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Delegates hear about ‘cytokine storm’ and its association with Covid-19

By Dermot - 12th Oct 2020 | 19 views

2019 novel coronavirus pneumonia spreading worldwide,Virus crisis, planet wearing medical mask

Consultant Rheumatologist at Mater Misericordiae University Hospital, Dublin, Dr John Stack presented clinical cases and targeted therapies in dealing with ‘cytokine storm’.

The topic was of particular interest to many, considering its increasingly recognised association with Covid-19. Dr Stack began by explaining the significance of cytokine storm, stating that it is a syndrome of severe, uncontrolled, self-perpetuating inflammation leading to a surge in
cytokine release and multi-organ failure associated with high mortality.

Clinical trials in Covid-19 may impact our understanding and treatment of cytokine storm and HLH, according to Dr Stack. “Many of you will be aware that a subset of patients with severe Covid-19 disease go on to develop a hyper-inflammatory syndrome characterised by ARDS [acute respiratory distress syndrome], cytokine storm and venous thromboembolism,” said Dr Stack.

“Cytokine storm since then has become widely publicised in the mainstream media, which has helped to raise awareness of this syndrome in the wider medical community. There are numerous trials underway evaluating the use of biologics in treating cytokine storm in the setting of Covid and these may shed light on our knowledge and understanding of other forms of cytokine storm, for example HLH.

“As rheumatologists we are inflammation specialists and have the most experience with biologics. Therefore, we have a lot to offer in terms of managing these patients. These patients will, however, present to lots of specialities, therefore a combined multidisciplinary team approach is needed.”

Terminology relating to cytokine storm, he said, can be confusing, and in fact there is no agreed terminology. Cytokine storm refers to the surge in cytokines that are released from immune cells as part of the syndrome and is also used as an umbrella term, describing several overlapping sub types.
He focused on haemophagocytic lymphohistiocytosis (HLH), an area of special interest, explaining that it is a historical term, which refers to the presence of haemophagocytes that can be present on bone marrow cytology.

Familial HLH is a genetic disease that occurs in neonates. Secondary HLH tends to occur in adults and while it is not a genetic disease, said
Dr Stack, there is some genetic susceptibility with acquired forms of HLH.
In outlining the pathogenesis of the disease, individual susceptibility factors can include underlying autoimmune disease or genetic susceptibility.

There are a number of common HLH triggers, such as a tumour or infection, which leads to antigen presentation and activation of the immune system.

“Under normal circumstances, regulatory T-cells control and dampen the immune response by causing lysis of tumour or virus infected cells, but in these individuals, that mechanism fails,” explained Dr Stack.

“This results in unopposed and uncontrolled immune activation, resulting in macrophage activation, release of inflammatory cytokines, known as cytokine storm, and then downstream results in fever, cytopaenias and organ dysfunction.”

The cardinal clinical feature of HLH persistent fever, cytopaenias and very high ferritin, usually over 5,000, but often greater than 10,000. Anyone presenting with these features, should prompt the question: ‘does this patient have HLH?’, said Dr Stack.

Other clinical features include altered mental status, rash, ARDS, multi organ failure, lymphadenopathy and hepatosplenomegaly. He recommended the H-score as a diagnostic tool in HLH. It provides a percentage probability of a patient having HLH, which can assist in making a diagnosis. He cautioned, however, that the tool has not been validated in a prospective cohort.

Dr Stack, after outlining recent cases of HLH treated, advised that early diagnosis and treatment of HLH is key to a successful outcome. Stress cardiomyopathy is a feature of HLH which patients can fully recover from with appropriate treatment. Definitive treatment of the underlying cause should start as soon as possible.

There are a number of challenges in treating patients with SLH, he said, as there is a limited evidence-base from which to guide treatment. Clinical features of HLH and sepsis overlap, which can make it difficult to distinguish between the two syndromes. It can seem counter-intuitive to immune suppress these patients, he said. Dr Stack stated that all of these challenges can result in delays in diagnosis and treatment.

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