Skip to main content

Advertisement

SpringerLink
Log in

Evaluation and Treatment of Pediatric Localized Scleroderma: Pearls and Updates

  • Scleroderma (S Bhattacharyya, Section Editor)
  • Published:
Current Treatment Options in Rheumatology Aims and scope Submit manuscript

Abstract

Purpose of review

Localized scleroderma (LS), also known as morphea, is a complex and poorly understood disorder in children. The various clinical subtypes of LS require different approaches to evaluation and treatment. Failure to recognize and appropriately treat the affected skin and underlying deep connective tissue can lead to long-term morbidity. We present a review of the current literature supporting treatment options for pediatric LS followed by a series of cases to highlight the complexity of treatment choices and identify clinical pearls.

Recent findings

Increasing evidence has emerged for the utility of systemic immunomodulation in treating localized scleroderma. Multiple consensus-based treatment protocols are now available, though underlying evidence is moderate. There are emerging reports utilizing modern biologic and small molecules, but these remain relatively sparse.

Summary

Therapeutic regimens for LS should be based upon a detailed physical examination augmented by the results of additional screening evaluations recommended for the subtype of LS. Close collaboration with multiple specialties may be needed to achieve optimal outcomes, including rheumatology, dermatology, physical therapy, and craniofacial plastic surgery. More study is needed to identify the efficacy of newer therapeutic options as well as the role for adjunctive therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

LS:

localized scleroderma

SSC:

systemic sclerosis

NRCOS:

National Registry for Childhood Onset Scleroderma

UV:

ultraviolet

CARRA:

Childhood Arthritis and Rheumatology Research Alliance

DMARD:

disease-modifying anti-rheumatic drug

MTX:

methotrexate

MMF:

mycophenolate mofetil

LoSCAT:

Localized Scleroderma Cutaneous Assessment Tool

MRI:

magnetic resonance imaging

CNS:

central nervous system

PDE4:

phosphodiesterase 4

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Herrick AL, Ennis H, Bhushan M, Silman AJ, Baildam EM. Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland. Arthritis Care Res. 2010;62(2):213–8. https://doi.org/10.1002/acr.20070.

    Article  Google Scholar 

  2. Beukelman T, Xie F, Foeldvari I. The prevalence of localised scleroderma in childhood assessed in the administrative claims data from the United States. J Scleroderma Relat Disord. 2019;4(1):77–8. https://doi.org/10.1177/2397198318798588.

    Article  Google Scholar 

  3. Wu EY, Li SC, Torok KS, Virkud YV, Fuhlbrigge RC, Rabinovich CE. Baseline description of the juvenile localized scleroderma subgroup from the childhood arthritis and rheumatology research alliance legacy registry. ACR Open Rheumatol. 2019;1(2):119–24. https://doi.org/10.1002/acr2.1019.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Condie D, Grabell D, Jacobe H. Comparison of outcomes in adults with pediatric-onset morphea and those with adult-onset morphea: a cross-sectional study from the morphea in adults and children cohort. Arthritis Rheum. 2014;66(12):3496–504. https://doi.org/10.1002/art.38853.

    Article  Google Scholar 

  5. Zulian F, Athreya BH, Laxer R, Nelson AM. Feitosa de Oliveira SK, Punaro MG et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology. 2006;45(5):614–20.

    Article  CAS  Google Scholar 

  6. Li SC, Zheng RJ. Overview of juvenile localized scleroderma and its management. World J Pediatr. 2020;16(1):5–18. https://doi.org/10.1007/s12519-019-00320-9.

    Article  PubMed  Google Scholar 

  7. Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg syndrome: a retrospective review of 54 patients. J Am Acad Dermatol. 2007;56(2):257–63. https://doi.org/10.1016/j.jaad.2006.10.959.

    Article  PubMed  Google Scholar 

  8. Kashem SW, Correll CK, Vehe RK, Hobday PM, Binstadt BA, Maguiness SM. Inflammatory arthritis in pediatric patients with morphea. J Am Acad Dermatol. 2018;79(1):47–51.e2. https://doi.org/10.1016/j.jaad.2018.03.005.

    Article  PubMed  Google Scholar 

  9. Reiff D, Crayne CB, Mannion ML, Cron RQ. Characteristics of coexisting localized scleroderma and inflammatory arthritis. Eur J Rheumatol. 2020;7(Suppl 1):S67–71. https://doi.org/10.5152/eurjrheum.2019.19147.

    Article  Google Scholar 

  10. Pequet MS, Holland KE, Zhao S, Drolet BA, Galbraith SS, Siegel DH, et al. Risk factors for morphoea disease severity: a retrospective review of 114 paediatric patients. Br J Dermatol. 2014;170(4):895–900. https://doi.org/10.1111/bjd.12758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Leitenberger JJ, Cayce RL, Haley RW, Adams-Huet B, Bergstresser PR, Jacobe HT. Distinct autoimmune syndromes in morphea: a review of 245 adult and pediatric cases. Arch Dermatol. 2009;145(5):545–50. https://doi.org/10.1001/archdermatol.2009.79.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dańczak-Pazdrowska A, Polańska A, Synakiewicz J, Gurgul E, Molińska-Glura M, Ruchała M, et al. Morphea and antithyroid antibodies. Postepy Dermatol Alergol. 2018;35(5):470–3. https://doi.org/10.5114/ada.2018.75839.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Laxer RM, Zulian F. Localized scleroderma. Curr Opin Rheumatol. 2006;18(6):606–13. https://doi.org/10.1097/01.bor.0000245727.40630.c3.

  14. Peterson LSN, Audrey M, Su WPD. Classification of morphea (localized scleroderma). Mayo Clin Proc. 1995;70(11):1068–76. https://doi.org/10/4065/70.11.1068.

  15. Kreuter A, Krieg T, Worm M, Wenzel J, Gambichler T, Kuhn A, et al. Diagnosis and therapy of localized scleroderma. J Dtsch Dermatologischen Gesellschaft. 2009;7(s6):S1–S12. https://doi.org/10.1111/j.1610-0387.2009.07178.x.

    Article  Google Scholar 

  16. Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol. 2011;65(5):925–41. https://doi.org/10.1016/j.jaad.2010.09.006.

    Article  CAS  PubMed  Google Scholar 

  17. Knobler R, Moinzadeh P, Hunzelmann N, Kreuter A, Cozzio A, Mouthon L, et al. European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol. 2017;31(9):1401–24. https://doi.org/10.1111/jdv.14458.

    Article  CAS  PubMed  Google Scholar 

  18. •• Florez-Pollack S, Kunzler E, Jacobe HT. Morphea: Current concepts. Clin Dermatol. 2018;36(4):475–86. https://doi.org/10.1016/j.clindermatol.2018.04.005Recent localized scleroderma review with helpful flow charts for treatment of both active and inactive disease.

  19. •• 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. 2012;64(8):1175–85. https://doi.org/10.1002/acr.21687Consensus treatment plans for localized scleroderma developed by CARRA including detailed medication dosing and taper information.

  20. Zulian F, Culpo R, Sperotto F, Anton J, Avcin T, Baildam EM, et al. Consensus-based recommendations for the management of juvenile localised scleroderma. Ann Rheum Dis. 2019;78(8):1019–24. https://doi.org/10.1136/annrheumdis-2018-214,697.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li SC, Feldman BM, Higgins GC, Haines KA, Punaro MG, O’neil KM. Treatment of pediatric localized scleroderma: results of a survey of North American pediatric rheumatologists. J Rheumatol. 2010;37(1):175–81. https://doi.org/10.3899/jrheum.090708.

    Article  PubMed  Google Scholar 

  22. Lythgoe H, Almeida B, Bennett J, Bhat C, Bilkhu A, Brennan M, et al. Multi-centre national audit of juvenile localised scleroderma: describing current UK practice in disease assessment and management. Pediatr Rheumatol. 2018;16(1):80. https://doi.org/10.1186/s12969-018-0295-0.

    Article  Google Scholar 

  23. Strickland N, Patel G, Strickland A, Jacobe H. Attitudes and trends in the treatment of morphea: a national survey. J Am Acad Dermatol. 2015;72(4):727–8. https://doi.org/10.1016/j.jaad.2014.11.019.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Hawley DP, Pain CE, Baildam EM, Murphy R, Taylor AEM, Foster HE. United Kingdom survey of current management of juvenile localized scleroderma. Rheumatology. 2014;53(10):1849–54. https://doi.org/10.1093/rheumatology/keu212.

    Article  CAS  PubMed  Google Scholar 

  25. Albuquerque JV, Andriolo BNG, Vasconcellos MRA, Civile VT, Lyddiatt A, Trevisani VFM. Interventions for morphea. Cochrane Database Syst Rev. 2019;7. https://doi.org/10.1002/14651858.CD005027.pub5.

  26. Li SC, Torok KS, Rabinovich CE, Dedeoglu F, Becker ML, Ferguson PJ, et al. Initial results from a pilot comparative effectiveness study of 3 methotrexate-based consensus treatment plans for juvenile localized scleroderma. J Rheumatol. 2019. https://doi.org/10.3899/jrheum.190311.

  27. • Do N, Ringold S, Sullivan E, Brandling-Bennett H. A retrospective study: Impact of consensus treatment plans on systemic therapy of pediatric morphea. Pediatr Dermatol. 2020;37(2):278–83. https://doi.org/10.1111/pde.14074Retrospective study showing adherence to 2012 Childhood Arthritis and Rheumatology Research Alliance localized scleroderma consensus treatment plans leads to improved outcomes.

  28. Fett N, Werth VP. Update on morphea: part II. Outcome measures and treatment. J Am Acad Dermatol. 2011;64(2):231–42; quiz 43–4. https://doi.org/10.1016/j.jaad.2010.05.046.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cunningham BB, Landells IDR, Langman C, Sailer DE, Paller AS. Topical calcipotriene for morphea/linear scleroderma. J Am Acad Dermatol. 1998;39(2):211–5. https://doi.org/10.1016/S0190-9622(98)70077-5.

    Article  CAS  PubMed  Google Scholar 

  30. Kreuter A, Gambichler T, Avermaete A, Jansen T, Hoffmann M, Hoffmann K, et al. Combined treatment with calcipotriol ointment and low-dose ultraviolet A1 phototherapy in childhood morphea. Pediatr Dermatol. 2001;18(3):241–5. https://doi.org/10.1046/j.1525-1470.2001.018003241.x.

    Article  CAS  PubMed  Google Scholar 

  31. Narbutt J, Hołdrowicz A, Lesiak A. Morphea – selected local treatment methods and their effectiveness. Reumatologia. 2017;55(6):305–13. https://doi.org/10.5114/reum.2017.72628.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Pope E, Doria AS, Theriault M, Mohanta A, Laxer RM. Topical imiquimod 5% cream for pediatric plaque morphea: a prospective, multiple-baseline, open-label pilot study. DRM. 2011;223(4):363–9. https://doi.org/10.1159/000335560.

    Article  CAS  Google Scholar 

  33. Rodríguez-Castellanos M, Tlacuilo-Parra A, Sánchez-Enríquez S, Vélez-Gómez E, Guevara-Gutiérrez E. Pirfenidone gel in patients with localized scleroderma: a phase II study. Arthritis Res Ther. 2014;16(6):510. https://doi.org/10.1186/s13075-014-0510-4.

    Article  CAS  Google Scholar 

  34. Moinzadeh P, Hunzelmann N, Krieg T. Pharmacology and rationale for imatinib in the treatment of scleroderma. J Exp Pharmacol. 2013;5:15–22. https://doi.org/10.2147/JEP.S26894.

  35. •• Constantin T, Foeldvari I, Pain CE, Pálinkás A, Höger P, Moll M, et al. Development of minimum standards of care for juvenile localized scleroderma. Eur J Pediatr. 2018;177(7):961–77. https://doi.org/10.1007/s00431-018-3144-8Consensus treatment guideline for localized scleroderma developed by the Pediatric Rheumatology European Society (PRES) scleroderma working group.

  36. Curtiss P, Singh G, Lo Sicco K, Franks AG. Wood’s lamp as a tool in the evaluation of morphea. J Am Acad Dermatol. 2018;78(2):e33–e4. https://doi.org/10.1016/j.jaad.2017.10.003.

    Article  PubMed  Google Scholar 

  37. Abbas LF, O’Brien JC, Goldman S, Pezeshk P, Chalian M, Chhabra A, et al. A cross-sectional comparison of magnetic resonance imaging findings and clinical assessment in patients with morphea. JAMA Dermatol. 2020;156(5):590–2. https://doi.org/10.1001/jamadermatol.2020.0036.

    Article  PubMed  Google Scholar 

  38. Zulian F, Cuffaro G, Sperotto F. Scleroderma in children: an update. Curr Opin Rheumatol. 2013;25(5):643–50. https://doi.org/10.1097/BOR.0b013e3283641f61.

    Article  PubMed  Google Scholar 

  39. Kreuter A, Hyun J, Stücker M, Sommer A, Altmeyer P, Gambichler T. A randomized controlled study of low-dose UVA1, medium-dose UVA1, and narrowband UVB phototherapy in the treatment of localized scleroderma. J Am Acad Dermatol. 2006;54(3):440–7. https://doi.org/10.1016/j.jaad.2005.11.1063.

    Article  PubMed  Google Scholar 

  40. Vasquez R, Jabbar A, Khan F, Buethe D, Ahn C, Jacobe H. Recurrence of morphea after successful ultraviolet A1 phototherapy: a cohort study. J Am Acad Dermatol. 2014;70(3):481–8. https://doi.org/10.1016/j.jaad.2013.10.018.

    Article  PubMed  Google Scholar 

  41. O’Brien JC, Nymeyer H, Green A, Jacobe HT. Changes in disease activity and damage over time in patients with morphea. JAMA Dermatol. 2020;156(5):513–20. https://doi.org/10.1001/jamadermatol.2020.0034.

    Article  PubMed  Google Scholar 

  42. Prasad S, Coias J, Chen HW, Jacobe H. Utilizing UVA-1 phototherapy. Dermatol Clin. 2020;38(1):79–90. https://doi.org/10.1016/j.det.2019.08.011.

    Article  CAS  PubMed  Google Scholar 

  43. Boozalis E, Shah AA, Wigley F, Kang S, Kwatra SG. Morphea and systemic sclerosis are associated with an increased risk for melanoma and nonmelanoma skin cancer. J Am Acad Dermatol. 2019;80(5):1449–51. https://doi.org/10.1016/j.jaad.2018.10.022.

    Article  PubMed  Google Scholar 

  44. •• Bae JM, Ju HJ, Lee RW, Oh SH, Shin JH, Kang HY, et al. Evaluation for skin cancer and precancer in patients with vitiligo treated with long-term narrowband UV-B phototherapy. JAMA Dermatol. 2020;156(5):529–37. https://doi.org/10.1001/jamadermatol.2020.0218 Longitudinal cohort analysis of repeat UVB phototherapy treatment in vitiligo demonstrating no increased risk of cancer.

  45. Besaratinia A, Synold TW, Chen H-H, Chang C, Xi B, Riggs AD, et al. DNA lesions induced by UV A1 and B radiation in human cells: comparative analyses in the overall genome and in the p53 tumor suppressor gene. PNAS. 2005;102(29):10058–63. https://doi.org/10.1073/pnas.0502311102.

    Article  CAS  PubMed  Google Scholar 

  46. Kreuter A, Gambichler T, Breuckmann F, Rotterdam S, Freitag M, Stuecker M, et al. Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma. Arch Dermatol. 2005;141(7):847–52. https://doi.org/10.1001/archderm.141.7.847.

    Article  CAS  PubMed  Google Scholar 

  47. 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. 2019;17(1):43. https://doi.org/10.1186/s12969-019-0350-5.

    Article  CAS  Google Scholar 

  48. Weibel L, Sampaio MC, Visentin MT, Howell KJ, Woo P, Harper JI. Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children. Br J Dermatol. 2006;155(5):1013–20.

    Article  CAS  Google Scholar 

  49. Torok KS, Arkachaisri T. Methotrexate and corticosteroids in the treatment of localized scleroderma: a standardized prospective longitudinal single-center study. J Rheumatol. 2012;39(2):286–94. https://doi.org/10.3899/jrheum.110210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zulian F, Martini G, Vallongo C, Vittadello F, Falcini F, Patrizi A, et al. Methotrexate treatment in juvenile localized scleroderma: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2011;63(7):1998–2006. https://doi.org/10.1002/art.30264.

    Article  CAS  PubMed  Google Scholar 

  51. Zulian F, Vallongo C, Patrizi A, Belloni-Fortina A, Cutrone M, Alessio M, et al. A long-term follow-up study of methotrexate in juvenile localized scleroderma (morphea). J Am Acad Dermatol. 2012;67(6):1151–6. https://doi.org/10.1016/j.jaad.2012.03.036.

    Article  CAS  PubMed  Google Scholar 

  52. Marrani E, Foeldvari I, Lopez JA, Cimaz R, Simonini G. Comparing ultraviolet light A photo(chemo)therapy with methotrexate protocol in childhood localized scleroderma: evidence from systematic review and meta-analysis approach. Semin Arthritis Rheum. 2018;48(3):495–503. https://doi.org/10.1016/j.semarthrit.2018.03.003.

    Article  CAS  PubMed  Google Scholar 

  53. Bedoui Y, Guillot X, Sélambarom J, Guiraud P, Giry C, Jaffar-Bandjee MC, et al. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019;20(20):5023. https://doi.org/10.3390/ijms20205023.

    Article  CAS  PubMed Central  Google Scholar 

  54. Seyger MM, van den Hoogen FH, van Vlijmen-Willems IM, van de Kerkhof PC, de Jong EM. Localized and systemic scleroderma show different histological responses to methotrexate therapy. J Pathol 2001;193(4):511–516.

  55. Falvey S, Shipman L, Ilowite N, Beukelman T. Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis. Pediatr Rheumatol. 2017;15(1):52. https://doi.org/10.1186/s12969-017-0180-2.

    Article  Google Scholar 

  56. Martini G, Ramanan AV, Falcini F, Girschick H, Goldsmith DP, Zulian F. Successful treatment of severe or methotrexate-resistant juvenile localized scleroderma with mycophenolate mofetil. Rheumatology. 2009;48(11):1410–3. https://doi.org/10.1093/rheumatology/kep244.

    Article  PubMed  Google Scholar 

  57. •• Arthur M, Fett NM, Latour E, Jacobe H, Kunzler E, Florez-Pollack S, et al. Evaluation of the effectiveness and tolerability of mycophenolate mofetil and mycophenolic acid for the treatment of morphea. JAMA Dermatol. 2020;156(5):521–8. https://doi.org/10.1001/jamadermatol.2020.0035Retrospective cohort study of mycophenolate mofetil showing safety and efficacy as first-line treatment for localized scleroderma.

  58. Mertens JS, Marsman D, van de Kerkhof PC, Hoppenreijs EP, Knaapen HK, Radstake TR, et al. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate. Acta Derm Venereol. 2016;96(4):510–3. https://doi.org/10.2340/00015555-2297.

    Article  CAS  PubMed  Google Scholar 

  59. Bullingham RES, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet. 1998;34(6):429–55. https://doi.org/10.2165/00003088-199,834,060-00002.

    Article  CAS  PubMed  Google Scholar 

  60. Roos N, Poulalhon N, Farge D, Madelaine I, Mauviel A, Verrecchia F. In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. J Pharmacol Exp Ther. 2007;321(2):583–9. https://doi.org/10.1124/jpet.106.117051.

    Article  CAS  PubMed  Google Scholar 

  61. Hinchcliff M, Toledo DM, Taroni JN, Wood TA, Franks JM, Ball MS, et al. Mycophenolate mofetil treatment of systemic sclerosis reduces myeloid cell numbers and attenuates the inflammatory gene signature in skin. J Investig Dermatol. 2018;138(6):1301–10. https://doi.org/10.1016/j.jid.2018.01.006.

    Article  CAS  PubMed  Google Scholar 

  62. Kumar AB, Blixt EK, Drage LA, el-Azhary RA, Wetter DA. Treatment of morphea with hydroxychloroquine: a retrospective review of 84 patients at Mayo Clinic, 1996–2013. J Am Acad Dermatol. 2019;80(6):1658–63. https://doi.org/10.1016/j.jaad.2019.01.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bali G, Frühauf J, Wutte N, Aberer E. Cyclosporine reduces sclerosis in morphea: a retrospective study in 12 patients and a literature review. DRM. 2016;232(4):503–10. https://doi.org/10.1159/000448171.

    Article  CAS  Google Scholar 

  64. Hirohata A, Hanafusa T, Igawa K, Inoue-Nishimoto T, Mabuchi-Kiyohara E, Nishide M, et al. Oral tacrolimus for the treatment of generalized morphea. Eur J Dermatol. 2016;26(1):112–3. https://doi.org/10.1684/ejd.2015.2689.

    Article  CAS  PubMed  Google Scholar 

  65. Thomas RM, Worswick S, Aleshin M. Retinoic acid for treatment of systemic sclerosis and morphea: a literature review. Dermatol Ther. 2017;30(2):e12455. https://doi.org/10.1111/dth.12455.

    Article  Google Scholar 

  66. Ferguson IDW, Toreok P, Kathryn S. A case report of succesful treatment of recalcitrant childhood localized scleroderma with infliximab and leflunomide. Open Rheumatol J. 2015;9:30–5. https://doi.org/10.2174/18743129014090100030.

  67. Diab M, Coloe JR, Magro C, Bechtel MA. Treatment of recalcitrant generalized morphea with infliximab. Arch Dermatol. 2010;146(6):601–4. https://doi.org/10.1001/archdermatol.2010.120.

    Article  PubMed  Google Scholar 

  68. Lythgoe H, Baildam E, Beresford MW, Cleary G, McCann LJ, Pain CE. Tocilizumab as a potential therapeutic option for children with severe, refractory juvenile localized scleroderma. Rheumatology. 2018;57(2):398–401. https://doi.org/10.1093/rheumatology/kex382.

    Article  PubMed  Google Scholar 

  69. • Kalampokis I, Yi BY, Smidt AC. Abatacept in the treatment of localized scleroderma: a pediatric case series and systematic literature review. Semin Arthritis Rheum. 2020. https://doi.org/10.1016/j.semarthrit.2020.03.020Case series and systemic literature review supporting the use of abatacept for treatment of localized scleroderma.

  70. Li SC, Torok KS, Ishaq SS, Buckley M, Edelheit B, Ede KC, Liu C, Rabinovich CE. Preliminary evidence on abatacept safety and efficacy in refractory juvenile localized scleroderma. Rheumatology (Oxford). 2020; keaa873. https://doi.org/10.1093/rheumatology/keaa873.

  71. Kim SR, Charos A, Damsky W, Heald P, Girardi M, King BA. Treatment of generalized deep morphea and eosinophilic fasciitis with the Janus kinase inhibitor tofacitinib. JAAD Case Rep. 2018;4(5):443–5. https://doi.org/10.1016/j.jdcr.2017.12.003.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Damsky W, Patel D, Garelli CJ, Garg M, Wang A, Dresser K, et al. Jak inhibition prevents bleomycin-induced fibrosis in mice and is effective in patients with morphea. J Investig Dermatol. 2020. https://doi.org/10.1016/j.jid.2019.12.019.

  73. Arkachaisri T, Pino S. Localized scleroderma severity index and global assessments: a pilot study of outcome instruments. J Rheumatol. 2008;35(4):650–7.

    PubMed  Google Scholar 

  74. Kelsey CE, Torok KS. The localized scleroderma cutaneous assessment tool: responsiveness to change in a pediatric clinical population. J Am Acad Dermatol. 2013;69(2):214–20. https://doi.org/10.1016/j.jaad.2013.02.007.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Skrzypek-Salamon A, Lis-Święty A, Ranosz-Janicka I, Brzezińska-Wcisło L. Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) adapted for use in adult patients: report from an initial validation study. Health Qual Life Outcomes. 2018;16(1):185. https://doi.org/10.1186/s12955-018-1010-z.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Teske NM, Jacobe HT. Using the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) to classify morphoea by severity and identify clinically significant change. Br J Dermatol. 2020;182(2):398–404. https://doi.org/10.1111/bjd.18097.

    Article  CAS  PubMed  Google Scholar 

  77. Lis-Święty A, Janicka I, Skrzypek-Salamon A, Brzezińska-Wcisło L. A systematic review of tools for determining activity of localized scleroderma in paediatric and adult patients. J Eur Acad Dermatol Venereol. 2017;31(1):30–7. https://doi.org/10.1111/jdv.13790.

    Article  PubMed  Google Scholar 

  78. Li SC, Liebling MS, Haines KA, Weiss JE, Prann A. Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma. Arthritis Care Res. 2011;63(5):735–42. https://doi.org/10.1002/acr.20407.

    Article  CAS  Google Scholar 

  79. Eutsler EP, Horton DB, Epelman M, Finkel T, Averill LW. Musculoskeletal MRI findings of juvenile localized scleroderma. Pediatr Radiol. 2017;47(4):442–9. https://doi.org/10.1007/s00247-016-3765-x.

    Article  PubMed  Google Scholar 

  80. Shahidi-Dadras M, Abdollahimajd F, Jahangard R, Javinani A, Ashraf-Ganjouei A, Toossi P. Magnetic resonance imaging evaluation in patients with linear morphea treated with methotrexate and high-dose corticosteroid. Dermatol Res Pract. 2018;2018:6. https://doi.org/10.1155/2018/8391218

  81. Martini G, Fadanelli G, Agazzi A, Vittadello F, Meneghel A, Zulian F. Disease course and long-term outcome of juvenile localized scleroderm: experience from a single pediatric rheumatology centre and literature review. Autoimmun Rev. 2018;17(7):727–34. https://doi.org/10.1016/j.autrev.2018.02.004.

  82. Hardy J, Boralevi F, Mallet S, Cabrera N, Belot A, Phan A, et al. Clinical profile of methotrexate-resistant juvenile localised scleroderma. Acta Derm Venereol. 2019;99(6):539–43. https://doi.org/10.2340/00015555-3155.

    Article  CAS  PubMed  Google Scholar 

  83. • Kurzinski KL, Zigler CK, Torok KS. Prediction of disease relapse in a cohort of paediatric patients with localized scleroderma. Br J Dermatol. 2019;180(5):1183–9. https://doi.org/10.1111/bjd.17312Cohort analysis suggesting ANA positivity, older age, and presence of ECMs as predictors of disease relapse.

  84. Martini G, Fadanelli G, Agazzi A, Vittadello F, Meneghel A, Zulian F. Disease course and long-term outcome of juvenile localized scleroderma: experience from a single pediatric rheumatology Centre and literature review. Autoimmun Rev. 2018;17(7):727–34. https://doi.org/10.1016/j.autrev.2018.02.004.

    Article  PubMed  Google Scholar 

  85. Kroft EBM, Creemers MCW, Hoogen FHJVD, Boezeman JBM, Jong EMGJD. Effectiveness, side-effects and period of remission after treatment with methotrexate in localized scleroderma and related sclerotic skin diseases: an inception cohort study. Br J Dermatol. 2009;160(5):1075–82. https://doi.org/10.1111/j.1365-2133.2008.09017.x.

    Article  CAS  PubMed  Google Scholar 

  86. Flores Quispe SKJ, Cavaliere A, Weber M, Stramare R, Zuliani M, Quaia E, et al. Sarcopenia in juvenile localized scleroderma: new insights on deep involvement. Eur Radiol. 2020. https://doi.org/10.1007/s00330-020-06764-2.

  87. Walker UA, Clements PJ, Allanore Y, Distler O, Oddis CV, Khanna D, et al. Muscle involvement in systemic sclerosis: points to consider in clinical trials. Rheumatology. 2017;56(suppl_5):v38–44. https://doi.org/10.1093/rheumatology/kex196.

    Article  PubMed  Google Scholar 

  88. Chughtai M, Newman JM, Sultan AA, Samuel LT, Rabin J, Khlopas A, et al. Astym ® therapy: a systematic review. Ann Transl Med. 2018;7(4):8. https://doi.org/10.21037/atm.2018.11.49.

    Article  Google Scholar 

  89. Rodriguez-Merchan EC, Corte-Rodriguez HDL, Roman-Belmonte JM. The current role of Astym therapy in the treatment of musculoskeletal disorders. Postgrad Med. 2020;132(1):66–71. https://doi.org/10.1080/00325481.2019.1654836.

    Article  PubMed  Google Scholar 

  90. Odhav A, Hoeltzel MF, Canty K. Pansclerotic Morphea with features of eosinophilic fasciitis: distinct entities or part of a continuum? Pediatr Dermatol. 2014;31(2):e42–e7. https://doi.org/10.1111/pde.12279.

    Article  PubMed  Google Scholar 

  91. Soh HJ, Samuel C, Heaton V, Renton WD, Cox A, Munro J. Challenges in the diagnosis and treatment of disabling pansclerotic morphea of childhood: case-based review. Rheumatol Int. 39(5):933–41. https://doi.org/10.1007/s00296-019-04269-w.

  92. Martini G, Campus S, Raffeiner B, Boscarol G, Meneghel A, Zulian F. Tocilizumab in two children with pansclerotic morphoea: a hopeful therapy for refractory cases? Clin Exp Rheumatol. 2017;35 Suppl 106(4):211–3.

    PubMed  Google Scholar 

  93. Schoch JJ, Schoch BS, Werthel JD, McIntosh AL, Davis DMR. Orthopedic complications of linear morphea: implications for early interdisciplinary care. Pediatr Dermatol. 2018;35(1):43–6. https://doi.org/10.1111/pde.13336.

    Article  PubMed  Google Scholar 

  94. Ardalan K, Zigler CK, Torok KS. Predictors of longitudinal quality of life in juvenile localized scleroderma. Arthritis Care Res. 2017;69(7):1082–7. https://doi.org/10.1002/acr.23101.

    Article  CAS  Google Scholar 

  95. Mishima K, Kitoh H, Matsushita M, Nagata T, Kamiya Y, Ishiguro N. Extensive bone lengthening for a patient with linear morphea. Case Rep Orthop. 2018;2018. https://doi.org/10.1155/2018/4535804.

  96. Handler MZ, Wulkan AJ, Stricker SJ, Schachner LA. Linear morphea and leg length discrepancy: treatment with a leg-lengthening procedure. Pediatr Dermatol. 2013;30(5):616–8. https://doi.org/10.1111/pde.12169.

    Article  PubMed  Google Scholar 

  97. Zigler CK, Ardalan K, Hernandez A, Caliendo AE, Magee KE, Terry MA, et al. Exploring the impact of paediatric localized scleroderma on health-related quality of life: focus groups with youth and caregivers. Br J Dermatol. 2020;n/a(n/a). https://doi.org/10.1111/bjd.18879.

  98. Glaser DH, Schutt C, Schollaert-Fitch K, Torok K. Linear scleroderma of the head - updates in management of Parry Romberg syndrome and en coup de sabre: a rapid scoping review across subspecialties. Eur J Rheumatol. 2020;7(Suppl 1):S48–57. https://doi.org/10.5152/eurjrheum.2019.19183.

    Article  PubMed Central  Google Scholar 

  99. Seese RR, Glaser D, Furtado A, Thakkar K, Torok KS. Unilateral Neuroimaging Findings in Pediatric Craniofacial Scleroderma: Parry-Romberg Syndrome and En Coup de Sabre. J Child Neurol. 2020 Oct;35(11):753–762. https://doi.org/10.1177/0883073820931253

  100. De Somer L, Morren M-A, Muller PCEH, Despontin K, Jansen K, Lagae L, et al. Overlap between linear scleroderma, progressive facial hemiatrophy and immune-inflammatory encephalitis in a paediatric cohort. Eur J Pediatr. 2015;174(9):1247–54. https://doi.org/10.1007/s00431-015-2532-6.

    Article  CAS  PubMed  Google Scholar 

  101. Chiu YE, Vora S, Kwon E-KM, Maheshwari M. A Significant proportion of children with morphea en coup de sabre and Parry-Romberg syndrome have neuroimaging findings. Pediatr Dermatol. 2012;29(6):738–48. https://doi.org/10.1111/pde.12001.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Doolittle DA, Lehman VT, Schwartz KM, Wong-Kisiel LC, Lehman JS, Tollefson MM. CNS imaging findings associated with Parry–Romberg syndrome and en coup de sabre: correlation to dermatologic and neurologic abnormalities. Neuroradiology. 2015;57(1):21–34. https://doi.org/10.1007/s00234-014-1448-6.

    Article  PubMed  Google Scholar 

  103. Stone J, Franks AJ, Guthrie JA, Johnson MH. Scleroderma “en coup de sabre”: pathological evidence of intracerebral inflammation. J Neurol Neurosurg Psychiatry. 2001;70(3):382–5. https://doi.org/10.1136/jnnp.70.3.382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lauesen SR, Daugaard-Jensen J, Lauridsen EF, Kjær I. Localised scleroderma en coup de sabre affecting the skin, dentition and bone tissue within craniofacial neural crest fields. Clinical and radiographic study of six patients. Eur Arch Paediatr Dent. 2019;20(4):339–50. https://doi.org/10.1007/s40368-019-00427-7.

    Article  CAS  PubMed  Google Scholar 

  105. Slack GC, Tabit CJ, Allam KA, Kawamoto HK, Bradley JP. Parry-Romberg reconstruction: optimal timing for hard and soft tissue procedures. J Craniofac Surg. 2012;23(7 Suppl 1):1969–73. https://doi.org/10.1097/SCS.0b013e318258bd11.

    Article  PubMed  Google Scholar 

  106. Bucher F, Fricke J, Neugebauer A, Cursiefen C, Heindl LM. Ophthalmological manifestations of Parry-Romberg syndrome. Surv Ophthalmol. 2016;61(6):693–701. https://doi.org/10.1016/j.survophthal.2016.03.009.

    Article  PubMed  Google Scholar 

  107. Salvarani C, Brown RD, Christianson TJH, Huston J, Giannini C, Miller DV, et al. Mycophenolate mofetil in primary central nervous system vasculitis. Semin Arthritis Rheum. 2015;45(1):55–9. https://doi.org/10.1016/j.semarthrit.2015.02.008.

    Article  CAS  PubMed  Google Scholar 

  108. Ebrahimi F, Koch M, Pieroh P, Ghadban C, Hobusch C, Bechmann I, et al. Time dependent neuroprotection of mycophenolate mofetil: effects on temporal dynamics in glial proliferation, apoptosis, and scar formation. J Neuroinflammation. 2012;9(1):89. https://doi.org/10.1186/1742-2094-9-89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Shapiro WR, Young DF, Mehta BM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293(4):161–6. https://doi.org/10.1056/NEJM197507242930402.

    Article  CAS  PubMed  Google Scholar 

  110. Elbadawi L, Burrus T, Mason T, Shin C, Moseley B. Favorable response to rituximab supports an autoimmune mediated pathogenesis in Parry-Romberg syndrome (P01.080). Neurology. 2012;78:P01.080–P01. https://doi.org/10.1212/WNL.78.1_MeetingAbstracts.P01.080.

    Article  Google Scholar 

  111. Denadai R, Raposo-Amaral CA, Buzzo CL, Raposo-Amaral CE. Isolated fat grafting for reconstruction of lower face volumetric asymmetry in skeletally immature patients: a clinical outcome study. Ann Plast Surg. 2019. https://doi.org/10.1097/SAP.0000000000001934.

  112. Slack GC, Tabit CJ, Allam KA, Kawamoto HK, Bradley JP. Parry-Romberg reconstruction: beneficial results despite poorer fat take. Ann Plast Surg. 2014;73(3):307–10. https://doi.org/10.1097/SAP.0b013e31827aeb0d.

    Article  CAS  PubMed  Google Scholar 

  113. Israel JS, Chen JT, Farmer RL, Siebert JW. Challenging traditional thinking: early free tissue transfer for active hemifacial atrophy in children. Plast Reconstr Surg. 2020;145(2):483–92. https://doi.org/10.1097/PRS.0000000000006511.

    Article  CAS  PubMed  Google Scholar 

  114. Chen JT, Schmid DB, Israel JS, Siebert JW. A 26-year experience with microsurgical reconstruction of hemifacial atrophy and linear scleroderma. Plast Reconstr Surg. 2018;142(5):1275–83. https://doi.org/10.1097/PRS.0000000000004922.

    Article  CAS  PubMed  Google Scholar 

  115. Chen JT, Eisinger B, Esquibel C, Poore SO, Eliceiri K, Siebert JW. Changes in cutaneous gene expression after microvascular free tissue transfer in Parry-Romberg syndrome. Plast Reconstr Surg. 2018;142(3):303e. https://doi.org/10.1097/PRS.0000000000004638.

    Article  CAS  PubMed  Google Scholar 

  116. Maier C, Ramming A, Bergmann C, Weinkam R, Kittan N, Schett G, et al. Inhibition of phosphodiesterase 4 (PDE4) reduces dermal fibrosis by interfering with the release of interleukin-6 from M2 macrophages. Ann Rheum Dis. 2017;76(6):1133–41. https://doi.org/10.1136/annrheumdis-2016-210,189.

    Article  CAS  PubMed  Google Scholar 

  117. • Torok KS, Li SC, Jacobe HM, Taber SF, Stevens AM, Zulian F, et al. Immunopathogenesis of pediatric localized scleroderma. Front Immunol. 2019;10. https://doi.org/10.3389/fimmu.2019.00908Review of the current model for the immunopathogenesis of localized scleroderma.

  118. Saracino AM, Denton CP, Orteu CH. The molecular pathogenesis of morphoea: from genetics to future treatment targets. Br J Dermatol. 2017;177(1):34–46. https://doi.org/10.1111/bjd.15001.

    Article  CAS  PubMed  Google Scholar 

  119. Mirizio E, Tabib T, Wang X, et al. Single-cell transcriptome conservation in a comparative analysis of fresh and cryopreserved human skin tissue: pilot in localized scleroderma. Arthritis Res Ther. 2020;22:263. https://doi.org/10.1186/s13075-020-02343-4.

  120. Mirizio, E., Tabib, T., Wang, X. et al. Single-cell transcriptome conservation in a comparative analysis of fresh and cryopreserved human skin tissue: pilot in localized scleroderma. Arthritis Res Ther 22, 263 (2020). https://doi.org/10.1186/s13075-020-02343-4

  121. Schutt C, Mirizio E, Salgado C, Reyes-Mugica M, Schollaert-Fitch K, Torok K. Genetic signatures support inflammation driven fibrosis in localized scleroderma [abstract]. Arthritis Rheum. suppl-10(71).

  122. Torok KS, Kurzinski K, Kelsey C, Yabes J, Magee K, Vallejo AN, et al. Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles. Semin Arthritis Rheum. 2015;45(3):284–93. https://doi.org/10.1016/j.semarthrit.2015.06.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. • O’Brien JC, Rainwater YB, Malviya N, Cyrus N, Auer-Hackenberg L, Hynan LS, et al. Transcriptional and cytokine profiles identify CXCL9 as a biomarker of disease activity in morphea. J Investig Dermatol. 2017;137(8):1663–70. https://doi.org/10.1016/j.jid.2017.04.008Identification of serum CXCL9 as possible biomarker for disease activity in localized scleroderma.

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Daniel Glaser MD, MPH & Kathryn S. Torok MD

  2. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Daniel Glaser MD, MPH & Kathryn S. Torok MD

Authors
  1. Daniel Glaser MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn S. Torok MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathryn S. Torok MD.

Ethics declarations

Conflict of Interest

Daniel Glaser declares no conflicts of interest. Kathryn Torok declares no conflicts of interest.

Consent for Publication

All patients were consented under the University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh academic photography consent, which includes manuscript publication identifying features in photographs.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Scleroderma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Glaser, D., Torok, K.S. Evaluation and Treatment of Pediatric Localized Scleroderma: Pearls and Updates. Curr Treat Options in Rheum 7, 1–20 (2021). https://doi.org/10.1007/s40674-021-00170-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40674-021-00170-5

Keywords

Search

Navigation