Clinical Features and Treatment Outcomes of Cutaneous Calciphylaxis in Paediatric Patients: A Systematic Review

To the Editor,

Calciphylaxis is a rare and life-threatening multisystemic condition characterized by calcium deposits in small blood vessels leading to painful ulcerations. ¹ The worldwide mortality rate for calciphylaxis varies from 40% to 80%. ² The current literature focuses on calciphylaxis in adults; thus, our study aimed to describe the presentation and management of calciphylaxis in children.

MEDLINE, Embase, and PubMed were searched on March 2024 using “calciphylaxis” as a search term according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, without restrictions (CRD42024493870). Article screening and extraction were performed by 3 reviewers (L.A.M., C.K.Z., and M.P.). Patients ≤18 years with calciphylaxis were included. Treatment outcomes for calciphylaxis were classified based on the lesion clearance: complete response (CR), partial response (PR), and no response (NR). L.A.M. performed a pooled analysis (verified by C.K.Z.; Supplementary Figure 1).

The search yielded 2333 entries. After removing duplicates and full screening, 19 articles met inclusion criteria, encompassing 19 cases (mean age at diagnosis: 12 ± 5.4 years; 9 females; Supplementary Table 1). Violaceous ulcers were the most common presentations, appearing in 52.6% of cases. All patients with ulcers had lower limbs involvement. Most patients reported pain (73.7%; Supplementary Table 2). Juvenile and type 2 diabetes mellitus were each identified once (10.5%). Obesity was documented in 3 cases (15.8%), and 2 were underweight (≥third percentile; 10.5%). Congenital disorders were reported in 42.1% of cases. Seven were diagnosed with hyperparathyroidism (36.8%). Renal impairment was reported in 16 cases (84.2%), with posterior urethral valves (37.5%) being the most commonly reported aetiology (Supplementary Table 3 and Supplemental Figure 2). Overall, 5 patients died from calciphylaxis progression (26.3%). Intravenous (IV) sodium thiosulfate (STS) was beneficial in all its reported cases (CR = 1; PR = 4; NR = 0). Pamidronate led to a range of responses (CR = 1; PR = 0, NR = 1). Wound care response varied (CR = 3, PR = 0, NR = 4), with sulfadiazine silver dressing (CR = 1, PR = 0, NR = 1) and topical antiseptic solutions (CR = 2, PR = 0, NR = 0) reporting best outcomes. Both oral and IV steroids were inefficient (CR = 0, PR = 1, NR = 3). All responder necessitated adequate calcium-phosphorus product control. Notably, 1 false-negative biopsy led to treatment discontinuation, supporting other studies that highlight the limited diagnostic accuracy of single biopsies for calciphylaxis, sometimes requiring subsequent excisional biopsies. Nonetheless, paediatric calciphylaxis remains exceedingly rare and necessitates histopathological confirmation^3,4 (Supplementary Table 4).

Calciphylaxis in children is a rare condition with severe mortality and morbidity, with no management guidelines. Although obesity and diabetes are known risk factors in adults, they were infrequently reported in children. Their unique phosphocalcic kidney or thyroid disorders responded well to IV STS without adverse events. Painful violaceus lower limbs ulceration and phosphocalcic dysregulations should warrant clinical suspicion and may require wide excisional biopsies at lesion’s border under local anaesthesia, despite negative punch biopsies. This systematic review underlines the need for standardized screening and treatment practices to assure timely diagnosis and reduce the burden of calciphylaxis in children.