A 36‐year‐old woman with recurrent high‐grade fevers, hypotension, and hypertriglyceridemia

Chou, Richard C.; Dinarello, Charles A.; Ferry, Judith A.; Cin, Paola Dal

doi:10.1002/acr.20024

Cited by 10 publications

(2 citation statements)

References 33 publications

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“…Most publications on cytokine storm syndromes describe subcutaneous use of anakinra; however, intravenous dos ing has been reported in eight patients (table 3, appendix pp 1-3) with equal gender distribution and a mean age of 22 years (range 22 months to 71 years). 41,[61][62][63][64][65][66] The reported underlying driver of cytokine storm in these patients included autoimmune or autoinflammatory diseases in three patients (one each with adultonset Still's disease, systemic juvenile idiopathic arthritis, and systemic lupus erythematosus). Underlying infection was diagnosed in three patients (one each with cytomegalovirus, septic arthritis, and human herpesvirus 8); one patient had both underlying auto immunity (vasculitis) and infection (cyto megalovirus); and another had underlying haema tological disease (myelodysplastic syndrome).…”

Section: Existing Evidence For Intravenous Anakinra In Cytokine Storm Syndromesmentioning

confidence: 99%

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

Mehta

Cron

Hartwell

et al. 2020

The Lancet Rheumatology

240

223

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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.

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Section: Existing Evidence For Intravenous Anakinra In Cytokine Storm Syndromesmentioning

confidence: 99%

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

Mehta

Cron

Hartwell

et al. 2020

The Lancet Rheumatology

240

223

View full text Add to dashboard Cite

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“…Naymagon, for instance, noted in a retrospective study of outcomes associated with anakinra treatment that those with rheumatologic condition-associated MAS experienced 75% OS, versus only 17% survival in patients with other underlying causes of sHLH [ 63 ]. Publications describing the use of anakinra for mHLH have been varied, ranging from frontline monotherapy use in Hodgkin lymphoma to relapsed/refractory HLH in myelodysplastic syndrome (MDS) and T cell lymphoma (TCL) [ 66 , 67 , 68 ]. The use of anti-IL6 therapy for adult HLH (with tocilizumab; no published data using siltuximab) has been extrapolated from its use in cytokine release syndrome (CRS) and COVID-19.…”

Section: Treatment Of Mhlhmentioning

confidence: 99%

Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis

Lee

Logan

2023

Cancers

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Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe, dysregulated inflammation driven by the inability of T cells to clear an antigenic target. When associated with malignancy (mHLH), the HLH syndrome is typically associated with extremely poor survival. Here, we review the diagnosis of secondary HLH (sHLH) syndromes in adults, with emphasis on the appropriate workup and treatment of mHLH. At present, the management of HLH in adults, including most forms of mHLH, is based on the use of corticosteroids and etoposide following the HLH-94 regimen. In some cases, this therapeutic approach may be cohesively incorporated into malignancy-directed therapy, while in other cases, the decision about whether to treat HLH prior to initiating other therapies may be more complicated. Recent studies exploring the efficacy of other agents in HLH, in particular ruxolitinib, offer hope for better outcomes in the management of mHLH. Considerations for the management of lymphoma-associated mHLH, as well as other forms of mHLH and immunotherapy treatment-related HLH, are discussed.

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A clinical perspective of IL‐1β as the gatekeeper of inflammation

2011

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An expanding spectrum of acute and chronic non-infectious inflammatory diseases is uniquely responsive to IL-1b neutralization. IL-1b-mediated diseases are often called ''auto-inflammatory'' and the dominant finding is the release of the active form of IL-1b driven by endogenous molecules acting on the monocyte/macrophage. IL-1b activity is tightly controlled and requires the conversion of the primary transcript, the inactive IL-1b precursor, to the active cytokine by limited proteolysis. Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase-1. Therefore, blocking IL-1b resolves inflammation regardless of how the cytokine is released from the cell or how the precursor is cleaved. Endogenous stimulants such as oxidized fatty acids and lipoproteins, high glucose concentrations, uric acid crystals, activated complement, contents of necrotic cells, and cytokines, particularly IL-1 itself, induce the synthesis of the inactive IL-1b precursor, which awaits processing to the active form. Although bursts of IL-1b precipitate acute attacks of systemic or local inflammation, IL-1b also contributes to several chronic diseases. For example, ischemic injury, such as myocardial infarction or stroke, causes acute and extensive damage, and slowly progressive inflammatory processes take place in atherosclerosis, type 2 diabetes, osteoarthritis and smoldering myeloma. Evidence for the involvement of IL-1b and the clinical results of reducing IL-1b activity in this broad spectrum of inflammatory diseases are the focus of this review.Keywords: Cytokines . Immunotherapy . Inflammation See accompanying reviews by Bevan and Tschopp, also winners of the 2010 Novartis Immunology Prizes, and the Forum article describing the Prizes Historical perspectiveIL-1 has a long history [1]; it begins with interest in the most salient manifestation of inflammation, fever. Indeed, the discovery of IL-1 as the quintessential inflammatory cytokine can be traced to the purification of the endogenous fever-producing molecule, leukocytic pyrogen, in 1977 [2]. Interest in this molecule increased when we reported that leukocytic pyrogen was the same molecule as lymphocyte activating factor [3], thus necessitating invention of the IL nomenclature. The term for IL-1 was assigned to the macrophage product and IL-2 for the T-cell product, even though there was no N-terminal amino acid sequence at that time that these were indeed different molecules. By the early 1980s, it was hypothesized, following on from experiments using purified preparations of IL-1 from human blood monocytes and other preparations by the laboratories of Eur. J. Immunol. 2011. 41: 1203-1217 DOI 10.1002 HIGHLIGHTS 1203 ReviewJean-Michel Dayer and Joost Oppenheim, that IL-1 possessed multiple and diverse properties such that it mediated the acute phase response to infection, injury and immune challenge [4]. The concept that IL-1 possessed these seemingly unrelated proper...

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A 36‐year‐old woman with recurrent high‐grade fevers, hypotension, and hypertriglyceridemia

Cited by 10 publications

References 33 publications

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

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

Diagnosis and Management of Adult Malignancy-Associated Hemophagocytic Lymphohistiocytosis

A clinical perspective of IL‐1β as the gatekeeper of inflammation

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