British Journal of Dermatology 1995; 132: 197-203. The association between lichen sclerosus and antigens of the HLA system P.MARREN, J.YELL, F.M.CHARNOCK,* M.BUNCE,t K.WELSHt AND F.WOJNAROWSKA Departments of Dermatology, 'Obstetrics and Gynaecology and 'f Transplant Immunology, The Churchill and John Radcliffe Hospitals, Oxford, U.K. Accepted for publication 14 April 1994 Summary Although frequently linked clinically with autoimmune disease, no immunogenetic basis for lichen sclerosus has ever been estabfished. In this study, we examined in detail the HLA antigens of 84 patients with histologically proven disease, compared with 357 controls. Patients with lichen sclerosus did not have the expected HLA Al, B8, DR3, DQ2 autoimmune profile. Instead, DQ7 was present in 39 of 78 (50%) of patients compared with 89 (25%) controls (P < 0-001). In addition, 61 of 78 patients (78%) had either DQ7, DQ8 or DQ9 antigens, or a combination of these, compared with 142 (40%) controls (P < 0-01). Raised levels of DQ7 correspond to a glutamic acid residue at position 45 of the DQBl locus. Proline amino acids at position 55 of this DQBl locus could explain the raised levels of DQ7, 8 and 9, and exert a secondary effect. There is preliminary evidence that the immunogenetic profile of patients with this disease may affect disease expression with regard to site and extent of involvement. Lichen sclerosus is a skin disease which characteristi- cally afi'ects the anogenital area in women, but occurs at all ages and in both sexes, and may affect skin at any site. Lesions are typically fiat, white and shiny, and telangiectasia, purpura and erosions can be found. These lesions may be asymptomatic at extragenital sites, but they are frequently a cause of intense prur- itus, discomfort and misery when they affect the geni- talia.^ The cause of lichen sclerosus is essentially unknown. Hormonal factors are considered by some to be impor- tant, as the disease generally arises at times of relative oestrogen deficiency, i.e. pre-menarche and after the menopause, but this is not invariable. Genetic factors have also been proposed, and there are approximately 15 reports of familial disease in the literature.^ How- ever, an association between lichen sclerosus and antigens of the HLA system has never been estab- lished. Several workers have addressed this issue in the past 12 years, with confiicting results. Meyrick Thomas, in 1984, investigated class I A and B antigens in 120 patients with lichen sclerosus, and found no association.^ No significant association has been found between lichen sclerosus and class II antigens, although few class II antigens have been examined to date. In contrast, the clinical association between lichen sclerosus and autoimmune disease is well established. In 1971, Wallace suggested the possibility of an asso- ciation between fichen sclerosus and vitiligo,* and subsequently Goolamali reported that approximately 40% of patients with lichen sclerosus had thyroid and parietal cell antibodies.^ Harrington and Dunsmore,^ and Meyrick Thomas et al.^'^ later reported a high incidence of autoimmune disease and autoantibodies both in affected individuals and their families. The present study was undertaken because advances in immunogenetic techniques now allow us to study HLA antigens much more comprehensively, looking particu- larly at class II DR and DQ antigens, which have been linked with many other autoimmune diseases.'" ^^ Methods Subjects We collected data on a patient population of 84 Caucasian females. These were randomly selected from our cfinic for vulval disease. All had clinical findings consistent with the diagnosis of lichen sclerosus, and in each case the diagnosis was also confirmed histologically, with the exception of three pre-pubertal girls in whom a biopsy was not performed. The age range was 7-91 years. All patients had anogenital involvement, and 13 had lichen sclerosus 197