Generality
Whipple's disease is an infectious systemic disease, fortunately rare, caused by the bacterium Tropheryma whipplei .
The distinctive element of this condition is the accumulation of lipid and glycoprotein material in the mucosa of the small intestine, in the lymphatic tissues of the mesentery and in the lymph nodes; for this reason, Whipple's disease is also called intestinal lipodystrophy . The exact circumstances favoring the infection are not yet known, but an immunological, acquired or genetic predisposition has been observed.
The clinical picture of Whipple's disease is variable. The effects of the pathology have a greater impact on the mucosa of the small intestine, but other organs are also involved, such as the heart, lungs, eyes and brain. Usually, patients suffering from it experience abdominal pain, fever, weight loss, diarrhea, intestinal malabsorption, skin hyperpigmentation and polyarthritis.
In most cases, the diagnosis is made through a histopathological evaluation of the infected tissues (intestinal mucosa, lymph nodes etc.) after biopsy . For confirmation, culture tests and molecular genetic analyzes, such as the polymerase chain reaction (PCR) may be useful.
Treatment of Whipple's disease is based on the administration of antibiotics to eradicate the bacterium. Once therapy is undertaken, clinical improvement is rapid, with resolution of fever and joint pain in a few days. Intestinal symptoms generally disappear within 1 to 4 weeks, although histological healing may occur after 2 years.
If it is not recognized and correctly diagnosed, Whipple's disease can lead the patient to disability or even death.
What's this
Whipple's disease is a rare chronic systemic pathology . This condition is characterized by the presence of lipid and glycoprotein aggregates in the intestinal mucosa and lymph nodes, from malabsorption, arthralgia, diarrhea, abdominal pain and weight loss.
Whipple's disease mainly affects the small intestine, but it does not spare other sites, such as joints, lungs, heart, spleen, liver, kidneys, skeletal musculature and central nervous system.
Causes
Whipple's disease is caused by a chronic infection, supported by the Gram-positive bacterium Tropheryma whippelii .
The main feature of the clinical picture is the appearance of a large number of macrophages, laden with lipids and glycoprotein, in the mucosa of the small intestine, in the lymphatic tissues of the mesentery and in the lymph nodes. The causes for which this happens are still unknown and, at present, are the subject of scientific study.
What causes Whipple's disease?
Whipple's disease is caused by Tropheryma whippelii (until 2001, called Tropheryma whipplei ). This rod-shaped bacterium is widespread in the environment, but has been found, in particular, in wastewater treatment plants . Tropheryma whippelii is excreted through feces by healthy carriers and people with Whipple's disease.
Conditions that promote infection are not yet known. However, in the etiopathogenesis an acquired and genetic immunological predisposition has been found: in Whipple's disease some defects of some HLA genes and a reduced immune response of the T lymphocytes (in particular, of Th1 type) are implicated.
Who is most at risk?
- Whipple's disease mainly affects men aged 30-60 years. In most cases, Caucasian subjects from Central Europe and North America are those who contract the infection.
- Whipple's disease is a rare systemic disease. In Central European countries, the estimated incidence is less than one case per million per year.
- Whipple's disease is common in workers in sewage treatment plants and farmers in contact with soil and animals, suggesting that the infection is acquired from these sources.
Symptoms and Complications
The symptoms of Whipple's disease are quite heterogeneous, as they vary according to which organs are most affected and the stage of the disease. Some manifestations are more frequent than others, even if they are not necessarily present in all patients; these include: weight loss, polyarthritis, diarrhea, malabsorption, fever and lymphadenopathy. In some cases, cerebral symptoms may be present, such as cognitive dysfunction, ophthalmoplegia and myoclonus.
Whipple's disease: what are the locations involved?
Whipple's disease is a disease in which almost all organs can be invaded by Tropheryma whipplei . The site most affected by Whipple's disease is the mucosa of the small intestine, but other organs are also involved, including the spleen, heart, lungs, liver, kidneys, joints, eyes and central nervous system.
Whipple's disease: how does it manifest?
The most frequent sign of presentation of Whipple's disease is an intestinal malabsorption syndrome .
In general, the first manifestations of the pathology include:
- Fever ;
- Abdominal pain ;
- Poliartralgia (joint pain);
- Arthritis (inflammation of the joints).
Whipple's disease is also characterized by:
- Anemia;
- Changes in skin pigmentation;
- Chronic cough and pleuritic pain.
Subsequently, Whipple's disease manifests itself with symptoms associated with severe intestinal malabsorption, including:
- Loss of appetite;
- steatorrhea;
- Watery diarrhea;
- Progressive weight loss.
Other possible manifestations of Whipple's disease include:
- Peripheral edema;
- Lymphadenopathy (the lymph nodes are enlarged, especially the mesenteric ones);
- Inflammations of the eye;
- Pleurisy;
- Recurrent tenosynovitis.
Sometimes, there are also cardiac symptoms (eg negative endocarditis on culture, cardiac pericarditis and valvulopathy) and neuropsychiatric (cognitive dysfunction, ophthalmoplegia and clonic contractions of facial musculature).
Whipple's disease: course
- If left untreated, Whipple's disease is progressive and leads to death due to decay and / or involvement of the central nervous system.
- With adequate antibiotic therapy, on the other hand, improvement from a clinical point of view is rather rapid.
- After the resolution of the infection, it is possible that recurrences may occur.
Possible complications
- Whipple's disease can give rise to a recently recognized complication called the immune reconstitution inflammatory syndrome ( SIIR ). This occurs in some patients, after starting therapy, due to the resumption of inflammation that no longer responds to antibiotics (note: in most cases, these drugs are effective in eradicating the bacterium). It should be noted that the inflammatory immune reconstitution syndrome is not a recurrence of Whipple's disease, but a complication in its own right.
- Whipple's disease not adequately treated with antibiotics is inexorably progressive and fatal.
Diagnosis
The diagnosis of Whipple's disease is formulated by histological examination after biopsy of a sample of lymph nodes or intestine. The analysis allows the electronic microscope recognition of the bastiform bacterium (phagocytosed or free), as well as identifying other specific alterations, such as the presence - at the level of the lamina propria of the mucosa of the small intestine or of other tissues - of swollen macrophages containing positive PAS granules (highlighted by Schiff's periodic-reactive acid staining).
For definitive confirmation it is possible to support culture tests, genetic tests and specific molecular analyzes, including PCR ( polymerase chain reaction ) on samples of extraintestinal tissue, such as cerebrospinal fluid, lymph nodes or synovial fluid.
Whipple's disease: differential diagnosis
The differential diagnosis of Whipple's disease should be made with diseases that cause a similar clinical picture, including:
- Seronegative polyarthritis;
- Ankylosing spondylitis;
- Endocarditis with negative culture test;
- vasculitis;
- Malabsorption syndrome;
- lymphoma;
- Cerebro-vascular disease;
- Dementia;
- HIV infection;
- Atypical mycobacteriosis;
- Sarcoidosis.
Treatment
Whipple's disease: how is it treated?
Treatment of Whipple's disease involves the use of antibiotics to eradicate the bacterium, initially intravenously, followed by 12 months of oral therapy. The most widely used drugs include tetracycline, chloramphenicol, chlortetracycline, sulfasalazine, ampicillin, penicillin and trimethroprim / sulfamethoxazole.
Currently, the therapy of choice for Whipple's disease results from the combination of trimethoprim + sulfamethoxazole . Another recommended combination, alternatively, is that consisting of cephalosporins or penicillins followed by tetracycline . The treatment protocol is long-term, ie it must be adopted for at least one year, after which it is possible to indicate a maintenance antibiotic therapy .
Antibiotic therapy usually correlates with good results .
Clinical improvement from a clinical point of view is rapid, with resolution of fever and joint pain in a few days. Intestinal symptoms generally disappear within 1 to 4 weeks, although histological healing may occur after 2 years.
Infection recurrences are possible and may occur years later, so a follow-up program must be established with the patient.
