New wrinkle in COVID-19 care: COVID-associated vasculitis or vasculitis mimic?

May 14, 2021

3 min read

Source/Disclosures

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Disclosures: McGonagle reports receiving honoraria from Roche and Sobi that make IL-6 and IL-1 blockers.

Clinicians who treat vasculitides are accustomed to uncertainty. Vasculitis, in its varied forms, shares symptoms with an entire cross-section of unrelated conditions that can prompt frequent misdiagnoses and potentially fatal treatment decisions.

A recent study in Lancet Rheumatology outlining vasculitis-like manifestations of severe COVID-19 has only served to further complicate this diagnostic puzzle.

"The report highlights that vascular thromboembolism in severe COVID-19 leads to small vessel occlusion that subsequently manifests as vasculitis but is actually a vasculitis mimic as the primary pathology is thrombosis or embolism," **Dennis McGonagle, PhD, FRCPI,** told *Healio Rheumatology*. *Source: Adobe Stock*

Dennis McGonagle, PhD, FRCPI, of St. James University Hospital, University of Leeds, in the U.K., and colleagues noted associations between COVID-19 and "histologically confirmed cutaneous vasculitis and a Kawasaki-like vasculitis," albeit with minimal lung involvement.

However, COVID-19 patients with severe disease may also develop cutaneous lesions that present as vasculitis, along with systemic arterial and venous thromboembolic events, sometimes marked by cryptogenic strokes and other vasculopathy features, according to the findings.

Dennis McGonagle

While the etiology of these events remains unknown, investigators have proposed mechanisms ranging from immune dysregulation, an antiphospholipid syndrome-like state and the complement system to viral dissemination with direct systemic endothelial infection, viral RNA-emia with immune-thrombosis, clotting pathway activation mediated by hypoxemia and immobility.

The current study reviewed data including imaging and post-mortem data for COVID-19 patients. The researchers attempted to explain, or at least gain some understanding of, these thromboembolic events. Investigating the mechanisms may have yielded insight into a novel vasculitis mimic associated with COVID infection.

"Therefore, severe COVID-19 pneumonia with extensive pulmonary intravascular coagulopathy might help to explain the numerous systemic complications of COVID-19, in which the demonstration of direct organ infection has not adequately explained the pathology," they wrote.

Healio Rheumatology spoke with McGonagle to discuss the implications of the study for both the rheumatology community and clinicians on the front lines of the battle against COVID-19.

Q : What does your report suggest about vasculitis and the vasculitis mimics related to COVID-19?

McGonagle: The report highlights that vascular thromboembolism in severe COVID-19 leads to small vessel occlusion that subsequently manifests as vasculitis but is actually a vasculitis mimic as the primary pathology is thrombosis or embolism. Thrombosis may arise due to the hypercoagulable state and circulating SARS-CoV-2 RNA that is known as RNA-emia.

We proposed a novel embolic source from the pulmonary venular territory with such emboli that are rich in inflammatory cells triggering tissue damage mimicking vasculitis. We contrasted these vasculitis mimics that can cause multiorgan damage including to the gut, brain, kidney and heart to the isolated self-limiting cutaneous vasculitis referred to as "COVID toes."

Q : How is a true vasculitis distinguished from these mimics?

McGonagle: True vasculitis is quite rare. The true vasculitis is somewhat like the multisystem inflammatory syndrome in children and adults, insofar that it is not usually linked to severe COVID-19 pneumonia and the virus may not be detectable by PCR. This is likely due to the vigorous anti-viral immune responses linked type-1 interferon. On the other hand, the vasculitis mimic is seen in severe COVID-19 pneumonia cases.

Q : What disparate manifestations of vasculitis/mimics are seen in different patients with COVID?

McGonagle: The easiest to recognize is the cutaneous vasculitis. Deterioration in renal function and hematuria may also occur. The brain involvement manifests with typical stroke features, but these may be difficult to recognize in severely ill hypoxemic cases. The commonest presentation of severe gut disease is with mesenteric infarction.

Q : What organ systems are most affected?

McGonagle: The diffuse vasculitis mimic pathology may be linked to the degree of cardiac output received by an organ; hence, brain disease with strokes termed "cryptogenic strokes" or cause unknown is common. Diffuse renal damage is also common, reflecting the large cardiac output of this organ. Intestinal ischemia and involvement of other organs may also occur.

Q : What do you think is driving vasculitis/mimics manifestations?

McGonagle: The bona fide vasculitis has been best understood in terms of an excessive type-1 interferon response in the skin. We proposed that dislodgement of pulmonary venular territory clots and their systemic circulation likely explained some of the vasculitis mimics. Hypercoagulability due to RNA-emia and severe immune activation may also play a role in the mimics.

Q : How do clinicians screen for or distinguish vasculitis from their mimics?

McGonagle: The major consideration of our article was to highlight how physicians recognize vasculitis mimics from various cardiac structures such as myxomas, endocarditis, endocardial thrombosis and arterial embolization from aneurysm and other mimics. We are simply saying, hey, take a step back and you see that the massive pulmonary venous drainage basis — the Amazon river basis of the circulatory system — is badly clogged up with COVID-19 immuno-thrombosis. This is likely to be a major hitherto unappreciated source of embolization and vasculitis mimics.

Q : How does the vasculitis/mimic origin change the treatment paradigm?

McGonagle: This is a tough question, but knowing the enemy is a good starting point. These pulmonary venule clots are full of white cell debris and may not respond to anti-coagulation, which, in fact, might make things worse due to pulmonary hemorrhaging from backpressure effects. The benefits of immunotherapy may be strongly linked to the dissolution of the early clot process in the lung. More work, including pathological studies, is needed to better define the concept.

For more information:

Dennis McGonagle, PhD, can be reached at Beckett St, Harehills, Leeds LS9 7TF, United Kingdom; email: D.G.McGonagle@leeds.ac.uk.

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