Clinical utility of anti-DFS70 for identifying antinuclear antibody-positive patients without systemic autoimmune rheumatic disease

INTRODUCTION@#The antinuclear antibody (ANA) test is a screening test for systemic autoimmune rheumatic disease (SARD). We hypothesised that the presence of anti-DFS70 in ANA-positive samples was associated with a false-positive ANA test and negatively associated with SARD.@*METHODS@#A retrospective analysis of patient samples received for ANA testing from 1 January 2016 to 30 June 2016 was performed. Patient samples underwent ANA testing via indirect immunofluorescence method and anti-DFS70 testing using enzyme-linked immunosorbent assay.@*RESULTS@#Among a total of 645 ANA-positive samples, the majority (41.7%) were positive at a titre of 1:80. The commonest nuclear staining pattern (65.5%) was speckled. Only 9.5% of ANA-positive patients were diagnosed with SARD. Anti-DFS70 was found to be present in 10.0% of ANA-positive patients. The majority (51/59, 86.4%) of patients did not have SARD. Seven patients had positive ANA titre > 1:640, the presence of anti-double stranded DNA and/or anti-Ro60. The presence of anti-DFS70 in ANA-positive patients was not associated with the absence of SARD (Fisher's exact test, p = 0.245).@*CONCLUSION@#The presence of anti-DFS70 was associated with a false-positive ANA test in 8.6% of our patients. Anti-DFS70 was not associated with the absence of SARD.

Recommendations for COVID-19 Vaccination in People with Rheumatic Disease: Developed by the Singapore Chapter of Rheumatologists

AimPeople with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD. MethodsSystematic literature reviews were performed to evaluate (1) outcomes in PRD with COVID-19; (2) efficacy, immunogenicity and safety of COVID-19 vaccination; and (3) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology. ResultsThe consensus comprises two overarching principles and seven recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommended that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommended that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titres against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference. ConclusionThese recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence. (words 247)

Adjunctive Corticosteroids for COVID-19: A Retrospective Cohort Study

BackgroundCoronavirus disease 2019 (COVID-19) is associated with severe pneumonia, respiratory failure and death. We aim to evaluate the efficacy of adjunctive corticosteroids in the management of COVID-19. MethodsThis is a retrospective cohort study of hospitalized adults ([≥]18 years) who were diagnosed with COVID-19 and were given treatment. Treatment included hydroxycholoroquine and lopinavir-ritonavir. Corticosteroids were included as adjunctive therapy in mid-April, 2020. We compared composite outcomes of clinical progression and invasive mechanical ventilation (MV) or death between group that received treatment only (Group A) versus group that received adjunctive corticosteroids (Group B). Entropy balancing was used to generate stabilized weight for covariates between treatment groups. Unweighted Kaplan-Meir curves, weighted and adjusted Cox regression analysis were used to estimate effect of adjunctive corticosteroids on composite outcomes. Subgroup analysis was performed on those with pneumonia. ResultsOf 1046 patients with COVID-19, 57 received treatment alone (Group A) and 35 received adjunctive corticosteroids in addition to treatment (Group B). Median day of illness at treatment initiation was 5 day. There were 44 patients with pneumonia; 68.9% of them were not requiring supplemental oxygen at treatment initiation. Overall, 17 (18.5%) of 92 patients had clinical progression including 13 (22.8%) of 57 patients in Group A versus 4 (11.4%) of 35 patients in Group B (p=0.172). Unweighted Kaplan-Meier estimates showed no significant difference in the proportion of patients who had clinical progression or invasive MV or death between the 2 treatment groups. However in those with pneumonia, there were lower proportions of patients in Group B with clinical progression (11.1%, 95% CI 0.0 - 22.2 versus 58.8%, 95% CI 27.3 - 76.7, log rank p<0.001); and invasive MV or death (11.3%, 95% CI 0.0 - 22.5 versus 41.2%, 95% CI 12.4. - 60.5, log rank p=0.016). In weighted and adjusted cox regression analysis, patients in Group B were less likely to have clinical progression, (adjusted HR [aHR] 0.08, 95% CI 0.01-0.99, p=0.049) but there was no statistical significant difference in risk of requiring invasive MV or death (aHR 0.22, 95%CI 0.02 - 2.54, p=0.22). In subgroup with pneumonia, patients in Group B were significantly at lower risk of clinical progression (aHR 0.15, 95% CI 0.06 - 0.39, p<0.001) and requiring invasive MV compared to Group A (aHR 0.30, 0.10-0.87, p=0.029). ConclusionsUse of adjunctive corticosteroids is associated with lower risk of clinical progression and invasive MV or death, especially in those with pneumonia. Concurrent use of antivirals and corticosteroids should be considered in the management of COVID-19 related pneumonia.

Impact of an interstitial lung disease service in the diagnosis and management of interstitial lung disease in Singapore

INTRODUCTION@#The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore.@*METHODS@#A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017.@*RESULTS@#Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service.@*CONCLUSION@#The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

Shellfish/crustacean oral allergy syndrome among national service pre-enlistees in Singapore

BACKGROUND: All Singaporean males undergo medical screening prior to compulsory military service. A history of possible food allergy may require referral to a specialist Allergy clinic to ensure that special dietary needs can be taken into account during field training and deployment. OBJECTIVE: To study the pattern of food allergy among pre-enlistees who were referred to a specialist allergy clinic to work up suspected food allergy. METHODS: Retrospective study of all pre-enlistees registered in the Clinical Immunology/Allergy New Case Registry referred to the Allergy Clinic from 1 August 2015 to 31 May 2016 for suspected food allergy. RESULTS: One hundred twenty pre-enlistees reporting food allergy symptoms other than rash alone were referred to the Allergy Clinic during the study period. Of these, 77 (64.2%) had food allergy. Among those with food allergy, mean age was 19.1 ± 1.5 years. They comprised predominantly Chinese (66.2%) and Malays (20.8%). The most commonly reported foods were shellfish/crustaceans (78%), peanut (15.6%), and egg (6.5%). Self-limiting oral allergy syndrome, OAS (itchy lips and throat with/without lip angioedema) was the most common manifestation (n = 33, 42.9%) followed by anaphylaxis (n = 23, 29.9%). Majority of OAS was from shellfish/crustacean (90.6%); of which shrimp (30.3%), crab (15.2%), and lobster (3.0%) were the most common. Mild childhood asthma (69.7%), allergic rhinitis (6.3%), and eczema (6.1%) were the most common atopic conditions among individuals with shellfish/crustacean OAS. This pattern was similar for shellfish/crustacean anaphylaxis. Skin prick tests were most commonly positive for shrimp (OAS 87.1% vs. anaphylaxis 100%), crab (OAS 95.8% vs. 90.9%), and lobster (OAS 91.7% vs. 63.6%). CONCLUSION: OAS to shellfish/crustaceans was more common than anaphylaxis among this study population of young males referred for food allergy symptoms other than rash alone.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.