Introduction: (Anti-TNF-α) therapy is widely used for the treatment of inflammatory diseases. The most frequent adverse events induced by anti-TNF-α therapy are infections and malignancies. However, reports of paradoxical sarcoidosis-like reactions are on the rise in patients receiving anti-TNF-α.
Clinical case: A 61-year old woman, with a medical history of sero-positive rheumatoid arthritis on Adalimumab treatment (anti-TNF-α), was referred to our outpatient clinic by her general practioner for a non-parathyroid hormone (PTH) driven hypercalcemia. Her calcium and PTH concentrations were respectively reported as 2.65 mmol/l and 3.0 ng/l. Additional testing confirmed low PTH with a normal 25-hydroxyvitamin D but an elevated 1,25-dihydroxyvitamin D (
Conclusion: 1,25-dihydroxyvitamin D induced hypercalcemia is a rare or underreported complication of anti-TNF-α therapy. An extensive work-up with exclusion of TBC and lymphoma is indicated. Although reports of sarcoidosis-like granulomatosis as a complication of anti-TNF-α are increasingly common, it remains a rare complication (1/2800). Nevertheless, it has to be included in the differential diagnosis of a 1,25-dihydroxyvitamin D induced hypercalcemia. In most cases, discontinuation of anti-TNF leads to recovery(4,5).
|Laboratory test||Results||Reference value|
|Calcium||2.60 mmol/l||2.22.55 mmol/l|
|Phosphorous||1.18 mmol/l||0.811.45 mmol/l|
|Albumin||40.4 g/l||3954 g/l|
|PTH||2.0 ng/l||1565 ng/l|
|25-hydroxyvitamin D||24.4 ng/ml||2030 ng/ml|
|1,25-dihydroxyvitamin D||133.1 ng/l||2080 ng/l|
|Creatinine||0.78 mg/dl||0.510.95 mg/dl|
|24h calciuria||12.2 mmol/24u||2.57.5 mmol/24u|
References: 1. Watrin A, Royer M, Legrand E, Gagnadoux F. Severe hypercalcemia revealing sarcoidosis precipitated by etanercept. Rev Mal Respir. 2014 Mar;31(3):2558.
2. Olivier A, Gilson B, Lafontaine S, Pautot JX, Bindi P. Pulmonary and renal involvement in a TNFα antagonist drug-induced sarcoidosis. Rev Med Interne. 2012 May;33(5):e257.
3. Tsevi YM, Aydin S Durez P, Labriola L. Life-threatening hypercalcemia and acute kidney injury induced by etanercept. Nephrol Ther. 2018 Nov;14(6):478482.
4. Daïen CI, Monnier A, Claudepierre P, Constantin A, Eschard JP, Houvenagel E et al. Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. Rheumatology (Oxford) 2009;48:8836.
5. Tong D, Manolios N, Howe G, Spencer D. New onset sarcoid-like granulomatosis developing during anti-TNF therapy: an under-recognised complication. Intern Med J. 2012 Jan;42(1):8994.
21 Oct 2019
Belgian Endocrine Society