Autoimmune manifestations of CTLA-4 haploinsufficiency in two patients of Southeast Asian ethnicity.

We report 2 patients who first developed cutaneous manifestations, followed by autoimmune phenomena, infections, and hypogammaglobulinemia. They were initially diagnosed with common variable immunodeficiency; however, the diagnosis was revised to cytotoxic T-lymphocyte antigen 4 haploinsufficiency after genetic and functional testing.

Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.

Inflammatory Arthritis Among Military Servicemen From a Rheumatology Center in Singapore.

INTRODUCTION: Musculoskeletal disorders are one of the most common reasons military servicemen seek medical care during their line of duty. This study aims to review the clinical profile and outcomes of military personnel with inflammatory arthritis (IA) referred to a specialist rheumatology center in Singapore. MATERIALS AND METHODS: Consecutive new case referrals from the Singapore Armed Forces medical centers during the study period January 1, 2010, to December 31, 2019, were retrospectively studied. RESULTS: There were 123 referrals, comprising 112 (91.1%) males, with the majority being Chinese (110, 89.4%). The mean age was 25.5 ± 11.1 years. The most common diagnoses were gout (including chronic tophaceous gout; 34, 27.6%), spondyloarthritis (18, 14.6%), palindromic rheumatism (8, 6.5%), rheumatoid arthritis (4, 3.3%), and juvenile idiopathic arthritis (4, 3.3%). Among servicemen with gout, all were male, the majority (31, 91.3%) were Chinese, and mean age was 34.1 ± 8.8 years. Mean body mass index (BMI) was 27.5 ± 3.9 kg/m2, of which 41.2% had moderate-risk and 47.1% high-risk BMI for cardiovascular disease and diabetes mellitus (DM). Comorbidities included hyperlipidemia (14), hypertension (6), and type 2 DM (3). Urate lowering therapy was initiated in 27 (79.4%) patients, comprising allopurinol (85.2%), probenecid (11.1%), and their combination (3.7%). One patient developed allopurinol-induced hepatitis; none had severe cutaneous adverse reactions. Among the remaining patients with IA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) used were sulfasalazine (8), methotrexate (4), hydroxychloroquine (4), and leflunomide (2). Biologic DMARDs used in five patients comprised adalimumab (3) and golimumab (2). CONCLUSION: Servicemen with IA and good functional status can still be physically fit and deployable into certain combat and service support vocations. This will optimize manpower resources in military organizations with a shrinking young workforce.

Autoimmune Rheumatic Disease Flares with Myocarditis Following COVID-19 mRNA Vaccination: A Case-Based Review.

Since the introduction of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccines, there have been multiple reports of post-vaccination myocarditis (mainly affecting young healthy males). We report on four patients with active autoimmune rheumatic diseases (ARDs) and probable or confirmed myocarditis following COVID-19 mRNA vaccination managed at a tertiary hospital in Singapore; we reviewed the literature on post-COVID-19 mRNA vaccination-related myocarditis and ARD flares. Three patients had existing ARD flares (two had systemic lupus erythematosus (SLE), one had eosinophilic granulomatosis polyangiitis (EGPA)), and one had new-onset EGPA. All patients recovered well after receiving immunosuppressants comprising high-dose glucocorticoids, cyclophosphamide, and rituximab. Thus far, only one case of active SLE with myocarditis has been reported post-COVID-19 mRNA vaccination in the literature. In contrast to isolated post-COVID-19 mRNA vaccination myocarditis, our older-aged patients had myocarditis associated with ARD flares post-COVID-19 vaccination (that occurred after one dose of an mRNA vaccine), associated with other features of ARD flares, and required increased immunosuppression to achieve myocarditis resolution. This case series serves to highlight the differences in clinical and therapeutic aspects in ARD patients, heighten the vigilance of rheumatologists for this development, and encourage the adoption of risk reduction strategies in this vulnerable population.

Characteristics of anti-transcriptional intermediary factor 1 gamma autoantibody-positive dermatomyositis patients in Singapore.

INTRODUCTION: This study aimed to determine the clinical profile and outcome of anti-transcriptional intermediary factor 1 gamma autoantibody (anti-TIF1-γ Ab)-positive dermatomyositis patients and propose cancer screening programmes based on regional cancer trends. METHOD: Data on history, physical findings and investigations were collected using chart review on dermatomyositis patients seen at a tertiary hospital in Singapore from 1 January 2015 to 30 June 2021. Comparisons were made between anti-TIF1-γ Ab-positive and anti-TIF1-γ Ab-negative dermatomyositis. RESULTS: Ninety-six dermatomyositis patients were analysed and 36 patients were positive for anti-TIF1-γ Ab. Anti-TIF1-γ Ab-positive patients had more frequent heliotrope rashes, shawl sign, periungual erythema, holster sign, Gottron's papules, dysphagia and truncal weakness (P<0.05). They had less frequent interstitial lung disease, polyarthritis, cutaneous ulcers, palmar papules and mechanic's hands (P<0.05). After 48 months of follow-up, a higher proportion of anti-TIF1-γ Ab-positive patients developed cancer compared with Ab-negative patients (63.9% versus 8.5%; odds ratio 19.1, 95% confidence interval 6.1-59.8; P<0.001). Nasopharyngeal carcinoma (NPC) and breast cancer were the most common malignancies, followed by bowel, lung and non-Hodgkin lymphoma. Most malignancies (78.3%) occurred within 13 months prior to, or 4 months after the onset of dermatomyositis. The mortality rate for anti-TIF1-γ Ab-positive patients was significantly higher than Ab-negative patients (36.1% vs 16.7%, P=0.031), and Kaplan-Meier survival estimates at 24 months were 66% and 89%, respectively (P=0.0153). CONCLUSION: These observational data support periodic screening of NPC and other malignancies in patients with anti-TIF1-γ Ab-positive dermatomyositis in Singapore.

Management of SARS-CoV-2 in the Military and Lessons for Future Pandemics.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in devastating consequences, with high death tolls and significant impact on global health, geopolitics, and socioeconomic aspects of society among others. Militaries around the world have been affected in many ways, in terms of force attrition and disruption to operations. MATERIALS AND METHODS: The Republic of Singapore Air Force (RSAF) had formulated multiple strategies and executed several contingency plans to respond swiftly and effectively to the pandemic. Measures taken by the RSAF included leveraging pandemic drawer plans, continuous medical intelligence gathering on SARS-CoV-2 characteristics, conducting rapid disease testing and contact tracing, formulating a risk assessment matrix for personnel based overseas, enforcing safe management measures and mask-wearing, and ensuring that critical medical functions were sustained. RESULTS: This article summarizes important lessons learnt that may be applied to future pandemics, including the importance of threat assessment, pandemic preparedness, adopting a tiered defense strategy, widespread testing, expeditious contact tracing and isolation, effective communication, and re-defining the new norms for post-pandemic recovery. CONCLUSION: The military remains essential to every country's defense and security. However, its unique construct and nature of operations may render it susceptible to uncontained viral transmission. To minimize manpower attrition and maximize force health in the face of a devastating pandemic, well-thought and tailored management measures must be implemented.

A Proposed Aeromedical Disposition Flowchart for Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem involvement. Clinical management of this condition has unique aeromedical considerations and an impact on subsequent aeromedical disposition. A comprehensive decision matrix would greatly benefit aviation medicine practitioners in the management of aircrew and personnel in flying-related vocations who are diagnosed with SLE.CASE REPORT: We describe the aeromedical management of a military air traffic controller who was diagnosed with SLE after presenting with cutaneous lupus, nonscarring alopecia, symmetrical small joint polyarthropathy, leukopenia, and presence of SLE-specific antibody. She was treated with hydroxychloroquine and low-dose systemic glucocorticoids, and allowed to return to duties with a proximity restriction and a bar on field deployments and night duties.DISCUSSION: Several SLE manifestations may have either incapacitating or distracting effects on aircrew and personnel in flying-related vocations. Some medications used in the treatment of SLE may similarly impact on an individuals ability to safely execute flight or air traffic control duties. We propose an aeromedical disposition decision flowchart that would guide aviation medicine practitioners in the management of individuals diagnosed with SLE to ensure optimal and safe performance in their respective occupational settings.Seah BZQ, Chua CG. A proposed aeromedical disposition flowchart for systemic lupus erythematosus. Aerosp Med Hum Perform. 2020; 91(10):826832.

Superior Mesenteric Artery Syndrome: A Potentially Fatal but Reversible Gastrointestinal Manifestation of Systemic Sclerosis.

Superior mesenteric artery syndrome (SMAS) is a rare gastrointestinal disorder characterised by vascular compression of the third part of the duodenum, in the angle between the superior mesenteric artery (SMA) and the abdominal aorta. It presents as an uncommon cause of upper gastrointestinal obstruction. In patients with systemic sclerosis (SSc), gastrointestinal involvement may result in oesophageal dysmotility, gastroesophageal reflux disease (GERD), gastroparesis, small intestinal bacterial overgrowth (SIBO), chronic intestinal pseudoobstruction (CIPO), and fecal incontinence. Malnutrition may thus result in weight loss and reduced mesenteric and retroperitoneal adipose tissue, decreasing the angle between the SMA and aorta causing SMAS. Enteral or parenteral feeding can potentially reverse SMAS in SSc. We report a case of SMAS in an elderly female with SSc and concurrent gastrointestinal involvement, and discuss the important management considerations and potential adverse outcomes when untreated.

Prevalence of refractive errors in teenage high school students in Singapore.

We aimed to study the prevalence of refractive conditions in Singapore teenagers. Grade 9 and 10 students (n = 946) aged 15-19 years from two secondary schools in Singapore were recruited. The refractive errors of the students' eyes were measured using non-cycloplegic autorefraction. Sociodemographic data and information on risk factors for myopia (such as reading and writing) were also obtained using an interviewer-administered questionnaire. The prevalence of refractive conditions was found to be: myopia [spherical equivalent (SE) at least -0.50 D] - 73.9%, hyperopia (SE at least +0.50 D) - 1.5%, astigmatism (cylinder at least -0.50 D) - 58.7% and anisometropia (SE difference at least 1.00 D) - 11.2%. After adjusting for age and gender, currently doing more than 20.5 h of reading and writing a week was found to be positively associated with myopia [odds ratio 1.12 (95% CI 1.04-1.20, p = 0.003)], as was reading and writing at a close distance and a better educational stream. The prevalence of myopia (73.9%) in Singapore teenagers is high. Current reading and writing habits, reading at close distances and a better educational stream are possible risk factors for myopia.