Jorge Santos-Juanes

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.

Ustekinumab induces rapid clearing of erythrodermic psoriasis after failure of antitumour necrosis factor therapies

and outpatient NB-UVB therapy for the treatment of vitiligo. In a randomized study in psoriasis, Koek et al. recently showed that home NB-UVB therapy was equally safe and effective, and a useful alternative to outpatient NB-UVB therapy. This outcome is in line with our results. Although this study has several limitations (retrospective, not randomized, based on daily practice, unbalanced regarding skin types involved, and based primarily on patient-reported outcomes), we provide preliminary evidence for the efficacy and safety of home NB-UVB therapy. Concerns about home NB-UVB therapy regularly expressed among dermatologists (over-treatment, higher occurrence of shortand long-term side-effects, and reduced treatment efficacy) could not be confirmed. In conclusion, this study shows that patient-reported outcomes of home and outpatient NB-UVB therapy are comparable, with similar repigmentation and occurrence of side-effects. However, satisfaction with the result was significantly lower in the home group. On the other hand, the time investment for home patients was significantly less. Therefore, we suggest that home NB-UVB therapy is a valuable alternative to outpatient NB-UVB therapy in the treatment of nonsegmental vitiligo.

Guttate psoriasis induced by infliximab in a child with Crohn's disease

and the mechanism of Crohn’s disease. More and more evidence has suggested that gut bacteria play a critical role in the development of inflammatory bowel disease, and Crohn’s disease seems to develop in the intestine largely as a result of aberrant interaction of gut bacteria and their components with the host. If this is true, we would have to answer how Crohn’s disease with the same nature occurred in the mouth and esophagus, where the amount of bacteria is very limited. Lesions of the intestine can usually be found at the same time or eventually show up in patients with “Crohn’s disease of the esophagus or the mouth.” It seems that lesions of the esophagus and mouth are more likely to be manifestations of intestinal Crohn’s disease rather to have originated locally. If this is the case, the lesions of the esophagus and mouth should probably be called oral or esophageal manifestations (or complications) of Crohn’s disease rather Crohn’s disease of the esophagus or the mouth, just like the uveitis in Crohn’s patients would be better called a manifestation of Crohn’s disease in the eye rather Crohn’s disease of the eye. Saying that Crohn’s disease can occur anywhere in the digestive tract seems to be a convenient but potentially misleading statement.

Mutation analysis of the LCE3B/LCE3C genes in Psoriasis

BackgroundAn association between a common deletion comprising the late cornified envelope LCE3B and LCE3C genes (LCE3C_LCE3B-del) and Psoriasis (Ps) has been reported. The expression of these LCE genes was induced after skin barrier disruption and was also strong in psoriatic lesions. The damage to the skin barrier could trigger an epidermal response that includes the expression of genes involved in the formation of skin barrier.MethodsWe determined the LCE3C_LCE3B-del genotype in 405 Ps patients and 400 healthy controls from a Northern Spain region (Asturias). These patients and controls were also genotyped for the rs4112788 single nucleotide polymorphism, in strong linkage disequilibrium with the LCE3C_B cluster. The LCE3B and LCE3C gene variant was determined in the patients through SSCA, DHPLC, and direct sequencing.ResultsAllele and genotype frequencies did not differ between patients and controls for the rs4112788 and LCE3C_LCE3B-del polymorphisms. However, del/del homozygotes were significantly higher among patients with chronic plaque type Ps who did not develop arthritis (p = 0.03; OR = 1.4; 95%CI = 1.03-1.92). The analysis of the coding sequence of LCE3B and LCE3C in the patients who had at least one copy of this showed that only one patient has a no previously reported LCE3B variant (R68C).ConclusionOur work suggested that homozygosity for a common LCE3C_LCE3B deletion contributes to the risk of developing chronic plaque type Ps without psoriatic arthritis. Our work confirmed previous reports that described an association of this marker with only skin manifestations, and supported the concept of different genetic risk factors contributing to skin and joint disease.

Psoriasis and hypertension: a case-control study

Background  Several studies stated that patient with psoriasis carried an increased risk of psoriasis but some studies did not demonstrate this association.

Psoriasis and type 2 diabetes risk among psoriatic patients in a Spanish population

There is accumulating evidence showing a relationship between psoriasis and an increased risk of developing cardiovascular risk factors, including diabetes mellitus type 2 and ischemic heart disease. Our aim was to investigate if there is any difference in the diabetes risk profile among psoriatic patients based on clinical findings. To test this, we carried out a prospective and descriptive hospital‐based study. Our results suggest that the highest risk of suffering from diabetes mellitus type 2 among psoriatic patients is in patients suffering from non‐familial and late‐onset disease and in patients suffering from psoriatic arthritis.

Acneiform lesions in Becker's nevus and breast hypoplasia

An 18‐year‐old woman was referred for the evaluation of a dull gray macule on the left breast. From the age of 13 years, the patient noted breast asymmetry beginning with the development of the left breast and the presence of a pigmented stain on its border. Physical exploration revealed hypoplasia of the left breast and a homogeneous, light brown macule on the side of the breast ( Fig. 1 ) without infiltration. Papules and pustules were located mainly around the Beckers nevus on the left anterior chest wall. Biopsy specimens with Fontanas stain disclosed a hyperpigmented acanthotic epidermis. A diagnosis of Beckers nevus, acne, and hypoplasia of the breast was made.

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.

Genetic variation at the CCR5/CCR2 gene cluster and risk of psoriasis and psoriatic arthritis

OBJECTIVES Inflammation plays a major role in psoriasis (Ps). The variation at several genes that encode components of the inflammatory pathways have been linked to the risk for Ps. Our objective was to examine the association between Ps and three polymorphisms at the chemokine receptors CCR5 and CCR2. METHODS A total of 382 Ps patients and 500 healthy controls from Spain were genotyped for the CCR5-32bp deletion (DeltaCCR5), the rs1799988 (CCR5 promoter), and the CCR2-I64V (rs1799864) polymorphisms. RESULTS Allele and genotype frequencies did not differ between patients and controls for any of the three polymorphisms. However, the frequency of the CCR2-64I carriers was significantly higher in the patients who developed arthritis (n=81) compared to patients without arthritis (p=0.0007). CONCLUSIONS Our work suggests that the genetic variation at the CCR2/CCR5 genes did not contribute to the risk for Ps, but CCR2 polymorphisms could modulate the risk for arthritis in patients with psoriasis.

Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis

Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first authors last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle–Ottawa scale. Crude RR was calculated from the data provided in each article. Meta‐analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta‐regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random‐effects analysis was determined to be 6·32 (95% CI, 4·02–9·93). Global proportions of positive samples were 0·79 (95% CI, 0·72–0·84) and 0·12 (95% CI, 0·08–0·19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non‐negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.