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Objective: To investigate the relationship between bullous pemphigoid (BP) and neurologic disease.Design: Case-control study.Setting: Tertiary care center for immunobullous diseases and skin tumor clinics at a university hospital in Oxford, England.Participants: Ninety consecutive patients with BP and 141 controls.Main Outcome Measures: Age-adjusted prevalence of neurologic disease in patients and controls. Time interval between the diagnosis of neurologic disease and BP and type of associated neurologic disease.Results: At least 1 neurologic diagnosis was present in 42 patients (46%) compared with 16 controls (11%). Pa-

SummaryBackgroundBullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids.MethodsWe did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604.FindingsBetween March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001.InterpretationStarting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term.FundingNIHR Health Technology Assessment Programme.

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The results of this study indicate that patients with BP and neurological disease exhibit an immune response to both BP180 and BP230, thus the link between the CNS and the skin is not dependent on a specific antigen, but possibly both antigens or their isoforms may be exposed following a neurological insult, and play a role in generation of an immune response.

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HighlightsLetrozole is a commonly used drug in breast cancer treatment.Letrozole induced cutaneous leukocytoclastic small vessel vasculitis: first UK case.There was extensive superficial skin necrosis; needed local and systemic steroids.Interestingly, the cancer shrank without treatment during the 3-4 month episode.Breast teams should be aware of this rare side effect.

Key Points Question What is the rate of incidental skin cancer detection in urgent skin cancer clinics, and are incidental cancers more likely to be detected in patients with a clinically suspicious index lesion than in those without? Findings In a cohort study including 4726 patients, 1117 malignant lesions were detected, 22% of which were identified incidentally by total body skin examinations corresponding to an incidental lesion detection rate of 5.1%. Detection of a malignant incidental lesion by total body skin examinations was significantly more likely in patients presenting with an index lesion suspicious for malignancy, compared with patients who presented with index lesions judged to be clinically benign. Meaning The findings of this study suggest that total body skin examinations may be useful for detecting incidental skin cancers and that patients with suspicious index lesions should be prioritized.