Chronic multifocal Langerhans cell histiocytosis
|Chronic multifocal Langerhans cell histiocytosis|
|Other names||Hand–Schüller–Christian disease, multifocal eosinophilic granuloma|
|A child with Hand-Schüller-Christian disease|
|Symptoms||Bulging eyes, breakdown of areas of bone, diabetes insipidus|
|Complications||Bone fractures (including spinal fracture), spinal cord injury, loss of teeth|
|Usual onset||2 to 6 years old|
|Causes||Genetic mutation during early development|
|Diagnostic method||Tissue biopsy|
|Differential diagnosis||Letterer-Siwe disease, mastocytosis|
|Treatment||Prednisone, vinblastine, cytarabine, mercaptopurine|
Chronic multifocal Langerhans cell histiocytosis, formally known as Hand-Schüller-Christian syndrome, is a type of Langerhans cell histiocytosis (LCH), which can affect multiple organs. Its three main features are bulging eyes, breakdown of areas of bone (often in the skull), and diabetes insipidus (excessive thirst and dilute urine). However, around 75% of cases do not have all three features. Other features may include an asymmetrical face, ear infections, and advanced gum disease.
It is due to a genetic mutation in the MAPKinase pathway that occurs during early development. The diagnosis may be suspected based on symptoms and MRI and confirmed by tissue biopsy. Blood tests may show low red blood cells, and occationally low white blood cells and low platelets.
Treatment may include some combination of prednisone, vinblastine, cytarabine, and mercaptopurine. The outlook depends on how many and how much organs are affected. In some people the condition is life-threatening. The disease is rare. Most cases occur in the 2 to 6 year old age group. Boys are more commonly affected than girls.
It was previously named after the American pediatrician Alfred Hand Jr., the Austrian neuroradiologist Arthur Schüller, and the American pathologist Henry Asbury Christian, who described it in 1893, 1915 and 1919, respectively. Before the Histiocyte Society classified histiocytoses in the 1980s, LCH was known as "histiocytosis X", where "X" denoted the unknown cause at the time.
Signs and symptoms
A combination of three features are seen in 25% of people with the condition, which usually presents before the age of five; one or both bulging eyes, breakdown of bone (lytic bone lesions often in the skull in a 'punched out' pattern), and diabetes insipidus (excessive thirst and passing urine). Around 75% of cases do not have all three traditional features.
Involvement of the skull is usually accompanied with jaw and basal skull involvement. The face may look asymmetrical and ear infections are common. Between 5 and 75% of cases have been reported to present with signs in the mouth. These include mouth ulcers, bad breath, swollen gums, loose teeth and an unpleasant taste. Destruction of part of the jaw bone may give the appearance of advanced gum disease.
Complications include fractures of long bones, compression of vertebrae, spinal cord damage, swollen and bleeding gums and loss of teeth.
Chronic multifocal Langerhans cell histiocytosis is due to a genetic mutation in the MAPKinase pathway that occurs during early development. While due to a genetic mutation, it is not inherited from a persons parents.
Tests usually include imaging using MRI. Findings include breakdown of bone and thickening of the pituitary stalk. The perivascular space may appear prominent, the pituitary gland cystic and there may be signs in the white matter, a mass in the hypothalamus and enhancement of the meninges.
Blood tests may show anaemia, and less commonly a low white blood cell count and low platelet count. Although the disease was once thought to be a lipid storage disease as the lesions have a high cholesterol content, the blood cholesterol is usually normal. Diagnosis is confirmed by tissue biopsy.
The outlook depends on the extent of organ involvement. The prognosis is poor if the disease presents in a young person with many affected organs. In a newborn with skin lesions only, the outlook is better. The prognosis is poor if the liver, spleen, lung, or bone marrow is affected. A good response to chemotherapy within the first six weeks of treatment, has been found to indicate a better prognosis. In some people the condition is life-threatening.
Chronic multifocal Langerhans cell histiocytosis was previously known as Hand–Schüller–Christian disease, and was named for the American pediatrician Alfred Hand Jr., the Austrian neuroradiologist Arthur Schüller, and the American pathologist Henry Asbury Christian, who described it in 1893, 1915 and 1919, respectively. Shortly afterwards, Letterer in 1924 and Siwe in 1933 described a fatal condition in children who presented with large livers and spleens, large lymph nodes and bone damage. In 1940, Louis Litchtenstein and Henry L. Jaffe described a self-limiting disease characterised by "isolated bone lesions". A common feature of all these conditions was revealed to be the histological findings of large numbers of histiocytes in the tissue biopsies, leading Litchtenstein to propose that the three described conditions were part of a spectrum of a disease he named "Histiocytosis X", where "X" denoted the unknown cause at the time. In 1973, Christian Nezelof recognised the abnormal cell as a 'Langerhans-like' cell, however it took another ten years for the disease to be accepted as one entity and the term 'Langerhans cell histiocytosis' to be internationally recognised. In 1987, the Histiocyte Society published their classification of the histiocyte disorders together with criteria for diagnosis and clinical assessment of Langerhans cell histiocytosis.
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