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OBJECTIVE: Skin conditions in individuals with undifferentiated connective tissue disease (UCTD) are poorly classified and characterized, and autoantibodies in serum can be heterogeneous and not always specific. We have identified a new subset of individuals with UCTD, interface dermatitis, and increased anti-thyroid antibodies. METHODS: We retrospectively reviewed 892 cases of individuals with UCTD. Serologic markers for CTD and autoantibodies against microsomes and/or thyroglobulin were analyzed. Skin lesions and medication history were documented, and persistent or recurrent skin lesions were biopsied. RESULTS: Anti-thyroid antibodies for thyroglobulin and/or microsomes (ATAb) were positive in 526 (59%). The ATAb(+) and ATAb(-) groups had similar antinuclear antibody (ANA) positivity (32% vs 28%, respectively), average age (59 vs 58 yrs), and female-male ratio (8:1 vs 6:1). ATAb positivity was significantly associated with a dermatitis manifested as erythematous macules/patches or papules on legs, upper arms, back, and shoulders in 9% (47/526) of ATAb(+) individuals versus 2% (7/366) in ATAb(-) individuals (p < 0.0001). Seventeen individuals with dermatitis, 15 ATAb(+) and 2 ATAb(-), had biopsies. Twelve biopsies (80%) from ATAb(+) individuals and one ATAb(-) individual showed a cell-poor lymphocytic interface dermatitis with vaculopathy of basal layer keratinocytes, dermal mucin deposition, and perivascular mononuclear inflammatory cell infiltrates in the upper dermis that spared eccrine glands. The interface dermatitis was not significantly associated with hypo- or hyperthyroidism, or medications. CONCLUSION: We describe an ATAb-associated interface dermatitis in roughly 9% of ATAb(+) patients with UCTD, which may represent a new subset of autoimmune disease. ATAb may be a useful marker for some individuals with UCTD.