Advances in Understanding and Managing Chronic Urticaria

There have been recent advances in the classification and management of chronic urticaria. The new term chronic spontaneous urticaria (CSU) has replaced chronic idiopathic urticaria and chronic autoimmune urticaria. In addition, chronic inducible urticaria (CINDU) has replaced physical urticaria and includes other forms of inducible urticaria, such as cholinergic and aquagenic urticaria. Furthermore, novel research has resulted in a new understanding with guidelines being revised in the past year by both the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO). There are some differences in the recommendations, which will be discussed, but the core updates are common to both groups. The basic treatment for chronic urticaria involves second-generation non-sedating non-impairing H1 antihistamines as first-line treatment. This is followed by up to a 4-fold increase in the licensed dose of these H1 antihistamines. The major therapeutic advance in recent years has been in third-line treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E (anti-IgE) antibody that prevents binding of IgE to the high-affinity IgE receptor. Several multicenter randomized controlled trials have shown safety and efficacy of omalizumab for CSU. There are also some small studies showing efficacy of omalizumab in CINDU. While there were previously many treatment options which were lacking in strong evidence, we are moving into an era where the treatment algorithm for chronic urticaria is simplified and contains more evidence-based, effective, and less toxic treatment options.

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Chronic Spontaneous Urticaria – Diagnosis and Management

10.5772/intechopen.97646 ◽

2021 ◽

Author(s):

Evmorfia Ladoyanni

Keyword(s):

Chronic Urticaria ◽

Psychological Factors ◽

Immunoglobulin E ◽

Immunoglobulin A ◽

Life Quality ◽

Chronic Spontaneous Urticaria ◽

Specific Stimulus ◽

Chronic Inducible Urticaria ◽

Number Of Patients ◽

Inducible Urticaria

Chronic urticaria can be subclassified into chronic spontaneous urticaria and chronic inducible urticaria. Up to 30% of cases are associated with functional immunoglobulin G antibodies to the high affinity immunoglobulin E receptor FcεRIα or to immunoglobulin A. Pathogenic activation of mast cells and basophils gives rise to release of pro-inflammatory mediators that lead to development of hives. CSU is a debilitating disease with a relapsing course. It affects 0.5–1% of the population at any given time. The duration of CSU is generally 1–5 years but can be longer in cases associated with angioedema and autoreactivity. CSU has detrimental effects on life quality with sleep-deprivation and psychiatric disorders being the most frequent. In a great number of patients an underlying cause or eliciting factor cannot be identified. Among the patients in which an aetiology is suspected, infections, medication, food and psychological factors are most commonly associated. A potential autoimmune cause has been reported in up to 50% of patients. Chronic inducible urticaria is characterised by its ability to be triggered consistently and reproducibly in response to a specific stimulus (pressure, temperature, vibration, water, heat, light). Antihistamines form the mainstay of therapy. In recalcitrant chronic urticaria, a variety of other drugs have been tried.

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Cholinergic urticaria: novel aspects of pathogenesis, diagnosis and management

Russian Journal of Skin and Venereal Diseases ◽

10.17816/dv72329 ◽

2021 ◽

Vol 24 (3) ◽

pp. 211-226

Author(s):

Elena Yu. Borzova ◽

Christina Yu. Popova ◽

Marcin Kurowski ◽

Maia T. Rukhadze ◽

Razvigor Darlenski ◽

...

Keyword(s):

Treatment Options ◽

Clinical Manifestations ◽

Main Research ◽

Cholinergic Urticaria ◽

Chronic Inducible Urticaria ◽

H1 Antihistamines ◽

Inducible Urticaria ◽

Diagnostic Approaches ◽

Challenge Tests ◽

Pathophysiologic Mechanisms

Cholinergic urticaria (CholU) is a chronic inducible urticaria, characterised by itchy pinpoint wheals up to 3 mm in diameter, surrounded by a prominent flare, that occur following an exposure to characteristic triggers such as active or passive heating, physical exercise, emotions, hot or spicy foods. Key pathophysiologic mechanisms include immediate hypersensitivity to autologous sweat antigens, functional sweating disorders, impaired acethylcholine metabolism, abnormal skin vascular permeability and disturbed skin innervation. Clinical manifestations of CholU may vary from typical itchy pinpoint urticarial lesions, angioedema to anaphylaxis. Atypical CholU forms include cholinergic pruritus, cholinergic dermographism, cold cholinergic urticaria and persistent cholinergic erythema. The diagnosis of cholinergic urticaria relies on patients history, сlinical manifestations and challenge tests. Treatment options include nonsedating H1 antihistamines in standard or increased doses. The evidence is accumulating for the use of biological treatment with omalizumab in cholinergic urticaria. The prospect of personalized treatment of cholinergic urticaria include autologous sweat desensitization. The main research efforts in ColdU are directed at optimizing diagnostic approaches and developing innovative therapeutic options.

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Association between Clinico-epidemiological Features in Chronic Urticaria with Autologous Serum Skin Test: A Cross-sectional Observational Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48816.15109 ◽

2021 ◽

Author(s):

Usha Rani Tirupathi ◽

Bhagya Rekha Manchiryala ◽

Sruthi Kareddy

Keyword(s):

Skin Test ◽

Chronic Urticaria ◽

Autologous Serum ◽

Clinical Test ◽

Cross Sectional ◽

Autologous Serum Skin Test ◽

Epidemiological Features ◽

Chronic Inducible Urticaria ◽

Autoimmune Urticaria ◽

Significant Difference

Introduction: Urticaria is a frequent and heterogeneous skin disease characterised by the development of wheals (hives), angioedema, or both. Chronic urticaria is characterised by the occurrence of wheals lasting less than 24 hours, with or without angioedema occurring daily or almost daily lasting more than six weeks. The two subtypes of chronic urticaria are Chronic Spontaneous Urticaria (CSU) and Chronic Inducible Urticaria (CIU). Autologous Serum Skin Test (ASST) is the simplest and the best in-vivo clinical test for the detection of basophil histamine- releasing activity. ASST has a sensitivity of approximately 70% and a specificity of 80%. Aim: To study the association between clinico-epidemiological features of CSU with positive and negative ASST. Materials and Methods: The cross-sectional study was conducted on 80 clinically diagnosed cases of CSU attending the Department of Dermatology Venereology Leprology Outpatient Department at Mahatma Gandhi Memorial Hospital (Kakatiya Medical College), Warangal, Telangana, India; during the period of January 2016 to September 2017. The detailed history was taken; complete physical and cutaneous examination and laboratory investigations like Complete Blood Picture (CBP), Absolute Eosinophil Count (AEC), Erythrocytic Sedimentation Rate (ESR), Thyroid Function Test (TFT) were carried out. ASST was done and read after 30 minutes. Chi- square test was applied and the results analysed using Statistical Package for the Social Sciences (SPSS) version 10.0. Results: Out of total 80 patients included in the study, ASST was positive in 36 (45%) and negative in 44 (55%). ASST positive patients showed longer duration of the disease with increased frequency of attacks and longer duration of wheals. However, both ASST positive and negative groups did not show statistically significant difference in the age of occurrence, gender, angioedema, dermographism. Conclusion: Autoimmune urticaria has no distinctive clinical features. ASST positive, autoimmune urticaria patients have more severe disease with greater impact on quality of life. Thus, they may need more aggressive treatment.

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Chronic inducible urticaria: Clinical presentation, diagnosis, and management

10.25259/ijsa_12_2021 ◽

2022 ◽

Vol 1 ◽

pp. 2-6

Author(s):

Pelin Kuteyla Can ◽

Daria Fomina ◽

Emek Kocaturk

Keyword(s):

Patient Education ◽

Disease Duration ◽

Clinical Presentation ◽

Treatment Approach ◽

Diagnosis And Management ◽

Physical Urticaria ◽

Chronic Inducible Urticaria ◽

Significant Difference ◽

Different Types ◽

Inducible Urticaria

Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria characterized by recurrent itchy wheals and/or angioedema for more than 6 weeks. CIndU has a longer disease duration than chronic spontaneous urticaria (CSU) and wheals are shorter lasting than CSU. CIndU incudes physical and non-physical urticaria. Triggers and diagnosis of subtypes of CIndU differ from each other. Patient education for avoiding triggers is an important aspect of the treatment of CIndU. There is no significant difference in the treatment approach for CIndU and CSU. In this article, we have discussed different types of CIndU, their clinical features, diagnosis, and management.

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The Use of Omalizumab in Chronic Urticaria: Available Data and Future Aspects of Anti-IgE Treatment

10.5772/intechopen.97226 ◽

2021 ◽

Author(s):

Young-Min Ye

Keyword(s):

Chronic Urticaria ◽

Efficacy And Safety ◽

Chronic Inducible Urticaria ◽

First Choice ◽

H1 Antihistamines ◽

Choice Of Treatment ◽

Inducible Urticaria ◽

Disease Modifying ◽

Impaired Quality

Chronic urticaria (CU) defined as repeatedly occurred itchy wheals and/or angioedema for at least 6 weeks. Due to the unpredictability, recurrent and disabling symptoms, and a considerably impaired quality of life, effective and tolerable treatment for CU patients is crucial. Almost a half of patients with CU are refractory to H1-antihistamines, even though the dose of antihistamines is increased up to 4-fold. Recently treatment modulating IgE levels and activities provides an efficient therapeutic approach. Omalizumab, the only approved anti-IgE treatment for chronic spontaneous urticaria (CSU) patients until now, with a strong evidence of the efficacy and safety, opened a new horizon in the care of the patients whose urticaria is not controlled with antihistamines. Recent international guidelines recommend omalizumab as the first choice of treatment for antihistamine-refractory CSU. However, as it is not curative neither disease-modifying agent, there is a subpopulation of CSU patients responding partly or never to omalizumab. The other things to be solved in the treatment of CU is that clinical evidence is still limited on chronic inducible urticaria (CIndU) and special populations. Thus, a new anti-IgE treatment, ligelizumab is actively evaluated in the efficacy compared with both placebo and omalizumab. Further understandings on the pathogenesis of CU can lead to the development of new mechanism-based therapeutics for CU patients.

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The Role of Anti-IgE Antibodies in Urticaria

10.5772/intechopen.97025 ◽

2021 ◽

Author(s):

Patrizia Pepe ◽

Victor Desmond Mandel

Keyword(s):

Chronic Urticaria ◽

Symptom Control ◽

Symptomatic Treatment ◽

Line Treatment ◽

Ige Antibodies ◽

H1 Antihistamines ◽

Inducible Urticaria ◽

Third Line ◽

Third Line Treatment

Chronic urticaria, a common mast cell driven disease, has been considered so far an underestimated and difficult to treat disease, very often resulting in high physical, psychological and socio-economic burden. More than 60% of these patients are unresponsive to second generation H1 antihistamines, the first-line symptomatic treatment for urticaria. However, anti-IgE drugs (omalizumab and ligelizumab) showed improved activity in urticaria-treated patients with inadequate symptom control. Omalizumab has been widely proven to be very effective and well-tolerated in patients with antihistamine-refractory chronic spontaneous urticaria and inducible urticaria and is currently licensed for these indication as third-line treatment. Ligelizumab, a next-generation monoclonal anti-IgE antibody with higher affinity to IgE compared to omalizumab and a similar safety profile, has recently demonstrated to be even more effective than omalizumab. This review is focused on the role of anti-IgE antibodies in chronic urticaria.

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Refractory Chronic Urticaria in Adults: Clinical Characterization and Predictors of Severity

10.21203/rs.3.rs-33896/v1 ◽

2020 ◽

Author(s):

Iolanda Alen Coutinho ◽

Frederico Soares Regateiro ◽

Rosa Anita Fernandes ◽

Joana Sofia Pita ◽

Raquel Gomes ◽

...

Keyword(s):

Disease Control ◽

Chronic Urticaria ◽

Standard Dose ◽

Symptom Control ◽

Autologous Serum ◽

Thyroid Peroxidase ◽

Clinical Predictors ◽

Chronic Inducible Urticaria ◽

Inducible Urticaria ◽

One Year

Abstract Background: Chronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks. Objectives: We aimed to characterize the phenotypesof patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control.Methods: Retrospective collection of data regarding clinical characteristics, manifestations, comorbidities, treatment,and disease control of all adult CU patients presenting to the Allergy and Immunology Department during one year. Descriptive and inferential analysis was performed to search for factors associated with disease control.Results: Sixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients and chronic inducible urticaria (ClndU)for44.3%. Angioedema was present in 55.7% of the patients. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in38.8% (n=19)of 49 tested patients.High C-reactive protein was presenti in 20.7% of 29 patients evaluated; half of these also had positive antinuclear antibodies.Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p=0.022), with a recent diagnosis (<1 year), and with higher UAS7 severity (p=0.006). Clnd Uassociated with poor symptom control(p=0.022) buthad less exacerbations requiring medical observation or hospitalization (p=0.015).Conclusions: About one thirdof patients with CU presented autoimmunity. UAS7 severity and Angioedema are associated with disease exacebations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment dosis. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.

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The challenges of chronic urticaria part 2: Pharmacological treatment, chronic inducible urticaria, urticaria in special situations

World Allergy Organization Journal ◽

10.1016/j.waojou.2021.100546 ◽

2021 ◽

Vol 14 (6) ◽

pp. 100546

Author(s):

Mario Sánchez-Borges ◽

Ignacio J. Ansotegui ◽

Ilaria Baiardini ◽

Jonathan Bernstein ◽

Giorgio Walter Canonica ◽

...

Keyword(s):

Chronic Urticaria ◽

Pharmacological Treatment ◽

Chronic Inducible Urticaria ◽

Inducible Urticaria

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Refractory Chronic Urticaria in Adults: Clinical Characterization and Predictors of Severity

10.21203/rs.3.rs-33896/v2 ◽

2020 ◽

Author(s):

Iolanda Alen Coutinho ◽

Frederico Soares Regateiro ◽

Rosa Anita Fernandes ◽

Joana Sofia Pita ◽

Raquel Gomes ◽

...

Keyword(s):

Disease Control ◽

Chronic Urticaria ◽

Standard Dose ◽

Symptom Control ◽

Autologous Serum ◽

Thyroid Peroxidase ◽

Clinical Predictors ◽

Chronic Inducible Urticaria ◽

Inducible Urticaria ◽

One Year

Abstract Background: Chronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks. Objectives: We aimed to characterize the phenotypes of patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control.Methods: Retrospective collection of data regarding clinical characteristics, manifestations, comorbidities, treatment, and disease control of all adult refractory CU patients presenting to the Allergy and Immunology Department during one year. Descriptive and inferential analysis was performed to search for factors associated with disease control. Results: Sixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients and chronic inducible urticaria (ClndU) for 44.3%. Angioedema was present in 55.7% of the patients. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in 45.2% (n=19) of 42 tested patients. High C-reactive protein was presenti in 14.3% (n=6) of 42 patients evaluated; half of these also had positive antinuclear antibodies. Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p=0.022), with a recent diagnosis (<1 year), and with higher UAS7 severity (p=0.006). ClndU associated with poor symptom control (p=0.022) but had less exacerbations requiring medical observation or hospitalization (p=0.015). Conclusions: About half of the patients with CU presented autoimmunity. UAS7 severity and Angioedema are associated with disease exacebations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment dosis. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.

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