Hemophagocytic Lymphohistiocytosis Secondary to Macrophage Activation Syndrome in Adult-Onset Still’s Disease: A Diagnostic and Therapeutic Challenge

Hemophagocytic Lymphohistiocytosis (HLH) is a rare and serious syndrome characterized by excessive inflammation and tissue damage due to abnormal immune activation. It presents in two main forms: a genetic variant predominantly affecting children, and an acquired form more common in adults, often secondary to infections, malignancies, or autoimmune diseases such as systemic lupus erythematosus (SLE). Macrophage Activation Syndrome (MAS), a subtype of HLH, frequently complicates rheumatologic conditions like systemic juvenile idiopathic arthritis (SJIA) and SLE. It is marked by intense inflammation driven by biomarkers such as interleukin (IL)-18 and IFN-γ. Clinical manifestations of HLH include persistent fever, enlargement of liver and spleen, blood cell deficiencies, elevated ferritin and triglyceride levels, abnormal liver function tests, decreased fibrinogen, and neurological symptoms, posing challenges in differential diagnosis. Diagnostic evaluation typically reveals blood cell deficiencies, elevated triglycerides, decreased fibrinogen, elevated ferritin, impaired natural killer cell function, and increased soluble IL-2 receptor levels. Early recognition and prompt intervention are crucial for improving outcomes in HLH and MAS. Diagnostic criteria incorporate clinical findings and laboratory parameters, supported by scoring systems such as HLH-2004 and HScore. Treatment strategies focus on limiting exposure to harmful agents and targeting specific cytokines like interferon gamma, IL-1, IL-18, and IL-6. Emerging therapies include corticosteroids, cyclosporine, anakinra, and, in severe cases, etoposide, showing promise in managing cytokine-release syndrome post-CAR T cell therapy. Adherence to standardized management protocols and evidence-based guidelines post-stem cell transplantation and CAR T cell therapy is essential for improving patient outcomes, including reduced mortality rates and faster resolution of inflammatory markers. This summary offers a comprehensive overview of HLH and MAS, highlighting diagnostic complexities, therapeutic approaches, and advancements in treatment aimed at enhancing patient care and prognosis.