Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4+ T cells, CD11c+ dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Sanofi and Regeneron Pharmaceuticals Inc.

No abstract

Abbott Laboratories.

Summary Background Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo. Objectives To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials. Methods We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47). Results In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis. Conclusions Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD). In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo. Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare. Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials. Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certa...

This study shows for the first time that IL-1β, TNF-α and IL-10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF-α and IL-1.

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient’reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence-based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy.