clinically, DISRs and sarcoidosis both present with bilateral hilar lymphadenopathy, cutaneous lesions, uveitis and hypercalcaemia, thereby posing difficulty in distinguishing one from another. Unlike sarcoidosis, the resolution of symptoms with cessation of the offending drug can favour a diagnosis of DISRs.
Case Summary: We presented a case of a 72-year-old male with severe hypercalcaemia of 3.84 mmol/L following the second cycle of immunotherapy with ipilimumab and nivolumab in the setting of metastatic melanoma with bone metastases. Further investigations demonstrated hilar lymphadenopathy, which was not present in previous imaging, and subsequent hypercalcaemia work-up demonstrated a significantly elevated serum calcitriol level as high as 429 pmol/L. A diagnosis of drug-induced sarcoid-like reactions or DISRs was made on the basis of hypercalcaemia and hilar lymphadenopathy following immunotherapy. Hypercalcaemia was effectively treated with intravenous fluids and medical therapy including a short course of subcutaneous calcitonin, a total of 120 mg of denosumab and oral prednisolone.
Conclusion: DISRs are a rare complication of immunotherapy and may mimic metastases. A temporal relationship between commencement of therapy and progression on clinical imaging is important in making an accurate diagnosis.Calcitriol-mediated hypercalcaemia secondary to DISRs is an important differential diagnosis to hypercalcaemia of malignancy and should be considered in patients who have undergone immunotherapy.Prednisolone should be considered as the next line of treatment after fluid therapy in patients with calcitriol-mediated hypercalcaemia. Prednisolone and denosumab both reach maximum clinical efficacy between 7 and 10 days. Therefore, treatment administration should be spaced out by at least five days to avoid iatrogenic hypocalcaemia.