Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review

INTRODUCTION@#We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.@*METHODS@#We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.@*RESULTS@#169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.@*CONCLUSION@#Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

Singapore Chapter of Rheumatologists Consensus Statement on the Eligibility for Government Subsidy of Biologic Disease Modifying Antirheumatic Agents for Treatment of Rheumatoid Arthritis (RA)

<p><b>INTRODUCTION</b>Up to 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional non-biologic disease modifying antirheumatic drugs (nbDMARDs), and may benefit from therapy with biologic DMARDs (bDMARDs). However, the high cost of bDMARDs limits their widespread use. The Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore aims to define clinical eligibility for government-assisted funding of bDMARDs for local RA patients.</p><p><b>MATERIALS AND METHODS</b>Evidence synthesis was performed by reviewing 7 published guidelines on use of biologics for RA. Using the modified RAND/UCLA Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations.</p><p><b>RESULTS</b>Ten recommendations including diagnosis of RA, choice of disease activity measure, initiation and continuation of bDMARD and option of first and second-line therapies were formulated. The panellists agreed that a bDMARD is indicated if a patient has (1) active RA with a Disease Activity Score in 28 joints (DAS28) score of ≥3.2, (2) a minimum of 6 swollen and tender joints, and (3) has failed a minimum of 2 nbDMARD combinations of adequate dose regimen for at least 3 months each. To qualify for continued biologic therapy, a patient must have (1) documentation of DAS28 every 3 months and (2) at least a European League Against Rheumatism (EULAR) moderate response by 6 months after commencement of therapy.</p><p><b>CONCLUSION</b>The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARDs usage accessible and equitable to eligible patients in Singapore.</p>

When traditional model meets competencies in Singapore: beyond conflict resolution

<p><b>INTRODUCTION</b>The implementation of competency-based internal medicine (IM) residency programme that focused on the assurance of a set of 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies in Singapore marked a dramatic departure from the traditional process-based curriculum. The transition ignited debates within the local IM community about the relative merits of the traditional versus competency-based models of medical education, as well as the feasibility of locally implementing a training structure that originated from a very different healthcare landscape. At the same time, it provided a setting for a natural experiment on how a rapid integration of 2 different training models could be achieved.</p><p><b>MATERIALS AND METHODS</b>Our department reconciled the conflicts by systematically examining the existing training structure and critically evaluating the 2 educational models to develop a new training curriculum aligned with institutional mission values, national healthcare priorities and ACGME-International (ACGME-I) requirements.</p><p><b>RESULTS</b>Graduate outcomes were conceptualised as competencies that were grouped into 3 broad areas: personal attributes, interaction with practice environment, and integration. These became the blueprint to guide curricular design and achieve alignment between outcomes, learning activities and assessments. The result was a novel competency-based IM residency programme that retained the strengths of the traditional training model and integrated the competencies with institutional values and the unique local practice environment.</p><p><b>CONCLUSION</b>We had learned from this unique experience that when 2 very different models of medical education clashed, the outcome may not be mere conflict resolution but also effective consolidation and transformation.</p>

Angioedema and systemic lupus erythematosus--a complementary association?

<p><b>INTRODUCTION</b>We report angioedema as a rare presentation leading to a diagnosis of systemic lupus erythematosus (SLE).</p><p><b>CLINICAL PICTURE</b>A diagnosis of angioedema was delayed in a patient presenting with limb and facial swelling until she developed acute upper airway compromise. After excluding allergic and hereditary angioedema, acquired angioedema (AAE) was suspected, possibly precipitated by respiratory tract infection. Associated clinical and laboratory features led to a diagnosis of SLE.</p><p><b>TREATMENT</b>Management proved challenging and included high dose steroids and immunosuppressants.</p><p><b>OUTCOME</b>The patient responded to treatment and remains in remission without recurrence of the angioedema.</p><p><b>CONCLUSION</b>AAE occurs due to the acquired deficiency of inhibitor of C1 component of complement (C1 INH). Lymphoproliferative disorders and anti-C1 INH antibodies are well-described associations. However, one should also consider the possibility of SLE.</p>