Efficacy of mTOR inhibitors (sirolimus) in isolated limb overgrowth: a systematic review

Abstract

We systematically assessed the literature on the use of sirolimus for the treatment of isolated limb overgrowth conditions and its various modalities of administration in PubMed, Scopus, Ovid MEDLINE, Web of Science, Google Scholar, Cochrane Database of Systematic Reviews, references of journals and grey literature using pre-trialled Medical Subject Headings terms and articles. Eleven articles were included, and 39 patients were identified for review. Sirolimus was given orally in 38 patients and topically in one patient. Sirolimus was found to be highly effective in treatment of isolated limb overgrowth conditions with improvement of symptoms (physical, emotional, social) reported in all but one patient. Dosage and adverse effects seemed to be closely correlated. The result of our study suggests that sirolimus should be considered as an adjuvant or first-line management in isolated limb overgrowth in prospective trials.

The Effect of Epiphysiodesis on the Longitudinal Bone Growth of Hands or Feet in Children With Macrodactyly Based on Long-term Quantitative Analysis

“…Common surgical options include epiphysiodeses, osteotomies, soft-tissue debulking, nerve resection, carpal tunnel releases, toe transfers and amputations 16. Recently, sirolimus, an mTOR inhibitor is considered as an adjuvant treatment for isolated limb overgrowth conditions 17. However, due to rare incidence and variability in clinical features of macrodactyly, there are limited long-term quantitative data and standard treatment protocols.…”

“…16 Recently, sirolimus, an mTOR inhibitor is considered as an adjuvant treatment for isolated limb overgrowth conditions. 17 However, due to rare incidence and variability in clinical features of macrodactyly, there are limited long-term quantitative data and standard treatment protocols. In the study, we performed epiphysiodesis in patients with growth potential, and investigated postoperative growth in terms of the longitudinal and appositional growth.…”

Macrodactyly

“…Thus, the potential use of rapamycin in the treatment of children affected with PROS should be carefully considered, taking numerous side effects into account. However, a recent review demonstrated only mild side effects in the treatment of isolated overgrowth with oral rapamycin [37]. Sandbank et al reported good responses to topical sirolimus in the case of vascular malformations, such as in the KTS-part of the PROS spectrum [38].…”