Case Reports

Solitary Morphea Profunda Following Trauma Sustained in an Automobile Accident

Cutis. 2015 January;95(1):32-36

References

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2. Nguyen JV, Werth VP, Fett N. Morphea treatment & management. Medscape Web site. http://emedicine.medscape.com/article/1065782-treatment. Updated July 21, 2014. Accessed December 16, 2104.

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9. Kreft B, Wohlrab J, Radant K, et al. Unrecognized radiation-induced localized scleroderma: a cause of postoperative wound-healing disorder [published online ahead of print June 22, 2009]. Clin Exp Dermatol. 2009;34:e383-e384.

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12. Wojas-Pelc A, Wielowieyska-Szybińska D, Kiełtyka A. Presence of the antinuclear antibodies and antibodies to Borrelia burgdorferi among patients with morphea en plaque, deep linear scleroderma and atrophoderma Pasini-Pierini [in Polish]. Przegl Lek. 2002;59:898-902.

13. Falanga V, Medsger TA Jr, Reichlin M, et al. Linear scleroderma. clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. 1986;104:849-857.

14. Kikuchi K, Sato S, Kadono T, et al. Serum concentration of procollagen type I carboxyterminal propeptide in localized scleroderma. Arch Dermatol. 1994;130:1269-1272.

15. Arnett FC, Tan FK, Uziel Y, et al. Autoantibodies to the extracellular matrix microfibrillar protein, fibrilin 1, in patients with localized scleroderma. Arthritis Rheum. 1999;42:2656-2659.

16. Savoia P, Zaccagna A, Bernengo MG. Guess what? inflammatory disseminated morphea profunda. Eur J Dermatol. 1999;9:654-656.

17. Igarashi A, Nashiro K, Kikuchi K, et al. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J Invest Dermatol. 1996;106:729-733.

18. Gilmour TK, Wilkinson B, Breit SN, et al. Analysis of dendritic cell populations using a revised histological staging of morphoea. Br J Dermatol. 2000;143:1183-1192.

19. Sayama K, Chen M, Shiraishi S, et al. Morphea profunda. Int J Dermatol. 1991;30:873-875.

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28. 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 [published online ahead of print February 4, 2009]. Br J Dermatol. 2009;160:1075-1082.

29. 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;155:1013-1020.

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The presence of ANAs in LS is controversial. According to Nguyen et al,² ANAs are present in approximately 46% to 80% of patients with morphea, with a higher prevalence in patients with generalized, linear, and deep subtypes. However, Savoia et al¹⁶ found that patients with morphea typically do not present with ANAs; rather ANAs usually are found in patients with EF.

Pathogenesis

After the inflammatory phase in LS, fibrillar collagen types I and III accumulate, causing dermal fibrosis. The extracellular matrix increases due to the activation of connective tissue growth factor, transforming growth factor β (TGF-β), TGF-β receptors, IL-4, and several other cytokines.¹⁷ The TGF-β receptors combine with the connective tissue growth factor released by fibroblasts to create an autocrine production loop that causes fibroblast and matrix production.¹⁷ As the inflammation progresses to sclerosis, the CD34 count decreases.¹⁸

Physical Findings

In patients with MP, lesions manifest as thickened taut skin with deep, solitary, and sclerotic indurated plaques. Clinically, plaques are mildly inflamed, hyperpigmented, symmetric, and somewhat ill defined, and the skin feels thickened and bound to the underlying fascia and muscle. Plaques usually are smooth and shiny, but areas of both dermal and subcutaneous atrophy may be present, particularly in chronic lesions.¹⁹ Morphea profunda also can be described as having a cobblestone or pseudocellulite appearance. The groove sign is used to describe a depression along the course of a vein and/or between muscle groups. Both clinical presentations may manifest later in the course of disease.²

Histopathology

Su and Person⁵ described 3 main characteristics of MP that stand out histopathologically. First, there is thickening and hyalinization of collagen bundles in the deep dermis, subcutis, and fascia that are prominent between the junction of the dermis and subcutaneous fat. There also are fewer sebaceous glands and hair follicles. Second, MP presents with an increased inflammatory cell infiltrate composed mainly of lymphocytes located around small blood vessels and the interstitium. In some patients, the lymphocytes consist predominantly of collections of plasma cells. Third, MP contains deposits of mucin in deep portions of the dermis with occasional eosinophils and mast cells. The presence of eosinophils allows EF to be a part of this spectrum and to be included as a differential diagnosis.⁵ Eosinophilic fasciitis has a similar presentation to MP because the fibrosis affects the dermis, subcutaneous fat, and underlying structures.²⁰ Although EF presents with the histopathologic characteristic of fascial fibrosis, a clear distinction between EF and morphea has not been established in the literature. Some authors classify EF as a variant of morphea, whereas others consider it as its own entity. We believe EF is its own entity. Eosinophilic fasciitis can be distinguished from morphea because 60% to 80% of patients with EF have peripheral eosinophilia and 20% to 70% of patients with EF have hypergammaglobulinemia. Additionally, morphea does not present as symmetrically or abruptly as EF.²¹

Treatment

To date, there is conflicting literature regarding the treatment regimen for MP. There is controversy regarding whether MP responds to corticosteroids.¹⁹ Different treatment regimens have been discussed for LS, but there is a lack of reports specifically describing therapies for MP and SMP. Because MP and SMP fall under the umbrella of LS, many investigators have reported using the following treatment regimens for patients with MP and SMP: bosentan,²² D-penicillamine,²³ phototherapy,^24-26 retinoids,²⁶oral steroids,²⁷ methotrexate,^27-29 vitamin D₃ (oral calcitriol),^30,31 cyclosporine,³² mycophenolate mofetil,³³ and extracorporeal photochemotherapy.³⁴

Falanga and Medsger²³ reported 64% (7/11) treatment success with D-penicillamine in patients who exhibited severe LS. Psoralen plus UVA,²⁴ methoxsalen, and UVA1 therapy are widely used in the treatment of LS.²⁵ Kreuter et al²⁵ advocated for phototherapy as the first approach in the management of LS after reporting improvement in all participants in their study (N=64), 2 participants with deep morphea while the rest exhibited other forms of morphea. Ozdemir et al²⁶ proposed that retinoic acid combined with psoralen plus UVA is a good treatment choice for plaque-type LS; however, UVA only has the ability to target the epidermis and dermis, which may not be useful for deep forms of morphea.

Several studies have shown positive results in patients treated with methylprednisolone combined with low-dose methotrexate sodium.^27-29 Kreuter et al³⁰ and Elst et al³¹ proposed that calcitriol is effective in treating LS, whereas Hulshof et al³⁵ indicated that it is not. It should be noted that none of these studies specifically mentioned MP. Martini et al³³ demonstrated success with mycophenolate mofetil in the treatment of 10 LS patients who were resistant to methotrexate sodium and corticosteroids. Although none of the participants in the study had MP, 2 patients had disabling pansclerotic morphea, 3 had generalized morphea, and 5 had linear scleroderma (morphea en coup de sabre) affecting the limbs (n=2) and face (n=3).³³ Because there is no established therapy or consensus for the treatment of MP, we have found success in starting with corticosteroids and then trying alternative therapies.