[Endocrinological mechanisms in the pathophysiology of hidradenitis suppurativa]. / Endokrine Mechanismen bei der Pathophysiologie der Hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent cutaneous disease of the terminal hair follicle which manifests with deep-seated, painful nodules, abscesses, and sinus tract formation. The pathophysiology of the disease includes among various factors also dermatoendocrinologic variables: Correlations with metabolic syndrome, obesity, sex steroid hormones, and the improvement after antiandrogen therapy are some of the key points presented in this review. Hormonal treatment of HS can be an effective and inexpensive alternative or add-on therapy to classic HS treatments, especially in cases where antibiotics and/or biologics are ineffective or contraindicated.

Low and high body mass index in hidradenitis suppurativa patients-different subtypes?

INTRODUCTION: Overweight is a well-established risk factor for hidradenitis suppurativa (HS). In this cross-sectional study, we compare HS patients with a high body mass index (BMI) with HS patients with a low BMI to investigate differences in disease characteristics. MATERIALS AND METHOD: Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35. RESULTS: Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient-reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack-years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients. DISCUSSION: Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non-linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity.

BACKGROUND: A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. OBJECTIVES: To develop and validate a novel dynamic scoring system to assess the severity of HS. METHODS: A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. RESULTS: Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36). CONCLUSIONS: The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real-life and the clinical trials setting.

[Two annular, atrophic plaques on the abdomen of a 35-year-old man]. / Zwei anuläre, atrophische Plaques am Abdomen bei einem 35-jährigen Patienten.

A 35-year-old man presented with two annular, reddish-brown, atrophic skin lesions in the navel and on the right lower abdomen. The lesions had persisted for more than 4 years and had remained unchanged and asymptomatic. Histology revealed annular atrophic lichen planus with a lichenoid lymphocytic infiltration and cystoid bodies. The patient was treated with local corticosteroids without improvement.

[Tumorogenesis and skin tumours in the elderly]. / Tumorigenese und Hauttumoren im Alter.

More than 1.5 million people were diagnosed with skin cancer in 2012 in Germany-of which 318,000 were malignant melanoma. The number of malignant skin tumours has increased by 60% since 2005. Epithelial skin cancers are even more common. Since 2012, 1.3 million diagnoses have been documented. This incidence represents an increase of 79% within 7 years. The number of skin cancer patients treated in German hospitals has also increased. In 2014, 99,613 patients were treated as inpatients with the diagnosis of skin cancer; in 2000 there were 57,147 patients. This was the largest growth rate among all cancer treatments in hospitalised patients. The continuously changing age pyramid leads to an expected further growth of the incidence of skin tumours. In parallel the development of molecular knowledge in tumorigenesis is also rapid. A series of cell-specific mutations have been described in recent years for various skin tumours. Mutations are found mainly in genes engaging their translation products at key positions in regulatory cell metabolism or cell division. These include oncogenes, which have greatly increased activity due to targeted mutations or tumor suppressor genes and act under physiological conditions as negative regulators that are inactivated by mutations. These findings have led to the development of a series of new promising compounds for the treatment of skin tumours.

Evaluation of the LIM homeobox genes LHX6 and LHX8 as candidates for Tourette syndrome.

The etiology and pathophysiology of Tourette Syndrome (TS) remain poorly understood. Multiple lines of evidence suggest that a complex genetic background and the cortico-striato-thalamo-cortical circuit are involved. The role of Lhx6 and Lhx8 in the development of the striatal interneurons, prompted us to investigate them as novel candidate genes for TS. We performed a comparative study of the expression of Lhx6 and Lhx8 and investigated genetic association with TS using two samples of trios (TSGeneSEE and German sample - 222 families). We show that Lhx6 and Lhx8 expression in the forebrain is evolutionarily conserved, underlining their possible importance in TS-related pathophysiological pathways. Our tagging-single nucleotide polymorphism (tSNP)-based association analysis was negative for association with LHX8. However, we found positive association with LHX6 in the TSGeneSEE sample (corrected P-value = 0.006 for three-site haplotype around SNP rs3808901) but no association in the sample of German families. Interestingly, the SNP allele that was identified to be significantly associated in the TSGeneSEE dataset, showed an opposite trend of transmission in the German dataset. Our analysis of the correlation of the LHX6 region with individual ancestry within Europe, revealed the fact that this particular SNP demonstrates a high degree of population differentiation and is correlated with the North to South axis of European genetic variation. Our results indicate that further study of the LHX6 gene in relation to the TS phenotype is warranted and suggest the intriguing hypothesis that different genetic factors may contribute to the etiology of TS in different populations, even within Europe.