Erdheim-Chester disease
Encyclopedia
Erdheim–Chester disease (also known as Erdheim–Chester syndrome or polyostotic sclerosing histiocytosis) is a rare disease characterized by the abnormal multiplication of a specific type of white blood cell
s called histiocyte
s, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell
histiocytosis
). Usually, onset is in middle age
. The disease involves an infiltration of lipid
-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocyte
s and histiocyte
s in the bone marrow
, and a generalized sclerosis
of the long bones.
Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed.
Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature. Exophthalmos
occurs in some patients and is usually bilateral, symmetric and painless. In most cases it occurs several years before the final diagnosis.
A review of 59 case studies by Veyssier-Belot, C et al. in 1996 reported the following symptoms in order of frequency of occurrence:
(LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100
or CD 1a, and electron microscopy of cell cytoplasm
does not disclose Birbeck granules
. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis
. Bone biopsy
is said to offer the greatest likelihood of reaching a diagnosis.
So in a nutshell, there is histiocyte proliferation and on staining, the section is CD68+ and CD1a-
ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive.
All current treatments have had varying degrees of success.
The vinca alkaloids
and anthracyclines have been used most commonly in ECD treatment.
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s called histiocyte
Histiocyte
A histiocyte is a cell that is part of the mononuclear phagocyte system . The mononuclear phagocytic system is part of the organism's immune system...
s, or tissue macrophages (technically, this disease is termed a non-Langerhans-cell
Langerhans cell
Langerhans cells are dendritic cells of the skin and mucosa, and contain large granules called Birbeck granules. They are present in all layers of the epidermis, but are most prominant in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as...
histiocytosis
Histiocytosis
In medicine, histiocytosis refers to an excessive number of histiocytes, , and is typically used to refer to a group of rare diseases which share this as a characteristic...
). Usually, onset is in middle age
Middle age
Middle age is the period of age beyond young adulthood but before the onset of old age. Various attempts have been made to define this age, which is around the third quarter of the average life span of human beings....
. The disease involves an infiltration of lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s and histiocyte
Histiocyte
A histiocyte is a cell that is part of the mononuclear phagocyte system . The mononuclear phagocytic system is part of the organism's immune system...
s in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, and a generalized sclerosis
Sclerosis (medicine)
In medicine, sclerosis refers to the stiffening of a structure, usually caused by a replacement of the normal organ-specific tissue with connective tissue.Types include:...
of the long bones.
History
The first case of ECD was reported by the American pathologist William Chester in 1930.Clinical presentation
ECD affects predominantly adults, with a mean age of 53 years.Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have some sort of extraskeletal involvement. This can include kidney, skin, brain and lung involvement, and less frequently retroorbital tissue, pituitary gland and heart involvement is observed.
Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature. Exophthalmos
Exophthalmos
Exophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral or unilateral . Measurement of the degree of exophthalmos is performed using an exophthalmometer...
occurs in some patients and is usually bilateral, symmetric and painless. In most cases it occurs several years before the final diagnosis.
A review of 59 case studies by Veyssier-Belot, C et al. in 1996 reported the following symptoms in order of frequency of occurrence:
- Bone painBone painBone pain is a debilitating form of pain emanating from the bone tissue. It occurs as a result of a wide range of diseases and/or physical conditions and may severely impair the quality of life for patients who suffer from it...
- Retroperitoneal fibrosisRetroperitoneal fibrosisRetroperitoneal fibrosis or Ormond's disease is a disease featuring the proliferation of fibrous tissue in the retroperitoneum, the compartment of the body containing the kidneys, aorta, renal tract and various other structures. It may present with lower back pain, renal failure, hypertension, deep...
- Diabetes insipidusDiabetes insipidusDiabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
- ExophthalmosExophthalmosExophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral or unilateral . Measurement of the degree of exophthalmos is performed using an exophthalmometer...
- Xanthomas
- NeurologicalNeurologyNeurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
signs (including AtaxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
) - DyspneaDyspneaDyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
caused by interlobular septal and pleural thickening. - Kidney Failure
- HypopituitarismHypopituitarismHypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
- Liver FailureLiver failureAcute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
Histology
Histologically, ECD differs from Langerhans cell histiocytosisLangerhans cell histiocytosis
Langerhans cell Histiocytosis is a rare disease involving clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes...
(LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100
S-100 protein
S-100 protein is a family of low molecular weight protein found in vertebrates characterized by two calcium binding sites of the helix-loop-helix conformation. There are at least 21 different types of S100 proteins...
or CD 1a, and electron microscopy of cell cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
does not disclose Birbeck granules
Birbeck granules
Birbeck granules, also known as Birbeck bodies, are rod shaped or "tennis-racket" cytoplasmic organelles with a central linear density and a striated appearance...
. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. Bone biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is said to offer the greatest likelihood of reaching a diagnosis.
So in a nutshell, there is histiocyte proliferation and on staining, the section is CD68+ and CD1a-
Diagnosis
Radiologic osteosclerosis and histology are the main diagnostic features. Diagnosis can often be difficult because of the rareness of ECD as well as the need to differentiate it from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis.ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive.
Treatment
Current treatment options include:- Surgical DebulkingDebulkingDebulking is the surgical removal of part of a malignant tumour which cannot be completely excised, so as to enhance the effectiveness of radiation or chemotherapy. It is used only in specific malignancies, as generally partial removal of a tumor is not considered a worthwhile intervention...
- High-dose CorticosteroidCorticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
therapy - Cyclosporine
- InterferonInterferonInterferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
-α - ChemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
- Radiation therapyRadiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
All current treatments have had varying degrees of success.
The vinca alkaloids
Vinca alkaloids
Vinca alkaloids are a set of anti-mitotic and anti-microtubule agents which were originally derived from the Periwinkle plant Catharanthus roseus.Vinca alkaloids are used in the treatment of cancer...
and anthracyclines have been used most commonly in ECD treatment.
Support groups
The Erdheim–Chester Disease Global Alliance is a support and advocacy group with the goal of raising awareness of and promoting research into ECD.External links
- Writeup at Harvard UniversityHarvard UniversityHarvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...