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 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.

Circulatory EVs as a predictor of chronic urticarial activity.

Background: Chronic urticaria (CU) is a common and complex disorder that occurs without any identifiable provoking factor. The mechanisms underlying CU pathogenesis are still not fully understood. The autoimmune theory of IgG autoantibodies to IgE/high-affinity receptor of IgE on mast cells and mast cell activation and autoallergy (IgE-mediated disease) might contribute to CU pathogenesis. Extracellular vesicles (EVs) are membranous vesicles released from apoptotic or activated cells of different types. In this study, we aimed to investigate circulating EVs as potential biomarkers in patients with CU compared with that in healthy controls. Methods: We studied 15 patients with CU and 16 healthy controls. Circulatory EVs (plasma) were characterized by the presence of externalized phosphatidylserine (annexin V staining). An unpaired t-test was used, and P < 0.05 was considered statistically significant. Results: We did not find significant differences in the total number of EVs in patients with CU. A significant decrease in the levels of T-cells (CD3) and endothelial cells (CD146) (P < 0.05) in these patients than in controls was found. No significant differences were observed between patients with CU and healthy controls in terms of platelets, macrophages, PECAM-1, B cells, and tissue factors. Conclusion: Endothelial cells have been shown to contribute to the pathogenesis of CU and are also targeted by mediators released by mast cells and other cellular infiltrates. We identified that circulatory endothelial and T-cell EVs might play an important role in CU pathogenesis. In addition, our study highlights the importance of EVs as future therapeutic targets to be investigated.

Correlation between skin test results and historical manifestations in patients with suspected lidocaine hypersensitivity.

BACKGROUND: Adverse reactions to local anesthetics (LA) are relatively common; however, true IgE-mediated allergy is extremely rare, estimated to occur in less than 1%. Investigating patients with suspected allergy to LA should begin with a detailed history to exclude other more common operation theater related culprit medications, followed by skin testing. The subcutaneous challenge is considered the gold standard for confirming true IgE-mediated allergy to LA. In this study, we have described the skin prick test results of patients with suspected lidocaine allergy who had historical reaction symptoms typical to IgE-mediated allergic reactions. METHODS: The data were retrieved from the allergy procedure log registry for patients who were referred to the allergy clinic with a suspected allergic reaction to lidocaine at the Hamad Medical Corporation between 2016 and 2020. These patients' symptoms of historical reactions to lidocaine were compared to their skin test results. RESULT: A total of 7 patients were identified. The skin test result for lidocaine was positive in only 1 patient; his historical reaction was anaphylaxis (urticaria/angioedema and shortness of breath). The remaining 6 patients had a negative result for skin and challenge tests. Of these 6 patients with negative results, 4 had only urticaria/angioedema as historical reactions; 1 had systematic manifestation (tachycardia) along with urticaria/angioedema, and 1 experienced systemic symptoms (shortness of breath, chest pain, and palpitation) with no skin or mucous membrane involvement (Table 1). CONCLUSION: Negative skin test and subcutaneous challenge with a history of generalized cutaneous symptoms and/or systemic symptoms during the reaction to LA can be attributed to many causes, such as an IgE-mediated reaction against a component other than lidocaine (e.g., latex), medication side effects (adrenaline in combined preparations), and/or symptoms of primary disease (chronic spontaneous urticaria/angioedema).

Aspirin challenge and desensitization in patients with suspected AERD in Qatar.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a chronic disease characterized by chronic rhinosinusitis, nasal polyposis, asthma, and intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin challenge is considered the gold standard for diagnosing AERD. Many patients with AERD have reported clinical benefits when desensitized to aspirin and maintained on daily aspirin therapy. In this study, we have summarized aspirin challenges and aspirin desensitization in our division during the past ten years. METHODS: We reviewed aspirin challenges and desensitization procedures performed in the Allergy and Immunology Division at the Hamad Medical Corporation, Doha, Qatar, between 2010 and 2020 from our procedures log registry and reported the results of the procedures. RESULTS: The procedures were performed for patients with chronic rhinosinusitis, nasal polyposis, and bronchial asthma with a historical reaction to NSAIDs or those never exposed to NSAIDs. The challenge and desensitization procedure protocol is outlined in table.1. Of the 45 procedures performed, 36 (80%) patients reacted during aspirin desensitization; and their characteristics, historical reaction to NSAIDs, provoking dose, length of desensitization, and types of reactions were reviewed. Of the reactors, 32 (88%) patients completed aspirin desensitization successfully. The mean ( ± SD) age of patients was 46 ( ± 11.6) years, and 51% were women. The historical symptoms were asthma symptoms (56%) and naso-ocular (21%). The common (71%) reaction during the procedure was asthma symptoms, and 29% had naso-ocular symptoms. The provoking dose was 50-75 mg in most patients. The desensitization procedure was carried out over 2 days in most patients; however, 29% of the patients needed more than 2 days to complete the desensitization. None of the reactors needed emergency epinephrine use or hospital admission. CONCLUSION: In our review, desensitization was successful in all the patients who reacted to aspirin, and it was the only therapeutic choice for patients with AERD before the era of biologics. The procedure was well tolerated in most patients. Aspirin challenge was positive in 80% of our patients with suspected AERD, and this has an important diagnostic value that may help in choosing the proper biologic, such as dupilumab, for these patients.

Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study.

BACKGROUND: Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to be affected by age, sex, atopy, and geographic location. This study aims to examine the common triggers of anaphylaxis in Qatar. METHODS: A total of 1068 electronic medical records were audited using power chart system: 446 from the medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors (EAIs) dispensed during January 2012-December 2017. RESULTS: Of 1068 patients, 574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients (77.9%) were less than 10 years old. The common triggers were food (n = 316, 55.0%), insect stings (n = 161, 28.0%), and drugs (n = 103, 17.9%). Common anaphylaxis food triggers were nuts (n = 173, 30.1%), eggs (n = 89, 15.5%), and seafood (n = 72, 12.5%), and common anaphylaxis medication triggers were antibiotics (n = 49, 8.5%) and nonsteroidal anti-inflammatory drugs (n = 30, 5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant stings. The anaphylaxis triggers varied significantly between children and adults. Among children (less than 10 years), three quarters of the events were triggered by food (223, 74.3%) while among adults (20-55 years), insect stings (n = 59, 43.0%) and drugs (n = 44, 32.0%) were dominant. DISCUSSION: This is the first national study stratifying anaphylaxis triggers among different age groups in Qatar. This study will serve as a guide for clinical practice in allergy clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar.

Aloin: a natural antitumor anthraquinone glycoside with iron chelating and non-atherogenic activities.

CONTEXT: The antitumor activity of aloin, the active anthraquinone of Aloe juice, against different murine and human tumors has been reported. OBJECTIVE: In the present study, the impact of repeated aloin treatment at its maximum tolerated dose on serum levels of lipid profile, some elements, iron status and kidney function, compared with doxorubicin (a cardiotoxic anthracycline and inhibitor of erythropoiesis), was assessed. MATERIALS AND METHODS: Rats were treated with a single dose of doxorubicin (30 mg/kg body weight, intraperitoneal) or aloin (50 mg/kg body weight, intramuscular) twice weekly over 2 weeks. RESULTS: Acute doxorubicin treatment elevated serum levels of triacylglycerols (59.90%), total cholesterol (42.29%), cholesteryl esters (54.75%), low density lipoprotein-cholesterol (230.16%), very low density lipoprotein-cholesterol (56.42%), urea (287.53%), and creatinine (85.38%), whereas serum high density lipoprotein-cholesterol, sodium, and calcium levels were reduced (44.61, 9.61, and 9.76%, respectively), as compared with controls. In contrast, aloin treatment showed insignificant changes in all the aforementioned parameters. Both doxorubicin and aloin induced erythropoiesis impairment demonstrated by a reduction in blood hemoglobin concentration. While aloin treatment elevated serum iron level (30.28%), doxorubicin treatment reduced serum levels of iron (51.47%) and percent transferrin saturation (55.21%), and in contrast, increased serum total iron binding capacity (34.85%). The chelating affinities of iron-aloin and -doxorubicin complexes, which contain bidentate iron-binding moieties, have been shown in the infrared spectra. DISCUSSION AND CONCLUSION: The non-cardiotoxic effect of aloin treatment was due to its non-atherogenic and iron-chelating activities, which might also contribute in part to its anti-proliferative activity.