G. B. E. Jemec

Background Hidradenitis suppurativa (HS) is a disease with an unmet need for treatment. Objective To examine tolerability, safety and efficacy of oral phosphodiesterase‐4 (PDE4) inhibitior orismilast 10–40 mg twice daily (BID) in HS. Methods A Phase 2a, single‐arm, single‐centre, open‐label, 16‐week trial in HS patients. Adjustments in maximal dose and titration were allowed, to improve tolerability, dividing the study population in two groups who completed and discontinued 16 weeks of treatment. Descriptive statistics were applied to efficacy data from patients who completed treatment and patients who discontinued treatment prematurely. A last‐observation‐carried‐forward (LOCF) approach was used for patients who discontinued treatment. The primary endpoint was percent change in the total number of abscesses and nodules (AN‐count) at Week 16, with the HS Clinical Response with a 50% reduction in the AN‐count (HiSCR50) as key secondary endpoint. Results Of the 20 patients included, 9 completed 16 weeks of treatment and 11 discontinued treatment prematurely. The mean AN‐count was reduced with 33.1% in patients who completed treatment and with 12.0% in patients who discontinued. HiSCR50 was achieved by 67.0% and 27.0% of patients who completed and discontinued treatment, respectively. Most adverse events were mild to moderate. Conclusions Oral orismilast demonstrated a dose‐dependent tolerability, with mild to moderate adverse effects. Further, the results of this exploratory trial indicate that orismilast may lead to clinical improvements in HS. However, larger trials with tolerable dose ranges are warranted. The Trial is registered at Clinicaltrials.gov (UNI50007201) and EudraCT.ema.europa.eu (2021‐000049‐42).

Common skin disorders such as acne vulgaris, rosacea and folliculitis are bothersome prevalent inflammatory diseases of hair follicles that can easily be investigated bedside using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) with micrometre resolution, opening a novel era for high‐resolution hair follicle diagnostics and quantitative treatment evaluation. EMBASE, PubMed and Web of Science were searched until 5 January 2023 to identify all studies imaging hair follicle characteristics by RCM and OCT for diagnosis and monitoring of treatment in hair follicle‐based skin disorders. This study followed PRISMA guidelines. After inclusion of articles, methodological quality was assessed using the QUADAS‐2 critical appraisal checklist. Thirty‐nine in vivo studies (33 RCM and 12 OCT studies) were included. The studies focused on acne vulgaris, rosacea, alopecia areata, hidradenitis suppurativa, folliculitis, folliculitis decalvans, lichen planopilaris, discoid lupus erythemasus, frontal fibrosing alopecia and keratosis pilaris. Inter‐ and perifollicular morphology including number of demodex mites, hyperkeratinization, inflammation and vascular morphology could be assessed by RCM and OCT in all included skin disorders. Methodological study quality was low, and interstudy outcome variability was high. Quality assessment showed high or unclear risk of bias in 36 studies. Both RCM and OCT visualize quantitative features as size, shape, content and abnormalities of hair follicles, and have potential to support clinical diagnosis and evaluate treatment effects. However, larger studies with better methodological quality are needed to implement RCM and OCT directly into clinical practice.