María Carmen González-Vela

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti‐TNF‐α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti‐TNF‐α monoclonal antibody adalimumab may improve insulin sensitivity in non‐diabetic patients with psoriasis.

Subcutaneous phaeohyphomycosis caused by Exophiala oligosperma in a renal transplant recipient.

horns in the present report probably originated from longstanding verruca vulgaris lesions. It had been widely accepted that the horn arising from an exaggerated verruca vulgaris seldom reaches a height of 0Æ5 cm, but the horns in this case were exceptionally large, with the longest one reaching 21 cm, possibly indicating very special individual features. Verrucae vulgaris (skin warts) are kinds of benign proliferating lesions in epithelia, often on hands, and are usually caused by HPV infection. The present case contained intact HPV-2a genome sequences, which may present in episomal form. Whole genome alignment analyses of this isolate revealed very high homology with the HPV-2a prototype. Although several mutations have been identified in various regions, e.g. in E1, E7 and the long control region (LCR), even a nucleotide exchange in the potential E2 binding site in the LCR, it is hard simply to ascribe the presence of multiple horns to virus infection, as none of our patient’s family members or close contacts appeared to have a similar disorder during a period exceeding 30 years. Although it has been reported that HPV-2-related warts respond only modestly to treatment, as they persisted in approximately 50% of all patients for more than 6 additional months, the patient infected with HPV-2a in this study was successfully cured with a combined therapeutic protocol of systemic administration of tretinoin (acitretin) and interferon alfa-2b, and local irradiation with X-rays or electron beams. No recurrence of warts on the extremities or trunk has been observed. Radiation may directly suppress active epidermal proliferation. Tretinoin inhibits hyperkeratosis of epidermis, induces growth arrest of actively proliferating epidermal cells and increases the sensitivity of HPV-infected cells to radiation. Although the mechanism of appearance of hundreds of horns in this case still remains unknown, the combined use of antiviral agents and physical and chemical inhibitors of epithelial proliferation seemed to be effective in removing the infected lesions and in preventing recurrence.

New-onset psoriasis following treatment with the interleukin-1 receptor antagonist anakinra

et al., 38 patients had HZ, followed later (days to years) by different localized disorders (including squamous cell carcinoma, basal cell carcinoma, leukaemia, granuloma annulare, Kaposi sarcoma and tinea). A few published case reports mention an LP eruption after healing of HZ lesions. In regard to LP, several variations of lesional arrangement occur, including linear and zosteriform manifestations. The dermatomal distribution seen in our patient strikingly differs from an orientation according to Blaschko’s lines, thereby – according to Happle – excluding the diagnosis of linear LP. Furthermore, serological analysis with an elevated VZV IgA concentration in serum supports the assumption of a postzoster LP and not a spontaneous LP in a zosteriform arrangement. Nevertheless, other linear and ⁄or zosteriform cutaneous disorders must be delineated, including lichen striatus, inflammatory linear verrucous epidermal naevus, naevus unius lateralis, porokeratosis (linear type), verruca plana and epidermodysplasia verruciformis. To summarize, our case of LP arranged in an unilateral dermatomal way may be best explained by an isotopic response following HZ sine herpete.

Recall injection-site reactions associated with etanercept therapy: report of two new cases with immunohistochemical analysis

Injection site reactions (ISRs) are the most common adverse effect reported with etanercept therapy. It has been observed that some patients treated with etanercept develop ‘‘recall ISRs’’, that are reactions at sites where etanercept was previously injected after the last injection. Etanercept‐associated recall ISRs have been scarcely published. We report two patients with rheumatoid arthritis who developed recall ISRs during etanercept therapy. Biopsy specimens from ISRs demonstrated a superficial perivascular lymphocytic infiltrated with a few eosinophils. Immunohistochemical study in both cases revealed that T cells bearing a CD4+ phenotype mostly composed the inflammatory infiltrate. Our observations suggest that ISRs may be mediated by classic cellular‐hypersensitivity reactions directed by CD4+ T lymphocytes.

HLA-DRB1 association with Henoch-Schonlein purpura

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype. This article is protected by copyright. All rights reserved.IgA vasculitis (Henoch‐Schönlein) (IgAV), formerly called Henoch‐Schönlein purpura, is the most common vasculitis in children, but it is not rare in adults. Increased familial occurrence supports a genetic predisposition to IgAV. In this context, an association with the HLA–DRB1*01 phenotype has been suggested in Caucasian individuals with IgAV. However, data on the potential association of IgAV with HLA–DRB1*01 were based on small case series. We undertook this study to further investigate this potential association by performing HLA–DRB1 genotyping in the largest series of IgAV patients ever assessed for genetic studies in Caucasians.

Anti–Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis–Associated Uveitis Refractory to Anti–Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients

To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis.

Anti-TNF-α therapy reduces retinol-binding protein 4 serum levels in non-diabetic patients with psoriasis: a 6-month prospective study.

Retinol‐binding protein‐4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate‐to‐severe psoriasis.

Shared Oncogenic Pathways Implicated in Both Virus-Positive and UV-Induced Merkel Cell Carcinomas

Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin whose molecular pathogenesis is not completely understood, despite the role that Merkel cell polyomavirus can play in 55-90% of cases. To study potential mechanisms driving this disease in clinically characterized cases, we searched for somatic mutations using whole-exome sequencing, and extrapolated our findings to study functional biomarkers reporting on the activity of the mutated pathways. Confirming previous results, Merkel cell polyomavirus-negative tumors had higher mutational loads with UV signatures and more frequent mutations in TP53 and RB compared with their Merkel cell polyomavirus-positive counterparts. Despite important genetic differences, the two Merkel cell carcinoma etiologies both exhibited nuclear accumulation of oncogenic transcription factors such as NFAT or nuclear factor of activated T cells (NFAT), P-CREB, and P-STAT3, indicating commonly deregulated pathogenic mechanisms with the potential to serve as targets for therapy. A multivariable analysis identified phosphorylated CRE-binding protein as an independent survival factor with respect to clinical variables and Merkel cell polyomavirus status in our cohort of Merkel cell carcinoma patients.

Golimumab in refractory uveitis related to spondyloarthritis. Multicenter study of 15 patients

OBJECTIVE To assess the efficacy of golimumab (GLM) in refractory uveitis associated to spondyloarthritis (SpA). METHODS Multicenter study of SpA-related uveitis refractory to at least 1 immunosuppressive drug. The main outcome variables were degree of anterior and posterior chamber inflammation, visual acuity, and macular thickness. RESULTS A total of 15 patients (13 men/2 women; 18 affected eyes; mean age 39 ± 6 years) were evaluated. The underlying SpA subtypes were ankylosing spondylitis (n = 8), psoriatic arthritis (n = 6) and non-radiographic axial SpA (n = 1). The ocular involvement patterns were recurrent anterior uveitis in 8 patients and chronic anterior uveitis in 7. Before GLM they have received methotrexate (n = 13), sulfasalazine (n = 6), pulses of methylprednisolone (n = 4), azathioprine (n = 3), leflunomide (n = 2), and cyclosporine (n = 1). Overall, 10 of them had also been treated with TNF-α blockers; etanercept (n = 7), adalimumab (n = 7), infliximab (n = 6), and certolizumab (n = 1). GLM was given at the standard dose (50mg/sc/monthly) as monotherapy (n = 7) or in combination with conventional immunosuppressive drugs (n = 8), mainly methotrexate. Most patients had rapid and progressive improvement of intraocular inflammation parameters. The median number of cells in the anterior chamber at 2 years [0 (0-0)] was significantly reduced compared to baseline findings [1 (0-3); p = 0.04]. The mean best corrected visual acuity value also improved (0.84 ± 0.3 at 2 years versus 0.62 ± 0.3 at baseline; p = 0.03). Only minor side effects were observed after a mean follow-up of 23 ± 7 months. CONCLUSIONS Our results indicate that GLM may be a useful therapeutic option in refractory SpA-related uveitis.

Metastasis from small cell carcinoma of the lung producing acute appendicitis

A case of acute gangrenous appendicitis with perforation caused by metastatie small cell carcinoma of the lung in a 65 year old man is reported. The manifestation of appendicitis occurred more than 4 years after the diagnosis of the bron‐chogenic carcinoma. With longer survival of patients with disseminated tumors it is probable that new manifestations of those malignancies will be discovered. Acute appendicitis due to metastasis from a distant neoplasm should be considered in the differential diagnosis of right lower abdominal pain in the oncology patient.