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Background: Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. Methods: SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. Findings: 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3 ± 16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05-4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49-4.38). While the highest incidence rates were in those aged 60-79 years old among females and >80 years old among males, the highest AAPC (â¼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72-29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64-4.76) in 1996 to 2.69 (95% CI 2.42-2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39-79.82) in the 0-19-year age group]. Interpretation: We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. Funding: National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.
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This case report describes 2 female patients who both presented with severe and recalcitrant Darier disease who were treated with type 2 inflammation inhibitors.
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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 6â months. While our results suggest a favourable efficacy of dupilumab omalizumab-resistant cases, future confirmatory studies are required.
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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.
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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.
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Fumarato Hidratasa , Leiomiomatosis , Mutación Missense , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Neoplasias Uterinas , Humanos , Fumarato Hidratasa/genética , Leiomiomatosis/genética , Leiomiomatosis/patología , Femenino , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Linaje , Mutación de Línea Germinal , Masculino , Adulto , Predisposición Genética a la Enfermedad , Persona de Mediana EdadRESUMEN
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)
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Humanos , Masculino , Niño , Urticaria , Anafilaxia , Respuesta al Choque por Frío , Angioedema , Vómitos , Dolor AbdominalRESUMEN
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.
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Anafilaxia , Angioedema , Urticaria Crónica , Agua Potable , Urticaria , Masculino , Humanos , Niño , Anafilaxia/diagnóstico , Anafilaxia/etiología , Urticaria/etiología , Urticaria/diagnóstico , FríoRESUMEN
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.
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Aprendizaje Automático , Psoriasis , Características de la Residencia , Factores Socioeconómicos , Humanos , Psoriasis/epidemiología , Incidencia , Quebec/epidemiología , Femenino , Masculino , Adulto , Características de la Residencia/estadística & datos numéricos , Factores de Riesgo , Persona de Mediana Edad , Anciano , Adulto JovenAsunto(s)
Dermatología , Internado y Residencia , Humanos , Dermatología/educación , Competencia ClínicaRESUMEN
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.
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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.
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Vacunas contra la COVID-19 , COVID-19 , Mastocitosis , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , Mastocitos , Urticaria , Vacunación/efectos adversos , Vacunas de ARNm/efectos adversos , Vacunas de ARNm/uso terapéuticoRESUMEN
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.