AUTOINFLAMMATORY DISEASES IN HEMATOLOGY FROM DIAGNOSIS TO TREATMENT

AUTOINFLAMMATORY_DISEASES_IN_HEMATOLOGY_FROM_DIAGNOSIS_TO_TREATMENTkapak

HEMOPHAGOCYTIC LENFOHISTIYOCYTOSIS

Buğra Sağlam

Medicalpoint Gaziantep Hospital, Department of Hematology, Gaziantep, Türkiye

Sağlam B. Hemophagocytic Lenfohistiyocytosis. In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.73-86.

ABSTRACT

Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by uncontrolled and excessive activation of the immune system. Although HLH was initially considered to be a childhood-associated disease, it has subsequently been observed in adulthood. In patients with acquired onset, genetic disorders can also be detected in treatment-resistant and recurrent forms. The pathophysiology of the disease is characterized by an excessive immunologic response to inflammation due to hyperactivated macrophages and T cells, resulting in tissue damage and multiorgan failure. The disease can manifest in genetic (familial HLH) or acquired (secondary HLH) forms. The genetic form is inherited in an autosomal recessive manner, while the acquired form is precipitated by triggers such as infections, malignancies, or autoimmune diseases. Symptoms of HLH frequently resemble those of sepsis, hepatitis, or encephalitis. Common clinical manifestations include high and persistent fever, organomegaly, cytopenias, liver dysfunction, neurological symptoms, and multiple organ failure. There is no specific laboratory test for diagnosis; rather, diagnosis is established using the HLH-2004 diagnostic criteria, which encompass laboratory tests demonstrating excessive activity of the inflammatory system and findings of affected organs. However, the most critical aspect in the diagnosis and treatment of the disease is the initiation of therapy without delay in cases of high clinical suspicion, even before the completion of diagnostic tests. Waiting for diagnostic tests to be completed can lead to fatal consequences and its contribution to treatment is very limited. Therefore, treatment should be initiated in case of clinical suspicion simultaneously while the diagnostic test processes are ongoing. The primary objective of treatment is to prevent excessive inflammatory stimulation and inflammatory cytokine production, thereby mitigating organ/tissue damage by controlling the activity of the immune system. To this end, corticosteroids, induction regimens including etoposide and cyclosporin, as well as agents such as IVIg and ruxolitinib can be utilized due to their immunomodulatory effects. Additionally, stem cell transplantation may be employed in the presence of underlying genetic disorders, malignancy, or relapsed refractory disease.

Keywords: Hemophagocytic lymphohistiocytosis; HLH; Organomegaly; Cytopenia; High fever

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