Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

Disease Spectrum of Anaphylaxis Disorders.

Anaphylaxis results from massive mast cell activation. Mechanisms of mast cell activation may involve IgE- and non-IgE-mediated triggers, clonal mast cell disease, or be idiopathic and may be modified by several factors including but not restricted to hormonal status, stress, heritable factors, mast cell burden, and simultaneous exposure to more than 1 factor. Patients with recurrent anaphylaxis with a nonidentifiable trigger present a particular challenge in diagnosis and management. Presence of clonal disease may be suggested by hypotensive episodes with urticaria and angioedema, and high baseline tryptase levels. A number of scoring systems have been developed to identify patients who are at high risk to have underlying mastocytosis. This review provides an overview of anaphylaxis disorders and our current understanding of their mechanisms of action, evaluation, and management.

Chronic Urticaria in Older Adults: Treatment Considerations.

Chronic urticaria is characterized by recurrent wheals and/or angioedema lasting for more than 6 weeks. Chronic urticaria is an extremely disabling disease limiting daily activities, compromising patient quality of life, and frequently associated with psychiatric comorbidities (depression and/or anxiety). Unfortunately, there are still gaps in the knowledge regarding treatment in special populations, especially in older patients. Indeed, there are no specific recommendations for the management and treatment of chronic urticaria in older people; therefore, recommendations for the general population are used. However, the utilization of some medications may be complicated by potential concerns of comorbidities or polypharmacy. Currently, the diagnostic and therapeutic procedures for chronic urticaria in the older patient are the same as those indicated for other age groups. In particular, there is a limited number of blood chemistry investigations for spontaneous chronic urticaria and specific tests for inducible urticaria. With regard to therapy, second-generation anti-H1 antihistamines are used and, in recalcitrant cases, omalizumab (an anti-IgE monoclonal antibody) and possibly cyclosporine A are additional choices. Nonetheless, it should be underlined that in older patients the differential diagnosis can be more difficult, owing to the lower frequency of chronic urticaria and the likelihood of other pathologies that are peculiar for this age group and that can be included in the chronic urticaria differential diagnosis. As far as therapy is concerned, the physiological characteristics of these patients, the possible comorbidities, and the intake of other medications often require a very attentive drug selection for chronic urticaria compared with other age groups. The purpose of this narrative review is to provide an update on the epidemiology, clinical characteristics, and management of chronic urticaria in older patients.

Clinical features of patients with chronic spontaneous urticaria associated with autoimmune thyroiditis.

The aim of the study was to focus on children with both chronic spontaneous urticaria (CSU) and autoimmune thyroiditis (AT) as this topic is rarely studied in children although some publications show a higher proportion of antithyroid antibodies in children with CSU. We highlight two cases of children with both CSU and AT and compare their data with reports from the literature. Since only case reports or case series were available, we performed a descriptive analysis of 15 patients. There were 7 (46.7%) cases of hypothyroidism and the rest were euthyroid. Hypothyroidism appears before, during, and after the diagnostic of CSU. One patient with hypothyroidism and one with euthyroidism receiving l-thyroxine experienced remission of urticaria. Three patients over 12 years of age (20%) received omalizumab. Three patients (20%) had another autoimmune disease and seven (58.3%) had a family history of thyroid disease or autoimmune disease. CONCLUSION: Children with CSU need repeated testing for antithyroid antibodies. Children with both CSU and AT require close medical supervision focused on the development of other autoimmune diseases. l-thyroxine may improve urticaria in patients with hypothyroidism, but there is not enough evidence for patients with euthyroidism. Omalizumab may be of benefit in this population but well-controlled studies in children with AT and CSU are needed.

Chronic Urticaria in Elderly-New Insights.

BACKGROUND: Many medical conditions have a unique profile in older adults. Chronic urticaria (CU) is a common disease, but data regarding elderly patients are limited. OBJECTIVE: To describe the demographics, clinical characteristics, comorbidities, and outcome of elder patients with CU. METHODS: This retrospective, single-center study included patients older than 65 years, diagnosed with CU in our clinic. Data for the entire cohort were retrieved from electronic medical records. RESULTS: Of 1859 patients older than 65 years, 181 patients diagnosed with CU were included: 166 had chronic spontaneous urticaria (CSU) and 15 chronic inducible urticaria. Most patients with CSU were female (119, 72%). The mean age at diagnosis was 72 ± 5.9 years. Comorbidities included autoimmunity in 38 (22.9%), malignancy in 23 (13.8%), and atopy in 19 (11.5%). The time to referral to a specialist was 22.8 ± 53 months from the onset of symptoms. Specialist intervention improved patient outcomes. This was evident by reduced systemic steroid use (odds ratio [OR] = 0.145, [95% confidence interval (CI): 0.08-0.26], P < .001), all-cause hospitalization (OR = 0.09, [95% CI: 0.01-0.75], P = .01), emergency department visits (OR = 0.08, [95% CI: 0.08-0.35], P < .001), and primary physician visits (P < .001, Cramer's V = 0.528). CONCLUSIONS: Older people with CU have unique characteristics, including high prevalence of autoimmunity and malignancy and lower prevalence of atopy. Raising awareness of CU in elderly and prompt referral to an allergy specialist may improve outcomes.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

Introduction: To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. Materials and Methods: A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Result: Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). Conclusions: The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Epidemiology of urticaria in China: a population-based study.

BACKGROUND: Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients' quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population. METHODS: This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria. RESULTS: In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P  < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P  < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. CONCLUSION: This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Type D Personality Is Associated with Poorer Quality of Life in Patients with Chronic Spontaneous Urticaria: A Cross-sectional Study.

Type D personality (TDp) is a stable personality type that has been associated with poor quality of life in the general population and in patients with a variety of diseases, such as cancer, cardiac diseases, and dermatological diseases (e.g. psoriasis). To date, the potential association between chronic spontaneous urticaria and TDp has not been studied. The aim of this study is to analyse the impact of TDp on patients with chronic spontaneous urticaria, regarding mood disturbances, quality of life, sexuality, and sleep disturbances. A cross-sectional study including 75 patients with chronic spontaneous urticaria was performed. Data on socio- demographic variables and disease activity, quality of life, sleep, sexual dysfunction, anxiety, depression and TDp were collected using validated questionnaires. TDp was present in 28% (21/75) of the patients. Although TDp was not related to worse disease control, the presence of anxiety and depression was higher in patients with TDp. Regarding quality of life, TDp was associated with poorer quality of life and higher frequency of sleep disturbances. Prevalence of TDp in patients with chronic spontaneous urticaria is similar to that in the general population. It is associated with mood status disturbances and worse quality of life regardless of disease severity, especially in the emotional and psychological domains. This group of patients could benefit from additional psychological support as a complement to their medical treatment.

What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center

Abstract Background: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline). Objective: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil. Methods: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary. Results: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%). Study limitations: Unicentered and retrospective. Conclusion: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients.

Hairdressers' occupational skin diseases in the Finnish Register of Occupational Diseases in a period of 14 years.

BACKGROUND: Hairdressers have a high risk of occupational contact dermatitis caused by exposure to wet work and allergens in hairdressing chemicals. OBJECTIVES: To examine the distribution of diagnoses of occupational skin diseases (OSDs) and their main causes in hairdressers based on a national register data on occupational diseases. METHODS: We retrieved cases of recognized OSDs in hairdressers from the Finnish Register of Occupational Diseases (FROD) in years 2005-2018. RESULTS: During the 14-year period, a total of 290 cases of recognized OSD in hairdressers were registered in the FROD. Allergic contact dermatitis (ACD) was diagnosed in 54%, irritant contact dermatitis in 44%, and contact urticaria (CU) in 5% of them. ACD was most commonly caused by hair dye products and their ingredients (N = 57), persulfates (N = 35), and preservatives (N = 35; mainly isothiazolinones). Acrylates emerged as hairdressers' occupational contact allergens (N = 8) probably due to introduction of structure nails into hair salons. Persulfates was the most common cause of CU. CONCLUSIONS: ACD was the most common OSD in hairdressers. Our analysis confirms that preservatives are important causes of ACD in hairdressers in addition to hair dye products and persulfates. Acrylates emerged as hairdressers' occupational contact allergens, but contact allergy to perming agents remained rare.

Contact urticaria and protein contact dermatitis in the Finnish Register of Occupational Diseases in a period of 12 years.

BACKGROUND: Although occupational contact urticaria (CU) and protein contact dermatitis (PCD) are considered frequent among workers with exposure to proteinaceous materials, data on occupations at risk and the main causes of these occupational skin diseases are relatively limited. OBJECTIVES: To report the causative agents and risk occupations for CU and PCD in the Finnish Register of Occupational Diseases (FROD). METHODS: We retrieved from the FROD all recognized cases of CU/PCD in the years 2005-2016. RESULTS: With 570 cases, CU and PCD constituted 11% of all recognized cases of occupational skin diseases in the study period. Occupations with the highest incidence of CU/PCD included bakers, chefs and cooks, farmers and farm workers, veterinarians, gardeners, and hairdressers. The most common causative agents were cow dander and flour and grain, followed by natural rubber latex (NRL) and other food. In food-related occupations, wheat and other flours were by far the most common cause of CU/PCD, with 76 cases, whereas fish and other animal-derived food caused 33 and other plant-derived food caused 23 cases. CONCLUSIONS: Apart from the Finnish peculiarity of cow dander allergy, a striking finding was a large share of CU/PCD caused by flours in food handlers as compared to other food.

12-year data on dermatologic cases in the Finnish Register of Occupational Diseases I: Distribution of different diagnoses and main causes of allergic contact dermatitis.

BACKGROUND: Skin diseases are among the most common occupational diseases, but detailed analyses on their epidemiology, diagnoses, and causes are relatively scarce. OBJECTIVES: To analyze data on skin disease in the Finnish Register of Occupational Diseases (FROD) for (1) different diagnoses and (2) main causes of allergic contact dermatitis (ACD). METHODS: We retrieved data on recognized cases with occupational skin disease (OSD) in the FROD from a 12-year-period 2005-2016 and used national official labor force data of the year 2012. RESULTS: We analyzed a total of 5265 cases, of which 42% had irritant contact dermatitis (ICD), 35% ACD, 11% contact urticaria/protein contact dermatitis (CU/PCD), and 9% skin infections. The incidence rate of OSD in the total labor force was 18.8 cases/100 000 person years. Skin infections concerned mainly scabies in health care personnel. Twenty-nine per cent of the ACD cases were caused by plastics/resins-related allergens, mainly epoxy chemicals. Other important causes for ACD were rubber, preservatives, metals, acrylates, and hairdressing chemicals. Cases of occupational ACD due to isothiazolinones reached a peak in 2014. CONCLUSION: Our analysis confirms that epoxy products are gaining importance as causes of OSD and the isothiazolinone contact allergy epidemic has started to wane.

Sex in Respiratory and Skin Allergies.

A bulk of literature demonstrated that respiratory allergy, and especially asthma, is prevalent in males during childhood, while it becomes more frequent in females from adolescence, i.e., after menarche, to adulthood. The mechanisms underlying the difference between females and males are the effects on the immune response of female hormones and in particular the modulation of inflammatory response by estrogens, as well as the result of the activity of various cells, such as dendritic cells, innate lymphoid cells, Th1, Th2, T regulatory (Treg) and B regulatory (Bregs) cells, and a number of proteins and cytokines, which include interleukin (IL)-4, IL-5, IL-10, and IL-13. As far as sexual dimorphism is concerned, a gender difference in the expression profiles of histamine receptors and of mast cells was demonstrated in experimental studies. A critical phase of hormone production is the menstrual cycle, which often is associated with asthma deterioration, as assessed by worsening of clinical symptoms and increase of bronchial hyperresponsiveness. In asthmatic woman, there is a high risk to develop more severe asthma during menstruation. The higher prevalence of asthma in females is confirmed also in the post-menopause age, but the underlying mechanisms are not yet understood. In pregnancy, asthma may worsen but may also improve or remain unchanged, with no significant difference in frequency of these three outcomes. For allergic rhinitis, the available studies indicate, likewise asthma, a male predominance in prevalence in childhood that shifts to a female predominance in adolescence and adulthood, but further investigation is needed.

Comorbidities in Dermatology: What's Real and What's Not.

Comorbidities affecting dermatologic patients are of significant importance to providers and highly relevant for appropriate patient counseling, screening practices, prevention, and treatment. This article seeks to highlight several of the newest findings in the literature regarding comorbidities associated with dermatologic diseases including atopic dermatitis, hidradenitis suppurativa, alopecia areata, chronic urticaria, and the pemphigus family of immunobullous diseases. Further investigation is needed for associations between atopic dermatitis and pancreatic cancer and pemphigus family diseases and chronic obstructive pulmonary disease in order to better characterize the strength of these associations and clinical relevance.