Locoregional treatments for digital ulcers in systemic sclerosis: A systematic review

The management of digital ulcers in systemic sclerosis is difficult. While the 2017 European League Against Rheumatism (EULAR) guidelines clearly defined the use of systemic therapies for digital ulcers, little is known about the efficacy of locoregional treatments. The aim of this review is to systematically assess the spectrum of published locoregional therapies for digital ulcers. A total of 58 studies were included. Among the different locoregional treatment strategies descri-bed, injections of fat-derived cells and botulinum toxin showed promising results in the reduction of pain and the number of digital ulcers. By contrast, this review found that sympathectomy yielded disappointing re-sults, with low rates of effectiveness and frequent recurrence. For other treatments, such as hyperbaric oxygen therapy, phototherapy (ultraviolet A), low-level light therapy, intermittent compression, Waon therapy, extracorporeal shockwave, vitamin E gel, and topical dimethyl sulphoxide, the conflicting results or limited published data reflected the low level of evi-dence. Larger randomized clinical trials are required to confirm the validity of promising techniques

Locoregional Treatments for Digital Ulcers in Systemic Sclerosis: A Systematic Review

The management of digital ulcers in systemic sclerosis is difficult. While the 2017 European League Against Rheumatism (EULAR) guidelines clearly defined the use of systemic therapies for digital ulcers, little is known about the efficacy of locoregional treatments. The aim of this review is to systematically assess the spectrum of published locoregional therapies for digital ulcers. A total of 58 studies were included. Among the different locoregional treatment strategies described, injections of fat-derived cells and botulinum toxin showed promising results in the reduction of pain and the number of digital ulcers. By contrast, this review found that sympathectomy yielded disappointing results, with low rates of effectiveness and frequent recurrence. For other treatments, such as hyperbaric oxygen therapy, phototherapy (ultraviolet A), low-level light therapy, intermittent compression, Waon therapy, extracorporeal shockwave, vitamin E gel, and topical dimethyl sulphoxide, the conflicting results or limited published data reflected the low level of evidence. Larger randomized clinical trials are required to confirm the validity of promising techniques

Étude observationnelle multicentrique française prospective de survenue d’effets indésirables ophtalmologiques chez les patients traités par dupilumab pour une dermatite atopique. Étude DUPI ŒIL

International audienc

Multicenter prospective observational study of dupilumab‐induced ocular events in atopic dermatitis patients

International audienceAbstract Background Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. Objective To examine the incidence, characteristics and risk factors of dupilumab‐induced ocular adverse events. Methods A prospective, multicenter, and real‐life study in adult AD patients treated with dupilumab. Results At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab‐induced blepharoconjunctivitis: either de novo ( n = 32) or worsening of underlying blepharoconjunctivitis ( n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938–30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635–21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158–13.90]; p = 0.031) were independent factors associated with dupilumab‐induced blepharoconjunctivitis. Limitations Our follow‐up period was 16 weeks and some late‐onset time effects may still occur. Conclusion This study showed that most dupilumab‐induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old