Qatar Medical Journal - 2 - Second Qatar Allergy Conference, April 2023

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.

Objective: Common variable immunodeficiency (CVID) is a complex inborn error of humoral immunity with complications of both infectious and non-infectious origins. Classifications of CVID patients provide a clearer understanding of the pathogenesis, prediction, and management of non-infectious complications. This study aims to classify Moroccan CVID patients based on the European classification (EUROclass).

Materials and Methods: We recruited 20 CVID patients meeting standard diagnostic criteria (5-6). After collecting clinical and demographic data, we used flow cytometry to analyze B-cell subsets and group patients and assess the relation of each group with clinical manifestations.

Results: 90% of the patients in our cohort study had a history of respiratory infections. The non-infectious manifestations included splenomegaly, autoimmunity, lymphadenopathy, and granulomatous diseases diagnosed in 50%, 45%, 40%, and 25% of patients, respectively. We observed significant co-occurrence of splenomegaly with autoimmunity and granulomatous diseases to a lesser extent. Patients had a significant reduction in total, switched memory, marginal zone-like, plasma blasts, and a substantial increase in the percentage of activated B cells, suggesting a defect in the late phases of B-cell differentiation. This condition was linked with an increased occurrence of splenomegaly and granulomatous affections. Besides, patients also had an expansion of CD21^low B-cells, which was strongly associated with splenomegaly.

Conclusion: The classification of the first Moroccan cohort of CVID patients showed agreement with previous results. It suggests the possibility of adopting this approach on a global scale for better diagnosis and follow-up of CVID patients.

Background and Aim: Chronic giardia infection can lead to non-erosive gastrointestinal disorders, including protein-losing enteropathy (PLE). This report describes non-diarrheal PLE in chronic giardiasis in children with defective humoral immunity.

Methods: The retrospective report is related to 2 children known to have a monogenic inborn error of immunity. The first patient is a 13-year-old boy with X-linked agammaglobulinemia (Patient-1), and the second is a 5-year-old boy with NF-kB inducing kinase (NIK) deficiency infection. Frequency, growth status, and serum immunoglobulin-G (IgG) trough and albumin levels were monitored (Patient-2).

Results: Patient-1 had more frequency of pneumonia but reported no symptoms of gastrointestinal disease, including alteration of bowel habits, change in stool consistency, nausea, vomiting, fatigue, bloating, and abdominal pain. No clinical oedema on examination. His weight remains static at 19-20 kg for about 1.5 years. Simultaneously, hypoproteinaemia was noted (Figure-1).

A trial of increasing IVIG (0.7 – 1 g/kg) and the use of subcutaneous immunoglobulin (0.2 g/kg) did not reverse the biochemical and clinical situation. Hypoproteinaemia workup revealed normal liver and kidney functions, normal cardiac function, and no proteinuria. Interestingly, his upper endoscopy showed mild duodenitis and the presence of giardia lamblia at the luminal surface (Figure-2).

Following this, a 2-week course of oral metronidazole (7.5 mg/kg/dose BID) resulted in a restoration of therapeutic serum IgG trough and albumin levels. Additionally, the child’s nutritional status improved, and the frequency of respiratory infections dropped. In Patient-2, progressive hypoproteinaemia was noted over nine months. Similarly, no gastrointestinal complaints; however, the family reported foul-smelling semisolid stools with regular consistency. His IgG trough level was 2 g/l, and his albumin level was 20 g/l. Despite maximizing IVIG, he developed two episodes of pneumonia and once otitis media. An empiric oral metronidazole course resulted in the amelioration of symptoms and restoration of proteinemia. Meanwhile, faeces microscopy confirmed the presence of Giardia lamblia.

Conclusions: Progressive hypoproteinaemia in children with humoral immunodeficiency is a clinical concern. Routine stool microscopy can identify giardia infection despite the ambiguity of gastrointestinal symptoms in such patients. However, a trial of empiric metronidazole therapy should be considered.

The constant progress of genomics and the establishment of new functional tests have paved the way for identifying monogenic defects conferring a selective predisposition to infections by certain microbes as a new type of inborn errors of immunity (IEIs). Mendelian susceptibility to mycobacterial diseases (MSMD) is the most characterized of these IEIs, with 36 different disorders found in 20 distinct genes (IFNGR1, IFNGR2, IFNG, IL12RB1, IL12RB2, IL23R, IL12B, ISG15, USP18, ZNFX1, TBX21, STAT1, TYK2, IRF8, IRF1, CYBB, JAK1, RORC, NEMO, and SPPL2A) over the last 20 years. MSMD confers a selective susceptibility to infections with weakly virulent mycobacteria, including the M. bovis Bacille Calmette-Guérin (BCG) vaccines and various environmental mycobacteria in patients, primarily children, without classical immune defects. These patients may also present severe forms of tuberculosis, and about half of them might develop non-typhoidal salmonellosis. In some cases, patients also suffer from chronic mucocutaneous candidiasis (CMC), while in others, patients also present severe viral, parasitic, fungal, and/or bacterial diseases. Despite this clinical and genetic heterogeneity, almost all genetic etiologies of MSMD alter the interferon-gamma (IFN-γ)-mediated immunity by impairing or abolishing IFN-γ production or the response to this cytokine. It was proven that the human IFN-γ level is a quantitative trait that defines the outcome of mycobacterial infection. The study of these monogenic defects contributes to understanding the molecular mechanism of mycobacterial diseases in humans and to the development of new diagnostic and therapeutic approaches to improve care and prognosis. For example, MSMD patients with impaired production of IFN-γ may benefit from injections of human recombinant IFN-γ, while for patients with abolished response to this cytokine, hematopoietic stem cell transplantation (HSCT) and promising gene therapy are the only current therapeutic options. These discoveries also bridge the gap between simple Mendelian inheritance and complex human genetics.

Introduction: Anti-centromere antibodies (ACAs) are a variety of anti-nuclear autoantibodies (ANA) directed against different kinetochore proteins. They are sought on HEp2 substrates by indirect immunofluorescence technique (IFI), where they appear in the form of about forty fine nuclear punctuations attached to the chromosomes during their different cell cycle phases. They are encountered in several autoimmune diseases (AID), frequently in scleroderma. This work aims to retrospectively analyze serum samples containing anti-centromere antibodies and the associated pathologies.

Materials and methods: Eleven serum positive for ACAs were studied among 821 requests for ANA analyses sent to the Immunology Department, Central Laboratory for Medical Analyzes, CHU Hassan II-Fez for three years. Two techniques were used: indirect immunofluorescence for the ANA research and ELISA or Immunodot for identifying antigenic specificities according to the suppliers’ recommendations (D-Tek).

Results: The mean age of patients was 50 ± 18 years. A female predominance (81.8%) was observed, with a sex ratio F/M of 4.5. The research of Anti-nuclear antibodies was positive in immunofluorescence in all cases. With a centromeric appearance in 9 cases and a speckled appearance in 2 cases, the titer varied between 160 and 1280. Antigenic identification by Immunodot showed that anti-CENP A and CENP B were found in 7 cases, and anti-CENP B was identified in 4 cases. The results by pathology show a significant association of ACAs with the clinical suspicion of systemic sclerosis (45%).

Conclusion: The presence of ACAs can be associated with several AIDs, mainly scleroderma. These autoantibodies represent an important diagnostic and prognostic tool by defining immuno-clinical forms of the disease.

Introduction: Soluble anti-antigen antibodies (Anti-ENA) represent a specificity of anti-nuclear autoantibodies (ANA), which are directed against nuclear particles composed of small RNA (Ribonucleic acid) and proteins. They are found during certain autoimmune diseases (ADs), most frequently during systemic lupus erythematosus (SLE) and Gougerot syndrome. The aim of this study is to retrospectively analyze the positive serum for Anti-ENA antibodies and associated pathologies.

Materials and methods: This study was carried out at the Immunology Department, Central Laboratory of Medical Analysis, University Hospital Hassan II - Fez, Morocco, for a period of 2 years. 821 serum samples were included. The indirect immunofluorescence method (IFI) was used to search the ANAs in the serums. In the case of a positive result, an identification of the antigenic targets was performed by the Immunodot technique according to the supplier’s recommendations (D-Tek).

Results: Eighty-eight serums were found positive for anti-ENA antibodies. The mean age in our series was 41 ±15.5 years. There were 80 women and 8 men with a sex ratio F/M of 10. The results by associated pathologies show a strong association of the anti-ENA antibodies’ positivity with lupus and Gougerot syndrome.

Conclusion: Anti-ENA antibodies are important immunological markers for lupus and Gougerot syndrome diagnosis.

Background: Obstructive sleep apnea (OSA) affects 1% to 5% of all children, with the most significant prevalence between ages 2 and 8. Correlations between OSA and Adenoid hypertrophy (AH) have been well-demonstrated in children. If untreated, OSA can cause growth impairment, neuro-cognitive and behavioral problems, and cardiovascular complications. Allergy was reported to be a vital risk factor for AH, among other inflammatory processes mentioned.

Objectives:

1. To demonstrate that the combination of nasal steroids and ani leukotriene reduces the number of adenectomies in children with OSA and adenoid hypertrophy in Saudi children.
2. To demonstrate the positive Correlation between allergic sensitization and OSA caused by adenoid hypertrophy

Methods: This retrospective study included 60 children with moderate/severe OSA attending a Pediatric Allergy Clinic in Saudi Arabia diagnosed using Sleep-Related Breathing Disorder Scale (pediatrics-related items). We had children with adenoid hypertrophy confirmed by soft neck tissue x-ray or both; children who suffer from obesity were excluded. Sensitization was defined as positive specific IgE and/or skin prick for food and/or inhaled allergens; allergic comorbidities were enumerated.

Results: Combination of nasal steroid and anti-leukotriene reduces adenectomy by 58.3 % in children with OSA caused by AH. 71.7% of Them were sensitized to inhaled food or both allergens.

Conclusion: Anti-inflammatory treatment with a combination of nasal steroids and anti-leukotriene remarkably reduces the adenectomy rate in children with OSA caused by AH. Our findings suggest that allergic sensitization, regardless of the allergen, increases children’s susceptibility to AH through the inflammatory process. This may be why nasonex and montelukast are effective treatments for OSA in children with AH.

Background: Every year, 14 million babies are born with low birth weight (LBW) and/or intrauterine growth restriction (IUGR) in developing countries. In Sudan, 15-25% of all newborns are born with LBW, with half being Term-LBW. The importance of nutrition in the first 1000 days of life has been well demonstrated. Evidence links IUGR to various health and developmental disorders, and intrauterine programming of the hypothalamic-pituitary-adrenal (HPA) axis has been strongly suggested as a possible mechanism. Sudan has been listed among the lowest four countries regarding food security which has a massive impact on maternal and infant health.

Hypothesis: We hypothesize that infants who suffer from intrauterine growth retardation will have exaggerated physiological and behavioural responses to physical stressors.

Objectives: To compare T-LBW with T-NBW on (a) Salivary cortisol level at rest and after a physical stressor and (b) Behavioural response to physical stressors.

Methods: Hospital-based matched case-control study. Cases were 65 T-LBW neonates, and controls were 67 T-NBW neonates matched for age 4-6 hours, gestational age, and mode of delivery—measurements: Anthropometry, salivary samples for cortisol before and after heel prick, and behavioural ratings.

Results: Compared with controls, the IUGR neonates were lighter, shorter, and thinner (p <0.0001) and had lower basal cortisol levels (p <0.03). Following stressors, IUGR neonates had lower (p >0.0001) and inhibited cortisol response (p <0.02), and cried less vigorously (p <0.0001). All anthropometric measures were significantly and positively correlated with behavioural responses and pre- and post-stress cortisol levels. Stunting was more strongly associated with behavioural inhibition than wasting.

Conclusion: The severity of intrauterine growth retardation correlated with behavioral and physiological inhibition, which can lead to the development of mismatch diseases such as allergies, autoimmune diseases, and conjunctive disorders.

Introduction: The periodic fever syndrome Familial Mediterranean Fever (FMF) is caused by mutations in MEFV, which promote inflammation and present with uncontrolled systemic and organ-specific inflammation that can resemble infectious conditions. It is diagnosed based on clinical criteria, including frequent symptoms such as abdominal and thoracic pain, family history, and response to treatment with colchicine, which is confirmed by genetic assessment. Herein, we present a case of FMF with a relatively uncommon presentation.

Case presentation: A 22-month-old female was referred to the allergy and clinical immunology clinic with eczematoid skin rashes. She was admitted to the hospital several times since the 2^nd day of life with different complaints like fever, seizure, and restlessness, and treated with the diagnosis of septicemia. Endoscopy and colonoscopy were done at the age of 6 months due to poor weight gain and bloody diarrhea, which revealed active crypt-destructive colitis with foci of erosion in favor of infectious or allergic colitis. The colon biopsy was negative for Cytomegalovirus (CMV). Regarding family history, she was the second child of the first cousin’s parents and had a healthy 12-year-old sister. There was a history of death for unknown reasons of her cousin, whose parents were related. The immunologic evaluation was done, which showed a relatively normal immunoglobulin level, antibody response, flow cytometry, and lymphocyte transformation test. Nonetheless, a genetic study was done, which showed a homozygote mutation in exon 10 of the MEFV gene in the patient and a heterozygote mutation in both her parents.

Conclusion: The periodic fever syndrome Familial Mediterranean Fever (FMF) is caused by mutations in MEFV, which promote inflammation and present with uncontrolled systemic and organ-specific inflammation that can resemble infectious conditions. The patient was diagnosed with FMF, and treatment was started using colchicine, which successfully controlled the patient’s symptoms and prevented the recurrence of fever and other inflammatory manifestations.