Update on the Systemic Treatment of Pediatric Localized Scleroderma
- 94 Downloads
Juvenile localized scleroderma (jLS) is an orphan disease that can lead to cosmetic disfiguration and orthopedic problems. Two recent publications review the current recommendations regarding diagnosis, assessment, follow up and treatment of pediatric localized scleroderma cases, both of which suggest the Localized Scleroderma Cutaneous Assessment Tool as an important instrument to assess activity and damage. This review focuses on the systemic treatment of jLS. Systemic treatment includes synthetic and biologic disease-modifying antirheumatic drugs. Systemic therapy is indicated if the lesion crosses any joint, or leads to potential cosmetic disfiguration or orthopedic problems. The only controlled trial of systemic treatment has shown the efficacy of methotrexate, which is the first choice of treatment. It appears superior to phototherapy according to a recently published meta-analysis. In case of methotrexate intolerance, mycophenolate mofetil is an option. In case of methotrexate nonresponse, addition of mycophenolate mofetil, tocilizumab or abatacept seems to be effective. Future treatment options derived and extrapolated from adult trials regarding treatment of skin involvement of systemic scleroderma or fibrosis are promising, as the final pathway in the skin seems to be similar in both diseases.
I thank Dr. Hanna Lythgoe from University Children’s Hospital in Manchester, UK for the thoughtful language review.
Compliance with Ethical Standards
No funding was received for the preparation of this review.
Conflict of interest
In the last 2 years, the author was a participant of an advisory board of Pfizer, Novartis, and BMS and worked as an advisor for Genentech, Bayer, Lilly, MEDAC, Sanofi, and Inventa.
- 10.Li SC, Torok KS, Pope E, Dedeoglu F, Hong S, Jacobe HT, et al. Development of consensus treatment plans for juvenile localized scleroderma: a roadmap toward comparative effectiveness studies in juvenile localized scleroderma. Arthritis Care Res (Hoboken). 2012;64(8):1175–85.PubMedPubMedCentralGoogle Scholar
- 18.Arkachaisri T, Vilaiyuk S, Li S, O’Neil KM, Pope E, Higgins GC, et al. The localized scleroderma skin severity index and physician global assessment of disease activity: a work in progress toward development of localized scleroderma outcome measures. J Rheumatol. 2009;36(12):2819–29.PubMedPubMedCentralCrossRefGoogle Scholar
- 27.Li SC, Fuhlbrigge RC, Laxer RM, Pope E, Ibarra MF, Stewart K, et al. Developing comparative effectiveness studies for a rare, understudied pediatric disease: lessons learned from the CARRA juvenile localized scleroderma consensus treatment plan pilot study. Pediatr Rheumatol Online J. 2019;17(1):43.PubMedPubMedCentralCrossRefGoogle Scholar
- 35.Rathinam SR, Gonzales JA, Thundikandy R, Kanakath A, Murugan SB, Vedhanayaki R, et al. Effect of corticosteroid-sparing treatment with mycophenolate mofetil vs methotrexate on inflammation in patients with uveitis: a randomized clinical trial. JAMA. 2019;322(10):936–45.PubMedCrossRefPubMedCentralGoogle Scholar
- 38.Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, et al. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018;77(2):212–20.PubMedCrossRefPubMedCentralGoogle Scholar
- 43.Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74(6):1110–7.PubMedCrossRefGoogle Scholar
- 46.Calvo-Rio V, Santos-Gomez M, Calvo I, Gonzalez-Fernandez MI, Lopez-Montesinos B, Mesquida M, et al. Anti-interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis-associated uveitis refractory to anti-tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthritis Rheumatol. 2017;69(3):668–75.PubMedCrossRefGoogle Scholar
- 50.Khanna D, Spino C, Johnson S, Chung L, Whitfield M, Denton CP, et al. Abatacept in early diffuse cutaneous systemic sclerosis—results of a phase 2 investigator-initiated, multicenter, double-blind randomized placebo-controlled trial. Arthritis Rheumatol. 2019. https://doi.org/10.1002/art.41055.CrossRefPubMedGoogle Scholar
- 54.Brunner HI, Tzaribachev N, Vega-Cornejo G, Louw I, Berman A, Calvo Penades I, et al. Subcutaneous abatacept in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study. Arthritis Rheumatol. 2018;70(7):1144–54.PubMedPubMedCentralCrossRefGoogle Scholar