Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management

Abstract

Macrophage activation syndrome (MAS), a form of secondary hemophagocytic lymphohistiocytosis, is a frequently fatal complication of a variety of pediatric inflammatory disorders. MAS has been most commonly associated with systemic juvenile idiopathic arthritis (sJIA), as approximately 10% of children with sJIA develop fulminant MAS, with another 30-40% exhibiting a more subclinical form of the disease. Children with other rheumatologic conditions such as systemic lupus erythematosus and Kawasaki disease are also at risk for MAS. Moreover, MAS also complicates various genetic autoinflammatory disorders such as gain of function mutations in the cytosolic inflammasome NLRC4, pediatric hematologic malignancies (e.g., T-cell lymphoma), and primary immunodeficiencies characterized by immune dysregulation. Disease-specific and broadly inclusive diagnostic criteria have been developed to facilitate the diagnosis of MAS. Recently, simple screening tools such as the serum ferritin to erythrocyte sedimentation rate ratio have been proposed. Early diagnosis and rapid initiation of immunosuppression are essential for the effective management of MAS. With a better understanding of the pathophysiology of MAS and the advent of novel therapeutics, a broad immunosuppressive approach to treatment is giving way to targeted anti-cytokine therapies. These treatments include agents that block interleukin-1 (IL-1), IL-6, IL-18, interferon-γ, as well as inhibitors of downstream targets of cytokine signaling (e.g., Janus kinases). Increased early recognition of MAS among pediatric inflammatory disorders combined with the use of effective and less toxic cytokine-targeted therapies should lower the mortality of this frequently fatal disorder.

Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

“…In the study of Dimopoulos et al, 78 eight severe COVID‐19 patients were positive for the hemophagocytosis score (HScore is composed of nine variables including ferritin 79 ) and were diagnosed with secondary hemophagocytic lymphohistiocytosis (sHLH), which can lead to 67% mortality after 28 days. All patients who show a clinical worsening including the increased levels of serum ferritin (maximum concentration 12 670 ng/mL), received anakinra treatment, and improved at the end of the treatment, showing a lower HScore and decreased sHLH parameters including ferritin.…”

The Rheumatologist’s Role in COVID-19

“…At this time, there is no uniformly accepted treatment algorithm for patients with CSS. The good and the bad news is that there is now a variety of therapeutic options available to treat CSS, but the ideal treatment (or combination of treatments) is unclear 13 . We can, however, learn from experience.…”

The off-label use of anakinra in pediatric systemic autoinflammatory diseases

“… 3 In suspicion of AIDs, ANA could be considered as an empiric treatment in case of temporary contraindication to glucocorticoids for diagnostic workup, while waiting to exclude infection or malignancy. 133 …”