Whipple's disease

Previously unknown disease was described by the American physician pathologist D. Whipple in 1907. The findings turned out to be so rare that only by 1988 did they accumulate data on 1000 patients.

Whipple's disease was diagnosed 100 years ago only in case of a sectional examination. And now there are difficulties associated with a variety of symptoms and course. More often the pathology is accompanied by intestinal dyspepsia, diarrhea, significant weight loss, anemia.

So far, the cause of the disease has not been identified. The first author of the research proposed the name "intestinal lipodystrophy", since in all cases a typical histological picture was found: enlarged lymph nodes of the intestine, fat deposition, inflammatory process in the serous membranes of internal organs.

Modern scientists have established a connection with the change in cellular immunity. There is a fact that white Whites at the age of 30-60 are prone to Whipple's disease, but cases of three-year-old children are described. Some authors believe that men are sick more often.

What is known about the causes of the disease?

The study of single cases of the disease made it possible to draw a conclusion about the main role of the infection. Probably, infection with a bacterium similar in type to actinomycetes occurs( called Tropheryma whippelii).

The initial assumption was based on findings in the biopsy specimens of macrophage lymph nodes with bacterial residues. The confirmation was then obtained by polymerase chain reaction. It was possible to isolate and cultivate a bacterium on a medium from human phagocyte cells.

Tropheryma whippelii is covered with three layers of the shell, contains a single chromosome, can form pathogenic and non-pathogenic strains of

. How the microorganism gets to a person is unclear. Transfers to close contacts do not occur. Therefore, there was a suspicion that additional factors are needed for infection. There is no consensus on the participation of cellular immunity in Whipple's disease, the problem continues to be studied. Researchers pay attention to the change in the ratio of types of T-lymphocytes, the vague loss of the ability of macrophages of the intestine to destroy bacteria.

What does histology show?

Histological examination allows to establish a characteristic damage of the intestinal mucosa in its own layer. It consists in shortening and thickening villi in the small intestine, changing their shape, infiltration of the mucosa by macrophages of large sizes.

In the cytoplasm of macrophages, a significant number of granules from glycoproteins having a relationship to a certain color( called PAS-positive) have been found in the disease. The cell type is described as "foamy".This sign is considered the main( pathognomonic) in diagnosis.

Other cellular elements of the intestine are unchanged in appearance, but they are significantly reduced in quantity, as they are replaced by macrophages. The wall of the intestine is filled with wide capillaries and lymphatic ducts with fatty inclusions.

On the outer side of the cells, there are also accumulations of fats. The superficial layer of the intestinal epithelium can have areas with nonspecific changes, but is practically not affected.

Electron microscopy made it possible to detect bacilliform bodies in Whipple's disease in the intestinal layer of the intestine. They are most concentrated in the zones around the vessels. They are also found in macrophages, rarely in leukocytes, plasma and endothelial cells.

The development mechanism of

The detection of foamy macrophages not only in the intestine, but also in the liver, brain, lung tissue, lymph nodes, heart, adrenal glands, joints, tells about the systemic nature of the pathology. Apparently, the disease spreads through the body.

The route of introduction of the pathogen remains unclear. Given the maximum changes in the intestine, it can be assumed that a specific reaction begins here. After infiltration of its own layer, it is difficult to absorb necessary substances through enterocytes. Bloody capillaries and lymphatic tracts are in a compressed state.

Lymph nodes of the mesenteric zone( mesentery) are significantly enlarged, the group is more rarely affected in the gates of the liver, in the retroperitoneal layer. The small intestine becomes denser, the folds become swollen, yellow nodular rashes appear on the shell. Perhaps the involvement of the large intestine with the development of similar changes.

However, it is noted that macrophages with inclusions in the mucosa of the large intestine are detected in the rectum and colon, not only in Whipple's disease, but also in healthy people, melanosis and histiocytosis. Inflammation of peritoneal sheets( peritonitis) is one of the most severe forms of a response to infection.

Pain is spastic, in untypical cases, constipation occurs

Symptoms of Whipple's disease

During the illness, there are 3 stages that have their signs. I - begins with extraintestinal symptoms, in 65% of cases the first appear unstable pain in small and large joints. There are no signs of inflammation( tumor, redness).

Polyarthritis is of a migratory nature, pain occurs in one or in other joints. Unlike rheumatoid arthritis, there is no deformation resistance. At the same time, the patient has a fever, a protracted tracheobronchitis with a cough is possible. Whipple's disease in this form lasts from three to eight years.

II( unfolded) is the stage of pronounced intestinal lesion. For her typical:

• Diarrhea is chronic painful, the stool is plentiful up to 10 times a day, stool contains a lot of fat, bleeding is possible with a typical "melena"( black liquid feces).The abdomen is swollen.
• Bleeding is associated with reduced blood coagulability caused by loss of vitamin K, stopping its absorption from food.
• Patients complain of constant pain around the navel, a feeling of raspiraniya in the abdomen, they decrease after the removal of gases and stool. With a sharp attack, the patient is taken to the surgical department. When examining the doctor, attention is drawn to enlarged lymph nodes on the periphery and in the mesentery of the intestine. They manage to palpate in the abdomen. The nodes are painless, mobile, not soldered to the skin.
• The signs of protein deficiency gradually increase, hypovitaminosis: appetite decreases, the patient loses weight, there is weakness and atrophy of muscles, swelling on the legs, intolerance of milk. Because of the impaired absorption of the necessary substances, all kinds of metabolism suffer.

III( stage of systemic manifestations of the disease) - characterized by the development of extraintestinal manifestations. They can be divided depending on the specific organ damage. Signs of adrenal insufficiency include: hypotension, refusal of food( anorexia), the appearance of skin pigmentation on the face, neck, hands, nausea, vomiting. In blood tests, hypoglycaemia is detected, and the sodium level is lowered.

Signs of skin lesion: development of erythematous rashes in the form of nodules is possible. Ophthalmic symptoms: inflammation of the ocular membranes( uveitis, keratitis, retinitis).Violation of the heart and vessels is manifested: fibrotic endocarditis, pericarditis, myocarditis, polyserositis. Coronarius gives a typical picture of angina pectoris.

The peripheral and central nervous system is affected. Patients experience loss of vision, hearing, paresis of the facial nerve with a characteristic asymmetry of the face, a violation of sensitivity, mobility, pain in the arms and legs as a polyneuropathy.

Diagnosis

Clinically, Whipple's disease can be suspected in a patient with joint pain and diarrhea. This is especially important if a person quickly loses weight, the temperature of an unclear origin remains, the enlarged lymph nodes are palpated, the type of joint damage can not be established.

Test shows in the blood of the patient with joint pain a negative or slightly positive test for rheumatoid factor and normal uric acid concentration

Laboratory signs of the disease

Laboratory tests can confirm indirect signs of internal organs damage.

• In the general analysis of the blood there is: hypochromic anemia, leukocytosis, high ESR, elevated level of platelets and eosinophils.
• In the analysis of urine: moderate proteinuria is possible.
• Coprology shows: massive excrement of feces, a significant amount of fat( steatorrhea), the presence of undigested muscle fibers, it is possible a positive reaction of Gregersen to the latent blood.

Biochemical tests confirm violation of all kinds of metabolism: the amount of total protein is significantly reduced due to albumin fraction, transaminases, bilirubin increase, blood concentration of iron, calcium, sodium, potassium decreases. A decrease in the level of glucose( hypoglycemia), prothrombin is determined.

What is detected using tool methods?

Ultrasound examination in Whipple's disease is not very informative, as it is aimed at revealing changes in dense tissues. It helps to detect enlarged groups of intestinal lymph nodes in the abdominal cavity( mesenteric, retroperitoneal, hepatic).

X-ray examination of the small intestine by taking a barium suspension by the patient. The small intestine looks enlarged, the contours form a large-toothed pattern, sometimes enlarged lymph nodes give a picture of the filling defect.

The folds on the mucosa are thickened and enlarged by infiltration. Reduced elasticity. The enlarged duodenal bend indicates an increase in retroperitoneal lymph nodes.

Lymphography - the method is associated with the introduction of a contrast medium into the general lymphatic duct with subsequent monitoring by X-rays. It allows to detect the phenomena of inflammation, stagnation in the lymphatic ducts. On a fibroesophagogastroduodenoscopy it is possible to reveal a concomitant gastritis.

Biopsy research method

Biopsy of the site of the small intestine mucosa is yet the only way to clarify the diagnosis of Whipple's disease and to conduct differential diagnosis with other similar lesions.

The material is collected when viewed with the endoscope of the duodenum. It is believed that this zone contains a maximum of histological evidence already in the initial stage of the disease.

Macrophages in Whipple's disease are detected with biopsy not only in the intestines, but also in other organs( spleen, liver),

lymph nodes. The most valuable are the following symptoms:

• revealing "foamy" macrophages in its own mucosal layer;
• confirmation of the presence of PAS-positive granules in macrophages using diamond fuchsin color;
• detection in the course of electron microscopy of "Whipple bodies", rod-like formations inside macrophages and in extracellular space;
• accumulation of fatty inclusions in the mucous membrane, lymph nodes;
• enlarged lumen and stagnation in lymphatic vessels.

What diseases are used for differential diagnosis?

Such little specific symptoms as weight loss, diarrhea, weakness, lymph node enlargement necessitates the differential diagnosis of Whipple's disease with the following diseases:

• lymphadenopathy of different etiology;
• with a cancerous tumor;
• by Crohn's disease;
• with ulcerative colitis;
• by Zollinger-Ellison syndrome;
• by chronic enterocolitis;
• sprue;
• with Addison's disease.

Treatment of

Patient with impaired absorption of nutrients from the intestine needs dietary nutrition. For correction, the diet should contain animal proteins up to 150 g / day, but a limited amount of fats( 30 g / day).Patient appointed special mixtures of nutritional components for food and additionally intravenously injected solution of albumin, amino acids.

Digestion support requires enzymatic preparations with lipase - Pangrol, Mezima. In the treatment of Whipple's disease, antibacterial agents are used.

The main task of destroying an infectious agent is performed by antibiotics. It is important to use drugs that have the ability to penetrate the blood-brain barrier, for the therapy of brain cells.

Antibiotics are used: tetracycline, doxycycline, taigecycline, metacyclin, penicillin derivatives, ampicillin, streptomycin, cephalosporin drugs. When the brain is affected, Rifampicin and Chloramphenicol are used.

Combinations of antibiotics with trimethoprim-sulfamethoxazole( analogues Biseptol, Co-trimoxazole)

are most effective. Treatment is carried out for a long time from 2 to 5 months. Antibiotics are changed to avoid addiction. Then 9 months the patient is offered intermittent therapy( 3 days to take medications, 4 days break and repeat).Co-trimoxazole is prescribed for 1-2 years as a maintenance treatment.

All drugs are administered intravenously and intramuscularly, taking into account the impaired intestinal absorption capacity. With pain in the abdomen, antispasmodics are shown, they are also able to slow intestinal peristalsis. In order to reduce the intake of water and electrolytes in the intestine, Imodium, Loperamide, is prescribed.

Enteric sorbents and bismuth preparations are used for excretion of slag substances. The elimination of immune disorders in the disease is helped by corticosteroid courses. Patients need symptomatic therapy: vitamins( groups B, C, K), iron preparations, electrolyte balance correction.

Criteria for the effectiveness of

Without the necessary therapy, Whipple's disease progresses rapidly, the result is a lethal outcome. The use of antibacterial agents allows one month to achieve the elimination of pain in joints, fever. Restoration of intestinal disorders is slow.

The effectiveness of therapy is assessed not only by clinical observations, but also by repeated studies of the biopsy specimen of the intestinal mucosa. The main sign of effectiveness is the disappearance of macrophages.

Usually, a repeat biopsy is performed after a year of treatment with

Under the influence of treatment, the structure of the villi of the intestinal mucosa is restored, the bacilli disappear from the intercellular space. In some cases, foci of macrophages with dilated vessels and accumulations of fatty inclusions remain.

There is still no talk of a full recovery and victory over the disease. Relapses can occur after many years. Doctors believe that patients with suspected Whipple disease should be referred for treatment and screening at specialized centers. This allows you to quickly diagnose and achieve the maximum possible results of therapy.