While general systemic manifestations were most common in the generalized subtype. in mixed and generalized subtypes. Conclusions High prevalence of concomitant and familial autoimmune disease, systemic manifestations, and ANA positivity in the generalized and possibly mixed subtypes suggest that these are systemic autoimmune syndromes and not skin only phenomena. This has implications for the management and treatment of these patients. Introduction Morphea is characterized by sclerosis of the skin and in some JK 184 cases underlying tissue, but is generally thought to be an autoimmune disorder affecting a single organ; the skin. Consequently, current classification schemes divide morphea into categories based solely on cutaneous morphology, without reference to systemic disease or autoimmune phenomena. This classification is likely incomplete. Rather, morphea may be a systemic autoimmune condition that has manifestations outside the skin.1,2,3,4,5,6,7,8 For example, case reports describe morphea coexisting with other Mouse monoclonal to CD55.COB55 reacts with CD55, a 70 kDa GPI anchored single chain glycoprotein, referred to as decay accelerating factor (DAF). CD55 is widely expressed on hematopoietic cells including erythrocytes and NK cells, as well as on some non-hematopoietic cells. DAF protects cells from damage by autologous complement by preventing the amplification steps of the complement components. A defective PIG-A gene can lead to a deficiency of GPI -liked proteins such as CD55 and an acquired hemolytic anemia. This biological state is called paroxysmal nocturnal hemoglobinuria (PNH). Loss of protective proteins on the cell surface makes the red blood cells of PNH patients sensitive to complement-mediated lysis autoimmune diseases, including systemic lupus erythematosus, vitiligo, primary biliary cirrhosis, autoimmune hepatitis,3 Hashimoto’s thyroiditis, and myasthenia gravis.9,1,2,3,4,5 A retrospective review of 750 children with morphea revealed a greater than expected prevalence of familial autoimmune disease. The same pediatric study found systemic complaints outside the area of morphea in 22.4% JK 184 of children including arthralgias and esophageal dysmotility. Data in adults is limited, with one case control study of 50 caucasian adult women reporting increased personal and familial autoimmunity, but ANA status and systemic manifestations were not reported. Many autoantibodies have been reported in patients with morphea, including antinuclear (ANA), anti-single stranded DNA (anti-ssDNA), anti-histone, anti-topoisomerase II, anti-phospholipid, and rheumatoid factor.10,11,12 The clinical and prognostic significance of these autoantibodies remains unclear. Taken together, these reports suggest that morphea is an autoimmune JK 184 disease with a spectrum of manifestations ranging from skin only to multiple organ involvement. What remains unclear is the prevalence of autoimmune and systemic disease in morphea and its subtypes and how these findings correlate with autoantibody profile. This uncertainty negatively impacts patient care as many patients are untreated or treated with skin directed therapy who may in fact require systemic therapy. This study aims to address this gap in knowledge by quantifying the prevalence of autoimmunity and systemic manifestations in adults and children with morphea. Patients and Methods Approval was obtained from the institutional review board to review the medical records of patients with morphea seen from 2001 to 2007 at all UTSW affiliated institutions (UT Southwestern faculty dermatology practice, Texas Scottish Rite Hospital, Children’s Medical Center, and Parkland Memorial Hospital). JK 184 432 potential adult and pediatric subjects were identified by International Classification of Diseases, Ninth Revision diagnosis code for morphea/localized scleroderma and lichen sclerosus (701.0). After review of the medical record, all patients determined to meet the clinical criteria for morphea (histopathologic results were reviewed when present but were not necessary for inclusion) were included for analysis. Patients found on review of the medical record to have lichen sclerosus alone or sclerosing skin conditions other than morphea were excluded (186/431). For subjects (n=245) who met the inclusion criteria, data was entered electronically into a Microsoft Access database. Data extraction included of rheumatic or other autoimmune disease; of rheumatic or other autoimmune diseases in 1st and 2nd degree relatives; and and progressive hemifacial.