PDAI may be reliable, easy-to-use pemphigus scoring system
Researchers from the University of Pennsylvania assessing the reliability and convergent validity of the PDAI (pemphigus disease area index) have found that the PDAI is more reproducible and correlates better with physician impression of extent of disease than the ABSIS (autoimmune bullous skin disorder intensity score) instrument.
A major obstacle in performing multicenter controlled trials for pemphigus has been the lack of a validated disease activity scoring system, so the investigators asked a group of 10 dermatologists to score 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS instrument. To assess convergent validity, these tools were also correlated with the Physician’s Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95 percent CI=0.61–0.91) for the PDAI and 0.77 (0.63–0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17–0.60) for the ABSIS and 0.86 (0.76–0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96–1.0) for the PDAI and 0.80 (0.65–0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS.
For more information on this study, visit www.nature.com/jid/journal/vaop/ncurrent/ abs/jid200972a.html. Citation: Rosenbach M, et al. Journal of Investigative Dermatology, April 9, 2009, published online ahead of print, doi: 10.1038/jid.2009.72
More than half the variation in melanoma development due to genetic influences
Researchers from Australia’s University of Queensland studying the heritability of risk toward developing cutaneous melanoma have found that 55 percent of the variation in liability to melanoma is due to genetic influences. While it has previously been established that melanoma runs within families, this may be due to either shared genetic or shared environmental influences within those families. The concordance between pairs of non-identical twins compared to that between identical twins can be used to determine whether familial aggregation is due to genetic or environmental factors. Mandatory reporting of melanoma cases in the state of Queensland yielded approximately 12,000 cases between 1982 and 1990. Twins in this study and from the adjacent state of New South Wales (125 pairs in total) were used to partition variation in liability to melanoma into genetic and environmental factors. Identical twins were more concordant for melanoma (4 of 27 pairs) than non-identical twins (3 of 98 pairs; p 0.04). Identical co-twins of affected individuals were 9.8 times more likely to be affected than by chance. However, nonidentical co-twins of affected individuals were only 1.8 times more likely to be affected than by chance. An MZ:DZ recurrence risk ratio of 5.6 suggests that some of the genetic influences on melanoma are due to epistatic (gene–gene) interactions.
For more information on this study, visit www.nature.com/jid/journal/vaop/ncurrent/abs/jid200948a.html. Citation: Shekar S, et al. Journal of Investigative Dermatology, April 9, 2009, published online ahead of print, doi: 10.1038/jid.2009.48.
Transforming growth factor reduces scarring after surgery or injury
Researchers from the University of Manchester assessing scar improvement with avotermin — recombinant, active, human transforming growth factor β3 (TGFβ3) — have found it has the potential to provide an accelerated and permanent improvement in scarring. In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0.25 to 500 ng/100 μL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 hours later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomization scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. In two studies, avotermin 50 ng/100 μL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range −2 to 14; p=0.001) at month 6 and 8 mm (−29 to 18; p=0.0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14.84 mm [95 percent CI=5.5-24.2] at 5 ng/100 μL per linear cm to 64.25 mm [49.4-79.1] at 500 ng/100 μL per linear cm). Nine (60 percent) scars treated with avotermin 50 ng/100 μL per linear cm showed 25 percent or less abnormal orientation of collagen fibers in the reticular dermis versus five (33 percent) placebo scars. Six weeks after wounding, avotermin 500 ng/100 μL per linear cm improved VAS score by 16.12 mm (95 percent CI=10.61-21.63). Adverse events at wound sites were similar for avotermin and controls. Erythema and edema were more frequent with avotermin than with placebo, but were transient and deemed by investigators to be consistent with normal wound healing.
For more information on this study, visit www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60322-6/abstract. Citation: Ferguson M, et al. The Lancet, April 11, 2009, 373:1264-1274.
Women with psoriasis may have greater risk of hypertension, diabetes
Researchers from Harvard Medical School evaluating the independent association between psoriasis and risk of diabetes and hypertension have found psoriasis to be independently associated with an increased risk of diabetes and hypertension. This prospective study of female nurses followed a cohort of 116,671 US women aged 27 to 44 years in 1991 from 1991 to 2005 as part of the Nurses’ Health Study II. The study analysis included 78,061 of these women who responded to a question about a lifetime history of physician-diagnosed psoriasis in 2005, with new diagnoses of diabetes or hypertension having been obtained from biennial questionnaires. Of the 78,061 women, 1813 (2.3 percent) reported a diagnosis of psoriasis. During the 14 years of follow-up, a total of 1560 incident cases (2 percent) of diabetes and 15,724 incident cases (20 percent) of hypertension were documented. The multivariate-adjusted relative risk of diabetes in women with psoriasis compared with women without psoriasis was 1.63 (95 percent CI=1.25- 2.12). Women with psoriasis were also at an increased risk for the development of hypertension (multivariate relative risk, 1.17; 95 percent CI=1.06-1.30). Age, body mass index, and smoking status did not significantly modify the association between psoriasis and risk of diabetes or hypertension (p values for interaction, .07). Investigators suggest future studies to determine whether psoriasis treatment will reduce the risk of diabetes and hypertension.
For more information on this study, visit http://archderm.ama-assn.org/cgi/content/short/145/4/379. Citation: Qureshi A, et al. Archives of Dermatology, April 2009, 145:379-382. •
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