Patients may present with single or multiorgan involvement.
Lesions often involve bone (especially skull and facial bones), skin, lungs, lymph nodes, spleen, thymus, pituitary, and hypothalamus.
Disease may be localized to a bone or soft tissue site, multifocal in bone only, or multifocal in bone and other sites.
The disease can occur in any bone. The skull, femurs, ribs, vertebrae (esp. cervical) and humeri are the most frequent sites involved.
In children, the most frequent site is a lytic lesion of the skull, either painful or not.
Bony involvement in the face bones has a several-fold risk of central nervous system involvement and diabetes insipidus.
Diabetes insipidus may appear early or late in the course and is the most frequent sign of central nervous system involvement.
Diabetes insipidus is the presenting symptom in approximately 4% of patients and 15% to 2% will develop diabetes insipidus during the course of the disease.
Uncommonly, other central nervous system effects of the disease occur (eg, mass lesions in gray or white matter, neurodegeneration with dysarthria, ataxia, dysmetria). Magnetic resonance imaging may show significant brain changes years before onset of clinical manifestations.
Cervical lymph nodes most common lymphatic site involved. The thymus and mediastinal nodes may be enlarged.
Infants may have fever, otitis media, or mastoiditis, with enlargement of liver, spleen, and lymph nodes, or self-limited skin lesions of head and neck.
Skin lesions can have seborrheic or eczematoid features, and in infants, can be mistaken as prolonged “cradle cap” and in adults as dandruff.
Skin lesions commonly affect skin flexures in groin, perianal area, the ears, the neck, the armpits, and below the breasts.
Skin lesions in older children and adults may appear as red papules. Lesions may ulcerate.
Skin lesions may precede more diffuse disease.
Oral mucosal lesions may include ulcers on the soft or hard palate, tongue, or lips. There may be gingival hypertrophy.
Children and adolescents often have pain, tenderness, swelling caused by lytic bone lesion(s); bleeding from gastrointestinal tract; polydipsia; and polyuria as a result of hypothalamic involvement.
Adult males may have primary pulmonary involvement, causing chronic nonproductive cough, chest pain, dyspnea, wheezing, with a high frequency of associated lung cancer.
Young women may have localized involvement of the genital tract or it may be part of multicentric involvement. Pregnancy is associated with exacerbation of diabetes insipidus.
There is a high risk of severe disease in sites including the liver, spleen, lung, and marrow.
Massive splenomegaly can result in cytopenias.
Liver enlargement can lead to dysfunction with low albumin, hyperbilirubinemia, and clotting factor deficiencies. Sclerosing cholangitis as a result of bile duct injury is a very serious complication.
Lung involvement is far more common in adults than children and is associated with cigarette smoking. Chest radiographs show an interstitial infiltrate but computed tomography uncovers cystic and nodular pattern characteristic of Langerhans cell histiocytosis. Later fibrosis can lead to severe pulmonary insufficiency.
Marrow involvement may be associated with hemophagocytic macrophages as a result of cytokine activation but bone or skin involvement and biopsy results should discriminate between hemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis.
There is a low risk of severe disease in sites including the skin, bone, lymph nodes, and pituitary gland singly or in any combination.