Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature.

OBJECTIVE: When faced with clinical symptoms of scarring alopecia-the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair follicles (HFs) containing living epithelial cells can offer a non-invasive approach to diagnosing inflammatory scalp lesions. METHODS: Lesional and non-lesional HFs were extracted from the scalp of patients with chronic discoid lupus erythematosus (CDLE), psoriasis and healthy controls. RNA was isolated from plucked anagen HFs and microarray, as well as quantitative real-time PCR was performed. RESULTS: Here, we report that gene expression analysis of only a small number of HF plucked from lesional areas of the scalp is sufficient to differentiate CDLE from psoriasis lesions or healthy HF. The expression profile from CDLE HFs coincides with published profiles of CDLE from skin biopsy. Genes that were highly expressed in lesional CDLE corresponded to well-known histopathological diagnostic features of CDLE and included those related to apoptotic cell death, the interferon signature, complement components and CD8+ T-cell immune responses. CONCLUSIONS: We therefore propose that information obtained from this non-invasive approach are sufficient to diagnose scalp lupus erythematosus. Once validated in routine clinical settings and compared with other scarring alopecias, this rapid and non-invasive approach will have great potential for paving the way for future diagnosis of inflammatory scalp lesions.

Development and testing of new candidate psoriatic arthritis screening questionnaires combining optimal questions from existing tools.

OBJECTIVE: Several questionnaires have been developed to screen for psoriatic arthritis (PsA), but head-to-head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments. METHODS: Data from the CONTEST study, a head-to-head comparison of 3 existing questionnaires, were used to identify items with a Youden index score of ≥0.1. These were combined using 4 approaches: CONTEST (simple additions of questions), CONTESTw (weighting using logistic regression), CONTESTjt (addition of a joint manikin), and CONTESTtree (additional questions identified by classification and regression tree [CART] analysis). These candidate questionnaires were tested in independent data sets. RESULTS: Twelve individual questions with a Youden index score of ≥0.1 were identified, but 4 of these were excluded due to duplication and redundancy. Weighting for 2 of these questions was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in 6 joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC curve analysis and discarded. The other 3 questionnaires were significant in all data sets, although CONTESTw was slightly inferior to the others in the validation data sets. Potential cut points for referral were also discussed. CONCLUSION: Of 4 candidate questionnaires combining existing discriminatory items to identify PsA in people with psoriasis, 3 were found to be significant on ROC curve analysis. Testing in independent data sets identified 2 questionnaires (CONTEST and CONTESTjt) that should be pursued for further prospective testing.

Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study.

The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine. The primary outcome was clinical response to hydroxychloroquine. We investigated the effects of disease attributes and metabolizing cytochrome P450 (CYP) polymorphisms on clinical outcome. Although the majority of patients responded to hydroxychloroquine, a significant proportion (39%) either failed to respond or was intolerant of the drug. Cigarette smoking and CYP genotype did not have any significant influence on response to hydroxychloroquine. Moreover, multivariate analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95% confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly associated with lack of response to hydroxychloroquine. These findings suggest that baseline lupus severity and SLE are predictors of response to hydroxychloroquine. A prospective study is now required to further investigate the relationship between disease activity and response to hydroxychloroquine. This will have the potential to further inform the clinical management of this disfiguring photosensitive disease.

Low-dose UVA1 phototherapy for proximal and acral scleroderma in systemic sclerosis.

Previous studies report the benefit of UVA1 phototherapy in treating acrosclerosis in patients with systemic sclerosis. We carried out a retrospective study to examine the effectiveness of UVA1 phototherapy in scleroderma affecting acral and proximal sites in patients with this disease. Patients with systemic sclerosis (diffuse type, n=5; limited type, n=3) underwent low-dose UVA1 radiation (30-40 J/cm(2)) thrice weekly. In all patients skin lesions improved, demonstrated by a fall in the modified Rodnan skin score ranging from 8 to 18 points in diffuse systemic sclerosis and 6 to 10 points in limited disease. This study would suggest that UVA1 phototherapy is effective for scleroderma affecting proximal and acral sites in patients with systemic sclerosis.

Paraneoplastic immunobullous disease with an epidermolysis bullosa acquisita phenotype: two cases demonstrating remission with treatment of gynaecological malignancy.

Two cases of paraneoplastic immunobullous disease occurring in women with gynaecological malignancies are reported. Both cases demonstrated mechanobullous mucocutaneous blistering as is typically seen in epidermolysis bullosa acquisita. Their immunopathology, however, favoured a dermal-binding mucous membrane pemphigoid (MMP) (or possibly bullous pemphigoid) for patient 1 and laminin-5 MMP for patient 2. Both patients showed resolution of blistering within 1 year of treatment of their malignancies; uterine and ovarian carcinoma, respectively. These cases are of interest because of their paraneoplastic nature; as well as overlapping clinicoimmunopathological features. In addition, patient 2 is, as far as we are aware, the first report of ovarian-carcinoma-associated laminin-5 MMP.