Itch

Chronic spontaneous urticaria (CSU) is defined as the recurrence of unprovoked transient wheals and itch for more than 6 weeks. Currently, there is an unmet need concerning response prediction in CSU. The present study investigated biomarkers of type I and type IIb autoimmunity as potential predictors of response to omalizumab in CSU. Differences in levels of IgG and IgE autoantibodies targeting the high- and low-affinity IgE receptors (FcεRI and FcεRII, respectively), as well as spontaneous and specifically triggered leukotriene C (LTC)4 release by basophils from the investigated subjects, were evaluated in 18 consecutive, prospectively enrolled CSU patients and 18 age- and sex-matched, healthy non-atopic controls. The patients with CSU had higher levels of anti-FcεRI IgE (542 (386.25-776.5) vs. 375 (355-418), optical density (OD), = 0.008), and IgG (297 (214.5-431.25) vs. 193.5 (118-275) OD, = 0.004) autoantibodies relative to the controls. Simultaneous anti-FcεRI IgG and IgE positivity (i.e., both autoantibody levels above the respective cut-offs) was recorded only in late- and non-responders (3/8 and 1/2, respectively). Significantly higher anti-FcεRI IgE autoantibody levels were found in the CSU patients as compared to the controls, supporting FcεRI as an autoallergic target of IgE (autoallergen) in the complex pathophysiological scenario of CSU. The co-occurrence of anti-FcεRI IgG and IgE autoantibodies was documented only in late- and non-responders, but not in early ones, crediting the co-existence of autoimmune and autoallergic mechanisms as a driver of late/poor response to omalizumab.

Transient Receptor Potential (TRP) channels are multifunctional sensory molecules that are abundant in the skin and are involved in the sensory pathways of itch, pain, and inflammation. In this review article, we explore the complex physiology of different TRP channels, their role in modulating itch sensation, and their contributions to the pathophysiology of acute and chronic itch conditions. We also cover small molecule and topical TRP channel agents that are emerging as potential anti-pruritic treatments; some of which have shown great promise, with a few treatments advancing into clinical trials-namely, TRPV1, TRPV3, TRPA1, and TRPM8 targets. Lastly, we touch on possible ethnic differences in TRP channel genetic polymorphisms and how this may affect treatment response to TRP channel targets. Further controlled studies on the safety and efficacy of these emerging treatments is needed before clinical use.

Keloids are chronic progressive dermal pseudo-tumors that can grow considerably in volume and surface area but do not invade other tissues. They are usually triggered by dermal injury or inflammation, but they are not scars in the normal sense of the word, since they enlarge and progress over decades. The phenomenon usually referred to as "hypertrophic scars" represents a kind of keloidal process that does not extend beyond the initial site of injury and spontaneously regresses in 12-24 months. The multiplication of keloids and hypertrophic scars in a single patient is known as keloid disease. Keloid disease is due to a familial predisposition (autosomal dominant) that preferentially affects people of non-European ancestry, especially those of sub-Saharan African descent. Keloid disease has a deep impact on quality of life, not only because of disfiguring lesions, but also because of the frequency of associated intense neurogenic pruritus and pain, as well as recurrent bouts of suppuration. Diagnosis relies primarily on a good knowledge of the clinical characteristics of keloids, thus warranting the inclusion of a clinical atlas in the first part of the review. The second part will deal with the pathology, pathophysiology and treatment of keloid disease.

Psoriasis is an inflammatory skin condition that can negatively affect numerous domains for quality of life, including sexual function. We aimed to systematically compare sexual function between women with and without psoriasis through meta-analysis. Databases were searched for studies assessing sexual function in women with and without psoriasis using the Female Sexual Function Index (FSFI). Meta-analyses were conducted in R (v4.1.2) to determine: (i) the odds ratio (OR) of sexual dysfunction and (ii) the mean difference (MD) for FSFI scores and sub-scores. Eight studies (five case-control, three cross-sectional) were eligible for review, encompassing 563 women with psoriasis and 525 controls. Risk of bias for included studies was considered as low to moderate. Psoriasis was associated with greater odds of female sexual dysfunction (OR 2.67, 95% CI 1.93,3.69; p < 0.0001). Compared to controls, women with psoriasis had significantly lower mean scores for desire (p < 0.0001), arousal (p = 0.002), lubrication (p = 0.003), orgasm (p < 0.0001), satisfaction (p < 0.0001) and total scores (p < 0.0001). Mean pain scores did not significantly differ between psoriasis patients and controls (p = 0.051). We identified significantly impaired sexual function in women with psoriasis compared to controls, suggesting that routine assessment of sexual health may be beneficial. Prospective studies of larger sample size are required in order to explore the underlying mechanisms and risk factors.

Psoriasis is a chronic, immune-mediated, skin disease with a significantly negative impact on patients' quality of life. Moderate-to-severe disease often requires systemic therapies and currently available ones still have numerous disadvantages or limitations. Tyrosine kinase 2 (TYK2) mediates immune signaling of IL-12, IL-23, and type I interferons, without interfering with other critical systemic functions. This article aims to review the current knowledge on deucravacitinib, a new oral drug which selectively inhibits TYK2, granting it a low risk of off-target effects. Two phase 3, 52-week trials evaluated deucravacitinib 6 mg against placebo and apremilast – POETYK PSO-1 and PSO-2 -, enrolling 1688 patients with moderate-to-severe psoriasis. At week 16, over 50% of patients treated with deucravacitinib reached PASI75, significantly superior to placebo and apremilast. Symptomatic improvement was also reported, with greater impact on itch. Deucravacitinib was well tolerated and safe. There were no reports of serious infections, thromboembolic events, or laboratory abnormalities. Persistent efficacy and consistent safety profiles were reported for up to 2 years. Deucravacitinib has the potential to become a safe, effective, and well-tolerated treatment for patients with moderate-to-severe disease. Future studies will be important to determine the exact role of this drug in the treatment of psoriasis.

Atopic dermatitis is a common chronic-relapsing, inflammatory and itchy eczematous skin disorder which occurs in both children and adults. AD pathogenesis is complex and several factors are implicated. Pruritus plays a pivotal role in disease's burden, significantly worsening atopic patient quality of life by limiting productivity and daily activities. AD diagnosis relies still on the experience of the healthcare professional and there are several unmet needs as for the diagnostic criteria, the management and the recognition of the burden of the disease. In this paper we present an indeep focus on the main clinical features of AD and the major unmet needs that should be addressed in the next research.