Treatment of morphea (localized scleroderma) in adults
- Heidi Jacobe, MD
Heidi Jacobe, MD
- Associate Professor, Department of Dermatology
- University of Texas Southwestern
Morphea, also known as localized scleroderma, is an idiopathic inflammatory disorder that causes sclerotic changes in the skin. Patients present with single or multiple inflammatory or sclerotic plaques. Disease activity typically persists for three to six years, although some patients develop more persistent or recurring episodes of activity.
The majority of adults with morphea are managed with observation, topical medications, or phototherapy. The level of disease activity, depth of involvement, body surface area involved, and the potential for functional impairment or cosmetic disfigurement determine the most appropriate approach to treatment. Aggressive systemic therapy is warranted for patients with active deep morphea or with lesions that are likely to cause significant cosmetic disfigurement, joint contractures, or other functional impairment. Occupational and physical therapy are additional important interventions for patients who have or are at risk for physical limitations.
Pharmacologic therapy, phototherapy, and other interventions for morphea in adults will be reviewed here. The pathogenesis, clinical manifestations, and diagnosis of morphea and the features and management of morphea in children are discussed elsewhere. (See "Pathogenesis, clinical manifestations, and diagnosis of morphea (localized scleroderma) in adults" and "Localized scleroderma in childhood".)
APPROACH TO THERAPY
A variety of treatment options are available for patients with active lesions of morphea; however, evidence in support of many of these therapies is limited. An algorithm for the treatment of patients with morphea is provided (algorithm 1).
The expected outcome of successful therapy for morphea is not the return to completely normal skin, although this may occur in very early inflammatory lesions. Therapeutic success for individual lesions is defined by improvement or resolution of erythema, lesion softening, or local hair regrowth. In patients with progressive disease, successful treatment arrests the formation of new lesions and limits disease spread. We have found that serial photographs are valuable for following the response to therapy.
- Zwischenberger BA, Jacobe HT. A systematic review of morphea treatments and therapeutic algorithm. J Am Acad Dermatol 2011; 65:925.
- El-Mofty M, Zaher H, Bosseila M, et al. Low-dose broad-band UVA in morphea using a new method for evaluation. Photodermatol Photoimmunol Photomed 2000; 16:43.
- Kreuter A, Hyun J, Stücker M, et al. 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; 54:440.
- de Rie MA, Enomoto DN, de Vries HJ, Bos JD. Evaluation of medium-dose UVA1 phototherapy in localized scleroderma with the cutometer and fast Fourier transform method. Dermatology 2003; 207:298.
- Kerscher M, Meurer M, Sander C, et al. PUVA bath photochemotherapy for localized scleroderma. Evaluation of 17 consecutive patients. Arch Dermatol 1996; 132:1280.
- Grundmann-Kollmann M, Behrens S, Gruss C, et al. Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy. J Am Acad Dermatol 2000; 42:134.
- El-Mofty M, Mostafa W, Esmat S, et al. Suggested mechanisms of action of UVA phototherapy in morphea: a molecular study. Photodermatol Photoimmunol Photomed 2004; 20:93.
- Grabell D, Hsieh C, Andrew R, et al. The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the Morphea in Adults and Children cohort IV. J Am Acad Dermatol 2014; 71:493.
- Kroft EB, Groeneveld TJ, Seyger MM, de Jong EM. Efficacy of topical tacrolimus 0.1% in active plaque morphea: randomized, double-blind, emollient-controlled pilot study. Am J Clin Dermatol 2009; 10:181.
- Mancuso G, Berdondini RM. Localized scleroderma: response to occlusive treatment with tacrolimus ointment. Br J Dermatol 2005; 152:180.
- Stefanaki C, Stefanaki K, Kontochristopoulos G, et al. Topical tacrolimus 0.1% ointment in the treatment of localized scleroderma. An open label clinical and histological study. J Dermatol 2008; 35:712.
- Mancuso G, Berdondini RM. Topical tacrolimus in the treatment of localized scleroderma. Eur J Dermatol 2003; 13:590.
- Vilela FA, Carneiro S, Ramos-e-Silva M. Treatment of morphea or localized scleroderma: review of the literature. J Drugs Dermatol 2010; 9:1213.
- Cunningham BB, Landells ID, Langman C, et al. Topical calcipotriene for morphea/linear scleroderma. J Am Acad Dermatol 1998; 39:211.
- Dytoc MT, Kossintseva I, Ting PT. First case series on the use of calcipotriol-betamethasone dipropionate for morphoea. Br J Dermatol 2007; 157:615.
- Dytoc M, Ting PT, Man J, et al. First case series on the use of imiquimod for morphoea. Br J Dermatol 2005; 153:815.
- Man J, Dytoc MT. Use of imiquimod cream 5% in the treatment of localized morphea. J Cutan Med Surg 2004; 8:166.
- Kroft EB, Berkhof NJ, van de Kerkhof PC, et al. Ultraviolet A phototherapy for sclerotic skin diseases: a systematic review. J Am Acad Dermatol 2008; 59:1017.
- Gruss C, Reed JA, Altmeyer P, et al. Induction of interstitial collagenase (MMP-1) by UVA-1 phototherapy in morphea fibroblasts. Lancet 1997; 350:1295.
- Scharffetter K, Wlaschek M, Hogg A, et al. UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo. Arch Dermatol Res 1991; 283:506.
- Petersen MJ, Hansen C, Craig S. Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts. J Invest Dermatol 1992; 99:440.
- Kreuter A, Hyun J, Skrygan M, et al. Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol 2006; 155:600.
- Kreuter A, Hyun J, Skrygan M, et al. Ultraviolet A1 phototherapy decreases inhibitory SMAD7 gene expression in localized scleroderma. Arch Dermatol Res 2006; 298:265.
- Gambichler T, Skrygan M, Tomi NS, et al. Significant downregulation of transforming growth factor-beta signal transducers in human skin following ultraviolet-A1 irradiation. Br J Dermatol 2007; 156:951.
- Usmani N, Murphy A, Veale D, et al. Photochemotherapy for localized morphoea: effect on clinical and molecular markers. Clin Exp Dermatol 2008; 33:698.
- Brownell I, Soter NA, Franks AG Jr. Familial linear scleroderma (en coup de sabre) responsive to antimalarials and narrowband ultraviolet B therapy. Dermatol Online J 2007; 13:11.
- Vasquez R, Jabbar A, Khan F, et al. Recurrence of morphea after successful ultraviolet A1 phototherapy: A cohort study. J Am Acad Dermatol 2014; 70:481.
- Tollefson MM, Witman PM. En coup de sabre morphea and Parry-Romberg syndrome: a retrospective review of 54 patients. J Am Acad Dermatol 2007; 56:257.
- Uziel Y, Feldman BM, Krafchik BR, et al. Methotrexate and corticosteroid therapy for pediatric localized scleroderma. J Pediatr 2000; 136:91.
- Seyger MM, van den Hoogen FH, de Boo T, de Jong EM. Low-dose methotrexate in the treatment of widespread morphea. J Am Acad Dermatol 1998; 39:220.
- Kreuter A, Gambichler T, Breuckmann F, et al. Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma. Arch Dermatol 2005; 141:847.
- Weibel L, Sampaio MC, Visentin MT, et al. Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children. Br J Dermatol 2006; 155:1013.
- Zulian F, Martini G, Vallongo C, et al. Methotrexate treatment in juvenile localized scleroderma: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2011; 63:1998.
- Schanz S, Henes J, Ulmer A, et al. Response evaluation of musculoskeletal involvement in patients with deep morphea treated with methotrexate and prednisolone: a combined MRI and clinical approach. AJR Am J Roentgenol 2013; 200:W376.
- Kroft EB, Creemers MC, van den Hoogen FH, et al. 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; 160:1075.
- Li SC, Torok KS, Pope E, 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; 64:1175.
- Joly P, Bamberger N, Crickx B, Belaich S. Treatment of severe forms of localized scleroderma with oral corticosteroids: follow-up study on 17 patients. Arch Dermatol 1994; 130:663.
- Amy de la Bretèque M, Rybojad M, Cordoliani F, et al. Relapse of severe forms of adult morphea after oral corticosteroid treatment. J Eur Acad Dermatol Venereol 2013; 27:1190.
- Hulshof MM, Pavel S, Breedveld FC, et al. Oral calcitriol as a new therapeutic modality for generalized morphea. Arch Dermatol 1994; 130:1290.
- Caca-Biljanovska NG, Vlckova-Laskoska MT, Dervendi DV, et al. Treatment of generalized morphea with oral 1,25-dihydroxyvitamin D3. Adv Exp Med Biol 1999; 455:299.
- Humbert PG, Dupond JL, Rochefort A, et al. Localized scleroderma--response to 1,25-dihydroxyvitamin D3. Clin Exp Dermatol 1990; 15:396.
- Hulshof MM, Bouwes Bavinck JN, Bergman W, et al. Double-blind, placebo-controlled study of oral calcitriol for the treatment of localized and systemic scleroderma. J Am Acad Dermatol 2000; 43:1017.
- Christen-Zaech S, Hakim MD, Afsar FS, Paller AS. Pediatric morphea (localized scleroderma): review of 136 patients. J Am Acad Dermatol 2008; 59:385.
- Maragh SH, Davis MD, Bruce AJ, Nelson AM. Disabling pansclerotic morphea: clinical presentation in two adults. J Am Acad Dermatol 2005; 53:S115.
- Schlaak M, Friedlein H, Kauer F, et al. Successful therapy of a patient with therapy recalcitrant generalized bullous scleroderma by extracorporeal photopheresis and mycophenolate mofetil. J Eur Acad Dermatol Venereol 2008; 22:631.
- Rose RF, Goodfield MJ. Combining PUVA therapy with systemic immunosuppression to treat progressive diffuse morphoea. Clin Exp Dermatol 2005; 30:226.
- Möhrenschlager M, Jung C, Ring J, Abeck D. Effect of penicillin G on corium thickness in linear morphea of childhood: An analysis using ultrasound technique. Pediatr Dermatol 1999; 16:314.
- Roldan R, Morote G, Castro Mdel C, et al. Efficacy of bosentan in treatment of unresponsive cutaneous ulceration in disabling pansclerotic morphea in children. J Rheumatol 2006; 33:2538.
- Diab M, Coloe JR, Magro C, Bechtel MA. Treatment of recalcitrant generalized morphea with infliximab. Arch Dermatol 2010; 146:601.
- Alarcon-Segovia D, Ramos-Niembro F, Ibanez de Kasep G, et al. Long-term evaluation of colchicine in the treatment of scleroderma. J Rheumatol 1979; 6:705.
- van Bergen BH, van Dooren-Greebe RJ, Fiselier TJ, Koopman RJ. [D-penicillamine in treatment of scleroderma "en coup de sabre"]. Hautarzt 1997; 48:42.
- Pérez Crespo M, Betlloch Mas I, Mataix Díaz J, et al. Rapid response to cyclosporine and maintenance with methotrexate in linear scleroderma in a young girl. Pediatr Dermatol 2009; 26:118.
- Strauss RM, Bhushan M, Goodfield MJ. Good response of linear scleroderma in a child to ciclosporin. Br J Dermatol 2004; 150:790.
- Neustadter JH, Samarin F, Carlson KR, Girardi M. Extracorporeal photochemotherapy for generalized deep morphea. Arch Dermatol 2009; 145:127.
- Cribier B, Faradji T, Le Coz C, et al. Extracorporeal photochemotherapy in systemic sclerosis and severe morphea. Dermatology 1995; 191:25.
- Karrer S, Abels C, Landthaler M, Szeimies RM. Topical photodynamic therapy for localized scleroderma. Acta Derm Venereol 2000; 80:26.
- Eisen D, Alster TS. Use of a 585 nm pulsed dye laser for the treatment of morphea. Dermatol Surg 2002; 28:615.
- Kineston D, Kwan JM, Uebelhoer NS, Shumaker PR. Use of a fractional ablative 10.6-μm carbon dioxide laser in the treatment of a morphea-related contracture. Arch Dermatol 2011; 147:1148.
- Zannin ME, Martini G, Athreya BH, et al. Ocular involvement in children with localised scleroderma: a multi-centre study. Br J Ophthalmol 2007; 91:1311.
- Kister I, Inglese M, Laxer RM, Herbert J. Neurologic manifestations of localized scleroderma: a case report and literature review. Neurology 2008; 71:1538.
- Roh MR, Jung JY, Chung KY. Autologous fat transplantation for depressed linear scleroderma-induced facial atrophic scars. Dermatol Surg 2008; 34:1659.
- Mertens JS, Seyger MM, Kievit W, et al. Disease recurrence in localized scleroderma: a retrospective analysis of 344 patients with paediatric- or adult-onset disease. Br J Dermatol 2015; 172:722.
- 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 Rheumatol 2014; 66:3496.
- APPROACH TO THERAPY
- TOPICAL AND INTRALESIONAL THERAPIES
- Topical tacrolimus
- Topical and intralesional corticosteroids
- Topical vitamin D
- SYSTEMIC THERAPIES
- Methotrexate and glucocorticoids
- Oral vitamin D
- OTHER THERAPIES
- OTHER INTERVENTIONS
- Functional impairments
- Extracutaneous disorders
- SUMMARY AND RECOMMENDATIONS