Background: Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor a. Aim: In the first randomised placebo controlled trial of any drug for the treatment of PG, we have studied the role of infliximab in this disorder. Subjects: Patients 18 years of age or older with a clinical diagnosis of PG were invited to take part. Methods: Patients were randomised to receive an infusion of infliximab at 5 mg/kg or placebo at week 0. Patients were then assessed at week 2 and non-responders were offered open labelled infliximab. The primary end point was clinical improvement at week 2, with secondary end points being remission and improvement at week 6. Results: Thirty patients were entered into the study. After randomisation, 13 patients received infliximab and 17 patients received placebo. At week 2, significantly more patients in the infliximab group had improved (46% (6/13)) compared with the placebo group (6% (1/17); p = 0.025). Overall, 29 patients received infliximab with 69% (20/29) demonstrating a beneficial clinical response. Remission rate at week 6 was 21% (6/29). There was no response in 31% (9/29) of patients.Conclusions: This study has demonstrated that infliximab at a dose of 5 mg/kg is superior to placebo in the treatment of PG. Open label treatment with infliximab also produced promising results. Infliximab treatment should be considered in patients with PG.

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.

Results from this large, prospective study are consistent with recent reports of increased incidence and prevalence of AD. Health planners can use our estimates of incidence and prevalence to project the number of children likely to suffer from AD during infancy and early childhood, and thus to determine the human and financial resources required.

Objective: To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease. Design: Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months. Results: Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal. Conclusions: Associations between parents' atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no ''parent-of-origin'' effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.A topic dermatitis is an inflammatory skin disease that is characterised by itching, redness, and scaling of the skin, predominantly in the skin creases. Although the causes of atopic dermatitis are unclear, the familial aggregation of the disease is well established through many family studies of atopic dermatitis, asthma, and allergic rhinitis.

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Mutations in the type VII collagen gene (COL7A1) are known to underlie different forms of the inherited blistering skin disease dystrophic epidermolysis bullosa (DEB). Most COL7A1 mutations are unique to individual families, and therefore it is usually necessary to screen all 118 exons of the gene to determine the molecular pathology in a patient with DEB. This study aimed to identify any recurrent mutations in COL7A1 that might be applicable to mutation-detection strategies in these patients. Mutational analysis was undertaken in 23 British patients with autosomal recessive DEB using PCR amplification of genomic DNA followed by heteroduplex analysis, nucleotide sequencing, and restriction site analysis. Two recurrent mutations were identified: R578X (6 of 46 alleles) and 7786delG (7 of 46 alleles). Haplotype analysis revealed that the mutations existed on similar allelic backgrounds in different patients, consistent with propagation of common British ancestral haplotypes, although R578X and 7786delG also have been described in DEB patients from other ethnic backgrounds. Given the high relative frequency of these two COL7A1 mutations, British patients with recessive DEB should be screened initially for these nucleotide changes by PCR amplification of genomic DNA and restriction analysis before more exhaustive screening of COL7A1.

Background The cause of pyoderma gangrenosum (PG) is unknown, but it is likely to be an immune-mediated disease because it is often associated with conditions such as inflammatory bowel disease and rheumatoid arthritis. T cells play an important role in these conditions and have been implicated in the pathogenesis of other skin diseases such as psoriasis.Objectives We examined the T-cell receptor repertoire in PG in order to test the hypothesis that if the T cells were responding to antigen, there would be expanded T-cell clones in the skin and the circulation of these patients. Patients and methods We studied five patients with PG and examined the T-cell receptor repertoire in cells taken from the peripheral blood and from biopsies of the ulcers, using complementarity determining region 3 spectratyping. Results We were able to demonstrate expanded clones in the peripheral blood lymphocyte population of each patient. Clonal expansions within the skin were found in four of the five patients. Most significantly, expanded clones that were shared between the blood and the skin were revealed in four of the five patients.Conclusions These findings imply that T cells play an integral role in the development of PG and suggest that T cells are trafficking to the skin under the influence of an antigenic stimulus.

-This article reviews the current literature relating to medical outpatient services. It has been produced as part of the RCP/NHS Confederation working party on outpatients departments. The article deals with surveys of patient views on outpatients, suggested ways of improving the service, and how best to accommodate teaching in this setting. An RCP booklet, 'How user friendly is your outpatient department?', has also been produced and is available from the college. KEY WORDS: ambulatory care, appointment, booking, clinic, outpatient, waiting timeMost physicians spend a significant part of their week working in the outpatient department but although the consultation in the outpatient clinic is an important part of patients' hospital care, it is traditionally an under-resourced area of the hospital. There has been little research into improving the service and, as a result, the experience for patients is not always as good as it should be.A well-run clinic will not only improve the experiences of patients but also the working lives of clinic staff. It may reduce the need for admission to hospital, both for disease control and for its investigation. 1 There is currently also political pressure for change, particularly regarding waiting times. The Government has recently issued a target of a maximum of three months wait for all outpatients' appointments by 2005. 2 This article reviews the literature relating to outpatients, with a focus on medical outpatients. The Working Party's aim was to develop recommendations to enable physicians to improve the experience for patients attending their clinics, and the work culminated in the publication of a booklet for health professionals. 3 Inevitably, in this paper there is some overlap with managerial issues (for example, direct booking systems or computer referral systems), and while some of these are beyond the scope of this article, they are addressed where physicians will be expected to work with managers to improve service delivery. Search strategyThe bibliographic databases Medline and Embase were searched for articles on outpatients, hospital outpatient clinics, outpatient departments or ambulatory care. Papers on day care were excluded. The results were limited to the UK, to the years 1966-2002 and to papers in English with abstracts available. Surveys of patient attitudes and satisfaction Waiting time and appointmentsLong waits for a first outpatient appointment are a common cause of patient dissatisfaction. However, one survey of a gastroenterology clinic showed that patients placed a similar value on waiting time for investigation and waiting for the first appointment: 4 a clinic that had a two-month wait for appointment, but offered immediate investigation was preferable to one with a two-week wait for appointment but a three-month wait for investigation. The authors suggest that to focus just on 'wait to first appointment' is too simplistic and does not take account of patient preferences.The length of time patients have to wait in the clinic before ...