Trimethoprim-sulfamethoxazole-induced lung injury: a case report.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child. Case Description: An eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D Salmonella bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital. Conclusions: Diagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

Transition readiness assessment in adolescents and young adults with rheumatic diseases: The Singapore experience.

BACKGROUND: Transition from pediatric to adult care is a challenging time for adolescents and young adults (AYA) with rheumatic diseases. Validated tools have been developed to assess transition readiness. AIM: To evaluate transition readiness among AYA with rheumatic diseases and to identify factors associated with transition readiness. METHODS: Patients ≥15 years old were enrolled into our transition program and administered a Transition Readiness Assessment Tool (TRAT) from July 2017. The TRAT consists of 3 components: (a) patient's perception on importance of transition and confidence toward transition on a Likert scale 0-10; (b) assessment of knowledge on medical and healthcare usage using a set of 23 questions; (c) transition readiness using the Transition Readiness Assessment Questionnaire (TRAQ). Differences between groups were compared to identify factors associated with transition readiness. RESULTS: Transition readiness assessment was performed in 152 patients. The median score for perception on transition importance was 7.0 (5.0-8.8) and the median score for confidence in transition was 7.0 (5.0-9.0). Majority of the patients (>50%) lack knowledge in health insurance, carrying health information, healthcare privacy changes and making own healthcare decision. Patients <20 years old were also deficient in knowledge in navigating healthcare systems. TRAQ scores were lowest in areas pertaining to healthcare insurance and obtaining financial help. CONCLUSION: Healthcare insurance literacy and self-management skills were lacking in the assessment of transition readiness in AYA with rheumatic diseases. Targeted intervention in these areas will improve transition readiness and promote successful transition processes.

Implementation of Universal Newborn Screening for Severe Combined Immunodeficiency in Singapore While Continuing Routine Bacille-Calmette-Guerin Vaccination Given at Birth.

Introduction: Severe Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth. Method: Newborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management. Results: Of the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/µL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months. Conclusion: Newborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination.

DISSEMINATED BACILLUS-CALMETTE-GUÉRIN INFECTIONS AND PRIMARY IMMUNODEFICIENCY DISORDERS IN SINGAPORE: A SINGLE CENTER 15-YEAR RETROSPECTIVE REVIEW.

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.