Identifying the most at-risk age-group and longitudinal trends of drug allergy labeling amongst 7.3 million individuals in Hong Kong.

BACKGROUND: Incorrect drug 'allergy' labels remain a global public health concern. Identifying regional trends of drug allergy labeling can guide appropriate public health interventions, but longitudinal or population drug allergy studies remain scarce. We analysed the serial epidemiology of drug allergy labeling to identify specific subgroups at highest risk of drug allergy labeling for potential interventions. METHODS: Longitudinal, population-wide drug allergy labels and clinical data from over 7,337,778 individuals in Hong Kong between 2016 and 2021 were analysed. RESULTS: The absolute prevalence and incidence of documented drug allergy were 5.61% and 277/100,000 population, respectively. Annual incidence of new allergy labels was stable between 2016 and 2019, until a significant drop in 2020 (-16.3%) during the COVID19 pandemic. The most common allergy labels were anti-infectives (245,832 [44.5%]), non-steroidal anti-inflammatory (106,843 [19.3%]), and nervous system drugs (45,802 [8.3%]). The most common labeled culprits for the most severe immediate-type (anaphylaxis) and non-immediate-type (Stevens-Johnson syndrome) reactions were beta-lactams and nervous system drugs, respectively. For individuals at highest risk of labeling, there was significantly higher incidence of overall drug and beta-lactam allergy labeling amongst individuals aged > 40 years which contributed to the majority of newly labeled allergies (377,004, 68.2%). CONCLUSIONS: Contrary to traditional dogma, we identified disproportionately higher incidence of drug allergy labeling amongst older individuals, rather than the paediatric age group. We advocate for more population-wide drug allergy studies to investigate this phenomenon in other cohorts as well as future preventative and delabeling efforts focusing on the adult population.

Ten-year outcomes of Perioperative Anaphylaxis Workup Study in Hong Kong (PAWS-HK): Performance of diagnostic modalities.

BACKGROUND: Studies on perioperative anaphylaxis (PA) in Asia are lacking. Furthermore, allergy workup for PA has largely been limited to the "silver standard" of skin tests (ST). Using in vitro tests as an adjunct to ST may improve and overcome these diagnostic challenges. OBJECTIVE: To evaluate the clinical characteristics and diagnostic tests of patients with suspected PA through the Perioperative Anaphylaxis Workup Study in Hong Kong cohort. METHODS: Patients with a diagnosis of PA over a 10-year period were recruited into the Perioperative Anaphylaxis Workup Study in Hong Kong. We reviewed the medical records, tryptase elevation, and diagnostic tests including ST, specific immunoglobulin E, and basophil activation tests (BAT). RESULTS: In 151 patients with PA, diagnosis was reached in three-fourths of the cases (113/151, 74.8%). The most common culprits identified were neuromuscular blocking agents (25.8%), ß lactams (17.2%) and chlorhexidine (13.9%). Severe anaphylaxis was associated with female sex, older age, elevated acute tryptase levels, and more cardiovascular manifestations during induction. Skin tests remained the most sensitive diagnostic modality overall (66.2%). BAT showed better performance for chlorhexidine and gelofusine anaphylaxis, with sensitivity of 80.0% and 79.6%, respectively. Specific Immunoglobulin E indicated even higher sensitivity (95.2%) than did ST (85.0%) and BAT (80.0%) for chlorhexidine anaphylaxis but performed poorly for other drugs. CONCLUSION: Neuromuscular blocking agents remain the most common culprit in PA. There was a higher prevalence of gelofusine anaphylaxis in our cohort than was seen in the literature. Skin tests remain the most sensitive testing modality. In vitro tests for chlorhexidine and gelofusine showed promising results, but more studies to further elucidate its use are warranted.

A case of persistent IgE sensitisation almost two decades following ampicillin anaphylaxis.

BACKGROUND: Although most immunoglobulin E (IgE)-mediated penicillin allergy wanes with time, sensitisation may occasionally persist for many years. Previous reports on the loss of penicillin-specific IgE sensitisation were based on non-anaphylaxis cases and, although uncommon, persistent sensitisation may still be possible in the minority of cases. OBJECTIVE: This case highlights that irrespective of the elapsed duration since the index reaction, it is important to remain vigilant when approaching patients with a history of severe reactions. MATERIAL AND METHODS: We described a case of persistent IgE sensitisation almost two decades following ampicillin anaphylaxis. RESULTS: A 78-year-old male with a history of perioperative penicillin anaphylaxis in 2003 was referred for allergy workup in 2022 before his knee joint replacement surgery. The patient had strictly avoided all beta-lactams since the index reaction. However, his penicillin-specific sensitisation persisted, evidenced by positive skin tests (with generalised urticaria after intradermal testing) and basophil activation tests. CONCLUSION: To our knowledge, this was the first case of positive BAT tested around two decades following the index reaction. This case illustrates that a cautious approach may still be warranted in patients with a history of severe reaction to penicillin regardless of the duration since the reported index reaction.

COVID-19 Vaccine Allergy Safety Track (VAS-Track) pathway: real-world outcomes on vaccination rates and antibody protection.

BACKGROUND: Misdiagnosed vaccine-related "allergies" lead to unnecessary vaccine deferrals and incomplete vaccinations, leaving patients unprotected against COVID-19. To overcome limitations and queues for Allergist assessment, the "VAS-Track" pathway was developed to evaluate patients via a multi-disciplinary triage model including nurses, non-specialists, and Allergists. OBJECTIVE: We assessed the effectiveness and safety of VAS-Track and evaluate its real-world impact in terms of vaccination rates and COVID-19 protection. METHODS: Patients referred to VAS-Track between September 2021 and March 2022 were recruited. Subgroup analysis was performed with prospective pre- and post-clinic antibody levels. RESULTS: Nurse-assisted screening identified 10,412 (76%) referrals as inappropriate. 369 patients were assessed by VAS-Track. Overall, 100% of patients were recommended to complete vaccination and 332 (90%) completed their primary series. No patients reported any significant allergic reactions following subsequent vaccination. Vaccination completion rates between patients seen by non-specialists and additional Allergist review were similar (90% vs. 89%, p = 0.617). Vaccination rates were higher among patients with prior history of immediate-type reactions (odds ratio: 2.43, p = 0.025). Subgroup analysis revealed that only 20% (56/284) of patients had seropositive COVID-19 neutralizing antibody levels (≥ 15 AU/mL) prior to VAS-Track, which increased to 92% after vaccine completion (pre-clinic antibody level 6.0 ± 13.5 AU/mL vs. post-clinic antibody level 778.8 ± 337.4 AU/mL, p > 0.001). CONCLUSIONS: A multi-disciplinary allergy team was able to streamline our COVID-19 VAS services, enabling almost all patients to complete their primary series, significantly boosting antibody levels and real-world COVID-19 protection. We propose similar multidisciplinary models to be further utilized, especially in the settings with limited allergy services.

The Role of the Allergist in Coronavirus Disease 2019 Vaccine Allergy Safety: A Pilot Study on a "Hub-and-Spoke" Model for Population-Wide Allergy Service.

BACKGROUND: Hong Kong started its coronavirus disease 2019 (COVID-19) vaccination program in February 2021. A territory-wide Vaccine Allergy Safety (VAS) clinic was set up to assess individuals deemed at "higher risk" of COVID-19 vaccine-associated allergies. A novel "hub-and-spoke" model was piloted to tackle the overwhelming demand of services by allowing nonallergists to conduct assessment. OBJECTIVE: To evaluate the outcomes of the VAS hub-and-spoke model for allergy assessment. METHODS: Records of patients attending the VAS hub-and-spoke Clinics between March and August 2021 were reviewed (n = 2725). We studied the overall results between the Hub (allergist led) and Spoke (nonallergist led) Clinics. The Hub and the Hong Kong West Cluster Spoke Clinic were selected for subgroup analysis as they saw the largest number of patients (n = 1411). RESULTS: A total of 2725 patients were assessed under the VAS hub-and-spoke model. Overall, 2324 patients (85.3%) were recommended to proceed with vaccination. Allergists recommended significantly more patients for vaccination than nonallergists (odds ratio = 21.58; P < .001). Subgroup analysis revealed that 881 of 1055 (83.5%) patients received their first dose of COVID-19 vaccination safely after assessment. Among those recommended vaccination, more patients assessed by allergists received their first dose of vaccination (odds ratio = 4.18; P < .001). CONCLUSION: The hub-and-spoke model has proven to be successful for the vaccination campaign. This study has illustrated the crucial role of allergists in countering vaccine hesitancy. Results from the study revealed considerable differences in outcomes between allergist-led and nonallergist-led clinics. Precise reasons for these differences warrant further evaluation. We are hopeful that the hub-and-spoke model can be similarly adapted for other allergist-integrative services in the future.

Skin prick testing a better predictor than blood testing for the diagnosis of peanut allergy in Chinese children.

BACKGROUND: Peanut allergy is common in Chinese children, yet the most predictive diagnostic cut-offs for skin prick test (SPT) and blood testing in this population are unclear. OBJECTIVES: We aimed to determine the optimal cut-off values for whole-peanut SPT, specific IgE (sIgE) and component-resolved diagnostics (CRD) for Chinese children based on outcomes of open oral food challenges (OFC) to peanut. METHODS: We recruited ethnic-Chinese patients 1-18 years old who were suspected of having peanut allergy based on a history of reactions after exposure or sensitization although peanut naïve. Considering the AUC value of 0.8, 80% power and 5% level of significance with two tails, 26 patients were needed. Sensitivities, specificities, positive and negative predictive values, and receiver operating characteristic curves (ROCs) and their area-under-curves (AUCs) for SPT, peanut sIgE, and CRD were compared. RESULTS: Thirty-one subjects participated. Only SPT reached statistical significance (AUC 0.91, p = 0.0001), but not the other tests. Seven retrospective data were added to optimize the power. SPT remained to be the best predictor, followed by Ara h 2 sIgE (AUC 0.72, p = 0.02). An SPT wheal size of 3 mm and Ara h 2 sIgE of 0.14 kU(A)/L yielded the highest Youden's index. The specificity of SPT and Ara h 2 sIgE reached 94% at 6 mm and 0.74 kU(A)/L, respectively. Comparisons of ROCs revealed that SPT was significantly better than Ara h 2 sIgE (p = 0.03) and whole-peanut sIgE (AUC 0.61, p = 0.26). CONCLUSION: In Chinese children, SPT appeared to be the best predictor for peanut allergy, followed by Ara h 2 sIgE.

Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM.

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10-7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10-5) and ASCT (p = 4.8 × 10-4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10-8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10-4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10-4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

Preoperative weight loss interventions before total hip and knee arthroplasty: a systematic review of randomized controlled trials.

BACKGROUND: The high co-prevalence of obesity and end-stage osteoarthritis requiring arthroplasty, with the former being a risk factor for complications during arthroplasty, has led to increasing interest in employing preoperative weight loss interventions such as bariatric surgery and diet modification. However, the current evidence is conflicting, and this study aimed to investigate the effect of weight loss intervention before arthroplasty in prospective randomized controlled trials. METHODS: Four electronic databases (MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) were searched for prospective randomized controlled trials that compared weight loss interventions with usual care from inception to October 2023 by following the PRISMA guidelines. The Cochrane risk of bias tool and GRADE framework were used to assess the quality of the studies. Meta-analyses were performed when sufficient data were available from 2 or more studies. RESULTS: Three randomized controlled trials involving 198 patients were identified. Two studies employed diet modification, and one study utilized bariatric surgery. All three studies reported significant reductions in body weight and body mass index (BMI), and intervention groups had fewer postoperative complications. There was no difference in the length of stay between the intervention group and the control group. Variable patient-reported outcome measures were used by different research groups. CONCLUSION: Weight loss intervention can achieve significant reductions in body weight and body mass index before arthroplasty, with fewer postoperative complications reported. Further studies with different populations could confirm the effect of these interventions among populations with different obesity characteristics.

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Feasibility of a drug allergy registry-based excipient allergy database and call for universal mandatory drug ingredient disclosure: the case of PEG.

Background: Excipient allergy is a rare, but potentially lethal, form of drug allergy. Diagnosing excipient allergy remains difficult in regions without mandatory drug ingredient disclosure and is a significant barrier to drug safety. Objective: To investigate the feasibility of a drug allergy registry-based excipient database to identify potential excipient culprits in patients with history of drug allergy, using polyethylene glycol (PEG) as an example. Methods: An excipient registry was created by compiling the excipient lists pertaining to all available formulations of the top 50 most reported drug allergy culprits in Hong Kong. Availability of excipient information, and its relationship with total number of formulations of individual drugs were analysed. All formulations were checked for the presence or absence of PEG. Results: Complete excipient information was available for 36.5% (729/2,000) of all formulations of the top 50 reported drug allergy culprits in Hong Kong. The number of formulations for each drug was associated with proportion of available excipient information (ρ = 0.466, p = 0.001). Out of 729 formulations, 109 (15.0%) and 620 (85.0%) were confirmed to contain and not contain PEG, respectively. Excipient information was not available for the other 1,271 (63.6%) formulations. We were unable to confirm the presence or absence of PEG in any of the top 50 drug allergy culprits in Hong Kong. Conclusion: In countries without mandatory drug ingredient disclosure, excipient databases are unlikely able to identify potential excipient allergy in drug allergy patients. Legislations to enforce mandatory and universal ingredient disclosure are urgently needed.

Epidemiology, outcomes, and disproportionate burden of food-dependent exercise-induced anaphylaxis from the Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI).

Background: Anaphylaxis is a life-threatening allergic reaction that poses a considerable burden on populations across all ethnicities and age groups. The Hong Kong Multidisciplinary Anaphylaxis Management Initiative (HK-MAMI) was established to streamline the assessment of patients with anaphylaxis via a multidisciplinary and protocol-driven approach. Objective: This prospective study aims to define the etiology, clinical manifestations, and treatment of patients with anaphylaxis in Hong Kong. Methods: Prospective clinical data from allergologic investigations from patients who completed evaluation by the HK-MAMI pathway between January 2017 and August 2022 were analyzed. Results: Of the 161 patients referred via the HK-MAMI, 131 (81.4%) met the diagnostic criteria for anaphylaxis. The median delay in diagnosis was 2 years (range 0-30 years). The majority of anaphylaxis cases were attributed to food-dependent exercise-induced anaphylaxis (FDEIA), especially wheat-dependent exercise-induced anaphylaxis. In acute management settings, paired tryptase samples were taken in only around one-third of anaphylaxis cases, with 82.5% of the samples demonstrating significant elevation. There was a general underprescription of adrenaline autoinjectors, especially for food-related anaphylaxis. Patients with FDEIA had later ages of onset and diagnosis, and they presented with more cardiovascular manifestations. Skin prick tests and specific IgE level tests were able to diagnose 95% of FDEIA cases. Conclusion: Our study highlights the significant burden of FDEIA, and especially WDEIA, in Hong Kong, its association with severe presentations, and difficulties encountered in emergency or primary care settings. We advocate appropriate adrenaline use during acute-care management and discharge plans, as well as taking serum mast cell tryptase samples during acute episodes. Interdisciplinary collaboration remains crucial to upholding proper and optimized care for patients with anaphylaxis in Hong Kong.

Long-term prophylaxis for hereditary angioedema: Initial experiences with garadacimab and lanadelumab.

Background: With no approved long-term prophylaxis (LTP) for the prevention of hereditary angioedema (HAE) attacks in Hong Kong, patients rely on compassionate use programs and drug trials. Moreover, studies regarding the use and efficacy of LTP in Asia are lacking. Objectives: Our aim was to assess 2 LTP medications for HAE in Hong Kong: lanadelumab and garadacimab. Methods: A prospective study was performed. Adult patients with a diagnosis of type I or type II HAE with 1 or more expert-confirmed attacks per month were consecutively recruited. The patients had been receiving treatment for at least 6 months. Clinical data were obtained, and questionnaires were administered before treatment periodically for at least 6 months following initiation of LTP. Results: Almost one-third of the patients with HAE experienced frequent attacks and began receiving LTP (8 of the 11 received garadacimab and 3 of the 11 received lanadelumab). At baseline, the time-normalized number of HAE attacks was 2.5 plus or minus 1.3 per month. At month 6, there was an overall reduction of time-normalized number of attacks per month of -2.4 attacks per month (95% CI = -3.3 to -1.5. [P < .01]). The time-normalized number of HAE attacks at month 6 was 0.1 plus or minus 0.1 per month. More than 70% of the patients (8 of 11) were completely attack-free during the 6-month period while receiving LTP, and no patients required hospitalization. LTP improved patients' scores of the Angioedema Quality-of-Life Questionnaire (P < .001) and reduced activity impairment due to health (P = .008). Patients experienced significant improvement across all dimensions of the Treatment Satisfaction for Medication Questionnaire (54.5%-76.8% [P = .002]), and no adverse events were reported. Conclusion: The patients receiving LTP with garadacimab and lanadelumab experienced a significant reduction in number of HAE attacks and improvement in quality of life, and they were satisfied with treatment.

Hong Kong-Macau Severe Hives and Angioedema Referral Pathway.

Background: Urticaria (defined as the presence of hives, angioedema, or both) can be caused by a variety of etiologies ranging from more common conditions such as chronic spontaneous urticaria (CSU) to rarer conditions such as hereditary angioedema (HAE). Specialist referral may be necessary in cases of severe urticaria or HAE, but access to specialist services remains limited in certain regions, such as the Greater Bay Area (GBA) of China. To address this, the Hong Kong-Macau Severe Hives and Angioedema Referral Pathway (SHARP) was initiated by the Hong Kong Institute of Allergy and Macau Society of Dermatology to promote multidisciplinary collaboration and regional exchange of expertise in the diagnosis and management of severe urticaria. Methods: A nominated task force of dermatologists and immunologists who manage patients with severe urticaria formulated the consensus statements (CS) using the Delphi method. The consensus was defined a priori as an agreement of ≥80%. Results: A total of 24 CS were formulated, including four statements on classifications and definitions, seven statements on diagnosis, and 13 statements on management and referral. The definitions for acute/chronic urticaria and severe CSU were stated. Unnecessary investigations and inappropriate medications were discouraged. The characteristics and recommended approach to suspected bradykinergic angioedema were specified. Stepwise treatment options using second-generation antihistamines, omalizumab, or cyclosporin for patients with CSU were addressed, and the importance of access to HAE-specific medications was emphasized. Furthermore, an integrated referral pathway for patients with severe hives and angioedema was constructed. Conclusion: The SHARP provides guidance for the management and specialist referral of patients with severe hives and angioedema in Hong Kong and Macau.

Comparative Effectiveness, Safety, and Real-World Outcomes of a Nurse-Led, Protocol-Driven Penicillin Allergy Evaluation From the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI).

BACKGROUND: There is a high prevalence of unconfirmed penicillin allergy, which is associated with a multitude of adverse clinical outcomes. With the overwhelming burden of currently incorrect labels and the lack of allergy specialist services, new delabeling strategies are urgently needed. OBJECTIVE: To assess the effectiveness, safety, and real-world outcomes of a nurse-led, protocol-driven evaluation of penicillin allergy, the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). METHODS: Adult patients with suspected penicillin allergy were recruited into HK-DADI. Allergy and postdelabeling outcomes were retrospectively compared between patients evaluated via HK-DADI or traditional allergist evaluation. RESULTS: A total of 312 completed penicillin allergy evaluation: 84 (27%) and 228 (73%) via HK-DADI and traditional pathways, respectively. Overall, 280 penicillin allergies were delabeled (90%). The delabeling rate between HK-DADI and traditional pathways was similar (90% vs 89%; P = .796). Among patients of the HK-DADI pathway, the delabeling rate was significantly higher among low-risk (LR) compared with non-LR patients (97% vs 77%; P = .010). Skin tests did not add diagnostic value among LR patients. No patients developed severe or systemic reactions during the evaluation. Upon 6- to 12-month follow-up (median, 10 months), 123 patients experienced infective episodes (44%) and 63 used penicillins again after delabeling (23%). This proportion was significantly higher in patients who were delabeled via HK-DADI compared with the traditional pathway (32% vs 19%; P = .026). CONCLUSIONS: The Hong Kong Drug Allergy Delabelling Initiative, a nurse-led, protocol-driven evaluation, was safe and effective in penicillin allergy delabeling. It led to an even higher rate of future penicillin use after delabeling and mitigated the need for unnecessary skin testing among LR patients.

Novel MAGT1 Mutation Found in the First Chinese XMEN in Hong Kong.

The availability of next-generation sequencing (NGS) helps to resolve many of the diagnostic odysseys. Common variable immunodeficiency disease (CVID) is an entity encompassing a heterogenous group of conditions with hypogammaglobulinemia, and it is a diagnosis of exclusion. In recent years, with the advances of molecular diagnostics, more and more patients have been reclassified with more defined entities after their genetic causes were found. Here, we reported a young man, who was managed as CVID since childhood, presenting with recurrent infection, hypogammaglobulinemia, and immune thrombocytopenia (ITP). Finally, more than a decade after initial presentation, gene panel testing revealed a novel mutation in the MAGT1 gene. Collectively, the genetic findings and clinical presentations confirm the diagnosis of X-linked immunodeficiency with magnesium defect and Epstein-Barr virus infection and neoplasia (XMEN). MAGT1 is an evolutionarily conserved, magnesium-specific transporter expressed in all mammalian cells that plays an essential role in magnesium homeostasis. MAGT1 also acts as an accessory protein for STT3B, as catalytic subunits of the oligosaccharyltransferase protein complex, which carries out glycan chain transfer to proteins in the endoplasmic reticulum during N-glycosylation. Glycans play an essential role in the stability, maturation, and localization in glycoproteins that are important in our immune cells' function. Mutation of the gene resulted in a rare X-linked recessive condition XMEN. The disease has complete penetrance but variable expressivity. It is mainly associated with immunodeficiency, immunodysregulation, and predisposition to EBV-associated lymphoproliferation. Extraimmune manifestations have also been reported in some patient cohorts, including hepatic and neurological abnormalities. Overall, the presentation varies among patients and overlaps with other clinical entities, in which diagnosis is challenging. Before the era of NGS, traditional workup hinges heavily on phenotype studies, followed by single-gene sequencing. The diagnostic yield is low, and a significant delay in diagnosis is common. This case illustrated the importance of early consideration of molecular studies in complex immunological cases without obvious secondary causes as an integral part of patient management.