Prevalence of omalizumab resistant chronic urticaria and real world effectiveness of dupilumab in omalizumab refractory chronic urticaria patients: a single center experience.

Chronic urticaria (CU) is characterized by wheals, angioedema, or both lasting for ≥ 6 weeks with chronic spontaneous urticaria (CSU) being the most common subtype. Omalizumab-resistant CSU cases represent an unmet clinical need. In this study, we aimed to assess the prevalence and predictors of omalizumab failure in a large cohort of CU patients and assess the effectiveness of dupilumab for omalizumab-recalcitrant CU. Of 338 CU patients, 33 received omalizumab. 69.7% (23 patients) were responders and 30.3% (10 patients) non-responders. Bivariate regression demonstrated that female sex (adjusted OR [aOR] = 1.53; 95%CI = 1.14-2.06), higher baseline UAS7 (aOR = 1.05; 95%CI = 1.01-1.09) and older age (controlling for sex) (aOR = 1.00; 95%CI = 1.00, 1.01) were associated with omalizumab failure. Of 10 omalizumab-refractory patients, three were well controlled with cyclosporine (all children), whereas the seven adults failed on average 5.6 ± 2.6 therapies including cyclosporine. All 7 achieved a complete response with dupilumab with time to response varying between 1 to 6 months. While our results suggest a favourable efficacy of dupilumab omalizumab-resistant cases, future confirmatory studies are required.

COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Segregation, immunohistochemical, molecular and functional analyses classify a novel missense variant in fumarate hydratase (FH) as pathogenic.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re-classification of the FH c.1039T>C variant to "pathogenic" based on ACMG/AMP criteria. Further insights into pathological recognition of FH-deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi-disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.

Tree-Based Machine Learning to Identify Predictors of Psoriasis Incidence at the Neighborhood Level: A Populational Study from Quebec, Canada.

BACKGROUND: Psoriasis is a major global health burden affecting ~ 60 million people worldwide. Existing studies on psoriasis focused on individual-level health behaviors (e.g. diet, alcohol consumption, smoking, exercise) and characteristics as drivers of psoriasis risk. However, it is increasingly recognized that health behavior arises in the context of larger social, cultural, economic and environmental determinants of health. We aimed to identify the top risk factors that significantly impact the incidence of psoriasis at the neighborhood level using populational data from the province of Quebec (Canada) and advanced tree-based machine learning (ML) techniques. METHODS: Adult psoriasis patients were identified using International Classification of Disease (ICD)-9/10 codes from Quebec (Canada) populational databases for years 1997-2015. Data on environmental and socioeconomic factors 1 year prior to psoriasis onset were obtained from the Canadian Urban Environment Health Consortium (CANUE) and Statistics Canada (StatCan) and were input as predictors into the gradient boosting ML. Model performance was evaluated using the area under the curve (AUC). Parsimonious models and partial dependence plots were determined to assess directionality of the relationship. RESULTS: The incidence of psoriasis varied geographically from 1.6 to 325.6/100,000 person-years in Quebec. The parsimonious model (top 9 predictors) had an AUC of 0.77 to predict high psoriasis incidence. Amongst top predictors, ultraviolet (UV) radiation, maximum daily temperature, proportion of females, soil moisture, urbanization, and distance to expressways had a negative association with psoriasis incidence. Nighttime light brightness had a positive association, whereas social and material deprivation indices suggested a higher psoriasis incidence in the middle socioeconomic class neighborhoods. CONCLUSION: This is the first study to highlight highly variable psoriasis incidence rates on a jurisdictional level and suggests that living environment, notably climate, vegetation, urbanization and neighborhood socioeconomic characteristics may have an association with psoriasis incidence.

Cold-induced anaphylaxis triggered by drinking cold water

Cold urticaria is an inducible urticaria in which hives and angioedema appear after exposure to cold. The symptoms of cold urticaria often are limited to hives/angioedema. However, in up to 20% of cases, cold exposure may trigger anaphylaxis. We report the case of an 11-year-old boy previously diagnosed with chronic spontaneous urticaria who developed facial swelling, itchy hives, difficulty in breathing, vomiting and abdominal pain within 5 minutes of drinking cold water. He received a standard dose of non-sedating second-generation antihistamines at home. He was observed in the emergency room for 2 hours and discharged with an epinephrin autoinjector. During the subsequent outpatient clinic visit, an ice cube test was performed which confirmed the new diagnosis of comorbid cold-induced chronic urticaria. On further questioning, the parents reported occurrence of hives following swimming in the swimming pool. Cold-induced urticaria should be suspected in cases of anaphylaxis associated with cold exposure. Patients with chronic forms of urticaria who present with new anaphylaxis should be assessed for a potential concomitant cold-induced form. (AU)

Cold-induced anaphylaxis triggered by drinking cold water.

Cold urticaria is an inducible urticaria in which hives and angioedema appear after exposure to cold. The symptoms of cold urticaria often are limited to hives/angioedema. However, in up to 20% of cases, cold exposure may trigger anaphylaxis. We report the case of an 11-year-old boy previously diagnosed with chronic spontaneous urticaria who developed facial swelling, itchy hives, difficulty in breathing, vomiting and abdominal pain within 5 minutes of drinking cold water. He received a standard dose of non-sedating second-generation antihistamines at home. He was observed in the emergency room for 2 hours and discharged with an epinephrin autoinjector. During the subsequent outpatient clinic visit, an ice cube test was performed which confirmed the new diagnosis of comorbid cold-induced chronic urticaria. On further questioning, the parents reported occurrence of hives following swimming in the swimming pool. Cold-induced urticaria should be suspected in cases of anaphylaxis associated with cold exposure. Patients with chronic forms of urticaria who present with new anaphylaxis should be assessed for a potential concomitant cold-induced form.

Rapid hair regrowth in an alopecia universalis patient with deucravacitinib: A case report.

Alopecia universalis is a severe, difficult to treat variant of alopecia areata that results in loss of hair on the scalp, eyebrows, eyelashes, and extremities. Deucravacitinib, a selective TYK2 inhibitor, has been recently approved in Canada, opening the door to novel uses of the drug. We present the case of a patient known for psoriasis who developed alopecia universalis resistant to many interventions (topical minoxidil and topical, intralesional, and systemic corticosteroids). We report the first case of successful rapid hair regrowth after starting deucravacitinib, which should prompt further inquiry into the use of TYK2 inhibitors in the management of alopecia areata.

Safety of COVID-19 mRNA vaccination and effects of SARS-CoV-2 infection in children and adults with mast cell disorders.

Mastocytosis is characterized by abnormal clonal mast cell proliferation. Given the paucity of data in patients with mastocytosis, it is crucial to assess the safety of COVID-19 vaccines in this population. We aimed to assess the risk of allergic reactions and the effect of COVID-19 infection among patients with mastocytosis. Participants were recruited from Canada and Israel between December 2021 and May 2022. Consenting participants were administered standardized questionnaires querying whether they were infected with COVID-19, if they received the first and second dose vaccines, and post-vaccination side effects including allergic reactions (urticaria/angioedema, current rash flaring, need for updosing medications, or respiratory symptoms) and common side effects including injection site reaction (ISR) and flu-like symptoms. Forty participants with mastocytosis were administered a standardized questionnaire (median age = 9, 59% male). Amongst all participants, 16 (39%) reported COVID-19 infection and most (75%) reported flu-like symptoms, 3 (19%) were asymptomatic, 1 suffered from shortness of breath/chest pain and 1 from facial flushing. Of the 25 participants who were eligible for vaccination (≥ 5 years old), 80% received a first-dose vaccine and 68% received a second-dose vaccine. Of those who received the first-dose vaccine, most (60%) remained asymptomatic, 20% developed flu-like symptoms, 20% had an ISR, and 1 patient had an allergic reaction (urticaria and swelling). Of those who received the second-dose vaccine, most (53%) were asymptomatic, and 1 had an allergic reaction. No significant difference was found between side effects of both vaccine doses. No reactions fulfilled the criteria for anaphylaxis in either dose. This study reveals that among patients with mastocytosis, COVID-19 vaccine and infection were well-tolerated in the majority of cases.

Morphea, Eosinophilic Fasciitis and Cancer: A Scoping Review.

Morphea is an autoimmune fibrotic skin disease. Eosinophilic fasciitis (EF) is considered to belong to the severe spectrum of morphea. We conducted a scoping review assessing the risk of secondary cancer among morphea/EF patients, paraneoplastic morphea/EF and morphea/EF developing secondary to cancer therapy. The search was conducted using MEDLINE, Embase, Cochrane databases for articles published from inception to September 2022 following the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines with no language or date restrictions. Two hundred and one studies were included. Of these, 32 studies reported on secondary cancer in morphea/EF patients, 45 on paraneoplastic morphea/EF and 125 on cancer-treatment-induced morphea/EF. While the current evidence remains limited, data suggest an increased risk of secondary cutaneous and possibly pancreatic malignancy in morphea patients, particularly the generalized subtype. There were insufficient data for EF. On the other hand, paraneoplastic morphea was anecdotal, whereas several observational studies suggested that ~10% of EF cases may be paraneoplastic, primarily in the context of hematologic malignancies. Radiotherapy-induced morphea is rare, seen in ~0.2% of treated patients and is usually localized to the treatment site, except in patients with pre-existing autoimmunity. While chemotherapy-induced cases are reported, immunotherapy morphea/EF cases are emerging and are preferentially seen with PD-1 and not CTLA-4 inhibitors. This study is limited by the type of articles included (case reports, case series and observational studies), and hence, additional research on this important topic is needed.

Burden and geographic distribution of oral cavity and oropharyngeal cancers in the Russian Federation.

Background: The global incidence of lip and oral cavity cancers (OCCs) and oropharyngeal cancers (OPCs) is steadily increasing. While tobacco and alcohol consumption are established risk factors, a considerable proportion of these cancers has become attributed to human papilloma virus (HPV) infection. We aimed to describe the occurrence and identify potential risk factors of OCCs and OPCs across the Russian Federation during 2007-2018. Methods: We conducted an ecological analysis using publicly accessible data from the P.A. Herzen Moscow Oncology Research Institute. Incidence and mortality rates by jurisdiction were mapped for geospatial analysis. We pre-defined 11 potential contributing risk factors and used univariable and multivariable Poisson regression model with backwards stepwise variable selection to identify associated factors with OCC and OPC. Results: A total of 190,585 individuals were diagnosed with OCCs and OPCs in Russia between 2007-2018. Non-uniform geographic distribution of cancer cases was noted where the Far Eastern Federal District had the highest rate of OCC and the Central Federal District of OPCs. Districts with high weekly alcohol consumption had significantly higher incidence and mortality rates in both sexes. Districts with high rates of daily smoking had higher incidence of OCC among females, and those with low smoking trends had lower mortality rates for OCCs and OPCs. Conclusion: We detail the burden of OCCs and OPCs across Russia, with the aim of elucidating modifiable risk factors and proposing evidence-based prevention strategies. Tobacco/alcohol sales control measures and smoking/drinking cessation programs should continue to be prioritized as public health measures, especially for females.

Assessing Skin Cancer Risk Factors, Sun Safety Behaviors and Melanoma Concern in Atlantic Canada: A Comprehensive Survey Study.

BACKGROUND: The incidence of cutaneous melanoma (CM) is increasing at an alarming rate in Canada and elsewhere around the world. Significant regional differences in CM incidence have been identified in Atlantic provinces. The goal of this study is to compare ultraviolet exposure, sun protective behaviours, level of worry and baseline CM knowledge in provinces with a high versus low incidence of CM as well, as between various demographic groups. METHODS: A cross-sectional survey study was conducted in Atlantic provinces between July 2020 and August 2022. All participants aged ≥ 16 years with a completed survey were eligible. Survey responses were summarized using frequency counts, percentages, and means. Two-sided Z-tests for equality of proportions and logistic regression models were used to compare the survey results between geographic and demographic groups. RESULTS: In total, 7861 participants were included (28.0% men; mean age 61.3 years; response rate 28%). Our results (gender- and age-adjusted odds ratio, 95% confidence interval) show that high-incidence provinces for CM (Prince Edward Island and Nova Scotia) had significantly more sunburns (OR 2.00, 1.72-2.31), total sun exposure (OR 2.05, 1.68-2.50), recreational sun exposure (OR 1.95, 1.61-2.35) and tans (OR 1.77, 1.53-2.05) than individuals in low-incidence provinces (Newfoundland and Labrador). However, individuals in high-incidence provinces displayed more protective behaviors: there were less tanning bed users (OR 0.82, 0.71-0.95), they checked their skin more frequently for new moles (OR 1.26, 1.06-1.51) and practiced more sun protection overall. Additional analyses are presented based on education, income, sexual orientation and gender. DISCUSSION: These findings suggest that future efforts aimed at reducing the CM burden in Atlantic Canada should be tailored for target geographic and/or demographic groups. LIMITATIONS: the study participants are not representative of the population in Atlantic Canada due to recruitment strategies.

The Role of Sex and Gender in Dermatology - From Pathogenesis to Clinical Implications.

BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.

Skin Cancer Prevention across the G7, Australia and New Zealand: A Review of Legislation and Guidelines.

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise globally in recent decades. While there has been a select focus on personal sun protection awareness, to our knowledge, there is a paucity of legislation in place to help support citizens' efforts to protect themselves from the harmful effects of ultraviolet radiation (UVR). Given this, we conducted a comprehensive review of legislation and guidelines pertaining to a variety of sun protection-related topics in countries of the Group of Seven (G7), Australia and New Zealand. Australia was the only country to have banned tanning beds for individuals of all ages, while other select countries have instituted bans for minors. In workplace policy, there is very little recognition of the danger of occupational UVR exposure in outdoor workers, and thus very few protective measures are in place. With regard to sports and recreation, certain dermatological/professional associations have put forward recommendations, but no legislation was brought forward by government bodies outside of Australia and New Zealand. With regard to youth, while there are various guidelines and frameworks in place across several countries, adherence remains difficult in the absence of concrete legislation and standardization of procedures. Finally, only Australia and a few select jurisdictions in the United States have implemented sales tax exemptions for sunscreen products. In light of our findings, we have made several recommendations, which we anticipate will help reduce the rates of melanoma and keratinocyte cancers in years to come. However, minimizing UVR exposure is not without risk, and we, therefore, suggest the promotion of vitamin D supplementation in conjunction with sun protective practices to limit potential harm.