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Allergy, Asthma, and Clinical... Aug 2023Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal... (Review)
Review
OBJECTIVES
Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them.
METHODS
We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models.
RESULTS
The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases.
CONCLUSIONS
Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.
PubMed: 37641141
DOI: 10.1186/s13223-023-00826-y -
Journal of Investigational Allergology... Dec 2023Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are... (Review)
Review
Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.
Topics: Humans; Conjunctivitis, Allergic; Histamine Antagonists; Histamine H1 Antagonists; Ophthalmic Solutions
PubMed: 38095492
DOI: 10.18176/jiaci.0963 -
The World Allergy Organization Journal Apr 2024Several observational studies suggest a possible link between lipid-lowering drugs and allergic diseases. However, inferring causality from these studies can be...
BACKGROUND
Several observational studies suggest a possible link between lipid-lowering drugs and allergic diseases. However, inferring causality from these studies can be challenging due to issues such as bias, reverse causation, and residual confounding. To investigate the potential causal effect of lipid-lowering drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, on allergic diseases (allergic asthma, allergic conjunctivitis, atopic dermatitis, allergic rhinitis, and allergic urticaria), we performed a Mendelian randomization (MR)-based study.
METHODS
We employed MR and summary-data-based MR (SMR), analyzing genome-wide association study (GWAS) data from people of European descent. Single nucleotide polymorphisms (SNPs) were employed as instrumental variables. We selected 2 types of genetic measures to represent the impact of lipid-lowering drugs, including genetic variants near or within drug target genes correlated with low-density lipoprotein cholesterol (LDL-C), and expression quantitative trait loci of drug target genes. The inverse-variance weighted (IVW)-MR approach was the primary utilized MR method, while sensitivity analyses were used to test the robustness of the results. We used SMR analysis as a supplementary analytical method, applying the heterogeneity in dependent instruments (HEIDI) test to assess if the observed correlation between gene expression and outcome was due to a linkage situation.
RESULTS
The IVW-MR analysis revealed significant evidence for an association between PCSK9-mediated LDL-C reduction and a decrease in the risk of allergic asthma (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.11-1.56; P < 0.01). Likewise, SMR analysis discovered an augmented expression of PCSK9 being linked with a heightened susceptibility to allergic asthma (OR = 1.21, 95% CI = 1.03-1.43; P = 0.02). No consistent evidence was found for other associations in either analysis.
CONCLUSION
Our findings support a potential causal relationship between PCSK9 activity and an increased risk of allergic asthma. Thus, PCSK9 inhibitors, which reduce PCSK9 activity, might be considered a priority in future clinical trials investigating drugs for allergic asthma prevention or treatment.
PubMed: 38623319
DOI: 10.1016/j.waojou.2024.100899 -
The Journal of Allergy and Clinical... Aug 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
OBJECTIVE
This study aimed to identify historical and clinical features and biomarkers associated with AD severity.
METHODS
A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity.
RESULTS
Participants with AD (N = 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001).
CONCLUSIONS
In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.
Topics: Humans; Dermatitis, Atopic; Ectropion; Respiratory Sounds; Phenotype; Biomarkers; Allergens; Conjunctivitis; Immunoglobulin E; Blepharitis; Severity of Illness Index
PubMed: 37182563
DOI: 10.1016/j.jaip.2023.04.052 -
Die Ophthalmologie Mar 2024In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and... (Review)
Review
BACKGROUND
In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief.
OBJECTIVE
Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given.
MATERIAL AND METHODS
Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented.
RESULTS
In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC).
CONCLUSION
A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Tacrolimus; Immunologic Factors; Adjuvants, Immunologic; Ophthalmic Solutions
PubMed: 38363381
DOI: 10.1007/s00347-024-01996-9 -
Frontiers in Immunology 2023The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only... (Review)
Review
The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy.
Topics: Humans; Food Hypersensitivity; Anaphylaxis; Immune Tolerance; Desensitization, Immunologic; Immunity
PubMed: 37744376
DOI: 10.3389/fimmu.2023.1229667 -
Clinical Gastroenterology and... Jan 2024Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes...
BACKGROUND & AIMS
Achalasia has been assumed to be an autoimmune disease targeting esophageal myenteric neurons. Recently, we proposed an alternative hypothesis that achalasia sometimes might be allergy-driven, caused by a form of eosinophilic esophagitis (EoE) in which activated eosinophils and/or mast cells infiltrating esophageal muscle release products that disrupt motility and damage myenteric neurons. To seek epidemiologic support for this hypothesis, we identified patients with achalasia in the Utah Population Database, and explored their frequency of having EoE and other allergic disorders.
METHODS
We used International Classification of Diseases codes to identify patients with achalasia and allergic disorders including EoE, asthma, atopic dermatitis, contact dermatitis, allergic rhinitis, allergic conjunctivitis, hives/urticaria, and anaphylaxis. We calculated relative risk (RR) for each allergic disorder by comparing the number observed in patients with achalasia with the expected number in individuals matched for birthyear and sex, and we performed subanalyses for patients age ≤40 versus age >40 years.
RESULTS
Among 844 patients with achalasia identified (55% female; median age at diagnosis, 58 years), 402 (47.6%) had ≥1 allergic disorder. Fifty-five patients with achalasia (6.5%) had EoE (1.67 EoE cases expected), for a RR of 32.9 (95% confidence interval, 24.8-42.8; P < .001). In 208 patients with achalasia age ≤40 years, the RR for EoE was 69.6 (95% confidence interval, 46.6-100.0; P < .001). RR also was increased significantly for all other allergic disorders evaluated (all greater than 3-fold higher than population rates).
CONCLUSIONS
Achalasia is strongly associated with EoE and other allergic disorders. These data support the hypothesis that achalasia sometimes might have an allergic etiology.
Topics: Humans; Female; Middle Aged; Adult; Male; Eosinophilic Esophagitis; Esophageal Achalasia; Asthma; Eosinophils
PubMed: 37391057
DOI: 10.1016/j.cgh.2023.06.013 -
Seminars in Ophthalmology Nov 2023To evaluate risk factors for pterygium and prevalence of periocular and systemic diseases among patients with pterygium. (Review)
Review
PURPOSE
To evaluate risk factors for pterygium and prevalence of periocular and systemic diseases among patients with pterygium.
METHODS
A retrospective case-control study was conducted among members of Clalit Health Services (CHS) in Israel, from 2001 to 2022. A total of 13,944 patients diagnosed with pterygium were included. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Mixed models were used to assess differences in demographic characteristics, ocular and systemic diseases between the groups. Generalized estimating equation (GEE) logistic regression was used to estimate the odds ratios (OR) and adjust for confounders.
RESULTS
The average age of pterygium patients was 49 ± 17 years; 51% were male. The results showed significant associations between pterygium and risk factors of vernal kerato-conjunctivitis (OR 2.52, 95% confidence interval [CI]: [1.96-3.24]), chronic allergic conjunctivitis (OR 1.98, 95% CI: [1.65-2.39]), blepharitis (OR 1.91, 95% CI: [1.78-2.04]), chalazion (OR 1.47, 95% CI: [1.30-1.67]) and unspecified systemic allergy (OR 1.21, 95% CI [1.09-1.34]), after adjusting for rural residency status. Glaucoma (OR 0.74, 95% CI [0.64-0.85]) and smoking (OR 0.70, 95% CI [0.66-0.75]) were protective factors against pterygium.
CONCLUSION
Systemic and periocular inflammatory and allergic diseases are risk factors for pterygium.
Topics: Humans; Male; Adult; Middle Aged; Aged; Female; Pterygium; Retrospective Studies; Case-Control Studies; Risk Factors; Prevalence; Conjunctivitis, Allergic
PubMed: 37303165
DOI: 10.1080/08820538.2023.2223266 -
Allergy Jan 2024Abrocitinib efficacy by comorbidity status in patients with moderate-to-severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Abrocitinib efficacy by comorbidity status in patients with moderate-to-severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities.
METHODS
Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI-75), ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient-Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment-emergent adverse events (TEAEs).
RESULTS
Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI-75, PP-NRS4, or DLQI 0/1 versus placebo-treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate.
CONCLUSIONS
Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities.
Topics: Humans; Asthma; Comorbidity; Conjunctivitis; Dermatitis, Atopic; Double-Blind Method; Eczema; Immunoglobulin A; Pruritus; Rhinitis; Severity of Illness Index; Treatment Outcome
PubMed: 37988255
DOI: 10.1111/all.15952 -
Cureus Apr 2024Allergic conjunctivitis (AC) is a prevalent ocular condition with a substantial impact on individuals' quality of life. This study aimed to explore the demographic...
BACKGROUND
Allergic conjunctivitis (AC) is a prevalent ocular condition with a substantial impact on individuals' quality of life. This study aimed to explore the demographic patterns, prevalence, symptoms, awareness, and attitudes associated with AC, while also examining potential associations with gender, age, and region of residence in Saudi Arabia.
METHODS
A cross-sectional study was conducted involving 487 participants. Data was collected through a self-administered questionnaire that included demographic information about AC prevalence, symptoms, attitudes, and awareness levels. Statistical analyses, including chi-square tests, were employed to examine associations between variables.
RESULTS
The study revealed a prevalence of AC (89, 18.3%) with common symptoms being eye redness (73, 82%) and itching (73, 82%). Participants displayed diverse awareness levels, with (376, 77.2%) correctly defining AC. The majority demonstrated either a good (230, 47.2%) or insufficient (196, 40.2%) attitude, while 54 (11.1%) had a sufficient attitude, and 7 (1.4%) exhibited an excellent attitude and awareness. Significant regional disparities were observed, impacting both prevalence and attitudes. While no gender differences were noted, the age group of 31-40 displayed a higher prevalence.
CONCLUSION
In this study, among 487 participants, the prevalence of AC was found to be 89 (18.3%). Meanwhile, attitude levels varied, with the majority demonstrating either a good or insufficient attitude. This provides valuable insights into the prevalence, symptoms, and awareness of AC in our population. The regional disparities underscore the need for tailored interventions addressing specific geographical contexts. The findings contribute to the broader understanding of AC, emphasizing the importance of targeted education and regional considerations in managing and preventing this condition.
PubMed: 38711709
DOI: 10.7759/cureus.57711