Chronic multifocal Langerhans cell histiocytosis, previously known as Hand–Schüller–Christian disease, is a type of

Langerhans cell histiocytosis Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Symptoms range from isolated bone lesions to multisystem d ...

(LCH), which can affect multiple organs. The condition is traditionally associated with a combination of three features; bulging eyes, breakdown of bone (lytic bone lesions often in the skull), and

diabetes insipidus Diabetes insipidus (DI), recently renamed to Arginine Vasopressin Deficiency (AVP-D) and Arginine Vasopressin Resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced ...

(excessive thirst and passing urine), although around 75% of cases do not have all three features. Other features may include a fever and weight loss, and depending on the organs involved there maybe rashes, asymmetry of the face, ear infections, signs in the mouth and the appearance of advanced

gum disease Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main caus ...

. Features relating to lung and liver disease may occur. It is due to a

genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in the MAPKinase pathway that occurs during early development. The diagnosis may be suspected based on symptoms and

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

and confirmed by

tissue biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...

. Blood tests may show

anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

, and less commonly a low white blood cell count and low platelet count. Treatment may involve surgery,

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

, and certain medicines. Updated 2017 Hand–Schüller–Christian disease was named for the American pediatrician Alfred Hand Jr., the Austrian neuroradiologist Arthur Schüller, and the American internist

Henry Asbury Christian Henry Asbury Christian (February 17, 1876 – August 24, 1951), was an American professor of pathology named in the condition Hand–Schüller–Christian disease. Biography Henry Asbury Christian was born in Lynchburg, Virginia on February 17, ...

, who described it in 1893, 1915 and 1919, respectively. Before the Histiocyte Society classified histiocytoses in the 1980s, the condition was also known as "Histiocytosis X", where "X" denoted the then unknown cause. It is now known as chronic multifocal Langerhans cell histiocytosis, a subtype of LCH. The disease is rare. Most present between the ages of two and six. The outlook depends on how many and how much organs are affected. In some people the condition is life-threatening.

Signs and symptoms

The traditional combination of three features are seen in 25% of people with the condition, which usually presents between the ages of two and six; one or both bulging eyes, breakdown of bone (lytic bone lesions often in the skull in a 'punched out' pattern), and

(excessive thirst and passing urine). The skin can be affected with rashes,

bumps A bumps race is a form of rowing race in which a number of boats chase each other in single file, each crew attempting to catch and ‘bump’ the boat in front without being caught by the boat behind. The form is mainly used in intercollegia ...

and

ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...

, and bones can be painful. There may be large lymph nodes and signs of lung and

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

. Affected people may present with fever and weight loss. 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 Bad breath, also known as halitosis, is a symptom in which a noticeably unpleasant breath odour is present. It can result in anxiety among those affected. It is also associated with depression and symptoms of obsessive compulsive disorder. Th ...

, swollen gums, loose teeth and an unpleasant taste. Destruction of part of the jaw bone may give the appearance of advanced

Cause

The cause is a

in the MAPKinase pathway that occurs during early development. The origin is a dendritic cell, although previously thought to be a

histiocyte A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...

, a term still used. The mutations causes white blood cells (lymphocytes, macrophages, and eosinophils) to move towards dendritic cells, resulting in damage in any organ except the heart and kidneys. The disease was once thought to be a

lipid storage disease A lipid storage disorder (or lipidosis) is any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some body cells and tissues. People with these disorders either do not produce enough of one ...

as the lesions have a high cholesterol content, but the

blood cholesterol Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence ...

is usually normal. Some sources such as the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

describe it as a type of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, while other sources specifically state it is not a type of cancer.

Diagnosis

Tests usually include imaging using

. Findings include breakdown of bone and thickening of the

pituitary stalk The pituitary stalk (also known as the infundibular stalk, Fenderson's funnel, or simply the infundibulum) is the connection between the hypothalamus and the posterior pituitary. The floor of the third ventricle is prolonged downward as a funnel- ...

. The

perivascular space A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role fo ...

may appear prominent, the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

cystic and there may be signs in the

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distributi ...

, a mass in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

and enhancement of the meninges.

X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

findings typically demonstrate sharp "punched out" lesions in the skull. The destruction of alveolar bone is usually more generalised and may appear as displaced teeth. Blood tests may show

, and less commonly a low white blood cell count and low platelet count. Other useful tests might include a

PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

. Diagnosis is confirmed by

Treatment

Treatment may involve surgery,

, and certain medicines.

Prognosis

The outlook depends on how many and how much organs are affected. The prognosis is poor if the disease presents in a young person with many affected organs, unless a newborn with skin lesions only, when the outlook is better. The prognosis is poor if 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. Hence, follow-up is long-term.

Epidemiology

The disease is rare. 70% of cases present before the age of 15. Around 75% of cases do not have all three traditional features.

History

MRI and CT scan findings in a

mummy A mummy is a dead human or an animal whose soft tissues and organs have been preserved by either intentional or accidental exposure to chemicals, extreme cold, very low humidity, or lack of air, so that the recovered body does not decay fu ...

have revealed evidence of the disease dating back to 900–790. B.C. The historic name of Hand–Schüller–Christian disease was named for the American pediatrician Alfred Hand Jr., the Austrian neuroradiologist Arthur Schüller, and the American pathologist

, who described it in 1893, 1915 and 1919, respectively.H. Christian. Defects in membranous bones, exophthalmos, and diabetes insipidus; an unusual syndrome of dyspituitarism. In: Contributions to medical and biological research, dedicated to Sir William Osler. New York, P. B. Hoeber, 1919, 1: 390-401. Medical Clinics of North America, Philadelphia, PA., 1920; 3: 849-871. 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 A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...

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. 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

. Hand–Schüller–Christian disease is now considered a subtype of LCH, chronic multifocal Langerhans cell histiocytosis.

References

External links

{{DEFAULTSORT:Hand-Schuller-Christian disease Monocyte- and macrophage-related cutaneous conditions Medical triads Histiocytosis Rare diseases