Timely recognition of histiocytic diseases can be lifesaving The most common histiocytic disease, Langerhans cell histiocytosis (LCH), rarely requires emergency care, whereas hemophagocytic lymphohistiocytosis (HLH) is a life-threatening illness that can be rapidly fatal without appropriate intervention CLINICAL PEARL AND PITFALLS Consider HLH in the acutely ill infant or young child as these patients can deteriorate quickly and require urgent oncologic consultation and critical care support Current Evidence Histiocytic diseases are a complex and sometimes confusing group of disorders for two reasons First, several different disease entities make up this group, although efforts have been made to simplify the terminology Second, significant clinical heterogeneity exists between the major disease entities Histiocyte is a term referring to several different cells that are thought to derive from a common CD34+ progenitor in the bone marrow Depending on the cytokines to which the progenitors become exposed, the differentiation can yield tissue macrophages, dermal/interstitial dendritic cells, or Langerhans cells In general, histiocytic diseases are rare; of the group, the most common is LCH, which has an incidence of three to five cases per million children Clinical Considerations Clinical Recognition LCH has clinical heterogeneity and the locations involved have implications for therapy and prognosis Low-risk LCH may present at any age and systemic symptoms are rare Skin, bone, lymph nodes, or a combination of these are most commonly involved Skin involvement can present as a red papular rash, resembling a candidal diaper rash, which may appear on the groin, abdomen, back, or chest There may also be seborrheic flaking of the scalp, often misdiagnosed as “cradle cap” in infants, draining otitis externa, or ulcerative lesions behind the ears, on the scalp, or in the genital region Bony involvement may be asymptomatic or painful A lytic lesion of the skull causing a tender mass is the most common but any bone may be involved Loose teeth from involvement of the jaw may occur Certain sites of disease have become known as “risk” organs because their involvement implies more aggressive disease These patients are often very young with disease that involves the lung, liver, spleen, and/or bone marrow Lung involvement is rare but worrisome and usually manifests first as hypoxia Liver and spleen involvement is