Biologic and Small Molecule Therapy for Treating Moderate to Severe Atopic Dermatitis: Mechanistic Considerations.

Atopic dermatitis (AD) is a complex and heterogeneous skin disease where achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. While traditionally characterized as a Th2-driven disease, extensive research has recently revealed the involvement of Th1, Th17, and Th22 immune pathways, as well as the interplay of pivotal immune molecules, such as OX40, OX40 ligand (OX40L), thymic stromal lymphopoietin (TSLP), and IL-33. This review will explore the mechanistic effect of treatments for AD, focusing on monoclonal antibodies and JAK inhibitors. It will describe how these treatments modulate immune pathways, and examine their impact on key inflammatory and barrier biomarkers.

Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities.

INTRODUCTION: Tape-strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma-specific biomarkers in the skin of children with allergic asthma. METHODS: Skin tape-strips were obtained and analyzed with RNA-Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma-related outcomes (exacerbation rate, lung function-FEV1, IOS-R5-20, and lung inflammation-FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways. RESULTS: RNA-Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p < .01). MAA and SAA shared downregulation of G-protein-coupled receptor (OR4A16, TAS1R3), upregulation of TGF-ß/ErbB signaling-related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial-related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two-gene classifier (TSSC4-FAM212B) was able to differentiate asthma from HCs with 100% accuracy. CONCLUSION: Tape-strips detected epithelial barrier and asthma-associated signatures in normal-appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes.

Trends in contact sensitization, results, and implications from a contact dermatitis clinic in Israel.

BACKGROUND: The baseline series includes common allergens, evolves over time, and differs by location. Our study aims to characterize allergen sensitization trends among the Israeli population during the last two decades, compare our results to American and European registries, as well as to highlight significant allergens in additional series outside the European baseline series (OEBS). METHODS: We analysed patch test results of 2086 patients from a designated contact dermatitis clinic in Tel Aviv between 2019 and 2022, compared them to European and North American registries and to 2156 patch test results conducted in Israel two decades ago. RESULTS: 38.6% of patients had at least one positive reaction to an allergen in the European baseline series (EBS), nickel sulphate (14.6%), fragrance mix I (4.6%), and Methylchloroisothiazolinone methylisothiazolinone (MCI/MI; 3.7%) were the most common among them. N-Isopropyl N-Phenyl-4-Phenylenediamine (NIPPD; 0%), Propolis (0.1%), Sesquiterpene lactone mix (0.1%), and Budesonide (0.1%) elicited a sensitization frequency significantly lower than the proposed threshold for baseline inclusion. Chi-square test revealed a statistically significant decrease (p < 0.05) in the sensitization frequency of fragrance mix I, Formaldehyde, Potassium dichromate, Neomycin sulphate, Myroxylon pereirae, Sesquiterpene lactone, and NIPPD during the last two decades. The overall sensitization frequency to the majority of allergens was lower in our cohort in comparison to the North American and European registries. CONCLUSIONS: MCI/MI and 2-hydroxyethyl methacrylate-2 (HEMA) are common, relevant allergens, with high SPIN (significance and prevalence index number) and should be better regulated by the authorities. While among the EBS, NIPPD, Propolis, Sesquiterpene lactone, and Budesonide usually do not elicit a positive reaction and therefore should be reconsidered in baseline series, among the OEBS, Chloramphenicol, Quaternium 15, Propyl gallate, and Amerchol L101 have elicited high SPIN values and should be vigilantly examined in the suitable clinical scenario. Significantly lower sensitization frequency to propolis raises the possibility of a protective effect due to early oral exposure among the Israeli population.

Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies.

BACKGROUND: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples. METHODS: To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold-change (FCH) ≥2.0 and false discovery rate <0.05. RESULTS: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape-strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape-strips showed higher FCHs for innate immunity (IL-1B, IL-8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL-13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL-22, S100As) and dermal cytokines (IFN-γ, CCL26). Itch-related genes (IL-31, TRPV3) were preferentially captured by tape-strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape-strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. CONCLUSIONS: Tape-strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD-related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies.

Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo.

BACKGROUND: Vitiligo is an autoimmune depigmenting disorder with no effective and safe treatments. Its pathogenesis is not fully elucidated. OBJECTIVE: This substudy of a randomized, double-blind, placebo-controlled phase 2b trial (NCT03715829) evaluated effects of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on skin and blood biomarkers in participants with nonsegmental vitiligo (NSV). METHODS: Sixty-five adults with NSV participated in the substudy and received daily treatment for 24 weeks with placebo (n = 14) or ritlecitinib with or without a 4-week loading dose: 200 (loading dose)/50 mg (n = 13), 100/50 mg (n = 12), 50 mg (n = 11), 30 mg (n = 8), or 10 mg (n = 6). Skin (lesional and nonlesional) biopsy samples were obtained at baseline and at 4 and 24 weeks. Changes from baseline to weeks 4 and 24 in skin and blood molecular and cellular biomarkers were evaluated by RNA sequencing, quantitative real-time PCR, proteomic analysis, and flow cytometry. RESULTS: Ritlecitinib-treated groups showed downregulation of immune biomarkers and upregulation of melanocyte-related markers at weeks 4 and 24 compared to baseline and/or placebo. Significant reductions were seen in CD3+/CD8+ T-cell infiltrates, with significant increases in melanocyte markers (tyrosinase; Melan-A) in NSV lesions in the 50 mg ritlecitinib groups (both P < .05). There was significant, dose-dependent downregulation in T-cell activation, NK, cytotoxic, and regulatory markers in lesional skin (IL-2, IL2-RA, IL-15, CCR7, CD5, CRTAM, NCR1, XCL1, KIR3DL1, FASLG, KLRD; P < .05). TH1 and TH2 markers were also downregulated in lesional skin and blood in a dose-dependent manner (P < .05). Changes in immune biomarkers correlated with clinical response. CONCLUSIONS: Ritlecitinib significantly downregulated proinflammatory biomarkers and increased melanocyte products in skin and blood of participants with NSV, suggesting its potential in treatment. Ritlecitinib-mediated changes positively correlated with clinical response.

Diversity of atopic dermatitis and selection of immune targets.

Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy remains difficult. This therapeutic challenge may be attributed to the complex pathogenesis of AD. Although the TH2 axis has been extensively studied, recent advancements have started to reveal the involvement of additional immune pathways including TH1, TH17, and TH22. Understanding the interplay of these immune axes may contribute to a more personalized therapeutic approach based on patients' molecular profile, with the prospect of improving clinical outcome. This review will discuss studies exploring the molecular profile of AD in both skin and blood across age, ethnicity/race, disease chronicity, IgE levels, filaggrin mutation status, and AD association with other atopic conditions. Moreover, it will explore the potential of personalized treatment strategies based on a patient's distinct immune signature.

Alopecia Areata: Current Treatments and New Directions.

Alopecia areata is an autoimmune hair loss disease that is non-scarring and is characterized by chronic inflammation at the hair follicle level. Clinically, patients' presentation varies from patchy, circumscribed scalp involvement to total body and scalp hair loss. Current management is guided by the degree of scalp and body involvement, with topical and intralesional steroid injections as primarily first-line for mild cases and broad immunosuppressants as the mainstay for more severe cases. Until recently, the limited number of blinded, randomized, placebo-controlled clinical trials for this disease had made establishing an evidence-based treatment paradigm challenging. However, growing insights into the pathogenesis of alopecia areata through blood and tissue analysis of human lesions have identified several promising targets for therapy. T-helper (Th) 1/interferon skewing has traditionally been described as the driver of disease; however, recent investigations suggest activation of additional immune mediators, including the Th2 pathway, interleukin (IL)-9, IL-23, and IL-32, as contributors to alopecia areata pathogenesis. The landscape of alopecia areata treatment has the potential to be transformed, as several novel targeted drugs are currently undergoing clinical trials. Given the recent US FDA approval of baricitinib and ritlecitinib, Janus kinase (JAK) inhibitors are a promising drug class for treating severe alopecia areata cases. This article will review the efficacy, safety, and tolerability of current treatments for alopecia areata, and will provide an overview of the emerging therapies that are leading the revolution in the management of this challenging disease.

Intralesional human papillomavirus vaccine for the treatment of recalcitrant cutaneous warts.

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results.

Pediatric Contact Dermatitis: A 10-Year Multicenter Retrospective Study.

Background: Although allergic contact dermatitis (ACD) is relatively common in the adult and pediatric populations alike, few studies describe the special features of contact sensitization among the Israeli pediatric populations, none of them is multicenter. Our study aims to describe and analyze patch test results and trends in 4 tertiary care centers between 2012 and 2022. Methods: We assessed the results of 357 patch tests performed on children 0-18 years old between 2012 and 2022 in designated clinics in 4 tertiary medical centers. All patients were tested using the European baseline series and additional series as clinically indicated. We assessed the demographic features, atopic features, and influence, as well as the main allergens to cause sensitization and allergic contact dermatitis among the pediatric population. Results: In total 69% of the study population were females, mainly 12-18 years old, 35% of the study population were previously diagnosed with atopic dermatitis, and 57% had an atopic diathesis. Females were more commonly sensitized (P < 0.05). Patients without atopic dermatitis were more commonly diagnosed with ACD and had more reactions on patch test (P < 0.05). The most common allergens to cause ACD are preservatives and metals, as previously described, however, acrylate sensitivity is an emerging group that has not been described among the Israeli pediatric population in previous studies. Fragrance mix 2 and Mroxylon pereirae are relatively rare allergens among the Israeli pediatric population, whereas linalool hyperoxide might be considered an emerging allergen. Methylisothiazolinone causes ACD more frequently among patients without atopic dermatitis (P < 0.05). Conclusions: Among the Israeli pediatric population, ACD is more common in females without atopic dermatitis. Acrylates become a common culprit and should be included in baseline series. Patients with atopic dermatitis are less frequently sensitized by methylisothiazolinone.

The Characteristics of Allergic Contact Dermatitis in Military and Civilian Populations: A Multicenter Cross-Sectional Study.

Background: Contact dermatitis is a common condition in the general population, with a global prevalence of 20%. It is an inflammatory skin disease that is classified as irritant contact dermatitis (80%) and allergic contact dermatitis (ACD) (20%). In addition, it is the most common presentation of occupational dermatoses and is one of the primary reasons for seeking medical attention among military personnel. Only few studies have compared the characteristics of contact dermatitis in soldiers and civilians. Objective: To compare the characteristics of ACD between civilians and soldiers. Methods: This large retrospective study was conducted in Israel and involved 1800 civilians and 750 soldiers with suspected ACD. All patients underwent relevant patch tests based on their clinical presentation and medical history. Results: At least 1 positive allergic reaction was found in 382 civilians (21.22%) and 208 soldiers (27.73%) (nonsignificant). Moreover, 69 civilians (18.06%) and 61 soldiers (29.32%) had at least 1 positive occupational allergic reaction (P < 0.05). Widespread dermatitis was significantly more common among soldiers. The most frequent occupations among civilians with positive allergic reactions were hairdressers/beauticians. "Professional, technical, and managerial occupations" were the most frequent categories among soldiers (24.6%), with computing professionals being the most common occupation (46.67%). Conclusion: Military personnel and civilians have different characteristics associated with ACD. Therefore, considering these characteristics before placement in a workplace can help prevent ACD.

Do Atopic Dermatitis Patient-Reported Outcomes Correlate With Validated Investigator Global Assessment? Insights From TARGET-AD Registry.

BACKGROUND: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL). METHODS: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children's) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models. RESULTS: The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD. CONCLUSIONS: In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.

Allergic Contact Dermatitis in the Older Adults: A Comparative Cross-Sectional Study.

Background: Allergic contact dermatitis (ACD) is a significant health problem in older adults. Reports in the literature regarding the prevalence of ACD in older adults are various and inconsistent. In contrast, the data regarding contact irritant dermatitis are more consistent. Objective: To compare ACD characteristics in older adults versus the adult population aged 18-45 years. Methods: We conducted a retrospective controlled study. Data were obtained from the medical records of 4199 patients. We collected information regarding age, gender, atopic diathesis, anatomical distribution of the rash, reactions to patch tests, and final diagnosis. Results: The frequency of positive reactions in patch testing was lower in the older adult group than in the younger population, but the frequency of clinically relevant positive reactions was higher in the older adults. There was no statistically significant difference in the final diagnosis of ACD between the groups. The most common allergens among the older adult population were fragrance mix, preservatives (Methylchloroisothiazolinone/methylisothiazolinone [MCI/MI]), and nickel sulfate. Conclusion: This study, the first of its kind in Israel to include a large group of older adult patients, contributes to a better understanding of clinical parameters related to ACD among older adults. Consequently, it will hopefully contribute to lowering the disease burden.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

Using the National Incident Management System to Prepare Physicians for Rapid Responses: A Pilot Study.

OBJECTIVE: The study objective was to determine the feasibility of training physicians in the principles of the National Incident Management System (NIMS) and Incident Command System (ICS) as applied to in-hospital rapid responses and to assess physicians' attitudes regarding rapid responses. METHODS: This was an educational pilot study. Resident physicians completed a pre-survey, followed by online training in the principles of NIMS and ICS, a knowledge test, and a post-survey. RESULTS: The number of residents who participated was 22. In the pre-survey, most (20/22) did not have a working understanding of NIMS/ICS. Participants (21/22) agreed that residents should have more training in resource organization. On the knowledge test, the median score was 9.5/10. In the post-survey, participants felt more comfortable clearing extra resources from the scene (P < 0.001) and that it would be easier to keep track of resources (P < 0.001). Most indicated that they had a working understanding of NIMS/ICS (P < 0.001) and felt more comfortable establishing command using NIMS/ICS (P < 0.001). All agreed that they would consider using an NIMS/ICS-based structure on their next rapid response. CONCLUSIONS: Training physicians in the principles of NIMS/ICS as they pertain to rapid responses is feasible and appears to change residents' attitudes about rapid responses.

Superimposed type 2 segmental atopic dermatitis: case series and review of the literature.

Generalized acquired dermatoses can seldom manifest more prominently or exclusively along the lines of Blaschko. Six individuals with segmental atopic dermatitis (AD) have been reported to date. We present three additional cases of segmental cutaneous manifestations superimposed on generalized AD, and review the relevant literature.

Role of Patch Testing in Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common debilitating condition. Although not completely understood, the main pathomechanism involves autoimmune-related mast-cell degranulation. Patch test (PT) is the gold standard for the diagnosis of type IV cutaneous hypersensitivity. The relevance of PT to the diagnosis of CSU is debatable. OBJECTIVE: We aimed at determining the role of PT in selected patients with CSU. METHODS: In this retrospective study, we reviewed cases of patients referred for patch testing at our clinic. We compared results of patients with CSU (n = 134) and patients with suspected allergic contact dermatitis (n = 680; control group). RESULTS: Among patients in the CSU group, 3% of patients had relevant reactions to PT, indicating that contact allergen avoidance resulted in resolution of all skin findings. Metals and textile dyes were the most relevant allergens. No significant differences were found between the groups with regard to the percentage of patients with positive PT and hapten reaction profiles. Patients from the CSU group were significantly older (4.1 years on average, P < 0.05), consisted of more females, and were less likely to have atopic trait (46% vs 58%, P<0.05). CONCLUSION: In some of patients, PT may assist in determining the cause of CSU.

Mental Health Self-Stigma of Syrian Refugees With Posttraumatic Stress Symptoms: Investigating Sociodemographic and Psychopathological Correlates.

Background: The high prevalence of mental disorders related to posttraumatic stress among Syrian refugees is often in contrast with their low utilization of mental health care in the host countries. Mental health self-stigma, i.e., internalized stigma of having a mental disorder, could prevent individuals from seeking mental health care. Therefore, we aimed to provide evidence on different aspects of mental health self-stigmatization among adult Syrian refugees with posttraumatic stress symptoms residing in Germany. Moreover, we investigated associations with sociodemographic and psychopathological variables in order to identify those at higher risk of self-stigmatization. Material and Methods: Overall, 133 participants with mild to moderate posttraumatic stress symptoms were recruited in the metropolitan areas of Leipzig, Dresden and Halle, Germany, using a multimodal approach. Mental health self-stigma was assessed using the Self-Stigma of Mental Illness Scale - Short Form (SSMIS-SF), consisting of four subscales (Stereotype awareness, Stereotype agreement, Application to self , Harm to self-esteem), each scoring from 5 (low) to 45 (high) points. Linear regression analysis was used to test associations of sociodemographic and psychopathological variables with self-stigma subscales. Results: On average, self-stigma ratings ranged from 16.5 (SD = 6.6) points on Application to self to 28.3 (SD = 7.5) points on Stereotype awareness. Results showed higher scores on Application to self for individuals who were younger (t = 2.65, p = 0.009) and single (F = 5.70, p = 0.004). Regression analyses yielded statistically significant associations between having multiple comorbidities and a higher Application to self stigma (ß = 0.18, p = 0.044), controlling for sociodemographic covariates. Discussion: Mental health self-stigma was increased among Syrian refugees in Germany. Correlates of increased self-stigma could inform efforts to improve access to mental health care among Syrian refugees with mental ill-health. Longitudinal studies following an intersectional approach by concurrently examining multiple forms of public and internalized stigma could provide helpful insights for developing tailored stigma reduction efforts in this context.