Inflammatory morphea in the context of Raynaud phenomenon
Published Web Locationhttps://doi.org/10.5070/D383s2r3x8
Inflammatory morphea in the context of Raynaud phenomenonDepartment of Dermatology, New York University
Naheed Abbasi MD MPH, Bahar Firoz MD MPH MD, Nicole M Bossenbroek MD, Shane A Meehan MD, Hideko Kamino MD, Andrew G Franks
Dermatology Online Journal 14 (10): 11
A 37-year-old woman presented with a one-year history of asymptomatic, red-brown patches and plaques on the abdomen and extremities, in the context of Raynaud phenomenon and anti-centromere antibodies. Two biopsy specimens confirmed the diagnosis of inflammatory morphea. Even in the absence of initial symptoms to support systemic disease, patients presenting with morphea in the setting of Raynaud phenomenon or anti-centromere antibodies deserve close surveillance for the possibility of CREST syndrome and systemic sclerosis.
|Figure 1||Figure 2|
A 37-year-old woman presented for initial evaluation at the Charles C. Harris Skin and Cancer Pavilion in October, 2007, with a one-year history of red-brown patches on the extremities and abdomen. The patches were neither pruritic nor painful but bothered the patient cosmetically. She denied fever, chills, weight loss, or other systemic symptoms. Medical history included type II diabetes mellitus that was controlled by dietary measures. The patient denied a personal or family history of connective-tissue disease. She also denied joint pains and malar eruption but did report digital pallor and pain in cold environments. The patient took no medications on a daily basis. She denied occupational or recreational exposure to wooded areas.
On the abdomen and extremities were several, ill-defined, 3-to 7-cm, erythematous-to-hyperpigmented patches and thin plaques. A few lesions appeared atrophic at the center. No scale was noted. Examination of the head and neck was unremarkable, and there was no visible joint swelling. Nail examination was unremarkable.
A complete blood count, chemistry panel, and urinalysis were normal. An antinuclear antibody (ANA) titer was 1:160 with a speckled pattern. Serum anti-histone antibody was negative, and anti-centromere antibody was positive. No abnormalities in C3, C4, Scl-70, SSA, SSB, and RNP antibodies were detected. A Lyme Western blot was negative.
There is a superficial and deep, perivascular infiltrate of lymphocytes with rare eosinophils and plasma cells. There is sclerosis of collagen bundles within the deep reticular dermis at the interface of the subcutis.
The term scleroderma encompasses a range of conditions from circumscribed cutaneous disease [morphea] to systemic sclerosis . Skin disease in the absence of systemic findings and Raynaud phenomenon classically differentiates localized scleroderma (i.e., morphea) from systemic sclerosis [2, 3].
An inflammatory sclerotic skin disease of unclear etiology, morphea typically presents between age 20 and 40 and affects women 2.6 times more than it does men . It has been classified into five general types that include plaque morphea, generalized morphea, bullous morphea, linear scleroderma, and deep morphea . Arthralgias, synovitis, uveitis, and joint contractures are more commonly associated with linear and deep subtypes than they are with other forms of morphea . While the literature reports that up to one quarter of patients with morphea develop one or more extracutaneous manifestations during the course of disease, this statistic applies more appropriately to pediatric patients and those with linear or deep morphea and probably overestimates the frequency of systemic disease in adults with other morphea subtypes [2, 3].
The etiology of morphea has not been established, and both trauma and Borrelia burgdorferi infection have been proposed and debated as potential causes [6, 7]. While a strong association with Borrelia infection is reported in some studies, this association may not be causal and is not observed in all patients with morphea . A variety of autoantibodies is seen in morphea, with titers generally correlating with disease activity. These antibodies include antinuclear antibodies (46% to 80%) and anti-histone antibodies (47%) . The literature reports strong associations between anti-centromere positivity and both CREST syndrome and Raynaud phenomenon . Thus, patients with a diagnosis of morphea in the setting of Raynaud phenomenon or anticentromere antibodies deserve close surveillance for the development of systemic symptoms and may in fact be patients with mild or early systemic sclerosis.
Histopathologically, morphea is characterized by increased collagen deposition in the dermis and subcutis, vascular wall thickening and luminal narrowing, and a variable inflammatory infiltrate. The overlying epidermis may be atrophic, normal, or slightly thick [10, 11]. Inflammation is more marked in early lesions (i.e., inflammatory morphea) and is composed of perivascular lymphocytes, macrophages, and plasma cells that may also be diffusely scattered in the lower dermis and subcutis . Treatment of morphea may be challenging, and the literature is lacking in double-blind trials. Traditional therapies have included topical, intralesional, and systemic glucocorticoids; topical and systemic calcipitriol; topical tacrolimus; hydroxychloroquine; and interferon- gamma . Phototherapy with UVA has been successfully employed, and a role for narrow-band UVB phototherapy has been suggested . Imiquimod and methotrexate also have been reported efficacious in small studies and case series [14, 15]. For Raynaud phenomenon, calcium channel blockers, angiotensin receptor antagonists, N-acetylcysteine, and bosentan may be effective .
References1. Chung L, et al. Systemic and localized scleroderma. Clin Dermatol 2006; 24: 374 PubMed
2. Laxer RM, Zulian F. Localized scleroderma. Curr Opinion Rheum 2006; 18: 606 PubMed
3. Zulian F, et al. Localized scleroderma in childhood is not just a skin disease. Arthritis Rheum 2005; 52; 2873 PubMed
4. Peterson LS, et al. Subspecialty clinics: rheumatology and dermatology classification of morphea (localized scleroderma). Mayo Clin Proc 1995; 70: 1068
5. Peterson LS, et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993. J Rheumatol 1997; 24: 73 PubMed
6. Aberer E, et al. Is localized scleroderma a Borrelia infection? Lancet 1985; 2: 278 PubMed
7. Eisendle K, et al. Morphoea: a manifestation of infection with Borrelia species? Br J Dermatol 2007: 1-10. [doi:10.1111/j.1365-2133.2007.08235.x] PubMed
8. Takehara K, et al. Localized scleroderma is an autoimmune disorder. Rheumatology 2005; 44: 274 PubMed
9. Buchanan RRC, Riglar AG. The titre of anti-centromere antibodies: its relationship to Raynaud's phenomenon and vascular occlusion. Br J Rheumatol 1989; 28: 221 PubMed
10. Weedon D. Skin Pathology. Elsevier Science 2002; 347
11. Morley SM, et al. Epidermal thickness in systemic sclerosis and morphoea. Clin Exp Dermatol 1985; 10: 51 PubMed
12. Serup J. Localized scleroderma (morphoea). Acta Derm Venereol 1986; 122: 1 PubMed
13. Brownell I, et al. Familial linear scleroderma (en coup de sabre) responsive to antimalarials and narrowband ultraviolet B therapy. Dermatol Online J 2007; 13: 11 PubMed
14. Dytoc M, et al. First case series on the use of imiquimod for morphoea. Br J Dermatol 2005; 153: 815 PubMed
15. Fitch PG, et al. Treatment of pediatric localized scleroderma with methotrexate. J Rheumatol 2006; 33: 609 PubMed
16. Zandman-Goddard G, et al. New therapeutic strategies for systemic sclerosis-a critical analysis of the literature. Clin Dev Immunol 2005; 12: 165 PubMed
© 2008 Dermatology Online Journal