Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa.

BACKGROUND: The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. OBJECTIVE: Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. METHODS: Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. RESULTS: Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. CONCLUSION: Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

[Epidemiology and clinical aspects of Adamantiades-Behçet disease in Gemany. Current data]. / Epidemiologie und Klinik des Morbus Adamantiades-Behçet in Deutschland. Aktuelle Daten.

Of the 721 documented patients in the German Registry for Adamantiades-Behçet disease (registered charity), 258 were of German and 308 of Turkish descent, along with 30 other countries of origin. The prevalence in Germany is 0.9:100,000. Manifestation of the disease was predominantly in the third decade of life (median age: 26.5 years) and in 10.7% the disease onset was under 16 years of age. The full clinical picture developed on average in 2.9 years (median 3 months). Patients of Turkish descent showed androtopism in contrast to those of German descent (female:male 1.9:1), which was also detected in the whole collective in a ratio of 1.4:1. In 12.4% there was a family history with differences between German and Turkish patients (3.8% versus 14.6%) as well as in patients with disease onset in young and adult age (25.0% versus 7.3%). Most frequent features included oral aphthae (98.5%), cutaneous lesions (81%), genital ulcers (64.7%), ocular manifestations (51.6%), arthritis (52.4%) and positive pathergy test (30.8%). Turkish patients suffered significantly more often from eye manifestations compared with Germans, while in German patients prostatitis/epididymitis and gastrointestinal involvement were more frequently documented. As serious complications arose blindness 6.8%, meningoencephalitis 4.0%, severe arthritis 2.6%, fatal outcome 1.2%, hemoptysis 1.1% and gastrointestinal perforation 0.5%. The HLA-B5 antigen was positive in 58.1% and showed an association with eye manifestations. The relative risk of HLA-B5 positive individuals is high in both Germans (6.57) and Turks (5.81).