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There is concern around coronavirus disease 2019 (COVID-19) and rheumatic diseases. Systemic vasculitis was the fourth most common rheumatic disease among patients hospitalised for COVID-19.1 However, the diagnosis of anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV) can be challenging during COVID-19 pandemic for several reasons: first, clinical presentation of patients with AAV partially overlaps with COVID-19; second, patients with initial symptoms of AAV may be concerned to seek medical help in order not to get into close contact with other patients; and third, diagnosis may be delayed because non-urgent tests and visits might have been postponed due to COVID-19 related closure of services. Herein, we report the poor and irreversible clinical outcomes of diagnostic delay of AAV during the COVID-19 pandemic.
We recently encountered a cluster of nine life-threatening presentations of new-onset or relapsing AAV admitted to a Verona hospital, all negative for SARS-CoV-2 by nasopharyngeal swab or bronchoalveolar fluid aspiration. We compared clinical characteristics of this group presenting in the time frame of 6 weeks during the second trimester of 2020 (1st April to 30th June), with AAV patients presented in the same period of 2018 and 2019 (table 1). While there were no differences in patterns of clinical variants, ANCA, age or comorbidities, the median Birmingham Vasculitis Activity Score at admission was noticeably higher in the 2020 cluster and almost all had Five-Factor Score >1. We noticed a lower frequency of ENT (ear, nose and throat) and ophthalmic symptoms but increased severe renal and pulmonary manifestations. All AAV patients presented with severe glomerulonephritis and two patients additionally revealed pulmonary haemorrhage. The latter complication was present only in one AAV patient in previous years.2 Seven out of nine (78%) patients were admitted to intensive care units for severe respiratory insufficiency (one patient in 2018 only). Seven out of nine (78 %) patients with glomerulonephritis required renal replacement therapy compared with no patient in the same period of 2019 and one in 2018; one patient required extracorporeal mechanical oxygenation for respiratory support. Although all patients received intense immune-suppression with high dose intravenous glucocorticoids, cyclophosphamide (n=3), rituximab (n=8) and plasma exchange (n=2), none returned to normal renal function. One patient died.
According to literature, AAV is preceded by a prodromal phase characterised by constitutional symptoms that pursue a waxing and waning course.3 Diagnostic delay at this stage is common, and it has been demonstrated that a longer prodromal phase associated with mortality 4 5 and end-stage renal disease.5 AAV should therefore always be considered as a possible differential diagnosis in patients with constitutional symptoms without a clear explanation.
We sought to investigate the symptoms in the prodromal phase of this novel cluster of AAVs by patient interviews. All patients reported non-specific symptoms such as arthralgia (n=3), fatigue (n=8), dyspnoea (n=4), malaise (n=8) and/or low-grade fever (n=4) for a median of 14 (12 to 17) weeks before the first assessment. Interestingly, this latency was longer than the median duration of diagnostic delay in our cohort in 2018 and 2019 (nine weeks). Noteworthy, eight out of nine patients did not consult their general practitioners.
During the lockdown, containment measures and fear may have induced AAV patients to downplay constitutional symptoms (eg, fever) and to underestimate their need for medical attention. The COVID-19 pandemic enlarged the challenge of ascertaining the protean manifestations of AAV. Conversely, this series highlights that there may be a ‘window of opportunity’ to reduce the disease burden of AAVs. Although telehealth has emerged as a strategy for the management of patients with rheumatic diseases during COVID-19 pandemic,6 validated tools and prioritisation strategies for the early diagnosis of complex rheumatic diseases with a high clinical impact are lacking. The COVID-19 pandemic should be regarded as a not-to-be-missed opportunity to improve early management of such patients.
Contributors AG: provided the conception of the study, literature search and interpretation of data, drafting the article and revised it critically for important intellectual content. RB: provided data search, interpretation of data, drafting the article and revised it critically for important intellectual content. All authors: revised the article critically for important intellectual content and gave final approval of the version to be submitted.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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