UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Road-traffic-related air pollution contributes to skin barrier alteration and growth defect of sensory neurons.

The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide-release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 µm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM-exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders.

Epidermal barrier function in dry, flaky and sensitive skin: A narrative review.

The stratum corneum (SC)-the outermost layer of the epidermis-is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin's microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment.

New human in vitro co-culture model of keratinocytes and sensory neurons like cells releasing substance P with an evaluation of the expression of ZIKV entry receptors: A potent opportunity to test Zika virus entry and to study Zika virus' infection in neurons?

During the course of acute ZIKV infection, pruritus is a cardinal symptom widely documented in the literature. Its frequent association with dysesthesia and several dysautonomic manifestations, suggests a pathophysiological mechanism involving the peripheral nervous system. The aim of this study was to develop a functional human model to potentially able to be infected by ZIKV: by demonstrating the functionality on a new human model of co-culture of keratinocyte and sensory neuron derived from induced pluripotent stem cells using a classical method of capsaicin induction and SP release, and verify the presence of ZIKV entry receptor in these cells. Depending of cellular type, receptors of the TAMs family, TIMs (TIM1, TIM3 and TIM4) and DC-SIGN and RIG1 were present/detected. The cells incubations with capsaicin resulted in an increase of the substance P. Hence, this study demonstrated the possibility to obtain co-cultures of human keratinocytes and human sensory neurons that release substance P in the same way than previously published in animal models which can be used as a model of neurogenic skin inflammation. The demonstration of the expression of ZIKV entry receptors in these cells allows to considerate the potent possibility that ZIKV is able to infect cells.

Positive Basophil Tests Are Linked to High Disease Activity and Other Features of Autoimmune Chronic Spontaneous Urticaria: A Systematic Review.

BACKGROUND: Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG autoantibodies. Basophil tests such as the basophil activation test (BAT) and basophil histamine release assay (BHRA) are considered the best single tests for an aiCSU diagnosis. To date, the strength of associations among a positive BAT and/or BHRA (BAT/BHRA+) and CSU features, patient demographics, and response to treatment remains poorly characterized. OBJECTIVE: To evaluate the strength of current evidence on basophil tests as parameters for CSU characteristics. METHODS: We performed a systematic literature search and review to assess the relationship between BAT/BHRA+ and clinical and laboratory parameters of CSU. Of 1,058 records found in the search, 94 studies were reviewed by experts in urticaria and 42 were included in the analysis. RESULTS: In CSU patients, BAT/BHRA+ showed a strong level of evidence for an association with high disease activity and low levels of total IgE. A weak level of evidence was shown for the association of BAT/BHRA+ and the presence of angioedema, and basopenia. CONCLUSIONS: Our results suggest that aiCSU defined by BAT/BHRA+ is more active or severe and is linked to other aiCSU markers such as low total IgE/basopenia. Basophil tests should be standardized and implemented in routine clinical care to improve the diagnosis and treatment of patients with aiCSU.

In vivo transepidermal water loss: Validation of a new multi-sensor open chamber water evaporation system Tewameter TM Hex.

BACKGROUND: Instrumentation technology for transepidermal water loss measurements has not been substantially modified since its introduction by Nilsson in 1977. Recent progress in sensor development allowed a new sensor arrangement using a matrix of 30 sensors. Raw measurement values are processed with spatial statistical analysis. We aimed to compare the new, multi-sensor probe (Tewameter TM Hex) with the established Tewameter TM 300 probe and to gain reference data for the new parameters of transepidermal energy loss and water vapor concentration on skin. MATERIAL AND METHODS: Baseline measurements and repeated measurements on the volar forearm and assessment on eight different anatomical locations were performed on 24 healthy volunteers (both gender) with the TM Hex and the TM 300. RESULTS: A significant correlation (p < 0.001; R-coefficient = 0.9) between TM Hex and the TM 300 with a low coefficient of variance (CV) 11% for TM Hex and 19% for TM 300, could be assessed. The CV ranged between 7% (right inner upper arm) and 14% (palms). Average transepidermal heat loss ranged from 12 W/m2 on the lower leg to 38.8 W/m2 on the palm. CONCLUSION: The correlation between TM Hex and TM 300 along with the robustness of the measurements with the TM Hex shows that the new probe for assessment of epidermal barrier function is comparable to the TM 300. In most conditions, TM Hex provides more accurate measurements than TM 300. New parameters open the field to studying skin's water and energy balance.

Skin Physiology, Mucosal Functions, and Symptoms Are Modulated by Grass Pollen and Ozone Double Exposure in Allergic Patients.

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.

A real-life comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2-biologics.

Background: Severe asthma (SA) with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with type 2 (T2) inflammatory endotype. Consequently, therapeutic targets are T2 biologics. The present retrospective study aimed to analyze and compare the clinical efficacy of mepolizumab, benralizumab, omalizumab, and dupilumab in patients with SA and comorbid CRSwNP. Methods: 115 adult patients with SA and CRSwNP receiving 1 of the 4 biologics (mepolizumab n = 31; benralizumab n = 27; dupilumab n = 27; omalizumab n = 30) were included in the retrospective open monocentric study. Pulmonary and rhinological parameters were evaluated by Asthma Control Test (ACT), FEV1%, GINA-severity grade, rhinological questionnaires (CRS VAS-scores and sinonasal QoL RSOM-31) before and after 4-6 months of therapy. Results: After 4-6 months of therapy, the Asthma Control Test and FEV1% significantly improved in all biologics groups (p < 0.01). GINA-score significantly improved in the omalizumab group only (p < 0.01). Overall, most nasal scores measured by VAS, total and nasal RSOM-31 subscores improved in all treatment groups (p < 0.05). Interestingly, the most significant differences in pre/post scores were observed in the patients receiving dupilumab, with the most notable improvement for all nasal symptoms, RSOM-31 total score, and RSOM-31 nasal subscore. There were no significant changes in the VAS scores loss of smell in the benralizumab group and postnasal drip in the mepolizumab group. Conclusion: T2-targeting biologics effectively treat asthma in patients with severe asthma and comorbid CRSwNP. However, the efficacy of T2 biologics differs regarding the outcome in CRSwNP.

S3 Guideline Urticaria. Part 2: Treatment of urticaria - German-language adaptation of the international S3 guideline.

This publication is the second part of the German-language S3 guideline on urticaria. It covers the management of urticaria and should be used together with Part 1 of the guideline on classification and diagnosis. This publication was prepared according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system conditions in German-speaking countries. Chronic urticaria has a high impact on the quality of life and daily activities of patients. Therefore, if causal factors cannot be eliminated, effective symptomatic treatment is necessary. The recommended first-line treatment is to administer new generation, non-sedating H1 antihistamines. If the standard dose is not sufficiently effective, the dose should be increased up to fourfold. For patients who do not respond to this treatment, the second-line treatment in addition to antihistamines in the treatment algorithm is omalizumab and, if this treatment fails, ciclosporin. Other low-evidence therapeutic agents should only be used if all treatments in the treatment algorithm agreed upon by the guideline group fail. Both the benefit-risk profile and cost should be considered. Corticosteroids are not recommended for long-term treatment due to their inevitable severe side effects.

S3 Guideline Urticaria. Part 1: Classification and diagnosis of urticaria - German-language adaptation of the international S3 Guideline.

The lifetime prevalence of urticaria, a severe allergic disease, is almost 20%. It not only limits the quality of life of those affected, but also their general performance at work and in their daily activities. This publication is the first section of the Urticaria Guideline. It covers the classification and diagnosis of urticaria, taking into account the major advances in research into its causes, triggering factors and pathomechanisms. It also addresses strategies for the efficient diagnosis of the different subtypes of urticaria. This is crucial for individual, patient-oriented treatment, which is covered in the second part of the guideline, published separately. This German-language guideline was developed according to the criteria of the AWMF on the basis of the international English-language S3 guideline with special consideration of health system characteristics in the German-speaking countries. This first part of the guideline describes the classification of urticaria, distinguishing spontaneously occurring wheals (hives) and angioedema from forms of urticaria with inducible symptoms. Urticaria is defined as sudden onset of wheals, angioedema, or both, but is to be distinguished from conditions in which wheals occur as a short-term symptom, such as anaphylaxis. The diagnosis is based on (a limited number of) laboratory tests, but especially on medical history. In addition, validated instruments are available to measure the severity, activity and course of the disease.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Les multiples fonctions protectrices de la peau découlent des interactions entre les cellules épithéliales de la peau et les cellules immunitaires, ainsi que le microbiote commensal. Développée au cours du dernier trimestre de la vie intra-utérine, la barrière cutanée s'adapte de manière dynamique après la naissance. Des différences spécifiques dans la structure et la physiologie ont été mises en évidence entre la peau des nourrissons et celle des adultes. La couche cornée des nourrissons est plus fine et structurée par des cornéocytes plus épais avec une surface plus anisotrope par rapport à la peau adulte. Des niveaux plus faibles des NMF et de ses constituants, ainsi qu'une activité protéasique accrue dans l'épiderme entraînent une sécheresse de la peau du bébé et une adaptation continue de la desquamation à l'environnement extra-utérin. L'épiderme du nourrisson est caractérisé par un taux de prolifération accéléré et une barrière de perméabilité cliniquement compétente chez les nouveau-nés nés à terme, malgré les valeurs de base plus élevées de la perte insensible d'eau transépidermique chez les nourrissons. La surface de la peau des nouveau-nés est moins acide, ce qui pourrait augmenter la susceptibilité aux dermatites fessières et atopiques. Immédiatement après la naissance, la peau est colonisée par des bactéries commensales-un processus dépendant du mode d'accouchement et d'une importance majeure pour la maturation du système immunitaire. La diversité et la dysbiose bactériennes de la peau ont été associées à différentes pathologies telles que la dermatite atopique et séborrhéique. Cet article se concentre sur l'adaptation structurelle, fonctionnelle et biochimique de la barrière cutanée humaine après la naissance. Nous discutons des interactions sur l'axe "barrière cutanée/microbiote/système immunitaire" et de leur rôle dans le développement d'une intégrité fonctionnelle compétente de la barrière épidermique.

Glycerol and natural sugar-derived complex modulate differentially stratum corneum water-binding properties and structural parameters in an in vitro Raman-desorption model.

The epidermal protective functions are closely associated with skin hydration homeostasis. The understanding of different states of water binding is a rising concept in assessing topically applied formulations and their interaction within the stratum corneum (SC). In addition to global water content, primary bound water, partially bound water, and unbound water and barrier-related lipid lateral packing and protein secondary structure can be measured by Raman spectroscopy. This study aimed to establish an in vitro SC model to evaluate differences in the efficacy of a natural sugar-derived complex in combination with glycerol and a botanical extract in modulating SC water binding and structural proteins and barrier lipids. These compounds were selected due to their water-binding and soothing properties. The SC water profiles were assessed at the surface and in 8 µm SC depth. After a 12-hour hyperhydration and subsequent product incubation the measurements were performed during a 6 hours desiccation phase. The maximal water caption and the time until reaching a steady state are measured as well as water retention and resistance against water loss. Global water content, partially bound, and unbound water, as well as lipid and protein structures were assessed with confocal Raman microspectroscopy. Both the natural sugar-derived mixture and more pronounced, the same mixture with additional glycerol increased all three water-binding parameters at the surface and in 8 µm SC depth at the beginning and during the desiccation phase. Further addition of botanical extract did not result in an additional increase of the water-binding. All three formulations showed an increase in the lipid lateral packing values prevented the protein alteration as measured by ß-sheets signal compared to blank. The present model is suited for screening studies comparing the specific effects of different compounds on hydration states. The natural sugar-derived mixture Aquaxyl showed evidence for an improvement of all SC hydration states, lipid and protein structure which was further enhanced by the addition of glycerol 5%. This improvement was evidenced at the surface and within the SC for all hydration-related parameters, and the lipid as well the protein structures. The addition of botanical extract phytoessence blue daisy did not show further improvement.

Acidic Skin Care Promotes Cutaneous Microbiome Recovery and Skin Physiology in an Acute Stratum Corneum Stress Model.

INTRODUCTION: Skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models can reveal pathological conditions and modulating effects. Here we investigated the cutaneous microbiome in relation to skin physiology after mild tape stripping (TS) without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3) in 25 healthy volunteers. METHODS: The microbiome was analyzed by 16S-rRNA-gene amplicon sequencing and put in relation to the following skin physiology parameter: epidermal barrier function (TEWA-Meter TM300), stratum corneum hydration (Corneometer CM 825), surface pH (pH-Meter), and skin erythema (Mexameter). RESULTS: TS reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alpha diversity already after 2 days with a slightly higher rate for the acidic lotion. After TS, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. The relative abundances of typical skin-associated genera were reduced after TS. Taxa compositions returned to normal levels after 7 days in all treatment groups. An accelerated normalization could be observed with both lotions already after 2 days. A significant difference in skin pH was observed on day 2 and day 7 with an increased pH for the alkaline lotion. Both lotions induced an increase in stratum corneum hydration. CONCLUSION: The study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha diversity, mean relative taxa, abundance of selected genera) normalized over 2-7 days. The following mechanisms could be responsible for the accelerated normalization of the microbiome: (a) optimized hydration during the recovery phase, (b) the composition of the lotion, (c) the induced repair mechanism. Thus, the formulation has a positive effect on the stratum corneum hydration and subsequently on cutaneous microbiome and skin physiology. Furthermore, this eventually has implications on the modulation of exogenous stress-induced epidermal alterations.

Skin Care Product Rich in Antioxidants and Anti-Inflammatory Natural Compounds Reduces Itching and Inflammation in the Skin of Atopic Dermatitis Patients.

The atopic dermatitis (AD) complex pathogenesis mechanism reveals marked changes of certain signaling factors as well as some morphological alterations in the epidermis. Reduced resilience against environmental factors and oxidative stress often makes the treatment with corticosteroids or tacrolismus ointments indispensable. In view of the correlation between oxidative stress and AD pathological factors, antioxidants can be incorporated into AD management strategies. This study investigates a curly kale, apple and green tea-containing natural extract rich in antioxidants for its effects on signaling inflammatory molecules and skin barrier enhancement in human epidermal keratinocytes- (NHEKs) based cell assays. Furthermore, the skin penetration on porcine ears was measured ex vivo using Raman micro spectroscopy. Finally, in a double-blind half-side, placebo-controlled clinical study, the effects of a formulation containing this extract were analyzed for the influence of lesion severity, epidermal barrier function, and pruritus in mild to moderately AD patients. Summarizing our results: The extract reduces expression of inflammatory cytokines in keratinocytes and increases barrier-related molecules. The verum formulation with a very high antioxidant capacity used in AD patients with mild to moderate lesions reduces itching, local SCORAD, and improves barrier function and the hydration of skin lesions.

Management of suspected and confirmed COVID-19 (SARS-CoV-2) vaccine hypersensitivity.

BACKGROUND: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS-CoV-2 vaccine hypersensitivity. METHODS: Totally, 334 individuals underwent an allergy work up regarding SARS-CoV-2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine-related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS-CoV-2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. RESULTS: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)-vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). CONCLUSION: Proven IgE-mediated hypersensitivity to SARS-CoV-2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered.

Chemokine Expression-Based Endotype Clustering of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) is a persistent, heterogeneous inflammatory condition affecting the upper respiratory tract. The present study aimed to improve the characterization of CRS endotypes based on the chemokine and cytokine expression pattern in the CRS tissues. Concentrations of chemokines and cytokines were measured in tissues from nasal biopsies obtained from 66 CRS patients and 25 control subjects using multiplexing or single analyte technologies. Cluster analysis based on the concentration of type-1 (MCP-3/CCL7, MIP-1 α/CCL3), type-2 (IL-5, MCP-3/CCL7, MIP-1 α/CCL3, TARC/CCL17, PARC/CCL18, IP-10/CXCL10, ECP), and type-3 (IL-22) chemokines and cytokines identified six CRS endotypes (clusters). Cluster 1 (type-3) and 2 (type-1) were associated with a low prevalence of nasal polyps, Cluster 3 (type-1, -2, -3) and Cluster 4 (type-2, -3, medium IL-22) with medium, and Cluster 5 (type-2, -3, high Il-22) and Cluster 6 (type-2) with high prevalence of nasal polyps. Asthma was highly prevalent in Cluster-6. Our findings add to the existing knowledge of CRS endotypes and may be useful for the clinical decision-making process. The advancement of biologics therapy for upper respiratory tract disorders rationalizes the personalized diagnostic approach to warrant a successful treatment and monitoring of CRS.

Sensitive Skin Syndrome: A Low-Noise Small-Fiber Neuropathy Related to Environmental Factors?

Background and Objectives: Patients frequently complain of mild, transient, unpleasant skin sensations that cannot be diagnosed as common neuropathies. Dermatologists have termed these symptoms "sensitive skin syndrome." This narrative review was performed for a better knowledge by other specialists. Databases and Data Treatment: Publications on pain in sensitive skin syndrome were obtained from PubMed. Results: There is a growing body of data supporting the concept that sensitive skin is a type of small-fiber neuropathy. The arguments are based on clinical data, a decrease in intra-epidermal nerve fiber density, quantitative sensory testing abnormalities and an association with irritable bowel syndrome and sensitive eyes. Sensitive skin is triggered by environmental factors. Sensitive skin is a frequent condition, with a lifetime prevalence of ~50% according to self-reports. Conclusions: Mild levels of skin pain or itch are frequently experienced by patients, who rarely report them. There is a need for a better knowledge of sensitive skin because it can be the first level of small-fiber neuropathies.

The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers.

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens. MCs can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, MCs indeed mediate acute inflammatory responses such as those evident in allergic reactions. Furthermore, MCs participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. The control of MC activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, MCs contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells. In this review, we provide a comprehensive overview of the functions of MCs in health and disease. Further, we discuss how mouse models of MC deficiency have become useful tools for establishing MCs as a potential cellular target for treating inflammatory disorders.