Histiocytic disorders: recent insights into pathophysiology and practical guidelines

The Histiocytoses are defined as non-malignant disorders due to abnormal accumulation and behavior of cells of the mononuclear phagocytic system. The best known histiocytoses, Langerhans cell histiocytosis (LCH), and hemophagocytic lymphohistiocytosis (HLH), each with an estimated incidence of 1/50,000 to 1/150,000, are sufficiently "common," complex and costly, to constitute an important problem in medical practice. At the same time, LCH, HLH and an array of other and more rare histiocytoses are sufficiently uncommon that most physicians lack the experience to diagnose, let alone care for patients with these conditions. The pathophysiology of most of the histiocytoses is unknown and, in the case of the widely-disseminated and potentially fatal forms, treatments to date have been variably effective and sometimes highly toxic. MAS has been reported to occur in association with almost any rheumatic disease, it is by far most common in the systemic form of Juvenile Idiopthic Arthritis (SoJIA). It is now recognized that MAS bears a close resemblance to Hemophagocytic Lymphohistiocytosis or HLH, and MAS is recognized as the major fatal complication of soJIA.