Langerhans cell histiocytosis, formerly known as histiocytosis X, can be divided into three subtypes: eosinophilic granuloma; Hand-Schüller-Christian disease; and Letterer-Siwe. Although patients classified into these separate subtypes are uncommon, such criteria are still valuable in classifying the clinical manifestations of Langerhans cell histiocytosis. The incidence of this disease is estimated to be between 1 in 200,000 and 1 in 2 million. It occurs mainly in infants and children, but also in adults and even in the elderly. Many reports mention a predominance of male patients. Signs and symptoms The signs and symptoms of the patient depend greatly on the organ(s) of infiltration. Bone, skin, teeth and gingival tissue, ear, endocrine organs, lungs, liver, spleen, lymph nodes and bone marrow can be invaded. Infiltration of cells may show functional impairment. Most cases are between 1 and 15 years old. Single and multiple eosinophilic granulomas occur mainly in older children and young adults (often near 30 years of age). Peak incidence occurs between 5 and 10 years of age. Single and multiple eosinophilic granulomas account for approximately 60% to 80% of cases of Langerhans cell histiocytosis. Patients with generalized invasion have similar bone damage, often with weight-bearing inability, and a soft, protruding surface mass (sometimes warm). Radiographic examination of the lesions is often clear, round or oval in shape with jagged edges, giving an impressive image. However, some lesions are difficult to differentiate from Ewing sarcoma and osteosarcoma. Hand-Schüller-Christian disease occurs in children 2-5 years of age, but is also seen in some older children and adults.Hand-Schüller-Christian disease accounts for approximately 15%-40% of cases of Langerhans histiocytosis. The disease is characterized by bony defects, proptosis due to orbital masses, optic nerve or oculocutaneous muscle invasion leading to hypotony or strabismus, and tooth loss due to gingival and mandibular infiltration. The most common sites of bone invasion are the flat bones (e.g., skull, ribs, pelvis, and scapula). The long bones and lumbar and sacral vertebrae are less commonly involved. Lesions on long bones resemble Ew-ing sarcoma, osteogenic sarcoma and osteomyelitis. Invasion of the wrist, head, knee, foot or cervical bones is rare. Parents often report premature teething, but this is actually due to gingival recession and exposure of immature dentition. Chronic otitis media and otitis externa due to temporal papillae and rocky areas are common. 5% to 50% of cases may develop uveitis, mainly in children with systemic disease and orbital and cranial invasion. 40% of children with systemic Langerhans cell histiocytosis present as dwarfs. Hypothalamic infiltration can cause hyperprolactinemia and hypogonadotropic hypogonadism. A variety of other rare symptoms have been reported. Letterer-Siwe disease is the most severe form of Langerhans cell histiocytosis, accounting for approximately 1% of cases. 1 typical case is an infant less than 2 years old with a scaly seborrheic eczema-like rash, sometimes presenting as a purpuric rash, invading the scalp, ear shell, abdomen, and folds of the neck and face. Skin lesions can become a portal for microbial invasion, leading to septicemia. Ear pus, lymphadenopathy, and hepatosplenomegaly are common. Severely ill children may have hepatic dysfunction with hypoproteinemia and decreased synthesis of coagulation factors, anorexia, agitation, and weight loss. There are obvious respiratory symptoms (e.g., cough, shortness of breath, pneumothorax), severe anemia, and sometimes neutropenia. Thrombocytopenia is often a precursor to death. Because of these presentations, young patients are often misdiagnosed or underdiagnosed. Diagnosis Clinical manifestations are the basis for differential diagnosis. The disease should be differentiated from immunodeficiency syndromes with graft-versus-host disease or viral infection, infiltrative diseases such as leukemia or lymphoma, reticuloendothelial cell storage disease, congenital infections, benign and malignant bone tumors, cysts, and papillary yellow tumors. The diagnosis of Langerhans cell histiocytosis is made on the basis of the histopathological features of the biopsy specimen. Langerhans cells are often predominant on pathological films and vary with the length of the lesion. In early lesions, the proliferating Langerhans cells are well differentiated. In the later stages of the lesion, there are fewer Langerhans cells, and in some cases they are absent. Occasionally, necrosis with very few Langerhans cells is seen. Multinucleated histiocytes are common and are present along with other inflammatory cells (e.g., granulocytes, eosinophils, macrophages, and rarely lymphocytes and plasma cells). Other diagnostic tests include positive immunochemical stains using ATPase, S-100 protein, alpha-D mannosidase, arachidonin receptor and elastin, which are sensitive but not specific. They are sensitive but not specific. They need to be evaluated in conjunction with histopathological findings. The diagnosis is confirmed by electron microscopic detection of Langerhans cells with Langerhans granules [X vesicles or racket-like vesicles (Birbeck granules)] or cell surface expression of CD1 antigen. Prognosis and treatment The low-risk group is >2 years old and has no hematopoietic system, liver, lung or spleen invasion. The risk group is <2 years of age, or with invasion of the aforementioned organs. Due to the persistence of the disease, patients are often unable to follow a strictly designed regimen and may develop symptoms of multiple organ involvement (Table 137-2). Patients in groups 0-II, especially those with individual systemic disease, require little systemic therapy and are rarely disabling or fatal. Some patients in group II and most patients in group III (i.e., with multisystem disease) require systemic therapy, but it is generally effective. Younger patients in group IV with multisystemic invasion have a disability and mortality rate of up to 20%, and although relapses are common, almost all patients with good outcomes can eventually discontinue treatment. In adult patients, there is also a chronic ebb and flow of disease. Severe patients should be hospitalized and given maximum doses of antibiotics, airway patency, nutritional support (including high energy nutrition), blood products, skin care, physical therapy, and medical care as needed. Strict hygiene measures can be effective in reducing hearing, skin and gum damage. Debridement and even removal of severely damaged gingival tissue can be performed to limit oral lesions. Seborrheic-like dermatitis of the scalp can be treated with a shampoo containing selenium (twice a week). If the shampoo is not effective, a small amount of topical corticosteroids may be used to control small lesions in the short term. Supplemental hormone therapy is mostly required for patients with uveitis or other symptoms of hypopituitarism.