What are the diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH)?

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Last updated: March 25, 2025View editorial policy

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Differential Diagnosis for HLH

  • Single most likely diagnosis
    • Familial Hemophagocytic Lymphohistiocytosis (FHL): This is a genetic disorder that affects the immune system, leading to an overactive and inappropriate immune response, which is a hallmark of HLH. The presence of a family history or early onset of symptoms increases the likelihood of this diagnosis.
  • Other Likely diagnoses
    • Secondary Hemophagocytic Lymphohistiocytosis (sHLH): This condition is triggered by infections, autoimmune disorders, or malignancies, leading to a similar immune dysregulation as seen in FHL. Recent infections, autoimmune symptoms, or a history of cancer could point towards this diagnosis.
    • Macrophage Activation Syndrome (MAS): Often associated with systemic juvenile idiopathic arthritis, MAS presents with symptoms overlapping those of HLH, including fever, hepatosplenomegaly, and cytopenias. A history of autoimmune disease, particularly rheumatologic conditions, supports this diagnosis.
  • Do Not Miss diagnoses
    • Sepsis: Although sepsis is a distinct clinical entity, its presentation can overlap with HLH, especially in the context of a severe infection triggering an overwhelming immune response. Missing sepsis could be fatal due to the need for prompt antibiotic therapy.
    • Malignancy: Certain cancers, like lymphomas or leukemias, can mimic or trigger HLH. Failing to diagnose an underlying malignancy could lead to delayed appropriate treatment and poor outcomes.
  • Rare diagnoses
    • Langerhans Cell Histiocytosis (LCH): A rare disorder characterized by the proliferation of Langerhans cells, which can lead to a variety of systemic symptoms, including those that overlap with HLH. The presence of characteristic skin rashes, bone lesions, or diabetes insipidus might suggest LCH.
    • Rosai-Dorfman Disease: A rare histiocytic disorder that can present with lymphadenopathy and systemic symptoms, occasionally mimicking HLH. The diagnosis is often made after histopathological examination of lymph node biopsies.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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