EULAR: Treat suspected cytokine storm syndromes in children with ‘urgency’
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Clinicians are encouraged to investigate and treat suspected macrophage activation syndrome and hemophagocytic lymphohistiocytosis in children with “urgency,” according to a speaker at the EULAR 2021 Congress.
“The rapidly emerging knowledge of the genetic causes of non-systemic autoinflammatory diseases, which present typically in early childhood with severe and chronic systemic and organ-specific inflammation, link the disease pathogenesis to the pathologic production of major pro-inflammatory cytokines,” Raphaela T. Goldbach-Mansky, MD, MHS, a senior investigator in the Translational Autoinflammatory Disease Studies Unit at the NIH, said in her presentation.
This knowledge has given rise to treatments that target pro-inflammatory cytokines and, consequently, “have changed patients’ lives,” according to Goldbach-Mansky.
It is in this setting that the EULAR group came together to create a document featuring recommendations for the management of IL-1-mediated and type-I interferonopathies, and for the early management of suspected Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis (MAS/HLH).
The document contains recommendations for diagnosis and management of these patient populations, along with guidance in transitioning them to adult care.
The methodology used by the guideline development team adhered to EULAR standard operating procedure. This included the formulation of population, intervention, comparison and outcome (PICO) questions, a literature review, a survey and, eventually, consensus meetings.
The IL-1 conditions included in the document were cryopyrinopathies (CAPS), TNF receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA).
The authors arrived at five overarching principles for these conditions. The first is that a multidisciplinary team should be used to manage these patients, while the second stipulates that a genetic and clinical workup should be performed, along with imaging analyses. The third principle calls for genetic sequencing to make a diagnosis. The fourth suggests that the goal of therapy should be to control signs and symptoms of the disease. For the fifth principle, it is suggested that treatment should be tailored for growing children, and that organ-specific inflammation should be targeted. In addition, patients are encouraged to self-manage their care in preparation for the transition to adulthood.
The type I interferonopathies included in the document were chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE)/proteasome-associated autoinflammatory syndrome (PRAAS), Aicardi Goutières syndrome (AGS) and STING-associated vasculitis with onset in infancy (SAVI).
Patients with these diseases can experience organ-specific inflammation and must be treated to prevent organ damage, morbidity and mortality, according to the first principle.
The second overarching principle states that genetic testing must be used in diagnosis, while the third calls for treatment of both systemic and organ-specific inflammation. The final principle for these patients is that a multidisciplinary team is necessary for long-term monitoring.
Goldbach-Mansky closed with commentary on MAS/HLH. “The genetic diseases presenting with ultra-high IL-18 levels, including Still’s-like conditions and/or with impaired cytotoxicity, converge on the production of high levels of interferon-gamma, that in the presence of high inflammatory markers and high ferritin levels represent life-threatening macrophage activation and/or tissue histiocytosis,” she said.
Advances in understanding of these events, along with the development of cytokine-targeted therapies, led to the task force convening to offer recommendations for this patient population, according to Goldbach-Mansky. “The task force focused on characterizing the recognizable patterns of clinical and laboratory features that should raise a high index of the presence of systemic hyper inflammation,” she said.
Regarding points to consider, ferritin levels are key to recognizing these events early. Goldbach-Mansky added that these hyperinflammatory events can occur on an “immunopathologic continuum.”
Another consideration is that MAS/HLH may occur in “nearly any inflammatory state,” according to the findings. Clinicians are encouraged to investigate and treat modifiable inflammation in patients who may be at risk for this outcome.
The final consideration is that suspected MAS/HLH should be treated with “urgency,” according to Goldbach-Mansky. “More on the details is to come in the full report,” she said.
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Goldbach-Mansky R. EULAR Recommendations for the management of 2 groups of Autoinflammatory diseases, IL-1-mediated and Type-I Interferonopathies, and for the early management of suspected Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis. Presented at EULAR 2021 Congress; June 2-6, 2021 (virtual meeting).
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