Langerhans cell histiocytosis (LCH), previously known as histiocytosis-X, is an uncommon reactive disorder of unknown pathogenesis, characterised by abnormal proliferation of Langerhan cells (LCs) into different body organs and tissues. LCH has a wide range of clinical presentations from single system involvment eg skin or bone to multi-focal disease involving: liver, lungs, bone marrow and central nervous system. Head and neck involvement is commonly encountered and presents a difficult management challenge. Current therapeutic options include: observations; aggressive local therapies eg surgical resection and radiotherapy; non-specific immunosuppression and cytotoxic chemotherapy. However, management should be tailored according to the circumstances of individual patients and at times a multidisciplinary approach is necessary.
Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow–derived Langerhans cells (LCs) and mature eosinophils. In 1868, Paul Langerhans discovered the epidermal dendritic cells that now bear his name. The ultrastructural hallmark of the LC, the Birbeck granule, was described a century later. The term LCH is generally preferred to the older term, histiocytosis X. This new name emphasizes the histogenesis of the condition by specifying the type of lesional cell and removes the connotation of the unknown (X) because its cellular basis has now been clarified.
The working group of the Histiocyte Society has divided histocytic disorders into 3 different groups: (1) dendritic cell histiocytosis, (2) erythrophagocytic macrophage disorders, and (3) malignant histiocytosis. LCH belongs in group 1 and encompasses a number of diseases. The clinical spectrum includes on one end, an acute fulminant, disseminated disease called Letterer-Siwe disease and, on the other end, solitary or few, indolent and chronic, lesions of bone or other organs called eosinophilic granulomas. The intermediate clinical form called Hand-Schüller-Christian disease is characterized by multifocal, chronic involvement and classically presents as the triad of diabetes insipidus, proptosis, and lytic bone lesions. A congenital self-healing form called Hashimoto-Pritzker disease has also been described.
Langerhans cell histiocytosis (LCH) is a rare spectrum of disorders characterized by overproduction (proliferation) and accumulation of a specific type of white blood cell (histiocyte) in the various tissues and organs of the body (lesions). The lesions may include certain distinctive granule-containing cells (Langerhans cells) involved in certain immune responses, as well as other white blood cells (e.g., monocytes, eosinophils). Associated symptoms and findings may vary from case to case, depending upon the specific tissues and organs affected and the extent of involvement. The pathogenesis (medical cause) is not clearly understood and an ongoing debate continues regarding its cause as a reactive or neoplastic (cancer causing) process. Most affected individuals have single or multiple bone lesions characterized by degenerative changes and loss of the calcium of bone (osteolysis). Although the skull is most commonly affected, there may also be involvement of other bones, such as those of the spine (vertebrae) and the long bones of the arms and legs. Affected individuals may have no apparent symptoms (asymptomatic), and may experience associated pain and swelling, and/or develop certain complications, such as fractures or secondary compression of the spinal cord. In some cases, other tissues and organs may also be affected, including the skin, lungs, or other areas. In some individuals, LCH may be associated with involvement of the pituitary gland leading to diabetes insipidus. The exact cause of Langerhans cell histiocytosis is unknown.
Langerhans cell histiocytosis was selected by the Histiocyte Society to replace the older, less specific term histiocytosis X. Histiocytosis X encompassed three entities known as eosinophilic granuloma, Hand-Schuller-Christian disease, and Letterer-Siwe disease that were characterized by the accumulation of histiocytes. The "X" denoted that the cause and development of the disorder was not understood. Langerhans cell histiocytosis was chosen because it is now known that Langerhans cells play the central role in the development of these disorders.
It is a rare condition affecting between about 0.5 and 5 people per million per year. It tends to affect white races more often. Boys are affected about twice as often as girls.
- Letterer-Siwe disease occurs mostly in children under 2.
- The chronic multifocal form, including Hand-Schuller-Christian syndrome, occurs most often between 2 and 10 years.
- Localized eosinophilic granuloma tends to affect those between 5 and 15 years.
- LCH is uncommon in adults and rare in the elderly but has been reported.
LCH can result in symptoms in one or several parts of the body. Common symptoms include:
- skin rash
- tenderness or pain originating from a bone
- loose or lost teeth
- swollen gums
- multiple ear infections
- eyelid swelling and other vision problems
- excessive thirst and urination
- fever and night sweats
- weakness and failure to gain weight
The symptoms of LCH vary widely and may resemble other medical conditions. Always consult your child's physician for a diagnosis.
The choice of a therapeutic regimen is based on the severity of the LCH. The International LCH Study of the Histiocyte Society proposes the stratification of LCH cases by the number of systems involved. They further categorize those cases with single-system involvement by the number of sites within that system (eg, monostotic vs polyostotic bone disease, solitary vs multiple lymph node involvement). In addition, the presence or the absence of organ dysfunction is used to stratify patients with multisystemic disease. The presence of any organ dysfunction is an indicator of a poorer prognosis.
This disorder is treated with corticosteroids, which suppress immune function (including the dangerous cells). Smoking may worsen the response to treatment and should be stopped.
Children may be given other medications depending on their estimated outlook. Such medications may include:
Radiation therapy or surgery may also be used to treat bone lesions.
Other treatments may include:
- Antibiotics to fight infections
- Breathing support (with a breathing machine)
- Hormone replacement therapy
- Physical therapy
- Special shampoos for scalp problems
- Supportive care to relieve symptoms
- Blood cell count
- Recommended baseline diagnostic evaluation includes a CBC count and differential, a reticulocyte count, an erythrocyte sedimentation rate, a direct and indirect Coombs test, and immunoglobulin levels.
- In case of anemia, leukopenia, or thrombocytopenia, a bone marrow aspirate is required.
- Coagulation studies may be indicated.
- If liver function test results are abnormal, a biopsy of the liver should be considered to differentiate LCH from cirrhosis.
- Urine osmolarity is measured after overnight water deprivation to screen for diabetes insipidus.
- Chest radiographs (posteroanterior and lateral)
- LCH can present as a micronodular and interstitial infiltrate in the mid zone and base of the lung, with sparing of the costophrenic angles.
- Older lesions show a honeycomb appearance.
- Patients with radiographically demonstrated pulmonary involvement, in whom chemotherapy is being considered, require a biopsy of the lung preceded by bronchoalveolar lavage (BAL) to exclude opportunistic infections. If the BAL is diagnostic, the biopsy of the lung can be obviated.
- Skeletal radiograph survey
- Unifocal LCH presents as a single osteolytic lesion, usually affecting long or flat bones (in children, the calvaria and the femur; in adults, the ribs).
- Multifocal LCH show osteolytic lesions involving the calvaria, the sella turcica, the mandible, the vertebrae, and/or the long bones of the upper extremities.
- Although a radionuclide bone scan is suggested for establishing the extent of osseous involvement, the latter is not as sensitive as the skeletal radiograph survey in most patients.
- CT scan or MRI of the hypothalamic-pituitary region may reveal abnormalities of these organs. In particular, magnetic resonance spectroscopy may be valuable in the early detection and evaluation of the neurodegenerative component.
This depends upon the type and extent of disease as well as response to treatment. Dysfunction of organs has a poor prognosis.
- For a single focus of disease prognosis is excellent. If no additional lesions present after a year it is unlikely that more will arise. There is usually full recovery from solitary lymph node involvement or isolated skin disease.
- With multi-focal disease 60% have a chronic course, 30% achieve remission and 10% die.
- Letterer-Siwe disease has a mortality of 50% and this is worse in the very young.
- The congenital form of histiocytosis tends to resolve spontaneously within weeks to months.
- A study of 60 children who had survived LCH was reported in 1980. In those whose disease involved soft tissue and bone 50% had severe disabilities. Treatment may have improved since then but such figures are cause for concern.
- A review from 1999 concluded that patients with isolated bone lesions have the best prognosis compared with involvement of other systems. 20% of patients with multisystem involvement have a progressive disease course despite treatment. The identification of prognostic indicators to facilitate appropriate treatment and long term follow-up surveillance is recommended.