The incidence of Langerhans cell histiocytosis (LCH) is approximately 5 per million children or 1 in 25,000 live births. Based on the U.S. census for 2000, this would mean approximately 300 new cases diagnosed each year in this country. LCH is the preferred term instead of the histiocytosis X syndromes (Letterer-Siwe disease, Hand-Schüller-Christian syndrome, and eosinophilic granuloma) because the proliferative cell associated with this disease is a bone marrow–derived dendritic histiocyte called the Langerhans cell. It contains characteristic pentalaminar Birbeck granules seen by electron microscopy. These cells also stain with monoclonal antibodies to the CD1a antigen and a newly recognized antigen, langerin, the protein of the Birbeck granules.

The Langerhans cell diseases are not malignant, despite the presence of clonal proliferations of the Langerhans cells in solitary or diffuse lesions. Current etiologic theories revolve around immunologic dysregulation, because no viral or other infectious cause has been identified. Like other antigen-processing cells, the Langerhans cells produce and receive cytokines to or from T lymphocytes and macrophages, including tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-1, interferon-gamma, and interleukin-10. Somewhere in the interactive cycle, regulatory elements are lost such that the histiocytes proliferate locally or diffusely along with lymphocytes, macrophages, and eosinophils.

Many patients present with a seborrheic rash of the scalp and periauricular regions similar to cradle cap or eczema (Box 314.1). Others have a diffuse erythematous, papular rash that may resemble a Candida diaper rash (Fig. 314.1). Copious white material draining from ears mimics chronic otitis externa. Most patients have painful lesions of the skull (Fig. 314.2), ribs, femurs, vertebra or mandible, skin, or lymph node involvement (low-risk disease). Hepatosplenomegaly, anemia, thrombocytopenia, and pulmonary disease with organ dysfunction occur in patients with the high-risk disease. Of the children presenting with generalized LCH, involvement of various organ systems is found in bone (100%), skin (88%), liver (71%), lung (54%), lymph nodes (42%), spleen (25%), bone marrow (18%), and central nervous system (CNS; pituitary or parenchymal lesions) (16%). Organ dysfunction includes evidence of hepatic failure by a total protein less than 5.5 g/dL, albumin less than 2.5 g/dL, total bilirubin of more than 1.5 mg/dL, edema, and ascites. Hematologic dysfunction is defined by a hemoglobin less than 10 g/dL, leukocyte count less than 4,000/μL, neutrophils less than 1,500/μL, and platelets less than 100,000/μL. Pulmonary dysfunction includes tachypnea, dyspnea, cyanosis, cough, pneumothorax, and pleural effusion.

Patient evaluation should include a complete history and physical examination with complete blood count, bone marrow aspirate and biopsy when an abnormal blood count is found, radiographic survey of the complete skeleton, skull survey, and chest radiography, as well as radionucleotide bone scan. A high-resolution chest computed tomography scan is done if abnormalities are seen by plain chest radiography or if respiratory distress is present. A magnetic resonance imaging (MRI) scan of the brain is indicated when CNS symptoms are present. If there are symptoms of diabetes insipidus, careful monitoring of liquid intake and output, serum, and urine osmolality and a water deprivation test are needed. The biopsy material from an affected site should be sent for immunocytochemistry evaluation with anti-langerin and CD1a stains and sometimes for electron microscopy to look for Birbeck granules.

It is critical that patients be registered on the most current treatment protocols of the Histiocyte Society so advances in the knowledge and treatment of these diseases can be achieved. (Contact the Histiocytosis Association of America for protocol information: 1-856-589-6606.)