hyperinflammatory

Hyperinflammatory refers to a state of excessive and dysregulated inflammatory response that can cause tissue damage and organ dysfunction. It is not a single disease but a spectrum of conditions characterized by an amplified immune reaction, including cytokine storm, macrophage activation syndrome (MAS), and secondary hemophagocytic lymphohistiocytosis (HLH). The underlying pathophysiology involves overproduction of proinflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-alpha, often with impaired cytotoxic regulation that allows sustained immune activation.

Causes and triggers commonly include severe infections, particularly viral infections like influenza and SARS-CoV-2, autoimmune or autoinflammatory diseases (for example systemic juvenile idiopathic arthritis and adult-onset Still's disease), malignancies, and certain therapies, including some cancer immunotherapies. Clinical presentation typically includes high fever and systemic symptoms, along with cytopenias, hepatosplenomegaly, jaundice, and signs of organ dysfunction such as liver injury, coagulopathy, or renal impairment. Laboratory features frequently show markedly elevated ferritin, C-reactive protein, D-dimer, triglycerides, low fibrinogen, and various cytopenias; soluble interleukin-2 receptor may be elevated in HLH.

Diagnosis relies on clinical criteria combined with laboratory and organ assessments; genetic testing may be used to identify familial forms of HLH. Treatment aims to rapidly reduce hyperinflammation and address the underlying trigger. Therapies commonly used include corticosteroids, immunomodulators such as anakinra (an IL-1 receptor antagonist) or tocilizumab (an IL-6 receptor blocker), intravenous immunoglobulin, and, in some cases, JAK inhibitors or chemotherapy regimens for HLH. Supportive care and management of organ dysfunction are essential. Prognosis varies with cause, timeliness of treatment, and treatment response.