Understanding the diagnosis and management of multisystem inflammatory syndrome in adults (MIS-A) in the UK: results of a national Delphi process.

Infection with SARS-CoV-2 may trigger a delayed hyper-inflammatory illness in children called paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS). A similar syndrome is increasingly recognised in adults termed multisystem inflammatory syndrome in adults (MIS-A) and may present acutely to medical or surgical specialties with severe symptoms, such as acute abdominal pain or cardiogenic shock. No national guidelines exist in the UK for the management of MIS-A and there is limited evidence to guide treatment plans. We undertook a national Delphi process to elicit opinions from experts in hyperinflammation about the diagnosis and management of MIS-A with the dual aim of improving recognition and producing a management guideline. Colleagues in paediatrics successfully initiated a national consensus management document that facilitated regional multidisciplinary referral and follow-up pathways for children with PIMS-TS, and we propose a similar system be developed for adult patients across the UK. This would facilitate better recognition and treatment of MIS-A across the multiple specialties to which it may present as well as enable follow-up with specialty services post-discharge.

Rheum to inspire: a medical student perspective on the impact of COVID-19 on medical education and child health

BackgroundWhen my Medical School announced my elective would be cancelled, and restricted to the local area, I was devastated. Months of planning which country to visit, medical opportunities there and making a holiday out of it were all lost. I had to quickly make a new plan. With no ideas for my future career, I considered specialities I had previously enjoyed: Paediatrics and Rheumatology.ObjectivesI hope to provide an alternative perspective of the challenges and opportunities faced by Medical students and Child Health.MethodsWith a large tertiary Children’s Hospital close by, I contacted the Paediatric Rheumatology department to enquire. I reflect now, eight weeks after starting my Paediatric Rheumatology elective, having found my future career.ResultsWith the COVID-19 pandemic came a new style of working. Consultations via telephone and video link became commonplace, a frustrating concept being it is difficult to learn from these without face-to-face interaction. There was the additional issue of room space. Often face-to-face consultations or ward rounds were limited to a small number of essential staff, leaving no capacity for me to join. This new style of working however did appear to work for some patients, especially those who would normally have to travel far. Children whose arthritis was stable, or anxious parents insistent on shielding appeared happy with telephone appointments. Whilst periodic examinations are important, I feel there is scope for technology being continued for consultations post-pandemic, especially in stable, well children and those who travel far.I did however witness the disruption COVID-19 has caused, especially on waiting times. Three month follow-ups became six months plus. Many children presented with worsening arthritis and increasingly problematic symptoms. Some had stopped their medication, either through parental fear of immunosuppression and COVID-19, side effects, or lack of motivation. Without regular follow-ups, these remained undetected for longer than previously. The increased number of arthritis flares I witnessed was supported by a service evaluation I conducted of steroid use prior to and during the pandemic. Preliminary results appear to show more ‘fire-fighting’ of flares during lockdown, and poorer outcomes. Lockdown has provided a unique opportunity to observe the need for a ‘zero tolerance’ approach to arthritis, something which should be imperative moving forward.With the pandemic, brought Paediatric Multisystem Inflammatory Syndrome Temporally associated with COVID-19 (PIMS-TS). This new syndrome added extra challenges and pressures to the Rheumatology team. There were critically unwell children with long admissions, added to the backlog of usual work. I witnessed an overworked and pressured team, who were still welcoming and advocating for their patients. This is something I admire and the team were clinicians I aspire to be.ConclusionsOverall, I have witnessed many challenges faced by children and their families in this pandemic. I have seen opportunities moving forward, for the integration of technology and proactive approach to treating arthritis. For me personally, the pandemic has brought many challenges, with loss of loved ones and disruption to medical training, yet I thank the pandemic for giving me the opportunity to find my future career.

Developmentally appropriate transitional care during the Covid-19 pandemic for young people with juvenile-onset rheumatic and musculoskeletal diseases: the rationale for a position statement.

BACKGROUND: The importance of developmentally appropriate transitional care in young people with juvenile-onset rheumatic and musculoskeletal disease is well recognised. The Paediatric Rheumatology European Society (PReS) / European League Against Rheumatism (EULAR) Taskforce has developed international recommendations and standards for transitional care and a growing evidence base supports the positive benefits of such care. However, there is also evidence that universal implementation has yet to be realised. In 2020, against this background the COVID-19 pandemic arrived with significant impact on all our lives, young and old, patient, public and professional alike. The unfortunate reality of the pandemic with potential for unfavourable outcomes on healthcare provision during transition was acknowledged by the PReS working groups in a position statement to support healthcare professionals, young people and their caregivers. AIM: The aim of this review is to present the literature which provides the rationale for the recommendations in the PReS Position Statement. The following areas are specifically addressed: the prime importance of care coordination; the impact of the pandemic on the various aspects of the transition process; the importance of ensuring continuity of medication supply; the pros and cons of telemedicine with young people; ensuring meaningful involvement of young people in service development and the importance of core adolescent health practices such as routine developmental assessment psychosocial screening and appropriate parental involvement during transitional care.

Multisystem inflammatory syndrome in adults following COVID-19 infection: A case report presenting with colitis.

BACKGROUND: Multisystem Inflammatory Syndrome in Adults (MIS-A) is a recently emerging condition that occurs as a delayed complication of COVID-19 infection. It involves inflammation of multiple extra-pulmonary organ systems. Diagnostic criteria and treatment recommendations have yet to be clearly defined. We present a case of a young adult with suspected MIS-A who initially displayed symptoms and radiological findings of colitis.Case: A 22-year-old male with no past medical history suffered a minor respiratory illness for a few days and tested positive on SARS-CoV-2 RT-PCR. Approximately 6 weeks later, he presents after 3 days of right-sided abdominal pain, diarrhoea and fever. He is initially admitted with a working diagnosis of gastroenteritis. Sustained fever and escalating blood markers of illness led to abdominal CT; showing inflammation of ascending colon as well as some loops of small bowel. Hypotension becomes increasingly pronounced and on the fourth day of admission he developed type 1 respiratory failure with evidence of fluid overload. He was transferred to critical care for vasopressor and respiratory support. All microbiological and autoimmune screens performed return negative results but inflammatory markers were significantly elevated, he was diagnosed as MIS-A. IVIg was added to the antibiotics on day 4. His clinical condition dramatically improved and he was discharged home after 10 days in hospital. His blood tests have returned to normal and he has no lasting complications from his illness. DISCUSSION: This case displays the potential for MIS-A to present in various ways, with this example a primarily gastroenterological illness. It therefore highlights the importance of physicians in different fields having an awareness of the condition, in order to identify when MDT input is required to guide treatment. We review the current literature on various presentations and treatments of MIS-A, and discuss the need for clear case definition.

The patient's perspective of remote respiratory assessments during the COVID-19 pandemic.

Forced vital capacity (FVC) is an essential respiratory measurement for assessment and monitoring of patients with Amyotrophic Lateral Sclerosis (ALS). Our clinic rapidly implemented remote assessment of FVC after COVID-19 related restrictions on respiratory testing were imposed, using mini-spirometers and video consultation. We sought to evaluate the patient's experiences of performing remote respiratory assessments to guide future development and optimisation of the service. Twenty-five patients completed surveys. The mean age was 65.2 years and average time from diagnosis was 17.04 (2-99) months. Seventy-two percent (n = 18) required help from a caregiver to perform the tests. Ninety-two percent (n = 23) of patients reported that overall, they were satisfied and were happy to continue with remote respiratory assessment. Reducing the number of clinic visits for review and assessment was valued by 92% (n = 23) and reducing the risk associated with COVID-19 was valued by 96% (n = 24). The highest frequency reported as acceptable for performing the remote breathing assessments was monthly (60%, n = 15), followed by every second month (28%, n = 7). Remote respiratory testing is viewed positively by patients. These technologies used in combination with video-consultations and other novel forms of remote monitoring implemented in response to the COVID-19 crisis will continue to be valuable tools for clinical care in future. However, further evaluation of the validity of remote respiratory assessment is required.

COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study.

BACKGROUND: A subset of patients with severe COVID-19 develop a hyperinflammatory syndrome, which might contribute to morbidity and mortality. This study explores a specific phenotype of COVID-19-associated hyperinflammation (COV-HI), and its associations with escalation of respiratory support and survival. METHODS: In this retrospective cohort study, we enrolled consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK with PCR-confirmed COVID-19 during the first wave of community-acquired infection. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI as a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 µg/L. Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model. FINDINGS: We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower median Charlson Comorbidity Index scores, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62-2·87]) after adjustment for age, sex, and comorbidity. INTERPRETATION: Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. COV-HI might be useful to stratify patient groups in trial design. FUNDING: None.

Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome.

The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.