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BACKGROUND: Bullous 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. METHODS: We 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 (

BackgroundBullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly.ObjectivesTo evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone.DesignPragmatic multicentre two-armed parallel-group randomised controlled trial with an economic evaluation.SettingA total of 54 dermatology secondary care centres in the UK and seven in Germany.ParticipantsAdults with BP [three or more blisters at two sites and positive direct and/or indirect immunofluorescence (immunoglobulin G and/or complement component 3 immunofluorescence at the dermal-epidermal junction)] and able to give informed consent.InterventionsParticipants were allocated using online randomisation to initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to 30 g/week of potent topical corticosteroids was permitted for weeks 1–3. After 6 weeks, clinicians could switch treatments or alter the prednisolone dose as per normal practice.Main outcome measuresPrimary outcomes: (1) the proportion of participants with three or fewer blisters at 6 weeks (investigator blinded) and (2) the proportion with severe, life-threatening and fatal treatment-related events at 52 weeks. A regression model was used in the analysis adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Secondary outcomes included the effectiveness of blister control after 6 weeks, relapses, related adverse events and quality of life. The economic evaluation involved bivariate regression of costs and quality-adjusted life-years (QALYs) from a NHS perspective.ResultsIn total, 132 patients were randomised to doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and baseline severity was as follows: mild 31.6% (three to nine blisters), moderate 39.1% (10–30 blisters) and severe 29.3% (> 30 blisters). For those starting on doxycycline, 83 out of 112 (74.1%) had three or fewer blisters at 6 weeks, whereas for those starting on prednisolone 92 out of 101 (91.1%) had three or fewer blisters at 6 weeks, an adjusted difference of 18.6% in favour of prednisolone [90% confidence interval (CI) 11.1% to 26.1%], using a modified intention-to-treat (mITT) analysis. Per-protocol analysis showed similar results: 74.4% compared with 92.3%, an adjusted difference of 18.7% (90% CI 9.8% to 27.6%). The rate of related severe, life-threatening and fatal events at 52 weeks was 18.2% for those started on doxycycline and 36.6% for those started on prednisolone (mITT analysis), an adjusted difference of 19.0% (95% CI 7.9% to 30.1%;p = 0.001) in favour of doxycycline. Secondary outcomes showed consistent findings. There was no significant difference in costs or QALYs per patient at 1 year between doxycycline-initiated therapy and prednisolone-initiated therapy (incremental cost of doxycycline-initiated therapy £959, 95% CI –£24 to £1941; incremental QALYs of doxycycline-initiated therapy –0.024, 95% CI –0.088 to 0.041). Using a willingness-to-pay criterion of ConclusionsA strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and considerably safer in the long term. The limitations of the trial were the wide non-inferiority margin, the moderate dropout rate and that serious adverse event collection was unblinded. Future work might include inducing remission with topical or oral corticosteroids and then randomising to doxycycline or prednisolone for maintenance.Trial registrationCurrent Controlled Trials ISRCTN13704604.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 10. See the NIHR Journals Library website for further project information.

The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

The aim of the study was to investigate the prevalence of hepatitis C (HCV) antibodies, hepatitis B surface antigen (HBsAg) carriage and liver disease in 100 females with genital lichen planus (LP) in Oxfordshire. Sera were screened for HCV antibodies (AxSYM HCV 3.0 Abbott), HBV surface antigen (AxSYM HBsAg V2 Abbott), mitochrondrial and anti-smooth muscle antibodies. Liver function tests were undertaken. All sera were negative for HCV antibody and HBsAg. Transiently abnormal liver function tests (2) and liver specific antibodies (2) were detected in four patients with no underlying liver disease. We found no association between HBV or HCV and genital LP in this population.

Summary Women with skin conditions may need topical corticosteroids during pregnancy. However, little is known about the effects of topical corticosteroids on the fetus. A guideline subcommittee of the European Dermatology Forum was organized to develop an evidence-based guideline on the use of topical corticosteroids in pregnancy (http://www.euroderm.org/edf/images/stories/guidelines/EDF-Guideline-on-Steroids-in-Pregnancy.pdf). The evidence from a Cochrane Review suggested that the major possible adverse effects on the fetus of topical corticosteroids were orofacial clefts when used preconceptionally and in the first trimester of pregnancy, and fetal growth restriction when very potent topical corticosteroids were used during pregnancy. To obtain robust evidence, a large population-based cohort study (on 84 133 pregnant women from the U.K. General Practice Research Database) was performed, which found a significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery and fetal death were found. Moreover, another recent Danish cohort study did not support a causal association between topical corticosteroid and orofacial cleft. The current best evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the associated risk of fetal growth restriction with the latter.

BACKGROUND The first choice of treatment for lentigo maligna (LM) is excision. Initial studies of treatment with imiquimod 5% cream have shown promising results with excellent cosmetic outcome, but the follow-up duration in these studies was short. OBJECTIVES To evaluate the results of treatment of patients with LM with imiquimod in routine clinical practice with long-term follow-up. METHODS We prospectively followed 10 patients with LM who were treated with imiquimod 5% cream between 2004 and 2007 with a median follow-up of 31 months (range 11-56 months). Histological clearance was assessed in all patients using post-treatment biopsies. RESULTS Complete clinical clearance was achieved in nine of 10 patients after treatment with imiquimod. During follow-up, three clinical and histological recurrences were observed at 9, 10, and 27 months after treatment cessation. In a fourth patient, histological recurrence without clinical signs was demonstrated 17 months after treatment. Five of 10 patients are in sustained clinical remission. CONCLUSIONS Imiquimod appears to be an effective treatment for a subset of patients with LM. We recommend long-term follow-up and taking multiple post-treatment biopsies, even in the absence of a clinical recurrence. This case series emphasizes the need for finding an optimal treatment regimen.

Summary Hypereosinophilic syndrome (HES) is a rare, heterogeneous group of systemic diseases characterized by sustained overproduction of eosinophils leading to variable end-organ damage. The skin is affected in 45–60% of patients and may be of diagnostic and prognostic value. In 1975, three criteria were suggested for the diagnosis of HES: (i) blood eosinophilia of > 1.5 × 109/L present for > 6 months, (ii) no apparent cause for the hypereosinophilia, and (iii) signs of end-organ dysfunction. We present a patient with hypereosinophilia in whom a delay in diagnosing HES occurred, partly due to his atopic constitution. However, atopy is not associated with such high or longstanding eosinophilia.

BACKGROUND: Mucous membrane pemphigoid and epidermolysis bullosa acquisita are rare acquired autoimmune blistering diseases of the skin. Both can result in scarring of mucous membranes which may lead to blindness and life threatening respiratory complications. OBJECTIVES: To assess the effects of treatments for mucous membrane pemphigoid and epidermolysis bullosa acquisita. SEARCH METHODS: We searched the Cochrane Skin Group Specialised Register (7th April 2005), the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2005), MEDLINE / PubMed (from 1966 to April 2005), EMBASE (from 1980 to April 2005), www.controlled‐trials.com (7th April 2005) and www.clinicaltrials.gov (7th April 2005) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of any treatments for mucous membrane pemphigoid or epidermolysis bullosa acquisita involving participants of any age with a diagnosis of either disease confirmed by immunofluorescence. DATA COLLECTION AND ANALYSIS: The data was independently extracted by three authors and subsequently checked for discrepancies. Two authors evaluated the studies in terms of the inclusion criteria. MAIN RESULTS: Two small randomised controlled trials of mucous membrane pemphigoid, both conducted in participants with severe eye involvement were identified. In the first trial, involving 24 participants, cyclophosphamide 2 mg/kg/day in combination with prednisone starting at 1 mg/kg/day and tapering was superior to prednisone alone (1 mg/kg/day) after 6 months of treatment. All 12 participants responded well to cyclophosphamide plus prednisone versus a good response in only 5 of 12 participants treated with prednisone (relative risk 2.40, 95% confidence interval 1.23 to 4.69). In the second trial, involving 40 participants, all 20 participants treated with cyclophosphamide (2 mg/kg/day) responded well after three months of treatment, but only 14 of 20 participants responded to treatment with dapsone (2 mg/kg/day) (relative risk 1.43, 95% confidence interval 1.07 to 1.90). All non‐responders had severe inflammatory activity. It was not explicitly stated whether these participants received prednisone in addition to dapsone or cyclophosphamide initially. Hair loss and suppression of the red and white blood cells were common adverse events in the cyclophosphamide groups. No randomised controlled trials of treatments for epidermolysis bullosa acquisita were identified. AUTHORS' CONCLUSIONS: There is limited evidence that mucous membrane pemphigoid involving the eyes responds best to treatment with cyclophosphamide combined with corticosteroids. However, mucous membrane pemphigoid with mild to modest inflammatory activity responds to dapsone in most participants and may therefore be best treated with dapsone due to its lower side effect profile compared to cyclophosphamide. Treatment with mycophenolate mofetil combined with topical steroids seems worth considering in a future randomised controlled trial for mucous membrane pemphigoid.

Objective To identify and critically evaluate evidence from randomized controlled trials for the efficacy of treatments for mucous membrane pemphigoid (MMP)/cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA). Search Strategy Review of MEDLINE from 1966 through March 2000, EMBASE from 1980 through March 2000, and the Cochrane Controlled Trials Register (February 28, 2001) to identify randomized controlled trials for the efficacy of treatments in MMP/CP and EBA. Selection Criteria All randomized controlled trials of therapeutic interventions that included patients with MMP/CP or EBA confirmed by immunofluorescence study findings. All age groups were included. Results We found 2 small randomized controlled trials of MMP/CP, both conducted in patients with severe eye involvement. We were not able to identify a randomized controlled trial of therapeutic interventions in EBA. Conclusions There is evidence from 2 small trials that severe ocular CP responds best to treatment with cyclophosphamide, and mild to moderate disease seems effectively suppressed by treatment with dapsone. No treatment recommendations can be made for EBA because to our knowledge no randomized controlled trials are published. Even though systemic corticosteroids are regarded as the gold standard in the treatment of MMP/CP and EBA, there is poor evidence from the literature that they are the best treatment for these diseases.

SUMMARY We report five patients who demonstrated clinical, histological and direct immunofluorescence (IF) features typical of linear IgA disease (LAD), but who also displayed IgG anti-basement membrane zone (BMZ) antibodies on indirect IF. The presence of circulating IgG anti-BMZ antibodies is often said to exclude the diagnosis of LAD. Unable to confidently classify these patients, we reviewed their clinical progress for unifying features. This revealed an almost universal benefit from dapsone therapy. We therefore propose that when strong linear IgA deposition is observed at the BMZ, a first line trial of dapsone is indicated, irrespective of the presence of circulating IgG. The class of antibody fixed in vivo appears to influence the clinical picture more than the class of circulating antibody.