Eosinophilic gastroenteritis
Encyclopedia
Eosinophilic gastroenteritis (EG) is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic
infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937
. Presentation may vary depending on location as well as depth and extent of bowel wall involvement and usually runs a chronic relapsing course. It can be classified into mucosal, muscular and serosal types based on the depth of involvement.
Any part of the GI tract can be affected, and isolated biliary tract involvement has also been reported.
The stomach
is the organ
most commonly affected, followed by the small intestine
and the colon
.
and elevated serum
IgE
are usual but not universal. The damage to the gastrointestinal tract
wall is caused by eosinophilic infiltration
and degranulation
.
As a part of host defense
mechanism, eosinophils are normally present in gastrointestinal mucosa, though the finding in deeper tissue
is almost always pathologic
.
What triggers such dense infiltration in EG is not clear. It is possible that different pathogenetic
mechanisms of disease is involved in several subgroups of patients. Food allergy
and variable IgE
response to food substances has been observed in some patients which implies role of hypersensitive
response in pathogenesis. Many patients indeed have history of other atopic
conditions like eczema
, asthma
etc.
Eosinophil recruitment into inflammatory tissue is a complex process, regulated by a number of inflammatory
cytokines. In EG cytokines IL-3
, IL-5
and granulocyte macrophage colony stimulating factor (GM-CSF) may be behind the recruitement and activation. They have been observed immunohistochemically
in diseased intestinal wall
.
In addition eotaxin
has been shown to have an integral role in regulating the homing
of eosinophils into the lamina propria
of stomach and small intestine
.
In the allergic subtype of disease, it is thought that food allergens cross the intestinal mucosa and trigger an inflammatory response that includes mast cell
degranulation and recruitment of eosinophils.
, vomiting, diarrhea
, weight loss
, and abdominal distension. Approximately 80% have symptoms for several years; a high degree of clinical suspicion is often required to establish the diagnosis, as the disease is extremely rare. Occasionally, the disease may manifest itself as an acute abdomen or bowel obstruction.
Hypereosinophilia
, the hallmark of allergic response, may be absent in up to 20% of patients, but hypoalbuminaemia and other abnormalities suggestive of malabsorption may be present.
CT scan may show nodular and irregular thickening of the folds in the distal stomach and proximal small bowel, but these findings can also be present in other conditions like Crohn's disease
and lymphoma
.
The endoscopic appearance in eosinophilic gastroenteritis is nonspecific; it includes erythematous, friable, nodular, and occasional ulcerative changes.
Sometimes diffuse inflammation results in complete loss of villi, involvement of multiple layers, submucosal oedema and fibrosis
.
Definitive diagnosis involves histological
evidence of eosinophilic infiltration in biopsy slides. Microscopy
reveals >20 eosinophils per high power field
. Infiltration is often patchy , can be missed and laparoscopic
full thickness biopsy may be required.
Radio isotope
scan using technetium (99mTc) exametazime-labeled leukocyte SPECT
may be useful in assessing the extent of disease and response to treatment but has little value in diagnosis, as the scan does not help differentiating EG from other causes of inflammation.
When eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems, the diagnosis of idiopathic
hypereosinophilic syndrome
should be considered.
), ketotifen
(an antihistamine
), and montelukast
(a selective, competitive leukotriene receptor antagonist
) have been proposed, centering around an allergic hypothesis, with mixed results. An elimination diet may be successful if a limited number of food allergies are identified.
EG can present at any age and across all races, with a slightly higher incidence in males. Earlier studies showed higher incidence in the third to fifth decades of life.
Eosinophilic
Eosinophilic refers to the staining of certain tissues, cells, or organelles after they have been washed with eosin, a dye.Eosin is an acidic dye; thus, the structure being stained is basic....
infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937
. Presentation may vary depending on location as well as depth and extent of bowel wall involvement and usually runs a chronic relapsing course. It can be classified into mucosal, muscular and serosal types based on the depth of involvement.
Any part of the GI tract can be affected, and isolated biliary tract involvement has also been reported.
The stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
is the organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
most commonly affected, followed by the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
and the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
.
Pathophysiology
Peripheral blood eosinophiliaEosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
and elevated serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
are usual but not universal. The damage to the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
wall is caused by eosinophilic infiltration
Infiltration (medical)
Infiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.-Classification:...
and degranulation
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
.
As a part of host defense
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
mechanism, eosinophils are normally present in gastrointestinal mucosa, though the finding in deeper tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
is almost always pathologic
.
What triggers such dense infiltration in EG is not clear. It is possible that different pathogenetic
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
mechanisms of disease is involved in several subgroups of patients. Food allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
and variable IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
response to food substances has been observed in some patients which implies role of hypersensitive
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
response in pathogenesis. Many patients indeed have history of other atopic
Atopy
Atopy or atopic syndrome is a predisposition toward developing certain allergic hypersensitivity reactions.Atopy may have a hereditary component, although contact with the allergen must occur before the hypersensitivity reaction can develop ....
conditions like eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
etc.
Eosinophil recruitment into inflammatory tissue is a complex process, regulated by a number of inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
cytokines. In EG cytokines IL-3
IL-3
IL-3 may refer to:* Interleukin 3* Illinois' 3rd congressional district* Illinois Route 3...
, IL-5
IL-5
IL 5 or IL-5 may refer to:* Interleukin 5* Illinois' 5th congressional district* Illinois Route 5...
and granulocyte macrophage colony stimulating factor (GM-CSF) may be behind the recruitement and activation. They have been observed immunohistochemically
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
in diseased intestinal wall
.
In addition eotaxin
Eotaxin
Eotaxin may refer to:* CCL11 * CCL24 * CCL26...
has been shown to have an integral role in regulating the homing
Homing
Homing is the process of determining the location of something, sometimes the source of a transmission, and going to it.More specifically, it may refer to:*Infrared homing*Semi-active radar homing*Active radar homing*Acoustic homing*Homing...
of eosinophils into the lamina propria
Lamina propria
The lamina propria is a constituent of the moist linings known as mucous membranes or mucosa, which line various tubes in the body ....
of stomach and small intestine
.
In the allergic subtype of disease, it is thought that food allergens cross the intestinal mucosa and trigger an inflammatory response that includes mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
degranulation and recruitment of eosinophils.
Symptoms and signs
EG typically presents with a combination of chronic nonspecific GI symptoms which include abdominal pain, nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
, and abdominal distension. Approximately 80% have symptoms for several years; a high degree of clinical suspicion is often required to establish the diagnosis, as the disease is extremely rare. Occasionally, the disease may manifest itself as an acute abdomen or bowel obstruction.
- Mucosal EG (25-100%)is the commonest variety, which presents with features of malabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
and protein losing enteropathyProtein losing enteropathyProtein losing enteropathy refers to any condition of the gastrointestinal tract that results in a net loss of protein from the body.-Presentation:...
. Failure to thrive and anaemia may also be present. Lower gastrointestinal bleedingLower gastrointestinal bleedingLower gastrointestinal bleeding, commonly abbreviated LGIB, refers to any form of bleeding in the lower gastrointestinal tract. LGIB is a common ailment seen at emergency departments. It presents less commonly than upper gastrointestinal bleeding . It is estimated that UGIB accounts for 100-200 per...
may imply colonic involvement. - Muscular EG (13-70%) present with obstruction of gastric outlet or small intestine; sometimes as an obstructing caecalCecumThe cecum or caecum is a pouch, connecting the ileum with the ascending colon of the large intestine. It is separated from the ileum by the ileocecal valve or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic...
mass or intussusceptionIntussusceptionIntussusception may refer to:* Intussusception * Intussusception...
. - SubserosalSerous membraneIn anatomy, serous membrane is a smooth membrane consisting of a thin layer of cells which secrete serous fluid. Serous membranes line and enclose several body cavities, known as serous cavities, where they secrete a lubricating fluid which reduces friction from muscle movement...
EG (4.5 % to 9 % in Japan and 13 % in the USA) presents with ascites which is usually exudative in nature, abundant peripheral eosinophilia, and has favourable responses to corticosteroids. - Other documented features are Cholangitis, pancreatitisPancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
, eosinophilic splenitis, acute appendicitisAppendicitisAppendicitis is a condition characterized by inflammation of the appendix. It is classified as a medical emergency and many cases require removal of the inflamed appendix, either by laparotomy or laparoscopy. Untreated, mortality is high, mainly because of the risk of rupture leading to...
and giant refractory duodenal ulcer.
Diagnosis
Talley et al. suggested 3 diagnostic criteria which is still widely used:- the presence of gastrointestinal symptoms,
- histologicalHistologyHistology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
demonstration of eosinophilic infiltration in one or more areas of the gastrointestinal tract or presence of high eosinophil count in ascitic fluid (latter usually indicates subserosal variety), - no evidence of parasitic or extraintestinal disease.
Hypereosinophilia
Hypereosinophilia
Hypereosinophilia is a disease characterised by a marked increase in the eosinophil count in the bloodstream.The eosinophil count in human blood is normally 0.4 × 109/L and results from a balance between production of eosinophils and emigration through post-capillary venules...
, the hallmark of allergic response, may be absent in up to 20% of patients, but hypoalbuminaemia and other abnormalities suggestive of malabsorption may be present.
CT scan may show nodular and irregular thickening of the folds in the distal stomach and proximal small bowel, but these findings can also be present in other conditions like Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
and lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
.
The endoscopic appearance in eosinophilic gastroenteritis is nonspecific; it includes erythematous, friable, nodular, and occasional ulcerative changes.
Sometimes diffuse inflammation results in complete loss of villi, involvement of multiple layers, submucosal oedema and 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...
.
Definitive diagnosis involves histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
evidence of eosinophilic infiltration in biopsy slides. Microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
reveals >20 eosinophils per high power field
High Power Field
High Power Field when used in relation to microscopy references the area visible under the maximum magnification power of the objective being used. Often, this represents a 400x magnification level when referenced in scientific papers....
. Infiltration is often patchy , can be missed and laparoscopic
Laparoscopy
Laparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...
full thickness biopsy may be required.
Radio isotope
Radionuclide
A radionuclide is an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide, in this process, undergoes radioactive decay, and emits gamma...
scan using technetium (99mTc) exametazime-labeled leukocyte SPECT
Single photon emission computed tomography
Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...
may be useful in assessing the extent of disease and response to treatment but has little value in diagnosis, as the scan does not help differentiating EG from other causes of inflammation.
When eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems, the diagnosis of idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
hypereosinophilic syndrome
Hypereosinophilic syndrome
The hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.HES is a diagnosis of exclusion, after clonal...
should be considered.
Management
Corticosteroids are the mainstay of therapy with a 90% response rate in some studies. Appropriate duration of steroid treatment is unknown and relapse often necessitates long term treatment. Various steroid sparing agents e.g. sodium cromoglycate (a stabilizer of mast cell membranesCell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
), ketotifen
Ketotifen
Ketotifen is a second-generation H1-antihistamine and mast cell stabilizer. It is most commonly sold in as a salt of Fumaric Acid, Ketotifen fumarate, and is available in two forms. In its ophthalmic form, it is used to treat allergic conjunctivitis, or the itchy red eyes caused by allergies. In...
(an antihistamine
Antihistamine
An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
), and montelukast
Montelukast
Montelukast is a leukotriene receptor antagonist used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally...
(a selective, competitive leukotriene receptor antagonist
Leukotriene antagonist
A leukotriene antagonist is a drug that inhibits leukotrienes, which are fatty compounds produced by the immune system that cause inflammation in asthma and bronchitis, and constrict airways....
) have been proposed, centering around an allergic hypothesis, with mixed results. An elimination diet may be successful if a limited number of food allergies are identified.
Epidemiology
Epidemiology may differ between studies, as number of cases are small, with approximately 300 EG cases reported in published literature.EG can present at any age and across all races, with a slightly higher incidence in males. Earlier studies showed higher incidence in the third to fifth decades of life.
Other gastrointestinal conditions associated with allergy
- Eosinophilic esophagitisEosinophilic esophagitisEosinophilic esophagitis is an allergic inflammatory condition of the esophagus. Symptoms are swallowing difficulty, food impaction, and heartburn. The disease was first described in children but occurs in adults as well...
- Eosinophilic ascites
- Coeliac diseaseCoeliac diseaseCoeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
- Protein losing enteropathyProtein losing enteropathyProtein losing enteropathy refers to any condition of the gastrointestinal tract that results in a net loss of protein from the body.-Presentation:...
from intolerance to cow's milk protein - Infantile formula protein intolerance