Leire González-Lara

Psoriasis, psoriatic arthritis and type 2 diabetes mellitus: a systematic review and meta-analysis

Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first authors last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty‐four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random‐effects analysis was determined to be 1·76 (95% CI 1·59–1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36–3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73–2·55) than the pooled OR. We perform meta‐regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta‐analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.

Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus

BACKGROUND Common DNA variants in IL12B, IL23R and IL23A have been associated with an increased susceptibility to psoriasis (Ps) and psoriatic arthritis (PsA). Metabolic comorbidities and cardiovascular risk factors have also been associated to both Ps and PsA. OBJECTIVE To analyze the effect of single nucleotide polymorphisms (SNPs) previously linked to Ps (IL12B rs6887695 and rs3212227, IL23R rs2201841 and rs11209026, and IL23Ars2066808) in the main phenotype and metabolic/cardiovascular characteristics among Ps patients from a Northern Spanish population. METHODS The aforementioned genetic variants were determined in a total of 405 chronic plaque Ps patients and 426 controls. Subsequent statistical analysis included stratification for psoriatic clinical characteristics (age of onset, disease severity, familial psoriasis, HLA-Cw6, nail psoriasis) plus diabetes mellitus type 2, arterial hypertension, dyslipidemia and ischemic cardiac events as comorbidities. RESULTS An association between IL23R rs11209026-GG genotype with a more severe disease (p=0.02, OR=2.11, 95% CI=1.13-3.95). Carriers of the IL23A rs2066808-A allele were significantly more frequent among PsA patients (p=0.016, OR= 3.04, 95% CI=1.19-7.78). We found significant associations between three SNP genotypes and type 2 diabetes: IL12B rs6887695-CC (p=0.03, OR=2.90, 95% CI=1.09-7.69), IL12B rs3212227-CC (p=0.035, OR=5.90, 95% CI= 1.35-25.73) and IL23R rs2201841-GG (p= 0.027, OR=2.69, 95% CI=1.09-6.66). CONCLUSION In our population, genetic variation at IL12B, IL23R and IL23A has an influence not only on the risk for Ps but also on disease severity and type 2 diabetes mellitus.

SNP rs11652075 in the CARD14 Gene as a Risk Factor for Psoriasis (PSORS2) in a Spanish Cohort

A recent genomic survey identified the association between a common single nucleotide polymorphism (SNP) at the CARD14 gene (SNP rs11652075; p.Arg820Trp) and psoriasis (Psor). Our aim was to replicate the association between this polymorphism and to determine whether other CARD14 variants could explain the association. A total of 400 Psor patients (mean age 47±15; 55% male) and 420 healthy controls (mean age 51±16; 56% male) all Caucasian were genotyped for rs11652075. The rs11652075 CC genotype was significantly associated with Psor in our population (p=0.003; odds ratios=1.59; 95% confidence intervals=1.16-2.19; statistical power >80). The sequencing of the whole CARD14 coding exons in a total of 15 patients did not identify other DNA variants that could explain this association. We did not find significant differences (allele/genotype frequencies) between the patients according to disease severity, presence of arthritis, onset of age, and family history of Psor. We confirmed the association between SNP rs11652075 at the CARD14 gene and Psor. The absence of other coding variants among our patients supported a direct role for this missense polymorphism on Psor risk.

The Cw6 and late-cornified envelope genotype plays a significant role in anti-tumor necrosis factor response among psoriatic patients.

Our aim was to determine whether the HLA-Cw6 and late-cornified envelope (LCE) deletion polymorphisms were related to disease improvement among psoriasis patients treated with anti-tumor necrosis factor (TNF) antibodies. The study included a total of 116 patients. Positive response (68%) was defined as a reduction of at least 75% of the Psoriasis Area and Severity Index (PASI) after 24 weeks of starting the anti-TNF therapy. We found a trend toward a better response among Cw6-positive patients. The frequency of patients who did not reach the PASI75 was higher among the LCE-DD patients (P=0.028; odds ratio=2.45, 95% confidence interval=1.09-5.52). Patients who were Cw6-positive and LCE-I carriers (ID/II) were significantly more likely to reach PASI75 than those who were Cw6-negative and LCE-DD (P=0.034; odds ratio=3.14, 95% confidence interval=1.07-9.24). In conclusion, we found an interaction between the HLA-Cw6 and LCE genotypes on disease improvement among psoriatic patients treated with anti-TNFs.

Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.

BACKGROUND The IL17 pathway plays an important role in the pathogenesis of psoriasis (PsO). OBJECTIVES To determine whether the variation at the IL17 pathway genes was linked to the risk for PsO or had an effect on disease severity and the risk for Psoriatic arthritis (PsA). METHODS Cross-sectional observational study of 580 psoriasis patients and 567 healthy controls who were genotyped for six single nucleotide polymorphisms (SNPs) in the IL17RA (rs4819554, rs879577), IL17A (rs7747909), IL17F (rs763780, rs2397084), and IL17E (rs79877597) genes. RESULTS We found significant higher frequencies of IL17RA rs4819554 G carriers among the patients (OR=1.33, 95%CI=1.05-1.69; p=0.017). The IL17RA rs4819554 G allele and IL17F rs2397084 TT genotype were significantly more frequent among Cw6 positive patients (p=0.037 and p=0.010, respectively). The IL17E rs79877597C allele was significantly more common among patients with severe forms of PsO (p=0.010; OR=2.42, 95%CI=1.23-4.76), and the CC genotype with the presence of arthritis (p=0.032; OR=1.50, 95%CI=1.04-2.18). CONCLUSIONS We identified the IL17RA rs4819554 SNP as a risk factor for PsO. The IL17E rs79877597 SNP was a modifier of the risk for PsO disease severity and PsA.

Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis

The CARD14 gene encodes a protein that enhances nuclear factor (NF)‐κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti‐TNF) therapies among patients with psoriasis.

NFKBIZ in Psoriasis: assessing the association with gene polymorphisms and report of a new transcript variant.

The IκBζ protein (NFKBIZ gene) is a nuclear inhibitor of NF-κB and plays an important role in the pathogenesis of Psoriasis (Psor). We sought to determine whether common NFKBIZ variants were associated with the risk of developing Psor. A total of 392 patients and 336 controls were genotyped for a common intron 10 indel that could affect pre-mRNA splicing. We found a significantly higher frequency of the insertion among the cw6-positive patients (p=0.01). Cw6-positive+intron 10 ins/ins were significantly more frequent in the patients (OR=3.61). The analysis of the cDNA from leukocytes showed a NFKBIZ transcript lacking exon 10, present in all the tested samples. This new alternative transcript lacks a domain predicted to interact with the NFKB1/p50 protein. Functional studies to define the effect of this alternative transcript on the regulation of the NF-κB pathway are necessary.

Value of dermoscopy for the differential diagnosis of Wolf's post herpetic isotopic response.

The development of an unrelated cutaneous disorder over the exact site of a previous healed skin disease (frequently post-herpetic) is known as Wolf’s isotopic response (WIR). This rare phenomenon is considered to be different from Koebner’s isomorphic response, where an already existing skin disease arises in a traumatised location. As WIR may often be misdiagnosed, correct treatment is usually delayed. Thus, we consider it worth presenting a patient in whom dermoscopy, combined with clinical history, facilitated the recognition of a granulomatous Wolf’s postherpetic isotopic response.

Dr K. Holubar (1936–2013)

bronchial cancer simulating keratoacanthoma. Bull Soc Fr Dermatol Syphiligr 1969; 76: 552. 6 Cassarino DS, Xue W, Shannon KJ. Widespread cutaneous and perioral metastases of mesothelioma. J Cutan Pathol 2003; 30: 582–585. 7 Aramburu-Gonzalez JA, Rodriguez-Justo M, Jimenez-Reyes J, et al. A case of soft tissue mesenchymal chondrosarcoma metastatic to skin, clinically mimicking keratoacanthoma. Am J Dermatopathol 1999; 21: 392–394. 8 Dessinioti C, Georgala S, Chatziolou E, et al. What is your diagnosis? The diagnosis: cutaneous metastases from non-small cell lung carcinoma [photo quiz] Cutis 2011; 87: 277, 281–283. 9 Sariya D, Ruth K, Adams-McDonnell R, et al. Clinicopathologic correlation of cutaneous metastases: experience from a cancer center. Arch Dermatol 2007; 143: 613–620.

Effect of the FTO rs9930506 polymorphism on obesity and the main clinical outcomes in patients with psoriasis

may increase the risk of photocarcinogensis. Certain other antipsoriatic monoor combination therapies are well known to increase the risk of developing NMSC very rapidly. For instance, ciclosporin has strong immunosuppressive properties and has been linked to an increase in the occurrence of UVBor psoralen plus UVA (PUVA)-induced malignancies in the short term. Bursts of skin tumours were observed within only a few months of the start of administration of ciclosporin. In particular, when a combination of ciclosporin and PUVA is given, simultaneously and in a sequential combination (ciclosporin after PUVA), the frequency of cutaneous squamous cell carcinoma dramatically increases in the short term. and cited therein Here we show that a combination of biologics with 311nm UVB phototherapy may be safe at least in the short-tointermediate term, and, thus, could be an option for induction treatment in difficult-to-treat cases. Indeed, the analysis of pooled data from our studies suggests that the ultimate response to the combination therapy may be higher than with either monotherapy alone (Table 1), based on a comparison to response rates and experience reported in the literature. This is consistent with the results of a recent study by Calzavara-Pinton et al. who demonstrated that in a subgroup of patients the combination of etanercept with 311nm UVB was more effective than the single treatments alone. However, our study has major limitations: it has a low number of patients and many variables, including the use of different biologics, different (and relatively short) observation times, and different preand post-treatments. Thus, additional data with larger numbers of patients and longer follow-up terms are needed to quantify the definitive potential risk of skin cancer upon combination treatment of UVB with biological agents. Analyses from patients’ registries may help to answer this question.