Øystein Grimstad

BACKGROUND: Interleukin-31 (IL-31), a novel cytokine, is upregulated in atopic dermatitis skin lesions in humans and skin lesions in the NC/Nga mice, a murine model for atopic dermatitis. OBJECTIVE: Here, we investigated the effect of a monoclonal IL-31 antibody on scratching behaviour, weight gain and dermatitis in NC/Nga mice. METHODS: Mice were divided into three groups, n = 10 in each group. Mice were given monoclonal IL-31 rat-anti-mouse antibody 10 mg/kg or albumin intraperitoneally every fifth day for seven weeks. In addition, the mice in one group were not exposed to any form of intervention. The dermatitis score was clinically assessed twice a week. The scratching behaviour was automatically detected and objectively evaluated. RESULTS: Intervention with IL-31 antibody 10 mg/kg intraperitoneally every fifth day in NC/Nga mice from age 7 weeks reduced the scratching behaviour, but did not have any impact on weight gain or dermatitis. CONCLUSION: IL-31 antibody reduces scratching behaviour in an atopic dermatitis-like murine model during the onset of clinical skin manifestations. Our findings suggest IL-31 antibody as a new potential therapeutic approach for pruritus in atopic dermatitis and other pruritic diseases.

INTRODUCTION: This second part of the S2k guidelines is an update of the 2015 S1 European guidelines. OBJECTIVE: These guidelines aim to provide an accepted decision aid for the selection, implementation and assessment of appropriate and sufficient therapy for patients with hidradenitis suppurativa/acne inversa (HS). METHODS: The chapters have been selected after a Delphi procedure among the experts/authors. Certain passages have been adopted without changes from the previous version. Potential treatment complications are not included, being beyond the scope of these guidelines. RESULTS: Since the S1 guidelines publication, validation of new therapeutic approaches has almost completely overhauled the knowledge in the field of HS treatment. Inflammatory nodules/abscesses/draining tunnels are the primary lesions, which enable the classification of the disease severity by new validated tools. In relation to the degree of detectable inflammation, HS is classified into the inflammatory and the predominantly non-inflammatory forms. While the intensity of the inflammatory form can be subdivided by the IHS4 classification in mild, moderate and severe HS and is treated by medication accordingly, the decision on surgical treatment of the predominantly non-inflammatory form is based on the Hurley stage of the affected localization. The effectiveness of oral tetracyclines as an alternative to the oral combination of clindamycin/rifampicin should be noted. The duration of systemic antibiotic therapy can be shortened by a 5-day intravenous clindamycin treatment. Adalimumab, secukinumab and bimekizumab subcutaneous administration has been approved by the EMA for the treatment of moderate-to-severe HS. Various surgical procedures are available for the predominantly non-inflammatory form of the disease. The combination of a medical therapy to reduce inflammation with a surgical procedure to remove irreversible tissue damage is currently considered a holistic therapeutic approach. CONCLUSIONS: Suitable therapeutic options while considering HS severity in the therapeutic algorithm according to standardized criteria are aimed at ensuring a proper therapy.

Acute wounds contain many biological active molecules, including several cytokines and growth factors. However, the cellular sources of each molecule, as well as the stimuli inducing them, are poorly characterized. We quantified the levels of 27 cytokines, chemokines, and growth factors in acute wound fluid in a luminex-based assay. The acute wound fluid contained particularly high levels of IL-6 and IL-8, as well as elevated levels of MCP-1, IL-1RA, PDGF, IP-10, IFN-γ, and TNF-α. Surprisingly, the amounts of IL-1β and IL-10 were relatively low. To characterize the cellular sources of these molecules, we analyzed supernatants from monocytes, neutrophils, keratinocytes, fibroblasts, and endothelial cells stimulated with pro- and anti inflammatory cytokines, and different Toll-like receptor (TLR) ligands. The different cell types showed overlapping but distinct patterns of production of signal molecules, as well as sensitivity to ligands. Among pro-inflammatory cytokines, IL-1β was the most potent inducer of signal molecule production. Furthermore, keratinocytes and endothelial cells were in particular responsive to the Toll-like receptor-3 ligand poly I:C. New interactions between cytokines and growth factors were revealed, which may have important roles in wound healing, including IL-1β-induced IFN-γ and IL-10-induced VEGF.

BACKGROUND: Botulinum toxin (BTX) is a potent neurotoxin with a long history of therapeutic application in neurological and dermatological conditions, with a strong efficacy and safety profile. OBJECTIVE: Our aim was to assess whether intradermal injection with BTX-B is an effective treatment for hidradenitis suppurativa (HS). METHODS: Twenty patients with HS stage I-III disease, according to Hurley's classification, were consecutively included for treatment with either a placebo or BTX-B. At the next intervention after 3 months, all participants received the active substance and another follow-up at 6 months. The primary outcome was quality of life, measured using the Dermatology Life Quality Index (DLQI), while secondary outcomes were the visual analogue scale (VAS) for pain in the worst boil and HS-related impairment of general health (VAS), as well as changes in physician-reported disease activity assessed as the number of total lesions, and reported adverse effects of treatment. RESULTS: The DLQI improved from a median of 17 at baseline to 8 at 3 months in the BTX-B group, compared with a reduction from 13.5 to 11 in the placebo group (p <0.05). Improvement of the patients' own ratings of symptoms and a reduction in total lesions supplemented the primary outcome. Fifty-five percent of the study population reported some degree of hyperhidrosis. CONCLUSION: BTX-B improves the quality of life in patients with HS. Furthermore, comorbidity between HS and hyperhidrosis is suggested. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03103074.