Approach to Hemophagocytic Syndromes

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory condition. It may occur as a primary (genetic) condition due to mutations in genes important in the cytolytic secretory pathway that cause perforin and granzymes to induce apoptosis in target cells. Primary HLH is divided into familial HLH (FHLH1-5), in which HLH is the only manifestation of disease, and other genetic causes in which HLH is one of several clinical manifestations. The identical clinical findings may arise secondary to infectious, rheumatologic, malignant, or metabolic conditions. Whether primary or secondary, HLH therapy needs to be instituted promptly to prevent irreversible tissue damage. It is helpful to think of HLH as the severe end of the spectrum of hyperinflammatory disorders when the immune system starts to damage host tissues (immunopathology). Therefore, no single clinical feature alone is diagnostic for HLH, and it is important that the entire clinical presentation be considered in making the diagnosis. This article contains a discussion of the genetic background, clinical presentation, diagnostic dilemmas, and features that are helpful in making the diagnosis of HLH, along with a discussion of common problems in its management.

Hemophagocytic Lymphohistiocytosis Secondary to <i>Mycoplasma pneumoniae</i> Infection without Pneumonia

“…The disease is characterized by: 1) hyperactivation of CD8 + T lymphocytes and macrophages; 2) the proliferation, ectopic migration and infiltration of these cells into various organs; and 3) hypercytokinemia with elevated levels of various cytokines, resulting in progressive organ dysfunction (7). Clinically, HLH primarily involves unremitting fever, hepatosplenomegaly, disseminated intravascular coagulation and cytopenia (at least two lineages).…”

“…Acquired HLH is primarily observed in adults; however, both types can occur in all age groups (7-9). Acquired HLH is a very heterogeneous disorder that can be triggered by various infections, malignancies and metabolic and autoimmune conditions (7)(8)(9). It is difficult and challenging for clinicians to diagnose HLH in the acute phase, as the presentation of the syndrome is nonspecific and there are no gold standard diagnostic criteria.…”

“…Various genetic abnormalities are associated with the former, which often develops during infancy and childhood (7)(8)(9). Acquired HLH is primarily observed in adults; however, both types can occur in all age groups (7-9).…”

“…First, the treatment of HLH aims to suppress the exaggerated immune reaction and unregulated hyperinflammation. Second, the underlying triggers of HLH should be identified and treated (7)(8)(9). To address the first aim, the HLH-2004 protocol recommends the use of chemoimmunotherapy for genetic HLH and EBV-HLH presenting with monoclonal expansion, including therapy with etoposide, dexamethasone and/or cyclosporine A (10).…”

Histoplasmosis diseminada con síndrome hemofagocítico asociado con infección por HTLV-1. Reporte de caso

“…Desde la primera descripción en 1939 por Scott y Robb Smith (2), se han descrito mejor sus mecanismos, clasificándolos como primarios o forma genética, predominante en población pediátrica y el secundario, asociado a infecciones, procesos autoinmunes o neoplasias (1,3), y con criterios diagnósticos propuestos por la Histiocyte Society (4). Los mecanismos fisiopatológicos en la etiología primaria, involucran defectos genéticos que conllevan a un estado de inmunodeficiencia, activación inmune significativa o inmunopatología anormal (5).…”