CRONKHITE-CANADA SYNDROME
AND OTHER RARE DIARRHEAL
DISORDERS
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Cronkhite-Canada syndrome is a rare, nonfamilial gastrointestinal polyposis syndrome that commonly presents with diarrhea. It is characterized by hyperpig-mentation, hair loss, and dystrophic changes in the fingernails. Individuals of European and Asian descent are most frequently affected, but the syndrome has been reported in all ethnic groups. The cause is not known, but the frequent association with hypothyroidism, systemic lupus erythematosus, rheumatoid arthritis, and scleroderma suggests an autoimmune origin. The syndrome is characterized by development of innumerable polyps throughout the gastrointestinal tract except in the esophagus. The polyps are hamartomas; there is an increased risk of colorectal cancer (25%), however. Patients commonly present with diarrhea and weight loss accompanied by typical dermatologic manifestations that include hyperpigmentation and onychodystrophy. Management is largely supportive, with nutritional support, accompanied by antisecretory and antiinflammatory treatment. Immunosuppressive therapy with glucocorticosteroids and azathioprine has also been reported to ameliorate symptoms, but the duration of treatment is not known.
Autoimmune
enteropathy is a rare malabsorptive disorder characterized by chronic diarrhea
resulting from immune-mediated injury of the small intestinal mucosa. It
presents more frequently in childhood but has been described in adults as well.
The underlying cause is not well understood, but the disorder has frequent
associations with immunoglobulin deficiencies and thymomas. The diagnosis is
based on the presence of small intestinal villous blunting and circulating
antienterocyte antibodies after exclusion of common malabsorptive disorders such
as celiac disease. Immunosuppression is the mainstay of treatment and
corticosteroids are commonly used; successful treatment with other
immunosuppressive agents such as cyclosporine, azathioprine, and even
anti–tumor necrosis factor (anti-TNF) agents has been reported.
Protein-losing
enteropathy is a rare syndrome characterized by excessive loss of serum protein
into the gastro-intestinal tract, resulting in hypoproteinemia and edema. Many
intestinal and extraintestinal disorders can lead to protein-losing
enteropathy, but the causes can be broadly grouped into erosive enteropathies,
nonerosive enteropathies, and disorders involving mesenteric lymphatic
obstruction or increased central venous pressure.
Erosive
intestinal disorders include benign conditions, such as Crohn disease and
enteropathy related to use of nonsteroidal antiinflammatory drugs, and
intestinal malignant diseases, such as lymphomas. A variety of intestinal
disorders, such as celiac disease, Whipple disease, small intestinal bacterial
overgrowth, and amyloidosis, can also lead to protein-losing enteropathy in the
absence of mucosal erosions or ulcerations. Lastly, impaired intestinal lymph
drainage as a result of a primary disorder of intestinal lymphatics or a
secondary cause such as constrictive pericarditis commonly presents as
protein-losing enteropathy.
The
diagnosis of protein-losing gastroenteropathy should be considered in patients
with hypoproteinemia after exclusion of other, more common causes such as
malnutrition and liver and renal diseases. Dependent edema is invariably
present, and when severe, ascites and pleural effusion can develop.
The
main laboratory findings are reduced serum concentrations of albumin, protein, γ-globulins, fibrinogen, transferrin,
and ceruloplasmin. Enteral protein loss can be confirmed by determining the
clearance of alpha-1 antitrypsin from plasma. Alpha-1 antitrypsin is a protein
synthesized in the liver and has a molecular weight similar to that of albumin.
Several unique properties make it ideal as a test for protein-losing
enteropathy. It is neither actively secreted by nor absorbed in the intestine
and resists proteolysis; therefore, it is excreted in the stool while still
intact. A blood sample and a 24-hour stool collection
are required to measure alpha-1 antitrypsin clearance. The presence of an
elevated alpha-1 antitrypsin level above the normal values is diagnostic;
diarrhea can interfere with the test, and if a gastric source of the protein is
suspected, the test should be performed while the patient is receiving anti-secretory
therapy.
The treatment of protein-losing enteropathy involves nutritional support and treatment of any underlying disorder. A diet rich in protein and low in fat is recommended. Supplementation of medium-chain or long-chain triglyceride that is directly absorbed in the portal venous circulation, bypassing the intestinal lymphatics, provides extra energy and lessens lacteal congestion and lymph loss. Protein intake as high as 3 g/kg/d y may be required to achieve a positive protein balance.
