Whipple’s disease: causes, symptoms, diagnosis and treatment

Whipple’s is a rare Multisystem pathology of infectious origin, occurring with a primary lesion of the lymphatic system of the small intestine and the synovial membranes of the joints.

Main clinical signs: diarrhea, fever, polyarthritis, joint pain, multiple swollen lymph nodes, lung damage, heart and Central nervous system.

Diagnosis is performed through the visual diagnostic tests (endoscopy, ultrasound, x-ray), biopsy of the tissues of the small intestine, blood tests and PCR diagnostics. Patients prescribed long-term antibiotic therapy, administration of corticosteroids, enzymes and multivitamin complexes.

Whipple’s

Whipple’s (lipophilicity intestinal granulomatosis, intestinal lipodystrophy) is a pathology named after who discovered it in 1907 by the American pathologist George H. Whipple. During the procedure, the autopsy, the scientist discovered the deceased patient’s mesenteric lymphadenopathy and lipid deposition in the intestinal wall.

This suggests that the basis of the disease is intestinal lipodystrophy ‒ a violation of the development and breakdown of fats. It was later proven the infectious nature of the disease, and in 1992 due to the method Credentiallevel pathogen. The frequency of occurrence of the disease is 0.5–1 case per 1 million population. According to statistics, pathology often affects people 40 or 50 years, in 80% of cases are males.

Causes of Whipple’s disease

The pathogen are gram-positive pathogens Tropheryma whippelii ‒ representatives of actinomycetes, possesses three-layered cell wall. Infection is the fecal-oral route in children and manifested short-term gastroenteritis. Was familial cases of disease, but no fact of the transfer of bacteria from person to person not reliably recorded. Some scientists believe that only certain pathogenic strains cause pathological changes.

Tropheryma Whipple detected in the mucosa of the intestines, other organs in the active phase of the disease. However, DNA of the pathogen can be detected in the saliva of patients without clinical signs of disease. There is the assumption that the manifestation of disease directly related to the breach reactions “media invasion”. Pathology is common among persons 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 characterized by accumulation of infiltrates, consisting of macrophages containing Tropheryma whippelii, in various organs. The presence of bacteria in phagocytes suggests that these cells are able to capture the microorganisms, but cannot exercise their lysis. It is caused by disorders of immune response (a reduction in the production of anti-inflammatory cytokine IL-12 and interferon-gamma, decreased lymphocytic response to antigens and the production of T-lymphocytes). As a result, the macrophages with pathogens are deposited in the mucosa of the small intestine and the lymph nodes of the mesentery, causing malabsorbtion diarrhea, and violation of lymphatic drainage.

The accumulation of infiltration in the synovial membranes contributes to the manifestation of arthritis. Further dissemination of the process is lymphokine, which explains the generalization of infection and the defeat of the serous membranes of the heart, eyeball, lungs, and brain. Arise multiple pathological lesions contributing to the progression of the disease and its complications.

Symptoms of Whipple’s disease

The fact of the Multisystem lesions, makes clinical picture of intestinal lipodystrophy are very variable. Two thirds of the patients the disease manifests itself lesions of the joints long before the development of the expanded gastroenterological picture. Have the wandering of polyarthritis or polyarthralgia of the large joints (wrist, knee, sacroiliac, ankle). The duration of attacks from a few hours to 3-4 days. In between attacks there is complete remission. Changing the shape of the joints or destruction is not observed. At the stage of extraintestinal manifestations in approximately half of patients have fever.

In the second stage in 85% of cases there is pain in the abdomen, diarrhoea, flatulence, nausea, vomiting, weight loss and fever. The frequency of bowel movements up to 10 times a day. Develop signs of exhaustion, in severe cases, cachexia. Pain localized in the navel area is paroxysmal in nature. The distinguishing feature of the transition of the disease to the second stage – generalized enlargement of lymph nodes, palpation they are flexible, but painless. In some cases, there is inflammation of various parts of the choroid of the eye (iris, ciliary body, choroidal).

The third stage – systemic lesions characterized by development of neurological symptoms. Suffer Central and peripheral nervous system, develops ataxia, polyneuropathy, decreased hearing and visual acuity. The involvement in the pathological process of the heart is manifested by endocarditis and pericarditis(often the pathology is only detected during echocardiographic study). In 30-50% of patients develop bronchopulmonary disease (bronchitis or exudative pleurisy). Due to the increase of mediastinal lymph nodes and compression of the trachea dyspnea, dry cough and feeling of suffocation.

Complications

Whipple disease – diseases with a chronic course characterized by periods of remissions and relapses. According to the observations, the complications manifest in moments of relapse that occur in the absence of preventive treatment. The main of them are neurological disease, including the progression of dementia, loss of coordination, hydrocephalus, ophthalmoplegia, and supranuclear myoclonia. In the latter case there is a loss of spinal cord or cerebral cortex. This leads to involuntary muscle spasms, tremor, and decreased physical and mental condition of the person.

Diagnosis

Since Whipple’s in the early stages is difficult to diagnose, most patients, the correct diagnosis is established only after several years.

To confirm the infectious origin of the disease and the typical pathological changes are the instrumental and laboratory tests:

• EGD with biopsy. Endoscopy upper gastrointestinal tract reveals edema, hyperemia, stretch and thickening of the folds of the duodenum. The mucosa becomes granular, and its villi become thickened and shortened. Histological study of the biopsy reveals macrophages with undigested pathogens, the study of PCR allows detection of Tropheryma whippelii and a Whipple’s confirm, even if the sample contains only traces of DNA of the pathogen.
• Radiation research. Have secondary importance. X-rays of the small intestine with contrast enhancement allows us to detect mucosal thickening, expansion of the colon and the duodenal flexure. Ultrasound of the mediastinum and abdominal cavity detects an increase in the mediastinal, mesenteric and retroperitoneal lymph nodes.
• Blood tests. For intestinal lipodystrophy characterized by the development of hypochromic anemia, increased ESR, giperlakotsitos, thrombocytosis. In the serum revealed a deficiency of protein, calcium, iron, and cholesterol. Impaired synthesis of albumin.

Variability of clinical manifestations of systemic infection include the mandatory differentiation of intestinal lipodystrophy with enteritis, Crohn’s disease, celiac disease, lymphosarcoma of the small intestine, Hodgkin’s disease, infectious endocarditis, and disorders of connective tissue. In the process of diagnosis is attended by gastroenterologists, infectious disease specialists, oncologists, cardiologists and rheumatologists.

Treatment of Whipple’s disease

In the pre-antibiotic era treatment of intestinal lipodystrophy was considered virtually impossible. Today, for the treatment of the disease shows etiotropic antibiotic therapy for 1-2 years. The choice of specific drugs (cephalosporins, tetracyclines, penicillins, sulfonamides, fluoroquinolones) is determined by the results of the diagnostic tests and current data on resistance Tropheryma whippelii to certain types of antibiotics.

The therapy at equal intervals of time is carried out the PCR analysis and morphological examination of biopsy specimens. In the absence of traces of the pathogen treatment stops. Detection of pathogens in test results after therapy may indicate the relapse of Whipple’s disease (occurs in 40% of cases) and requires further treatment for two years. The complex therapy includes administration of glucocorticoids, cytostatics and inhibitors of TNF (in the presence of arthritis), enzymes, multivitamin complexes. In the presence of pathologies of the CNS, in particular seizures, are shown receiving antiepileptic drugs. In cases of hydrocephalus are shunt operation.

Prognosis and prevention

When you assign their temporary and adequate therapy, the outcome of the disease conditionally favorable. The improvement of patients noted after 1-2 weeks after the start of treatment, but regression of the morphological changes over long and not always complete. In the presence of recurrent re-treatment is shown.

Specific immune prophylaxis of intestinal lipodystrophy are not developed. Preventive measures are to prevent possible recurrence. Patients who underwent Whipple’s must undergo clinical supervision by a gastroenterologist every 3 months and visit the infectious diseases every six months.