Patient-Reported Outcome Measures in Atopic Dermatitis and Chronic Urticaria Are Underused in Clinical Practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated and standardized tools that complement physician evaluations and guide treatment decisions. They are crucial for monitoring atopic dermatitis (AD) and chronic urticaria (CU) in clinical practice, but there are unmet needs and knowledge gaps regarding their use in clinical practice. OBJECCTIVE: We investigated the global real-world use of AD and CU PROMs in allergology and dermatology clinics as well as their associated local and regional networks. METHODS: Across 72 specialized allergy and dermatology centers and their local and regional networks, 2,534 physicians in 73 countries completed a 53-item questionnaire on the use of PROMs for AD and CU. RESULTS: Of 2,534 physicians, 1,308 were aware of PROMs. Of these, 14% and 15% used PROMs for AD and CU, respectively. Half of physicians who use PROMs do so only rarely or sometimes. Use of AD and CU PROM is associated with being female, younger, and a dermatologist. The Patient-Oriented Scoring Atopic Dermatitis Index and Urticaria Activity Score were the most common PROMs for AD and CU, respectively. Monitoring disease control and activity are the main drivers of the use of PROMs. Time constraints were the primary obstacle to using PROMs, followed by the impression that patients dislike PROMs. Users of AD and CU PROM would like training in selecting the proper PROM. CONCLUSIONS: Although PROMs offer several benefits, their use in routine practice is suboptimal, and physicians perceive barriers to their use. It is essential to attain higher levels of PROM implementation in accordance with national and international standards.

Aeroallergens sensitization pattern in atopic patients in Qatar: A retrospective study.

BACKGROUND: Allergic respiratory diseases (allergic rhinitis and asthma) are major health problems with high prevalence causing significant patient morbidity as well as an economic burden (1). Sensitization to inhaled allergens is a major factor in the pathogenesis of allergic respiratory diseases (2). This study aims to determine the commonest aeroallergen sensitization in patients with allergic symptoms who attended an Adult Allergy Clinic in Qatar. METHODS: This retrospective study reviewed the skin prick test results database of 20 aeroallergens performed between January 1st to December 31st, 2022, at an Adult Allergy clinic in Qatar. Based on skin test results, the most prevalent aeroallergens were determined. RESULTS: A total of 554 patients (43% males, 57% females), aged between 12-87 years, 36±13.8 (mean ± SD), underwent skin prick test, of which 378 patients (68%) had positive results. There were no significant sex differences in the frequency of atopy (males: 60% versus females: 65% p= .076). Of the total 554 patients, 62% were diagnosed with Allergic rhinitis, 19% with non-allergic rhinitis, 32% with asthma, 6.7% with chronic urticaria, and 6.5% with atopic dermatitis. The frequency of sensitivity to aeroallergens was Dermatophagoides pteronyssinus 49.5%, Dermatophagoides farina 38.6%, Cat 37.3%, American Cockroach 25.9%, Russian thistle 24%, German cockroach 20%, Rough pigweed 19%, Bermuda grass 11%, and 8% to seven grass mix. 61 % were sensitized to indoor aeroallergens and 31% to different pollens (outdoor). Of the 378 patients who were sensitized, 145 patients (38%) were monosensitized, and 233 (62%) were polysensitized (≥2 allergens). There were no significant differences in the frequency of polysensitization between males and females (M:F: 1:1, p=0.938). CONCLUSION: Insects (house dust mites and cockroaches) and animal protein (cat hair) were the most prevalent positive aeroallergen by skin tests. However, weed, tree pollens (Russian thistle, Rough pigweed, Mesquite tree), and grass pollens (Bermuda and seven grass mix) were also positive for a minority of patients. 62% of patients were polysensitized to aeroallergens.

Subcutaneous immunoglobulin therapy for adult patients with primary immunodeficiency disease: Qatar experience.

INTRODUCTION: Subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) are used for the treatment of primary immunodeficiency (PIDD). SCIG is as effective as IVIG in preventing infections.1 However, SCIG has advantages over IVIG as it causes fewer systemic reactions and can be infused at home by the patient leading to improved quality of life.2 Methods: We retrospectively analyzed adult patients with PIDD who received SCIG in an Adult Allergy Clinic in Qatar. Patients who received IVIG before SCIG and are naïve to IgG replacement were included. We compared Serum IgG levels, the number of antibiotic courses received, and the number of hospital admissions one year before and one year after starting SCIG. SF36 score was used to compare health-related quality of life scores before SCIG and after one year of SCIG. RESULTS: Twenty patients were included in the study, of which 17 were on prior IVIG replacement, and three were naive to replacement. SCIG replacement resulted in the maintenance of serum IgG levels in those who received IVIG prior. SCIG resulted in a statistically significant reduction in the number of antibiotics prescribed and hospitalization in the naïve subgroup but no substantial change in the prior IVIG group. 6/20 patients developed side effects like injection site pain, swelling, and headache. No patients developed significant systemic side effects. 10/20 patients discontinued the SCIG therapy, four patients due to side effects, and others due to noncompliance and financial reasons. SF36 Score was compared for the five patients in IVIG prior group and showed no significant improvement in individual score but improvement in the overall score (p=0.003) Conclusions: In our experience, SCIG therapy effectively prevents recurrent infection in PIDD patients, and patients did not experience any significant systemic side effects. There is a substantial improvement in the quality of life. However, compliance continues to be a problem.

A review of patch-test data over the period of eight years in the allergy and immunology department in Qatar.

BACKGROUND: Patch testing is the primary diagnostic approach for contact dermatitis,1 an inflammatory skin reaction caused by exposure to external irritants. The pathophysiology of contact dermatitis may entail an immunological response (hypersensitivity type IV), a non-immunological response (irritant contact dermatitis), or a mix of the two. The diagnosis of contact dermatitis requires a correlation between a positive patch test and clinical relevance.2 This study aims to determine the prevalence of allergy sensitization among adults in Qatar and the allergens most frequently associated with positive patch test findings. METHODS: Retrospective analysis used patch testing data from 2015 to 2022. RESULTS: Of the 87 patients tested, 43 had at least one positive reaction (mean age 41.7; range 19-68). Females were 33 of the total patients (76.7%). Thirteen (30%) patients had two or more positive reactions. The most common allergen groups associated with positive patch test reactions were nickel sulfate no. 12 (27.9%), and all reactants were female. followed by gold sodium thiosulfate no. 10 (23.3%, F:M = 2.3), p-phenylenediamine no. 10 (23.3%, F:M = 1.5), and p-tert-butylphenol formaldehyde resin no. 7 (16.2%, F:M = 6). Twenty-six reactants had one or more allergic disorders (allergic rhinitis, asthma, drug allergy, insect bite allergy, or chronic idiopathic urticaria), and 11 had atopic dermatitis. CONCLUSION: Triggering agents for contact dermatitis vary among geographic regions and populations. This study gives an idea of the allergens that are the most common sensitizers among the contact dermatitis population in the adult allergy clinic in Qatar.

Circulating microRNA signatures in patients with chronic Urticaria.

Background: Chronic Urticaria (CU) is a complex skin disease that appears as recurrent raised itchy rash/angioedema or both for more than six weeks. The pathophysiology of CU is complex and has yet to be understood entirely. It is predominantly a mast cell-driven disease with the possible involvement of type 2 inflammation. Current evidence largely favors mast cell activation by an IgE-mediated autoallergic mechanism or an autoimmune mechanism by IgG autoantibodies to IgE/ high-affinity receptor of IgE. MicroRNAs (miRNA) are small coding RNAs regulating gene expression at the post-transcription level. This study aimed to investigate the circulating miRNA as potential biomarkers in CU patients compared to healthy controls. Methods: The miRNA gene expression was done in seven patients with CU and seven healthy controls. The expression of miRNA is done using TaqMan openArray human advanced miRNA Panel. ExpressionSuite Software (Thermo Fischer Scientific, Waltham, MA, USA) is used for data analysis to quantify the miRNA expressions. P<0.05 is considered to be statistically significant. Results: A significant upregulation (p<0.05) in the miR-451a, miR-9-5p, miR-150-5p, miR-296-5p, and miR-182-5p was observed in CU compared to controls. Dysregulation of miR-451a is identified as an early biomarker in allergic diseases. Functional enrichment analysis with the KEGG pathway and disease ontology databases showed that these miRNAs were associated with skin diseases and inflammation. The differentially expressed miRNAs contribute to determining the genes regulated in CU. miRNA-based therapies that target different genes in a given pathway might be a potential candidate for treating CU. Conclusion: miRNA field has grown steadily over the past few years, but the role of circulating miRNAs in CU remains relatively unexplored. This study showed that the upregulated circulating miRNA might play an essential role in CU pathogenesis and inflammation. Also, our study highlights the importance of miRNAs as a future biomarker and potential therapeutic target to be investigated.

The rate of exacerbations in patients with asthma in Qatar: A retrospective study during 2019-2021.

Background: The prevalence of asthma is 9% among adults in Qatar, and its severity can be attributed to intrinsic and extrinsic factors such as environmental changes. As part of the project to investigate the association between air pollution and asthma severity, the rate of exacerbations in adult patients with asthma has been studied in Qatar. Methods: Retrospective data of patients with asthma (16-70 years) from January 2019 to December 2021 was retrieved from Cerner medical records. Frequencies of exacerbations in inpatient and outpatient departments were analyzed using means ± SD and median (IQR) for descriptive data and frequency and percentage for categorical data. Exacerbations were divided into single, double, and more than double for each quarter of the year (January 2019-December 2021) using SPSS and Minitab statistical packages. Results: A total of 6977 exacerbations visits (representing 6558 patients) were identified during the study period. The mean ± SD age was 41±14.3 years, with a female: male ratio of almost 1:1. The patients from the MENA region, including Qataris, presented 67% compared to 33% from the Indian subcontinent and other countries. The number of patient visits for hospitalization due to exacerbations showed a distinctive pattern during the three years. The highest record of asthmatics with exacerbations was observed in 2019 (42.7%) compared to half the rate in 2020 and 2021 (28.5%, 28.8%), respectively. The single exacerbation group was almost five times higher than 2 or >2 exacerbation groups in all years (2019-2021). Conclusion: This preliminary overview provides the rate of exacerbation episodes in patients with asthma in Qatar. One cause of these exacerbations can be attributed to air quality changes. The drop in the exacerbation rate observed in 2020-2021 could be explained by COVID-19 lockdown regulations or patients' adherence to prescribed meds. We aim to propose preventive and therapeutic strategies to alleviate asthmatics' symptoms and improve their quality of life.

The first case report of complement component 7 deficiency in Qatar and a 10-year follow-up.

Introduction: Neisseria meningitidis is a significant cause of bacterial meningitis and septicemia worldwide. Recurrent Neisseria meningitidis is frequently associated with terminal complement protein deficiency, including Complement component 7. This report discusses the first case of C7 deficiency in Qatar. Case report: A 30-year-old Qatari man presented with a meningococcal infection, which was verified by a blood culture. He experienced two episodes of meningitis caused by an undetermined organism. His blood tests revealed low levels of CH50 and C7. His C7 gene testing revealed a homozygous mutation in exon 10 (c.1135G>C p.Gly379Arg), a mutation that has not been previously documented in Qatar. However, it has been observed in 1% of Moroccan-origin Israeli Jews who also exhibit C7 deficiency. Regular prophylactic quadrivalent vaccinations against types A, C, Y, and W-135 with azithromycin tabs were administered. Over the last 10 years of follow-up, he remained in good health, with no further meningitis episodes. Conclusion: To our knowledge, this is the first confirmed case of C7 deficiency reported in the Arabian Gulf countries. Such rare diseases should be a public health priority. Awareness among medical practitioners and the community should help with early detection of C7 deficiency and the prevention of its consequences.

Expert opinion on management of moderate-to-severe atopic dermatitis in Qatar.

Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Severe exercise-induced anaphylaxis in a hot and humid area successfully treated with omalizumab: a case report.

Exercise-induced anaphylaxis (EIA) is a rare disorder in which anaphylaxis occurs exclusively after physical activity. Here, we report a case of severe EIA where anaphylaxis was initially only induced by strenuous exercise. Suddenly the anaphylaxis got out of control to the degree that usual daily activities triggered it. Exposure to a hot and humid environment appeared to be a cofactor for the development of severe symptoms resistant to usual preventive measures. Treatment with omalizumab (anti-IgE) was initiated and resulted in marked improvement. We discuss unique aspects of this case in comparison to published information on the clinical features, triggering cofactors, diagnosis, and treatment of EIA.

Epidemiology of combined immunodeficiencies affecting cellular and humoral immunity- a multicentric retrospective cohort study from the Arabian Peninsula.

AIMS: To understand the characteristics of combined immunodeficiency disorders that affect cellular and humoral immunity (CID) in the Arabian Peninsula. METHODS: Retrospective study of 236 patients with CID from the region were enrolled from 2004 to 2022. RESULTS: 236 patients were included with a majority being profound CID. Among patients with a family history of CID, the ages at onset and diagnosis, and the delay in diagnosis were lower compared to those with no family history of CID, but this did not affect time to transplant. HSCT was performed for 51.27% of the patients with median time from diagnosis to HSCT of 6.36 months. On multivariate analysis, patients who underwent early transplant had increased odds of having CD3 count ≤1000 cell/µl, diagnosed by screening or erythroderma. CONCLUSION: There is a delay in diagnosis and treatment of CID in our region. Establishing newborn screening programs and HSCT units in our region are the urgent need.

Fc Epsilon RI-Neuroimmune Interplay in Pruritus Triggered by Particulate Matter in Atopic Dermatitis Patients.

Atopic dermatitis (AD) is the most common chronic relapsing neuroinflammatory skin disease that is characterized by a complex and multifactorial pathophysiology. It reflects a profound interplay between genetic and environmental factors, and a recently disclosed neuroimmune dysregulation that drives skin barrier disruption, pruritus, and microbial imbalance. In terms of the key external environmental players that impact AD, air quality and itch severity linkage have been thoroughly researched. The impact of ambient air pollutants including particulate matter (PM) and AD pruritic exacerbation has been recorded despite reductions in air pollution levels in in developed countries. The developing countries have, on the contrary, experienced significant urbanization and industrialization with limited environmental protection standards in the past decades. This unprecedented construction, petrochemical industry utilization, and increment in population counts has been paired with consistent exposure to outdoor PM. This may present a key cause of AD pruritic exacerbation supported by the fact that AD prevalence has intensified globally in the past 50 years, indicating that environmental exposure may act as a trigger that could flare up itch in vulnerable persons. At the molecular level, the impact of PM on severe pruritus in AD could be interpreted by the toxic effects on the complex neuroimmune pathways that govern this disease. AD has been recently viewed as a manifestation of the disruption of both the immune and neurological systems. In light of these facts, this current review aims to introduce the basic concepts of itch sensory circuits in the neuroimmune system. In addition, it describes the impact of PM on the potential neuroimmune pathways in AD pathogenesis with a special focus on the Fc Epsilon RI pathway. Finally, the review proposes potential treatment lines that could be targeted to alleviate pruritus based on immune mediators involved in the Fc Epsilon signaling map.

Auto-immunoproteomics analysis of COVID-19 ICU patients revealed increased levels of autoantibodies related to the male reproductive system.

Background: Coronavirus disease (COVID-19) manifests many clinical symptoms, including an exacerbated immune response and cytokine storm. Autoantibodies in COVID-19 may have severe prodromal effects that are poorly understood. The interaction between these autoantibodies and self-antigens can result in systemic inflammation and organ dysfunction. However, the role of autoantibodies in COVID-19 complications has yet to be fully understood. Methods: The current investigation screened two independent cohorts of 97 COVID-19 patients [discovery (Disc) cohort from Qatar (case = 49 vs. control = 48) and replication (Rep) cohort from New York (case = 48 vs. control = 28)] utilizing high-throughput KoRectly Expressed (KREX) Immunome protein-array technology. Total IgG autoantibody responses were evaluated against 1,318 correctly folded and full-length human proteins. Samples were randomly applied on the precoated microarray slides for 2 h. Cy3-labeled secondary antibodies were used to detect IgG autoantibody response. Slides were scanned at a fixed gain setting using the Agilent fluorescence microarray scanner, generating a 16-bit TIFF file. Group comparisons were performed using a linear model and Fisher's exact test. Differentially expressed proteins were used for KEGG and WIKIpathway annotation to determine pathways in which the proteins of interest were significantly over-represented. Results and conclusion: Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (p ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients who served as controls. Both cohorts showed substantial similarities (r 2 = 0.73) and exhibited higher autoantibody responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. The sequences for SPANXN4 and STK25 were cross-validated using sequence alignment tools. ELISA and Western blot further verified the autoantigen-autoantibody response of SPANXN4. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19-associated male reproductive tract complications, and warrants further research.

Uncovering a neurological protein signature for severe COVID-19.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has sparked a global pandemic with severe complications and high morbidity rate. Neurological symptoms in COVID-19 patients, and neurological sequelae post COVID-19 recovery have been extensively reported. Yet, neurological molecular signature and signaling pathways that are affected in the central nervous system (CNS) of COVID-19 severe patients remain still unknown and need to be identified. Plasma samples from 49 severe COVID-19 patients, 50 mild COVID-19 patients, and 40 healthy controls were subjected to Olink proteomics analysis of 184 CNS-enriched proteins. By using a multi-approach bioinformatics analysis, we identified a 34-neurological protein signature for COVID-19 severity and unveiled dysregulated neurological pathways in severe cases. Here, we identified a new neurological protein signature for severe COVID-19 that was validated in different independent cohorts using blood and postmortem brain samples and shown to correlate with neurological diseases and pharmacological drugs. This protein signature could potentially aid the development of prognostic and diagnostic tools for neurological complications in post-COVID-19 convalescent patients with long term neurological sequelae.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.