Acquired hemophagocytic syndrome: comment to the case report.

Abstract

Hemophagocytosis represents the peculiar pathological feature of activated macrophages engulfing hematopoietic cells as a result of an immune dysregulatory disorder. This finding is the hallmark of a rare hyperinflammatory disease known as hemo phagocytic ly mphohistiocytosis (HLH). HLH is a severe condition characterized by an abnormal ineffective immune response caused by an uncontrolled activation and proliferation of macrophages, natural killer (NK) cells and T-helper lymphocytes, leading to excessive cytokine production, subsequent amplification of pathologic immune stimulation, increased phagocytic activity and tissue damage [1]. Typically, heat shock proteins (HSP) are associated with a peculiar combination of clinical and biochemical features, including prolonged high fever, pancytopenia, hepatosplenomegaly, hypertriglyceridemia, hyperferritinemia and hemophagocytosis in the bone marrow. If undiagnosed or not promptly treated, HLH almost inevitably results in death. First described in 1939 by Scott and Robb-Smith [2] as a life-threatening disorder characterized by histiocytic proliferation with erytrophagocytosis in the lymphoreticular system, it was named ‘histiocytic medullary reticulosis’ (HMR) and ascribed among malignant histiocytosis. In the following years, HSP were considered a hereditary immune dysregulatory disorder, called ‘familial hemophagocytic reticulosis’ [3], until Risdall described a viral association with HLH, highlighting a possible acquired etiology and therefore referring to it as ‘reactive hemophagocytic syndrome’ [4]. Subsequently, several cases have been involved in the genesis of sporadic HLH, including infections, malignancies, autoimmune diseases and metabolic co nditions. Therefore, HLH can be etiologically classified into a primary (genetic) or a secondary (acquired) disorder. All forms of HLH share hereditary or acquired immune defects characterized by impaired function of NK cells and cytotoxic T cells. Primary HLH includes two groups: first, the familial hemophagocytic lymphohistiocytosis syndromes (FHLH1–5), in which HLH is the sole manifestation of the disease, and second, immunodeficiency syndromes associated with albinism (Chediak Higashi syndrome, Griscelli syndrome type II, Hermansky-Pudlak syndrome type II) or other primary immunodeficiencies (i.e., X-linked lymphoproliferative disorder type I or II), where the hemophagocytosis is a part of a complex landscape of clinical manifestations [5]. Although not yet entirely identified, the known genetic abnormalities cause defect in proteins (like perforin, MUNC13.4, syntaxin-11 and STXBP2) that play a key role in granule-dependent lymphocyte cytotoxicity, impairing the maturation or the secretion cytotoxic granules during target cell killing, thus prejudicing the immune response [6]. Hereditary HLH usually occurs in infants or young children, with clear familial inheritance, is associated with high risk of recurrence and short life expectancy without hematopoietic cell transplantation. Commentary