Showing papers by "John R. Ingram published in 2013"

Absence of pathogenic γ-secretase mutations in a South Wales cohort of familial and sporadic hidradenitis suppurativa (acne inversa).

Abstract: Loss-of-function mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 have recently been reported to underlie a subset of familial hidradenitis suppurativa (HS) in Chinese,(1-3) Japanese(4) and European(5-7) populations. In most cases, the HS phenotype was relatively severe and extensive and patients were drawn from multiplex kindreds. Of note, pathogenic γ-secretase mutations were found in only two of seven HS pedigrees examined in a UK study(5) and three out of 14 pedigrees from France.(7) In addition, mutational analysis of NCSTN, PSENEN, and PSEN1 in 48 HS patients referred to a tertiary UK clinic, 20 of whom reported a family history of HS, demonstrated only two pathogenic mutations.(6).

The natural history of eczema from birth to adult life: a cohort study.

Abstract: Background Eczema is common in infancy; however, there is little evidence about its natural history to adulthood. Objectives To study the natural history of eczema from birth to young adult life with particular reference to its relation to atopy. Methods A birth cohort of children with atopic family histories was followed for 23 years. Clinical examinations were conducted until the age of 7 years, skin-prick tests and serum total IgE were recorded in infancy and at ages 7 and 23 years, and questionnaires about eczema symptoms were completed at 15 and 23 years. Results Information was obtained on 497 subjects at birth, 482 at 1 year, 440 at 7 years, 363 at 15 years and 304 at 23 years. Eczema usually remitted from age 1 to 7 years but became more persistent from the age of 15 years, especially in those who were atopic. The prevalence of eczema rose in women from age 15 to 23 years but declined in men. Adults with eczema had higher IgE than those without at 3 months (geometric mean 3·0 vs. 1·7 kU L-1; P = 0·01), 7 years (107·9 vs. 45·2 kU L-1; P = 0·01) and 23 years (123·4 vs. 42·3 kU L-1; P = 0·01), and were more likely to have had positive skin-prick tests at 1 year of age. Current eczema was associated with raised IgE in infancy and adulthood but not in childhood. Conclusions Predisposed infants and children with eczema usually grow out of the disease, but in adolescence it is more likely to persist. Adult eczema is related to atopy from the age of 3 months. What's already known about this topic? Eczema is associated with atopy, asthma and rhinoconjunctivitis. Eczema in infancy usually remits but is more likely to persist if the child is atopic. After puberty eczema often persists to adult life. What does this study add? Adult eczema is associated with atopy from the age of 3 months. Atopy increases the likelihood of persistence after adolescence.

Difficulty giving feedback on underperformance undermines the educational value of multi-source feedback

Abstract: Background: Multi-source feedback (MSF) was intended to provide both a summative and formative assessment of doctors’ attitudes and behaviours. Aims: To explore the influences of feedback quality and trainees’ acceptance of the assessment on formative educational gains from MSF. Methods: Semi-structured interviews were conducted with a convenience sample of eight dermatology trainees, from an insider researcher position, following two pilot interviews. Interviews were manually transcribed and coded to permit template analysis, a subtype of thematic analysis. Results: The interview data indicated that MSF provides relatively little formative educational gains largely because of a paucity of constructive feedback on sub-optimal performance. This was due to difficulties encountered by raters giving developmental feedback, in particular, potential loss of anonymity, and by trainees selecting raters expected to give favourable comments. Dual use of MSF as a summative assessment in annual appraisals also inhibited educational gains by promotion of a ‘tick box’ mentality in which trainees’ need to pass their assessment superseded their desire for self-improvement. Conclusions: A relative lack of developmental feedback limits the formative educational gains from MSF and could provide false reassurance that might reinforce negative behaviours.

Segmental cherry angiomas associated with extragenital lichen sclerosus: a report of two cases.

Abstract: Cherry angiomas (Campbell de Morgan spots) are common acquired red skin papules composed of dilated capillary loops, usually of unknown aetiology. Extragenital lichen sclerosus (LS) presents as porcelain-white scaly atrophic lesions with or without genital involvement. We report two cases of segmental multiple cherry angiomas in association with extragenital LS. Two unrelated women, aged 46 and 66 years, presented with extragenital LS affecting their axillae and lower abdomen. During the examination, both patients were noted to have several hundred red skin papules in a segmental distribution, affecting the left thigh and flank of one woman, and the right abdomen and back of the other. Clinically and histologically, the papules were consistent with cherry angiomas. The striking segmental distribution of multiple cherry angiomas may be due to genetic mosaicism; however, segmental Fabry disease was excluded by sequence analysis of the α-galactosidase A gene. Any causal link between cherry angiomas and LS remains uncertain.

Interpreting outcome measures and defining treatment success

Abstract: When a case of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) presents, a management plan must be instigated immediately. Along with discontinuation of the culprit drug, institution of optimal supportive care is mandatory. Specialist dermatology nursing, local treatment of skin and mucous membranes, fluid replacement, nutrition and analgesia are all essential to improve the chances of survival and minimize sequelae. However, dermatologists are also prompted to consider prescribing active therapy in an attempt to ‘switch off’ keratinocyte apoptosis and limit the extension of skin involvement. Over the past 15 years, intravenous immunoglobulin (IVIg) has been used to this end, and many papers have been published indicating efficacy. However, in 2012 Huang et al. published a systematic review and meta-analysis of all studies using IVIg in the treatment of SJS/TEN and concluded that the evidence does not support unambiguous therapeutic benefit. In the current issue of the BJD, Lee et al. have presented the outcome of 64 patients with SJS/TEN treated with IVIg in one specialist centre. This is a retrospective analysis using SCORTEN (a validated severity-of-illness score) at presentation to predict patient mortality. All 64 patients received IVIg in combination with a standardized regimen of supportive care. Twenty of 64 patients (31%) died; the standardized mortality rate was 1 10 (95% confidence interval 0 62–1 58), indicating that, in keeping with the conclusions of Huang et al., IVIg does not appear to confer a survival benefit in TEN and may in fact be harmful. In previous studies authors have argued that the benefit of IVIg is achieved using higher doses; in the study by Lee et al. there was no mortality difference between patients when stratified for high dosage (≥ 3 g kg ) vs. low dosage (< 3 g kg ). The study’s conclusion was that IVIg does not produce a survival benefit in SJS/ TEN. Despite the findings from the study of Lee et al., and the conclusions from the meta-analysis by Huang et al., we suspect that many dermatologists will continue to prescribe IVIg. When managing a patient with a life-threatening illness (SJS/TEN has an overall mortality of ~25%), clinicians are compelled to prescribe a drug that may halt the disease process. The momentum behind IVIg is strong and reflects impressive results reported in the original paper by Viard et al., and subsequently endorsed by a number of case series published in the 2000s. More recently, as published in the BJD, researchers have expressed scepticism in the efficacy of IVIg in SJS/TEN. The question of a therapeutic effect of IVIg will be answered only by a controlled trial, the design of which might consist of three arms: IVIg, placebo and supportive care alone. Such a study would ideally use longterm morbidity as an end point, in addition to mortality, the former having been relatively neglected in previous studies. However, the rarity of SJS/TEN presents inherent challenges in conducting a controlled trial. Useful clinical studies in this disease will be achieved only through the creation of a national network of specialist TEN centres. Standardization of all aspects of case management is necessary, including case validation and dataset collection, as well as the delivery of structured supportive care. If a specialist network can be established we will be in a stronger position to undertake the investigative work needed to clarify uncertainties surrounding therapy in SJS/TEN.