Whipple’s disease is a rare infectious disease that occurs with a predominant lesion of the lymphatic system of the small intestine and the synovial membranes of the joints. The main clinical signs are diarrhea, fever, polyarthritis and joint pain, multiple enlargement of lymph nodes, lung, heart and central nervous system damage. Diagnosis is made by performing imaging diagnostic tests (ultrasound, X-ray), biopsy of small intestine tissues, blood tests and PCR diagnostics. Patients are shown long-term antibiotic therapy, the appointment of glucocorticosteroids, enzymes and multivitamin complexes.
ICD 10
K90.8 Other intestinal absorption disorders
General information
Whipple’s disease (lipophagic intestinal granulomatosis, intestinal lipodystrophy) is a pathology named after the American pathologist George H. Smith, who discovered it in 1907. Whipple. During the autopsy procedure, the scientist discovered mesenteric lymphadenopathy and lipid deposition in the intestinal wall of the deceased patient. This suggested that the basis of the disease is intestinal lipodystrophy ‒ a violation of the production and breakdown of fats. Later, the infectious nature of the disease was proved, and in 1992, thanks to the PCR method, the pathogen was identified. The incidence of the disease is 0.5–1 case per 1 million population. According to statistics, pathology more often affects people 40-50 years old, in 80% of cases, male patients turn out to be.
Causes
The causative agent of infection in Whipple’s disease are gram‒positive pathogens Tropheryma whippelii – representatives of actinomycetes with a three-layer cell wall. Infection is carried out by fecal-oral route in childhood and is manifested by short-term gastroenteritis. Family cases of morbidity have been registered, but not a single fact of transmission of the bacterium from person to person has been reliably recorded. Some scientists believe that only certain pathogenic strains cause pathological changes.
Whipple tropherymes are found in the intestinal mucosa and other organs in the active phase of the disease. However, the DNA of the pathogen can also be detected in the saliva of patients who do not have clinical signs of pathology. There are suggestions that the manifestation of the disease is directly related to the violation of the reaction of the “carrier to invasion”. Pathology is common among people with impaired humoral or cellular immunity. The likelihood of developing the disease increases with dysfunction of the endocrine glands, especially the adrenal glands.
Pathogenesis
Intestinal lipodystrophy is characterized by the accumulation of infiltrates consisting of macrophages containing Tropheryma whippelii in various organs. The presence of bacteria in phagocytes suggests that these cells are capable of capturing microorganisms, but cannot carry out their lysis. This is due to disorders of the immune response (a decrease in the production of anti-inflammatory cytokine IL-12 and gamma interferon, a decrease in lymphocytic response to antigens, as well as the production of T-lymphocytes). As a result, macrophages with pathogens settle in the small intestine mucosa and mesentery lymph nodes, causing malabsorption diarrhea and impaired lymph outflow.
The accumulation of infiltrate in the synovial membranes contributes to the manifestation of arthritis. The further spread of the process occurs lymphogenically, which explains the generalization of infection and damage to the serous membranes of the heart, eyeball, lungs, brain. There are multiple pathological foci that cause the progression of the disease and its complications.
Symptoms
The fact of a multisystem lesion makes the clinical picture of intestinal lipodystrophy very variable. In two-thirds of patients, the disease manifests itself as a joint lesion long before the development of a detailed gastroenterological picture. There are wandering polyarthritis or polyarthralgia of large joints (wrist, knee, sacroiliac, ankle). The duration of seizures ranges from several hours to 3-4 days. In the period between seizures, complete remission is observed. There is no change in the shape of the joints or their destruction. At the stage of extra-intestinal manifestations, about half of the patients have fever.
At the second stage, in 85% of cases, abdominal pain, diarrhea, flatulence, nausea, vomiting, weight loss and fever appear. The frequency of bowel movements reaches 10 times a day. Signs of exhaustion develop, in severe cases ‒ cachexia. Pain with localization in the navel area has a paroxysmal character. A distinctive sign of the transition of the disease to the second stage is a generalized enlargement of the lymph nodes, with palpation they are mobile, but painless. In some cases, there is inflammation of various parts of the vascular membrane of the eye (iris, ciliary body, choroid).
The third stage – systemic lesions – is characterized by the development of neurological symptoms. The central and peripheral nervous system suffers, ataxia, polyneuropathy develops, hearing and visual acuity decrease. Involvement in the pathological process of the heart is manifested by endocarditis and pericarditis (often pathology is detected only during echocardiographic examination). 30-50% of patients develop bronchopulmonary pathologies (bronchitis or exudative pleurisy). Due to an increase in the lymph nodes of the mediastinum and compression of the trachea, shortness of breath, dry cough and a feeling of suffocation occur.
Complications
Whipple’s disease is a pathology with a chronic course, which is characterized by periods of remissions and relapses. According to observations, complications manifest themselves at the moments of relapses that occur in the absence of preventive treatment. The main ones are neurological pathologies, including the progression of dementia, impaired coordination of movements, hydrocephalus, supranuclear ophthalmoplegia and myoclonia. In the latter case, there is a lesion of the spinal cord or cerebral cortex. This leads to involuntary muscle cramps, tremors, as well as deterioration of the physical and mental state of a person.
Diagnostics
Since Whipple’s disease is difficult to diagnose in the early stages, most patients are diagnosed correctly only after several years. To confirm the infectious genesis of the disease and typical pathomorphological changes, the following instrumental and laboratory tests are performed:
- Endoscopic examination. During the EGDS, swelling, hyperemia, stretching and thickening of the folds of the duodenum are revealed. The mucous membrane becomes granular, its villi thicken and shorten. Histological examination of the biopsy reveals macrophages with undigested pathogens, PCR examination allows detecting Tropheryma whippelii and confirming Whipple’s disease, even if only traces of the pathogen DNA are present in the sample.
- Radiation studies. Have an auxiliary value. An X-ray of the small intestine with contrast enhancement reveals thickening of the mucosa, expansion of the intestine and duodenal bending. Ultrasound of the mediastinum and abdominal cavity reveals an increase in mediastinal, mesenteric and retroperitoneal lymph nodes.
- Blood tests. Intestinal lipodystrophy is characterized by the development of hypochromic anemia, increased ESR, hyperleukocytosis, thrombocytosis. There is a deficiency of protein, calcium, iron and cholesterol in the blood serum. The synthesis of albumins is disrupted.
Variability of clinical manifestations of systemic infection implies mandatory differentiation of intestinal lipodystrophy with enteritis, Crohn’s disease, celiac disease, lymphosarcoma of the small intestine, Hodgkin’s disease, infectious endocarditis, as well as connective tissue pathologies. Gastroenterologists, infectious diseases specialists, oncologists, cardiologists and rheumatologists take part in the diagnosis process.
Treatment
In the pre-antibiotic era, therapeutic treatment of intestinal lipodystrophy was considered almost impossible. Today, etiotropic therapy with antibiotics for 1-2 years is indicated for the treatment of the disease. The choice of specific drugs (cephalosporins, tetracyclines, penicillins, sulfonamides, fluoroquinolones) is determined by the results of diagnostic tests and current data on the resistance of Tropheryma whippelii to certain types of antibiotics.
In the course of therapy, PCR analysis and morphological examination of biopsies are performed at regular intervals. In the absence of traces of the pathogen, treatment is discontinued. Detection of pathogens in the test results after discontinuation of therapy may indicate a relapse of the disease (occurs in 40% of cases) and requires continued treatment for two years. The complex therapy includes the appointment of glucocorticoids, cytostatics and TNF inhibitors (in the presence of arthritis), enzymes, multivitamin complexes. In the presence of pathologies of the central nervous system, in particular, seizures, antiepileptic drugs are indicated. In cases of hydrocephalus detection, shunting operations are performed.
Prognosis and prevention
When prescribing their own temporary and adequate therapy, the outcome of Whipple’s disease is conditionally favorable. Improvement in the condition of patients is noted 1-2 weeks after the start of treatment, but the regression of morphological changes is longer and not always complete. In the presence of a recurrent course, repeated treatment is indicated. Specific immunoprophylaxis of intestinal lipodystrophy has not been developed. Preventive measures are reduced to the prevention of possible relapses. Patients who have had Whipple’s disease should undergo a dispensary observation by a gastroenterologist every 3 months and visit an infectious disease specialist every six months.
