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Whipple disease

Whipple's disease is a rare disease caused by the bacteria Tropheryma whipplei. more...

Waardenburg syndrome
Wagner's disease
WAGR syndrome
Wallerian degeneration
Warkany syndrome
Watermelon stomach
Wegener's granulomatosis
Weissenbacher Zweymuller...
Werdnig-Hoffmann disease
Werner's syndrome
Whipple disease
Whooping cough
Willebrand disease
Willebrand disease, acquired
Williams syndrome
Wilms tumor-aniridia...
Wilms' tumor
Wilson's disease
Wiskott-Aldrich syndrome
Wolf-Hirschhorn syndrome
Wolfram syndrome
Wolman disease
Wooly hair syndrome
Worster-Drought syndrome
Writer's cramp

It was first described by George Hoyt Whipple in 1907.


  • arthritis
  • malabsorption
  • intestinal lipodystrophy (accumulation of fatty deposits in lymph nodes of the intestine)
  • lymphadenopathy
  • abdominal pain
  • diarrhea
  • fever


Diagnosis is made by intestinal biopsy, which shows as PAS-positive macrophage inclusions.

At times, small bowel X-rays may show some thickened folds.


Treatment is with penicillin, ampicillin, tetracycline or co-trimoxazole for 4-6 months.


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Pernicious anemia
From Gale Encyclopedia of Medicine, 4/6/01 by Rosalyn S. Carson-DeWitt


Pernicious anemia is a disease in which the red blood cells are abnormally formed, due to an inability to absorb vitamin B12. True pernicious anemia refers specifically to a disorder of atrophied parietal cells leading to absent intrinsic factor, resulting in an inability to absorb B12.


Vitamin B12, or cobalamin, plays an important role in the development of red blood cells. It is found in significant quantities in liver, meats, milk and milk products, and legumes. During the course of the digestion of foods containing B12, the B12 becomes attached to a substance called intrinsic factor. Intrinsic factor is produced by parietal cells which line the stomach. The B12-intrinsic factor complex then enters the intestine, where the vitamin is absorbed into the bloodstream. In fact, B12 can only be absorbed when it is attached to intrinsic factor.

In pernicious anemia, the parietal cells stop producing intrinsic factor. The intestine is then completely unable to absorb B12. So, the vitamin passes out of the body as waste. Although the body has significant amounts of stored B12, this will eventually be used up. At this point, the symptoms of pernicious anemia will develop.

Pernicious anemia is most common among people from northern Europe and among African Americans. It is far less frequently seen among people from southern Europe and Asia. Pernicious anemia occurs in equal numbers in both men and women. Most patients with pernicious anemia are older, usually over 60. Occasionally, a child will have an inherited condition which results in defective intrinsic factor. Pernicious anemia seems to run in families, so that anyone with a relative suffering from the disease has a greater likelihood of developing it as well.

Causes & symptoms

Intrinsic factor is produced by specialized cells within the stomach called parietal cells. When these parietal cells shrink in size (atrophy), they produce less and less intrinsic factor. Eventually, the parietal cells stop functioning altogether. Other important products of parietal cells are also lessened, including stomach acid, and an enzyme involved in the digestion of proteins.

People with pernicious anemia seem to have a greater chance of having certain other conditions. These conditions include autoimmune disorders, particularly those affecting the thyroid, parathyroid, and adrenals. It is thought that the immune system, already out of control in these diseases, incorrectly becomes directed against the parietal cells. Ultimately, the parietal cells seem to be destroyed by the actions of the immune system.

As noted, true pernicious anemia refers specifically to a disorder of atrophied parietal cells leading to absent intrinsic factor, resulting in an inability to absorb B12. However, there are other related conditions which result in decreased absorption of B12. These conditions cause the same types of symptoms as true pernicious anemia. Other conditions which interfere with either the production of intrinsic factor, or the body's use of B12, include conditions that require surgical removal of the stomach, or poisonings with corrosive substances which destroy the lining of the stomach. Certain structural defects of the intestinal system can result in an overgrowth of normal bacteria. These bacteria then absorb B12 themselves, for use in their own growth. Intestinal worms (especially one called fish tapeworm) may also use B12, resulting in anemia. Various conditions that affect the first part of the intestine (the ileum), from which B12 is absorbed, can also cause anemia due to B12 deficiency. These ilium related disorders include tropical sprue, Whipple's disease, Crohn's disease, tuberculosis, and the Zollinger-Ellison syndrome.

Symptoms of pernicious anemia and decreased B12 affect three systems of the body: the system that is involved in the formation of blood cells (hematopoietic system); the gastrointestinal system; and the nervous system.

The hematopoietic system is harmed because B12 is required for the proper formation of red blood cells. Without B12, red blood cell production is greatly reduced. Those red blood cells that are produced are abnormally large and defective in shape. Because red blood cells are responsible for carrying oxygen around the body, decreased numbers (termed anemia) result in a number of symptoms, including fatigue, dizziness, ringing in the ears, pale or yellowish skin, fast heart rate, enlarged heart with an abnormal heart sound (murmur) evident on examination, and chest pain.

Symptoms that affect the gastrointestinal system include a sore and brightly red tongue, loss of appetite, weight loss, diarrhea, and abdominal cramping.

The nervous system is severely affected when pernicious anemia goes untreated. Symptoms include numbness, tingling, or burning in the arms, legs, hands, and feet; muscle weakness; difficulty and loss of balance while walking; changes in reflexes; irritability, confusion, and depression.


Diagnosis of pernicious anemia is suggested when a blood test reveals abnormally large red blood cells. Many of these will also be abnormally shaped. The earliest, least mature forms of red blood cells (reticulocytes) also will be low in number. White blood cells and platelets may also be decreased in number. Measurements of the quantity of B12 circulating in the bloodstream will be low.

Once these determinations are made, it will be important to diagnose the cause of the anemia. True pernicious anemia means that the parietal cells of the stomach are atrophied, resulting in decreased production of intrinsic factor. This diagnosis is made by the Schilling test. In this test, a patient is given radioactive B12 under two different sets of conditions: once alone, and once attached to intrinsic factor. Normally, large amounts of B12 are absorbed through the intestine, then circulate through the blood, and enter the kidneys, where a certain amount of B12 is then passed out in the urine. When a patient has pernicious anemia, the dose of B12 given by itself will not be absorbed by the intestine, so it will not pass into the urine. Therefore, levels of B12 in the urine will be low. When the B12 is given along with intrinsic factor, the intestine is able to absorb the vitamin. Urine levels of B12 will thus be higher.


Treatment of pernicious anemia requires the administration of lifelong injections of B12. Vitamin B12 given by injection enters the bloodstream directly, and doesn't require intrinsic factor. At first, injections may need to be given several times a week, in order to build up adequate stores of the vitamin. After this, the injections can be given on a monthly basis. Other substances required for blood cell production may also need to be given; they may include iron and vitamin C.


Prognosis is generally good for patients with pernicious anemia. Many of the symptoms improve within just a few days of beginning treatment, although some of the nervous system symptoms may take up to 18 months to improve. Occasionally, when diagnosis and treatment have been delayed for a long time, some of the nervous system symptoms may be permanent.

Because an increased risk of stomach cancer has been noted in patients with pernicious anemia, careful monitoring is necessary, even when all the symptoms of the original disorder have improved.

Key Terms

A condition in which those elements of the blood responsible for oxygen delivery throughout the body (red blood cells, hemoglobin) are decreased in quantity or defective in some way.
Refers to the shrinking in size of an organ or cell.
Autoimmune disorder
A disorder in which the immune system, (responsible for fighting off such foreign invaders as bacteria and viruses), begins to attack and damage a part of the body as if it were foreign.
Hematopoietic system
The system in the body which is responsible for the production of blood cells.
Intrinsic factor
A substance produced by the parietal cells of the stomach. In order to be absorbed by the intestine, vitamin B must form a complex with intrinsic factor.
Parietal cells
Specific cells which line the inside of the stomach. These cells are responsible for producing intrinsic factor, acid, and pepsin.
An early, immature form of a red blood cell. Over time, the reticulocyte develops to become a mature, oxygen-carrying red blood cell.

Further Reading

For Your Information


  • Babior, Bernard M., and H. Franklin Bunn. "Megaloblastic Anemias." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.
  • Babior, Bernard M. "The Megaloblastic Anemias." In Williams' Hematology, edited by E. Beutler, et al. New York: McGraw-Hill, 1995.


  • Hawley, Kelly. "Pernicious Anemia: How to Recognize and Manage This Insidious Condition." American Journal of Nursing 96, no. 11 (November 1996): 52+.
  • Toh, Ban-Hock, et al. "Pernicious Anemia." The New England Journal of Medicine 337, no. 20 (November 13, 1997): 52+.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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