T-cell receptor repertoire in pyoderma gangrenosum: evidence for clonal expansions and trafficking.

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.

Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial.

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 alpha. 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.

Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study.

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.

Medical outpatients: changes that can benefit patients.

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.

A prospective study of the prevalence and incidence of atopic dermatitis in children aged 0-42 months.

BACKGROUND: There is strong evidence that the incidence and prevalence of atopic diseases is increasing. However, estimates of the prevalence of atopic dermatitis (AD) have varied greatly in the U.K. and most parts of the developed world. OBJECTIVES: The aim of the study was to estimate the prevalence and incidence of AD between the ages of 0 and 42 months in children born in the 1990s in a defined population in the U.K. DESIGN: We used data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a large population-based study in the U.K. that enrolled all pregnant mothers who were resident in Avon and had their delivery date falling between 1 April 1991 and 31 December 1992. Since then ALSPAC has collected a wide range of data from the newborns and their parents. Data reported here were collected at 6, 18, 30 and 42 months using parental reports in a postal questionnaire. Of the 14 009 children originally enrolled 8530 provided information on AD in each of the four follow-up questionnaires. We defined AD as a report of rash in at least two of the four questionnaires. Incidence risk was defined as the percentage of new cases of AD between follow-up questionnaires, out of the total number of children whose parents had not reported that they had AD by the time of the previous follow-up. RESULTS: Period prevalence of 21.0%, 25.6%, 23.2% and 19.9% were observed at ages 0-6, 6-18, 18-30 and 30-42 months, respectively. The corresponding incidence risks were 21.0%, 11.2% and 3.8%, at 0-6, 6-18 and 18-30 months, respectively. There were no gender differences in either the incidence or prevalence of the disease. CONCLUSIONS: 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.

Polymorphic eruption of pregnancy developing in the puerperium.

Polymorphic eruption of pregnancy is an uncommon disorder, usually developing in the third trimester and rapidly resolving in the first few weeks postpartum. It has been suggested that multiple pregnancy and excessive weight gain are associated features. We report a patient with the clinical and histological features of polymorphic eruption of pregnancy, whose rash developed 4 weeks after delivery of a singleton pregnancy. An unusual feature of this case was the occurrence of the rash on the face. We discuss this case with respect to the recent literature.

Twice-daily vs. once-daily inpatient dithranol for psoriasis.

The aim of this study was to compare the efficacy and tolerability of twice-daily vs. once-daily regimes of dithranol (anthralin) in Lassar's paste. Over a 4-year period, 61 inpatients with stable plaque psoriasis gave informed consent and entered a randomized controlled trial, having twice or once-daily application of dithranol in Lassar's paste as part of otherwise standard Ingram's regime. Primary outcome measurements were time required in hospital, nursing time, changes in total body surface area affected by psoriasis and thickness of a target plaque and in some patients, an assessment of the recurrence of psoriasis. Doctors were blinded as to the regime being used. At entry, mean patient age, lesional surface area and target plaque thickness were comparable in both groups and no patient had received systemic therapy in the preceding 3 months. Forty-two patients completed the study, two (11%) in the twice-daily group withdrawing due to skin irritation or 'burning'. Mean lesional surface area and target plaque thickness were similar in both groups at hospital discharge. Mean (+/- SD) time spent in hospital was not significantly different in each group, being 13.3 (+/- 6.2) days and 13.9 (+/- 4.5) days for the twice-daily and once-daily groups, respectively (P = 0.36). Duration of hospitalization did not correlate with surface area or plaque thickness on admission. Mean (+/- SD) nursing time spent on treatment was significantly greater in the twice-daily group, at 0.82 (+/- 0.33) hours per day compared with 0.51(+/- 0.25) hours per day in the once-daily group. Relapse rate at 6 months was not different between the two groups.