Ullrich Krüger

Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis.

Background  Interleukin (IL) 19, IL‐20 and IL‐24 belong to the IL‐10 cytokine family and have been identified to play a role in the regulation of epidermal functions and in inflammation. The genes encoding IL‐19, IL‐20 and IL‐24 are located within a gene cluster on chromosome 1q31–32 and carry frequent genetic variations.

Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases

Infliximab is a monoclonal antibody directed against TNF-α. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role.

Lymph node ultrasound during melanoma follow-up significantly improves metastasis detection compared with clinical examination alone: a study on 433 patients.

Early detection of melanoma metastases is essential for effective treatment and may be crucial for the prevention of systemic metastases and patient survival. However, data demonstrating the reliability and accuracy of ultrasound examination for the detection of lymph node metastases, in addition to clinical examination, are rare. We have examined 433 melanoma patients with stage-dependent follow-up intervals of 3 to 12 months. One thousand three hundred and thirty-two paired clinical and nonblinded sonographic tests of the locoregional lymph node areas were performed. Lesions suspicious of melanoma metastases were examined histopathologically. Of note, sensitivity [0.9394 (95% confidence interval: 0.7977–0.9926)] and specificity [0.9808 (95% confidence interval: 0.9717–0.9875)] of combined clinical and sonographic investigations were significantly (P<0.0001) higher than clinical results alone. Significant differences between clinical follow-up and sonographically assisted follow-up were found for American Joint Committee on Cancer 2002 melanoma stages I (P=0.0389), III (P=0.0101), and IV (P=0.0016). For stage II melanoma, a trend was detected (P=0.0821). Lymph node metastases were detected sonographically in 1.73% of clinically metastasis-free investigations (n=22). Our data suggest that high-frequency sonography should be part of all melanoma follow-up investigations, independent of melanoma type, melanoma stage, or lymph node biopsy status.

Association analysis of IL20RA and IL20RB genes in psoriasis

The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. Its ligands are the three members of the IL19 subfamily of cytokines, IL-19, IL-20 and IL-24. These cytokines are important in the manifestation of psoriatic lesions and, recently, an association of polymorphisms of IL20 with psoriasis has been described. In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n=254) and healthy controls (n=224). We found no association of any of the investigated SNPs with the disease. Analysis of pairwise linkage disequilibrium (LD) across studied markers revealed a strong level of LD between SNPs within the IL20RA gene and SNPs within the IL20RB gene, and, for both genes six common haplotypes were identified with an estimated frequency ⩾1%. Haplotype analyses suggested that the IL20RA haplotype CCG (rs1184860, rs1167846, rs1167849) is significantly associated with psoriasis (OR 3.14, 95% CI 1.61–6.14), whereas the TTG haplotype had a protective effect (OR 0.20, 95% CI 0.07–0.55). The risk haplotype defining SNPs 1167846 and 1184860 were found to modify paired box 5 and homeobox A9 sites, respectively, two transcription factors related to the differentiation of immune cells. Further studies are needed to confirm the genetic association and to investigate the functional relevance of IL20RA haplotypes in psoriasis.

Successful Use of Vacuum-Assisted Closure Therapy for Leg Ulcers Caused by Occluding Vasculopathy and Inflammatory Vascular Diseases – A Case Series

Background: Leg ulcers caused by vasculitis, small vessel occlusion or other rare conditions often prove to be very difficult to treat. Despite polypragmatic, systemic and localized therapy, many of these wounds are progressive and characterized by severe pain. Methods and Results: We here portray the cases of 5 patients with ulcers resistant to systemic therapy for the underlying disease, who were treated successfully using vacuum-assisted closure (VAC) for wound management. We present the advantages and disadvantages of this method, as well as illustrating the essential and known therapeutic principles. Conclusions: Our experience shows VAC to be an excellent and effective alternative in the treatment of therapy-resistant chronic wounds caused by vasculopathy (small vessel occlusion or vasculitis). We did not observe any pathergy or proinflammatory effects caused by VAC.

Variations in the genes encoding the peroxisome proliferator-activated receptors α and γ in psoriasis

The three peroxisome proliferator-activated receptor (PPAR) subtypes α, δ (β), and γ belong to the group of nuclear receptors that act as ligand-activated transcription factors. Recently, expression of PPARα and γ in keratinocytes has been demonstrated, and ligands of PPARα and γ have been found to enhance epidermal maturation and protect against cutaneous inflammation. There is evidence for a possible role of PPARs in psoriasis, as the expression of PPARα and γ is decreased in lesional skin and treatment with PPARγ agonists improves psoriatic keratinocyte pathology in vitro and in vivo. We performed a case-control study to search for possible associations between variations in the genes encoding PPARα and γ and psoriasis. Seven variations in these genes were analyzed in 192 patients with chronic plaque-type psoriasis and 330 healthy controls by PCR-based methods. No association between any of the investigated PPAR variants and psoriasis was found. Our findings argue against a significant contribution of the investigated PPAR variations to the genetic basis of psoriasis.

Distal and proximal interleukin ( IL ) -10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case–control study

Inherited promoter polymorphisms of the interleukin (IL)-10 gene resulting in altered IL-10 production may contribute to a genetic susceptibility for melanoma. We investigated the role of a haplotype from distal as well as proximal polymorphic sites [−7400InDel, −6752AT (rs6676671), −3538AT (rs1800890), −1087AG (rs1800896), −597AC (rs1800872)] of the IL-10 5′-flanking region in a hospital-based case–control study of 165 Caucasian patients with cutaneous melanoma from Germany in comparison with 162 healthy cancer-free Caucasian control participants from the same area matched by age. Using multivariate analysis for the number of nevi and skin type, the IL-10 ‘higher producing’ haplotype ITAGC was found to be significantly associated with a reduced risk of developing melanoma (adjusted P=0.02). Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma.

Further association analysis of chr 6q22-24 suggests a role of IL-20RA polymorphisms in psoriasis

In our previous studies we obtained evidence that the interleukin-19 (IL19) gene cluster and interleukin-20 receptor alpha (IL20RA) gene may represent susceptibility regions for psoriasis [1], [2], [3]. The aim of the present study was to scan an additional set of single nucleotide polymorphisms (SNPs) in the chromosomal region 6q22-24, which contains IL20RA, the genes for interleukin-22 receptor alpha 2 (IL22RA2) and interferon-gamma receptor 1 (IFNGR1) for association with psoriasis...

Photosensitive Psoriasis Vulgaris Inducible by a Single Suberythematous Dose of Ultraviolet B Irradiation

Sir, Although ultraviolet (UV) irradiation is a standard treatment for psoriasis, it can lead to an exacerbation of psoriatic skin disease in some patients. Psoriatic lesions can be triggered by both UVA and UVB irradiation; in general doses above the minimal erythema dose (MED) are required to trigger photosensitive psoriasis. We report here a patient with photosensitive psoriasis (PP) in whom new psoriatic lesions could be induced by a single suberythematous dose of UVB irradiation.