Penicillin allergies are frequently reported, yet up to 90% of cases are not true allergies upon further evaluation [1]. Drug provocation testing (DPT) remains the gold standard for diagnosis. Prolonged DPT may enhance diagnostic sensitivity [2] and patient confidence in future penicillin usage [3], though concerns about unnecessary antibiotic exposure remain. The latest European Academy of Allergy & Clinical Immunology (EAACI) position paper calls for further evidence to clarify its role [4]. In this prospective study, we aimed to evaluate our centre's multidisciplinary penicillin allergy evaluation programme, focusing on the safety and utility of a 5-day prolonged DPT for patients with delayed onset or unknown reactions. From March 2019 to May 2023, adults referred to the Singapore General Hospital outpatient allergy centre for suspected penicillin allergy were recruited, excluding those with severe cutaneous adverse reactions. At the initial visit, detailed clinical histories and patient backgrounds were recorded. Reactions were classified as 'Immediate' (within 6 h of antibiotic consumption) or 'Delayed' (after 6 h). On challenge day, skin prick testing (SPT) and intra-dermal testing (IDT) were conducted, following European Network of Drug Allergy (ENDA) and EAACI guidelines [5, 6]. Negative skin tests were followed by graded in-clinic DPT, conducted with divided doses every 30 min until full therapeutic dose. Patients were then observed in clinic for an hour; if no objective reaction occurred, an immediate reaction was considered excluded. For patients with index reactions with delayed/unknown onset, and/or unknown clinical history, delayed IDT reading was performed, and if negative, a 5-day at-home prolonged DPT was then implemented. Patients were monitored through follow-up calls to ensure compliance and document reactions. Suspected positive reactors were encouraged to submit photographs or return for in-clinic evaluation. A total of 321 patients were included. The most commonly investigated drug was co-amoxiclav (87.2%), followed by amoxicillin (10.0%). The index reaction occurred within 6 h in 78 patients (24.3%), after 6 h in 81 (25.2%), while 162 (50.5%) were unable to recall their onset. The most common index reactions were rash (46.7%), angioedema (24.3%) and itch (15.0%). Of the 320 patients who completed evaluation (Figure 1a), 17 (5.3%) had positive skin tests. The remaining 303 underwent in-clinic DPT, with 33 (10.9%) having positive reactions. One patient had a positive delayed IDT. Among the 200 patients proceeding to prolonged DPT, 34 (17.0%) had positive reactions, mostly occurring after Day 3 (70.6%) (Figure 1b). The most frequent reactions included rash (23, 67.6%), itch (19, 55.9%) and/or angioedema (9, 26.5%). None exceeded the index reaction's severity; all were managed conservatively without corticosteroids or hospitalisation. Overall, 85 (26.6%) patients were confirmed to have true penicillin allergy, while 235 (73.4%) were safely de-labelled. Secondary analysis showed that patients with positive prolonged DPT or delayed IDT were less likely to report urticaria (11.3% vs. 30.0%, p = 0.043) as their index reaction. Additional information about study methods and findings is available in the following repository: https://doi.org/10.5281/zenodo.14690499. In our study, prolonged DPT identified 34 (17.0%) additional cases of true penicillin allergy, increasing diagnostic yield by 40.0% compared to single-day DPT alone. These findings are consistent with prior studies [2, 7], including a large systematic review by Kulalert et al., where prolonged DPT nearly doubled diagnostic yield (Risk ratio 1.94) [8]. The mechanism underlying delayed positive challenge reactions is presently unclear. It is generally accepted that prolonged DPT aims to identify delayed hypersensitivity reactions; in our cohort, patients with positive delayed challenges were less likely to present with urticaria (11.4% vs. 30.0%, p = 0.043). However, we hypothesise that prolonged DPT can also identify immediate reactors who were re-sensitised, which could explain why some reactions only manifest after Day 3. Identifying these reactions is critical, as they might otherwise be misdiagnosed as non-allergic following a single-day DPT. We acknowledge that it is challenging to determine whether delayed reactions during prolonged DPT stem from prolonged antibiotic intake, or would have occurred following the in-clinic DPT dose alone. One potential solution is the use of a washout period; however, this may reduce compliance. Moreover, Chiriac et al.'s 20-year study of single-day DPTs for suspected beta-lactam allergies found that only 1.1% of positive provocations occurred after 48 h [9]. In our cohort, most positive prolonged DPT reactions (70.6%) emerged only from Day 3 onwards, suggesting these are true allergies that would have likely been missed without prolonged DPT. We also cannot exclude that a proportion of positive prolonged DPT reactions were due to re-sensitisation or de novo sensitisation. However, it is arguable that these reactions might have occurred irrespective of prolonged DPT if the patient had been prescribed a full penicillin course during a subsequent illness, which would be inconvenient and unpleasant. Additionally, some delayed reactions were self-reported, potentially contributing to the higher rates of delayed positive reactions observed. While patients were encouraged to submit photographs or return for in-clinic evaluation, some were unable or declined. The absence of post-challenge follow-up to confirm future penicillin tolerance is another limitation. Further studies are required to address these gaps. In conclusion, our findings suggest that a 5-day prolonged DPT may enhance diagnostic yield for suspected penicillin allergy in adults, while remaining safe. Patients with delayed onset or unknown index reactions may benefit from prolonged DPT. Further research is needed to determine the optimal duration and assess the utility of a washout period. H.Y.L. and K.J.L.C. contributed to the conception of the study. A.J.S.A. and C.J.C. were involved in data collection and verification. A.J.S.A. and K.J.L.C. were involved in data analysis. All authors contributed to the writing and/or proofreading of the manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Early studies have reported delayed injection-site reactions in up to 0.8% of individuals receiving Moderna messenger RNA (mRNA) vaccine.1 These are believed to be benign and do not contraindicate subsequent doses.2 Injection-site reactions after Pfizer-BioNTech mRNA vaccine have been less clearly described.3 This study reports the characteristics of mRNA COVID-19 injection-site reactions post-Moderna and Pfizer- BioNTech vaccinations.
Thoracic myelopathy occurs less frequently than lumbar myelopathy. There are several causes of thoracic myelopathy of which ossification of the ligamentum flavum (OLF) is one. OLF has several unique features, arising posteriorly and causing proprioceptive issues first before extending to cause motor and sensory loss. We present a case of a 58-year-old gentleman with a six-month history of progressive lower limb weakness, numbness, back pain and recurrent falls due to OLF. Magnetic resonance and computed tomography imaging revealed extensive thoracic OLF and concomitant facet hypertrophy involving T6-7, T7-8, T9-10, T10-11 and L1-2. Severe central canal stenosis and L1-2 cauda equina root compression were also seen on radiological imaging. The patient developed sphincter disturbance during his admission and had difficulty passing urine. He underwent physiotherapy but was only able to sit and stand with the help of a walking frame at best. He did not regain motor or sensory function in his lower limbs although his back pain improved. Surgical decompression is associated with good neurological outcomes in OLF. Despite this, our patient declined surgery and opted for conservative therapy instead. We wish to highlight a rare case of thoracic myelopathy and the potentially irreversible neurological deterioration that occurs if there is no early surgical intervention.
Introduction: Exertional rhabdomyolysis (ER) is caused by myocyte breakdown after strenuous physical activity. In recent years, the incidence of spin-induced ER (SER) has been increasing. We describe the clinical characteristics, management and outcomes of patients admitted for SER. Method: A review was conducted for all patients admitted to Singapore General Hospital for SER from 1 March 2021 to 31 March 2022. All patients with the admission diagnosis of “rhabdomyolysis”, “raised creatine kinase (CK) level”, or “elevated CK level” with a preceding history of spin-related physical exertion were included. Patients without a history of exertion, with a history of non-spin related exertion, or with a peak serum CK <1000 U/L were excluded. Results: There were 93 patients in our final analysis; mean age was 28.6±5.6 years and 66 (71.0%) were female patients. Mean body mass index was 25.0±5.7 kg/m2; 81 (87.1%) patients were first-time spin participants. All patients had muscle pain, 68 (73.1%) had dark urine, 16 (17.2%) muscle swelling and 14 (15.1%) muscle weakness. There were 80 (86.0%) patients with admission CK of >20,000 U/L. Mean admission creatinine was 59.6±15.6 μmol/L. Mean intravenous (IV) hydration received was 2201±496 mL/ day, oral hydration 1217±634 mL/day and total hydration 3417±854 mL/day. There was 1 (1.1%) patient with acute kidney injury, which resolved the next day with IV hydration. Conclusion: Inpatient management of SER includes laboratory investigations, analgesia and hydration. Risk of complications is low in SER patients. SER patients without risk factors for complications can be considered for hospital-at-home management with bed rest, aggressive hydration and early outpatient review.
An elderly female patient with left pyelonephritis developed worsening left flank pain, hypotension and a drop in haemoglobin (Hb) from 97 g/L to 67g/L on the third day of her admission. There was no recent trauma, history of coagulopathy or risk factors for renal malignancy or vascular disease. A contrasted CT scan of the kidneys revealed a 3.8 cm left renal subcapsular haematoma with no active contrast extravasation. Her atraumatic subcapsular haematoma fulfils two out of three clinical features of Lenk’s triad (acute flank pain, hypovolaemic shock), suggestive of Wunderlich syndrome. Urine and blood cultures grew Klebsiella pneumoniae and she was managed conservatively with culture-directed antibiotics, fluids and blood products. Wunderlich syndrome is a rare complication of pyelonephritis and should be considered in patients with pyelonephritis who develop acute severe flank pain, Hb drop and haemodynamic instability. Appropriate medical and surgical therapies need to be instituted early to ensure good outcomes.
Infective endocarditis (IE) can often present with neurological manifestations, due to embolization from valvular vegetation, but the presentation is often variable and unpredictable. Septic emboli to both occipital lobes supplied by the posterior cerebral arteries, resulting in visual disturbances are also an uncommon presentation of IE reported in the literature. While S. gallolyticus is a classical cause of IE, it is less common and usually occurs in a less suspecting group of patients with no predisposing cardiac conditions. We report the case of a 48-year-old man, who presented with predominant complaints of blurring of vision and temporal headache, without any other infective symptoms. The procalcitonin level was also normal even in the setting of bacteremia with septic embolism. The initial magnetic resonance imaging (MRI) showed multifocal enhancing lesions in cerebral hemispheres, cerebellum, and brainstem, with leptomeningeal enhancement. Transesophageal echocardiography and blood cultures subsequently confirmed diagnosis of S. gallolyticus IE of the mitral valve. The patient was treated with antibiotics upon diagnosis of IE. However, he developed intracranial hemorrhage secondary to mycotic aneurysms, and partial seizures. He eventually succumbed to the intracranial hemorrhage. This case serves to highlight that neurological manifestations can precede symptoms or signs of IE and the presentation are often variable. A high degree of clinical suspicion is needed to suspect neurological manifestations of IE, especially in patients without risk factors.
Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels.All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded.A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited.Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated.
The Pfizer-BioNTech (BNT162b2 mRNA) and Moderna (mRNA-1273) COVID-19 vaccinations were approved for use in Singapore in December 2020 and February 2021, respectively.To date, over 10 million doses of mRNA vaccines have been administered for the primary series and booster doses. 1 Initial studies have shown that 0.8% of individuals who received Moderna mRNA vaccine developed delayed injection-site reactions.3][4][5] Such reactions to the Moderna mRNA vaccine are thought to be generally benign and not a contraindication to further doses.On the other hand, injection-site reactions associated with the Pfizer-BioNTech mRNA vaccine are less clearly defined.In this current study, we report the characteristics of mRNA COVID-19 injection-site reactions, comparing the clinical features between Moderna (mRNA-1273) and Pfizer-BioNTech (BNT162b2) reactions in the Singapore adult population.We retrospectively reviewed patients referred to the Dermatology Service/Allergy Centre at the Singapore General Hospital for reactions post COVID-19 vaccination from 10 January to 26 August 2021.Inclusion criteria were adult patients who developed a localised injection-site reaction after either Moderna or Pfizer-BioNTech mRNA COVID-19 vaccination.Patients who developed non-injection site reactions or had reactions assessed as unrelated to vaccination were excluded.Patient's demographics, clinical history, management and recurrence of subsequent reactions were collected and analysed.Data are presented as median for discrete data, and counts or percentages for categorical data.Fisher's Exact test was performed in comparison of categorical variables between groups, and Mann-Whitney U test was performed for discrete variables.P value of ≤0.05 was considered statistically significant.The data were analysed using SPSS Statistics version 22 (IBM Corp, Armonk, US).During the study period, there were 322 patients referred for post-COVID-19 vaccine cutaneous reactions.Of these, 21 developed post-vaccination injection-site reactions.Eleven (52%) had received the Moderna mRNA vaccine while the remaining 10 (48%) received the Pfizer-BioNTech mRNA vaccine.The median age (range) was 55 years (24-80), with 17 (81%) being
This study aims to report the prevalence of cardiovascular risk factors (CVRFs) and other non-communicable diseases among migrant workers in Singapore admitted for COVID-19 infection, to highlight disease burden and the need for changes in health screening and healthcare delivery in this unique population.The study was conducted in the largest tertiary hospital in Singapore.Retrospective cross-sectional study.883 migrant workers who had mild or asymptomatic COVID-19 infection admitted to three isolation wards between 6 April 2020 and 31 May 2020 were included in this study.The outcome measures were the prevalence of pre-existing and newly diagnosed comorbid conditions and the prevalence of CVRFs-diabetes mellitus, hypertension and hyperlipidaemia-and non-communicable diseases at the time of discharge. The OR of having specific CVRFs depending on country of origin was generated via multivariate logistic regression analysis.The median age of our study population was 45 years. 17.0% had pre-existing conditions and 25.9% received new diagnoses. Of the new diagnoses, 15.7% were acute medical conditions and 84.3% chronic medical conditions. The prevalence of CVRFs was higher in Southeast Asian and South Asian migrant workers compared with Chinese. The prevalence of non-communicable diseases on discharge was highest among Southeast Asians (49.4%).The COVID-19 outbreak in a large number of migrant workers in Singapore unmasked a significant disease burden among them, increasing stakeholders' interests in their welfare. Moving forward, system-level changes are necessary to deliver healthcare sustainably and effect improvements in migrant workers' health.
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