Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis

Abstract

Background: Ectopic calcification is inappropriate biomineralization of soft tissues occurring due to genetic or acquired causes of hyperphosphataemia and rarely in normophosphataemic individuals. Tumoral Calcinosis (TC) is a rare metabolic bone disorder commonly presenting in childhood and adolescence with periarticular extra-capsular calcinosis. Three subtypes of TC have been recognised: primary hyperphosphataemic familial TC (HFTC), primary normophosphataemic familial TC and secondary TC most commonly seen in chronic renal failure. In the absence of established treatment, management is challenging due to variable success rates with medical therapies and recurrence following surgery.

Aim: We outline the successful treatment approaches in four children with TC (2 normophosphatemic TC, 2 HFTC) aged 2.5-10 years at initial presentation.

Cases: Patient 1 (P1) presented at 10 years with a painless lump behind the right knee, P2 with swelling of the right knee anteriorly at 9 years, P3 and P4 with pain and swelling over the right elbow at 5 and 2.5 years respectively. All patients were of Black African-Caribbean origin and were previously reported to be fit and well with no family history of TC.

Results: P1, P2 had normophosphataemic TC and P3, P4 had HFTC with genetically confirmed GALNT3 mutation. All four patients had initial surgical resection with TC confirmed on histology. P1 had complete surgical resection with no recurrence at 27 months post-operatively. P2 had significant overgrowth of the tumour following surgery and was subsequently successfully managed with 25 % topical sodium metabisulphite (total duration of 8 months with a 4 month gap during which there was recurrence). P3 had post-surgical recurrence of TC on the right elbow and a new lesion on left elbow which resolved with oral acetazolamide monotherapy (15-20 mg/kg/day). P4 had recurrence of right elbow lesion following surgery and developed an extensive new hip lesion on sevelamer therapy which resolved completely with additional acetazolamide therapy (18-33 mg/kg/day). Acetazolamide was well tolerated with normal growth for 5 years in P3 and 6.5 years in P4 and no recurrence of lesions.

Conclusion: The frequent post-surgical recurrence in TC and successful medical therapy on the other hand indicates that medical management as first line therapy should be adopted. Monotherapies with topical 25 % sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated.

Keywords: Calcification; Calcinosis; Carbonic anhydrase inhibitor; FGF23; Hyperphosphataemia; Metabisulphite.