We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis.

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Psoriatic plaque thickness is a clinical measure of psoriasis severity. We have observed that patients tend to revert to a baseline thickness of psoriatic plaques when in an untreated state, and hypothesized that other features of psoriasis could associate with this trait. Data prospectively collected on 500 participants in the Utah Psoriasis Initiative were used for the study. In response to a question assessing plaque thickness when disease was at its worst, 144 (28.8%) reported thick plaques, 123 (24.6%) reported thin plaques, and 233 (46.6%) reported intermediate thickness. For patients with "worst-ever" disease at enrollment (n=122), there was significant correlation of thickness between assessment by the patient and the physician (r=0.448, P-value 0.01). Thick plaques associated with male gender, increased body mass index, nail disease, psoriatic arthritis, larger plaques, more body sites, and greater total body surface area affected. Thin plaques associated with eczema, guttate psoriasis, and skin cancer. We suggest that this is preliminary evidence that plaque thickness is an easily measured trait that associates with other clinical features of psoriasis, and that stratification on this phenotype may be useful in further defining the genetic basis of this disease.

Background To properly evaluate therapies for cutaneous dermatomyositis (DM), it is essential to administer an outcome instrument that is reliable, valid, and responsive to clinical change, particularly when measuring disease activity. Objective The purpose of this study is to compare two skin-severity DM outcome measures, the Cutaneous Disease and Activity Severity Index (CDASI) and the Cutaneous Assessment Tool-Binary Method (CAT-BM), with the physician global assessment (PGA) as the ‘gold standard’. Methods Ten dermatologists evaluated fourteen patients with DM using the CDASI, CAT-BM, and PGA scales. Inter-, intra-rater reliability, validity, responsiveness, and completion time were compared for each outcome instrument. Responsiveness was assessed from a different study population, where one physician evaluated 35 patients with 110 visits. Results The CDASI was found to have a higher inter- and intra-rater reliability. Regarding construct validity, both the CDASI and the CAT-BM were significant predictors of the PGA scales. The CDASI had the best responsiveness among the three outcome instruments examined. The CDASI had a statistically longer completion time than the CAT-BM by about 1.5 minutes. Limitations The small patient population may limit the external validity of the findings observed. Conclusions The CDASI is a better clinical tool to assess skin severity in DM.

Panniculitis is an uncommon cutaneous manifestation of connective tissue diseases. Our discussion will include panniculitis occurring in the setting of lupus erythematosus, dermatomyositis, and scleroderma/morphea. These subtypes of panniculitis are unified by an active inflammatory stage of the disease that can progress to develop scarring, atrophy, and calcifications. Treatment is most effective if initiated during the active phase of the disease and often requires systemic therapy because of the location of the inflammation. Antimalarials are the initial treatment of choice for most cases of lupus erythematosus panniculitis, whereas corticosteroids in combination with other steroid-sparing immunosuppressive agents are the first-line treatment for panniculitis in patients with dermatomyositis. The appropriate treatment for panniculitis in the setting of morphea/scleroderma varies based on clinical severity.