Multifocal stenosing ulceration of the small intestine is a rare condition that is characterised by recurrent ulcers of the small intestine.

Presentation

The clinical features of this condition are variable. Features associated with it include: * Abdominal pain * Abdominal distension * Fatigue * Weight loss * Fever * Malaise * Joint symptoms Faecal occult blood testing is usually positive. Laboratory investigations normally 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 low

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

Cause

A mutation in the cytosolic phospholipase A2-α gene (

PLA2G4A Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the ''PLA2G4A'' gene. Function This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to r ...

) has been identified as the cause of this disease in one family.Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, Warner TD, Kelsell DP, Macdonald TT (2012) Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α. Gut In this family the mutation was inherited as an autosomal recessive. It is not yet known if this gene is the cause of this disease in other families. The gene encoding cytosolic phospholipase A2-α is found on

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non- sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which ...

. Cytosolic phospholipase A2-α acts on membrane phospholipids to release arachidonic acid a precursor in the synthesis of

eicosanoid Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a s ...

s. The eicosanoids are involved in multiple regulatory pathways.

Pathology

This disease is characterised by multifocal stenosing ulceration of the small intestine. The ulcers are circular or irregular in shape and their margins are always clear. The intervening mucosa appears normal. The lesions involve only the mucosa and submucosa and are confined to the

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...

and proximal

ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...

. Nonspecific inflammatory changes are present.

Giant cell A giant cell (also known as multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. Although there is typically a focus on the pathologica ...

s or other typical features of granulomatous inflammation are not found. Multiple stenoses are typically present (mean 8: range 1-25).

Diagnosis

This may be difficult given the non specific nature of the presenting symptoms and the rarity of the condition itself. It is normally made by the combination of the clinical picture, endoscopic findings and typical histology. Radiology may also be helpful. Other conditions such as infections and vasculitis should be ruled out with the relevant laboratory investigations.

Differential diagnosis

* Idiopathic ulcerative jejunoileitis *

Lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

* Infectious agents ('' Campylobacter'', '' Salmonella'', ''

Shigella ''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to '' E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in 1 ...

'', ''

Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of ''Yer ...

'' and others) * Infections in the immunosuppressed with unusual organisms * '' Tropheryma whipplei, Mycobacterium avium intracellulare'' * Drug induced (nonsteroidal anti-inflammatory drugs,

gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile me ...

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

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 ...

) * Zollinger-Ellison syndrome * Heterotopic functioning gastric mucosa *

Meckel's diverticulum A Meckel's diverticulum, a true congenital diverticulum, is a slight bulge in the small intestine present at birth and a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct or yolk stalk). It is the most common malformat ...

* Crohn's disease * Traumatic injury (surgical, seat belt injury, endoscopic biopsy, cautery during endoscopy, foreign body ingestion particularly batteries) * Ischemia * Thrombotic diseases * Degos disease *

Pseudoxanthoma elasticum Pseudoxanthoma elasticum (PXE) is a genetic disease that causes mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis. PXE is cau ...

Myeloproliferative disorders Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid growt ...

Antithrombin III deficiency Antithrombin III deficiency (abbreviated ATIII deficiency) is a deficiency of antithrombin III. This deficiency may be inherited or acquired. It is a rare hereditary disorder that generally comes to light when a patient suffers recurrent venous ...

Vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...

Coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the ey ...

Treatment

Steroids seem to relieve the symptoms but long term treatment may be required.Freeman HJ (2009) Multifocal stenosing ulceration of the small intestine. World J Gastroenterol 15(39): 4883–4885 Other immunosuppressants appear to be less effective. Surgery may be curative in ~40% but a second operation may be required later.

Prognosis

This condition may be lifelong. Although not normally fatal it may necessitate admission to hospital for transfusions, control of bleeding or other complications. Because of its rarity to date there have been no controlled trials. Treatment remains empirical and symptomatic.

History

This disease was first recognised in 1959.Rocha A, Artigas V (1959) Stenosing ulcerous disease of the jejuno-ileum. Arch Mal Appar Dig Mal Nutr 48:1230–1236 It was redescribed and named 'cryptogenetic plurifocal ulcerative stenosing enteritis' in 1964.Debray C, Besancon F, Hardouin JP, Martin E, Marche C, Khoury K (1964) Cryptogenetic plurifocal ulcerative stenosing enteritis. Arch Mal Appar Dig Mal Nutr. 1964;53:193–206

References

{{Gastroenterology Abdominal pain Inflammations Noninfective enteritis and colitis