Whipple disease
Introduction
Introduction to Whipple's disease Whipple's disease is a rare systemic disease. Its clinical features are intestinal malabsorption, fever, skin pigmentation, anemia, lymphadenopathy, arthritis, joint pain, pleurisy, valvular endocarditis and central nervous system symptoms. In 1907, Whipple reported the disease for the first time and described its clinical features and pathological changes in the small intestine and lymph nodes. He used silver infiltration to stain a large number of rod-shaped microorganisms with a length of about 2 m in a lymph node, and called the disease "small intestinal fat malnutrition", which may be considered a fatty metabolic disease. In 1952, Faul1ey reported an ideal combination of antibiotics and glucocorticoids. basic knowledge The proportion of illness: 0.006%-0.008% Susceptible people: people who are 30 to 50 years old Mode of infection: non-infectious Complications: conjunctivitis keratitis hypotension hyponatremia hyperkalemia hypoglycemia pleural effusion peritonitis ascites
Cause
The cause of Whipple's disease
Bacteria (35%):
It has been confirmed that bacteria are the main cause of disease. In addition to the rod-shaped bacteria (gram-positive bacilli) described by Whipple, there are also coryneform bacteria, bacteroids, streptococci, -streptococci, Haemophilus, and cloths. Bacillus.
Reduced body resistance (30%):
The pathogenic bacteria lurk in the body during the quiescent period. When the body's resistance decreases, the bacteria proliferate and can cause disease. It is currently believed that these microorganisms can cause the body to produce periodic acid-Schiff staining (PAS staining)-positive macrophages, resulting in mechanical obstruction of intestinal villi causing diarrhea, or diarrhea caused by macrophage damage to intestinal mucosal epithelium causing malabsorption. . In some patients with synovial biopsy specimens, there is no PAS-positive substance, which may mean that arthritis is caused by inflammatory mediators released by allergic reactions. From the low blood test of the disease hemagglutinin test and the skin tuberculin test, the host has delayed prolonged allergic reaction and cellular immunity, which leads to protracted bacterial infection, indicating that the delayed reaction is the decisive factor of the disease. factor. From the reduction of some patients: IgG, IgA, the pathogenic effect of humoral immunodeficiency on this disease can not be ignored.
Pathology (20%):
In all cases, the small intestine is involved, and sometimes the colon can be involved. Gross wall thickness and edema were observed by the naked eye. The surface of the mucosa under the microscope was flat or curled, and no fluff or fluff was thickened. The mucosal lamina propria has extensive macrophage infiltration with villus structural deformation. Infiltration of infiltrating macrophages by PAS often reveals a large amount of glycoprotein particles in the cytoplasm. The macrophage positive for PAS staining replaces the normal cellular components of the lamina propria and is a characteristic pathological change of the disease. Mucosal and submucosal lymphatic vessels dilated, a large amount of fat was seen on the slices that were not treated with the fat-dissolving agent, and fat droplets were seen in the interstitial cell space. Under the electron microscope, there are many bacilli in the lamina propria. These bacilli are mostly located around the absorbing epithelial blood vessels, with typical bacterial cell walls and a pale nucleolar structure in the center. The central nucleolus structure is double-cleaved. In macrophages positive for PAS staining, phagocytized bacilli are seen and are in a denatured and disintegrated state. In the heart, lung, liver and spleen, endocrine glands, etc., macrophages positive for PAS staining were observed. Endocardial macrophage infiltration can lead to valvular endocarditis.
Prevention
Whipple disease prevention
1. Eliminate and reduce or avoid the disease factors, improve the living environment, develop good living habits, prevent infection, pay attention to food hygiene, and rational good food distribution.
2. Pay attention to exercise, increase the body's ability to resist disease, do not fatigue, excessive consumption, quit smoking and alcohol.
3. Early detection and early diagnosis and early treatment, establish confidence in the fight against disease, adhere to treatment.
Complication
Hewlett-Packard disease complications Complications Conjunctivitis keratitis hypotension hyponatremia hyperkalemia hypoglycemia pleural effusion peritonitis ascites
The eye and nervous system can be complicated by conjunctivitis, keratitis, uveitis, vitreitis, supranuclear ophthalmoplegia and progressive encephalopathy. The circulatory system can be combined with bacterial endocarditis, when secondary adrenal cortical function occurs. When hypothyroidism, may be associated with hypotension, hyponatremia, hyperkalemia and hypoglycemia, sometimes pleurisy, accompanied by pleural effusion, individual patients may have non-specific peritonitis, hypoproteinemia ascites, Liver, spleen, and swollen lymph nodes.
Symptom
Hewlett-Packard Symptoms Common Symptoms Dyspnea, nausea, low fever, abdominal pain, anorexia, chest pain, gastrointestinal symptoms, diarrhea, constipation, weakness
The ratio of male to female incidence is 4 to 8:1, with more than 30 to 50 years old, and the average age of onset is 39 years. The clinical symptoms are prolonged and intermittent, and a small number of patients can die within a few months. Most people have weight loss, fatigue and fever. The severity of clinical manifestations depends on the organ involved and the length of the disease.
Digestive system
Abdominal pain accounted for 82%, diarrhea accounted for 76%, recessive bleeding accounted for 64%, ascites accounted for 15%, and abdominal mass accounted for 13%. Diarrhea is the patient's complaint. The bowel movement is 5 to 10 times a day. The stool is watery and has a foul odor. It is a steatorrhea containing a lot of foam. There is less blood in the naked eye, which may be related to hypoprothrombinemia caused by secondary malabsorption. Abdominal pain is the most common symptom, the nature of the pain is sputum, and the pain is uncertain. Anorexia is more common than idiopathic steatorrhea and can be accompanied by a sharp weight loss, which can lead to severe cachexia. Severe anorexia. Patients with diarrhea may have vitamin deficiency if they are not corrected in time. Ascites may occur in individual patients, which may be associated with hypoproteinemia, non-specific peritonitis, and is often misdiagnosed as tuberculous peritonitis or cirrhosis ascites. When the mesenteric lymph nodes are enlarged, the mass may be touched on the abdomen, which may be misdiagnosed as a malignant tumor of the abdominal cavity or lymphoma.
Joint
More than 2/3 of the patients have arthritis. Arthritis is characterized by intermittent and migratory, sometimes lasting only 1 to 4 weeks, and both large and small joints can be involved. The affected joints show pain, redness and localized fever. Arthritis episodes are common with polyarthritis, with occasional single joint attacks. The most commonly affected joints are the wrist and knee joints, followed by the metacarpophalangeal joint, the metacarpophalangeal joint, the ankle joint, the spinal joint, the hip joint, the shoulder joint, and the elbow joint. A few patients may develop ankylosing spondylitis, which is characterized by lower back pain or limited spinal motion.
3. Eye and nervous system
There may be conjunctivitis, keratitis, uveitis, vitreitis, supranuclear ophthalmoplegia and progressive encephalopathy. Orientation disorders, memory loss, and various signs of cerebral nerve palsy can also occur. These signs include ophthalmoplegia, nystagmus, and facial paralysis. Mental disorders and behavioral abnormalities can also occur. Wernick encephalopathy can occur in the later stages of the disease, and some patients can experience Alzheimer's dementia years ago. Peripheral neuritis manifests as a paresthesia or allergy to the extremities.
4. Circulatory system
Heart valvular lesions can occur in some patients, and systolic murmurs can be heard in the mitral or aortic valve area. Tricuspid and pulmonary valves can also be affected. When there is fever at the same time, the possibility of combining bacterial endocarditis should be considered. Especially when diastolic murmurs or systolic murmurs are changed, the likelihood of secondary acute or subacute bacterial endocarditis is greater. Some patients may have pericarditis or pericardial effusion.
5. Other
More than half of the patients may have different degrees of fever, chills, mostly intermittent low fever, a small number of patients may be high fever, in the acute phase may be characterized as persistent high fever. There are also reports of myositis and pneumonia. Low blood calcium caused by malabsorption can cause hand and foot spasm, and severe cases may have low blood calcium and can cause purpura caused by coagulation mechanism disorder. Severe diarrhea associated with loss of intestinal protein may result in hypoproteinemia peripheral edema. About half of the patients have swollen lymph nodes. The swollen lymph nodes are hard, non-tender and moveable. Both superficial and deep lymph nodes can be swollen. When secondary adrenal insufficiency occurs, different degrees of hyperpigmentation, hypotension, hyponatremia, hyperkalemia, and hypoglycemia may occur. Sometimes pleurisy can occur with pleural effusion. Skin changes in addition to purpura, occasionally visible glossitis, cheilitis and red desquamation rash. Many patients may have clubbing fingers, which may be related to malnutrition or heart disease. Individual patients may have liver, spleen, and lymph nodes.
Examine
Hewlett-Packard's disease check
1. Blood routine and blood sedimentation
Almost all patients have anemia, can be low hemoglobin or positive pigment anemia, can also be megaloblastic anemia, about 35% of patients with hemoglobin less than 70g / L, an average of 79g / L, 1/3 of patients have Leukocytosis, the majority of patients with increased erythrocyte sedimentation rate.
2. stool examination
Some patients had a positive occult blood test, and the stool was positive for Sudan III due to steatorrhea.
3. Biochemical inspection
Most patients have hypocalcemia, lower cholesterol, and decreased carotene. When there is secondary adrenal insufficiency, 17-hydroxycorticosterone, 17-ketocortisol decreases, blood potassium rises, blood sodium decreases, and most The patient may have hypoalbuminemia.
4. Immunological examination
There may be a decrease in IgG, IgM, IgA, a decrease in the number of E-rosette formation, a decrease in lymphocyte transformation rate, a negative rheumatoid factor, a negative LE cell, and a negative antinuclear antibody.
5. Cerebrospinal fluid examination
When the disease involves the nervous system, the cerebrospinal fluid smear can be stained with PAS. If there is a positive finding, the diagnosis can be confirmed. In addition, Maiwald M et al reported that the cultivation of Whipplelii bacteria in cerebrospinal fluid was successful.
6. Digestive tract barium meal check
Show duodenal and jejunal mucosal folds (plicae circulares), due to enlarged lymph nodes in the posterior abdomen, can cause duodenal fistula enlargement, gastric and ureteral shift, ultrasound, CT and MRI can show abdominal enlargement Lymph nodes and large folds of the intestinal mucosa, CT and MRI can also be used to examine central neuropathy. When the brain is involved, it can show a sparsely occupied area. The chest radiograph sometimes shows mediastinal or hilar lymph node enlargement, pulmonary fibrosis. A small number of patients have consolidation of the lungs and pleural effusion, more common joints, occasional bone erosion, narrowing of the joint cavity, and joint stiffness is rare, sometimes showing ankle arthritis, spondylitis is rare.
7. Endoscopy
Yellow-white small nodules or granules can be seen on the duodenum and jejunum mucosa. The size is 2~3mm, and the mucosal fragility is increased. Similar to Candida albicans infection, these nodules are composed of thick villi filled with macrophages. Duodenal or jejunal mucosal biopsy, if macrophage infiltration with PAS-positive particles is found, a diagnosis can be established.
8. Electron microscopy
Electron microscopy of the biopsy tissue of the patient showed that there were small coryneform bacteria in the macrophage, which were rod-shaped and had three layers of membranes (1~2) m×0.2m, namely Whipplelii, which is the gold standard for diagnosis. Degradation of bacteria in macrophages can also be observed.
Diagnosis
Hewlett-Packard disease diagnosis and identification
diagnosis
In patients with seronegative arthritis and recurrent rheumatism, such as lymphadenopathy, central nervous system symptoms, vitreitis or diarrhea, the disease should be considered, according to the patient's malabsorption syndrome and other organ system involvement. Lymph node, small intestinal mucosal biopsy, and the pathological features of typical PAS-positive macrophages and small intestinal mucosa can confirm the disease.
Differential diagnosis
Blind syndrome
From the point of view of malabsorption syndrome, the disease is easily confused with blind sputum syndrome, but the latter often has a history of abdominal surgery or other intestinal diseases, no joint symptoms and fever, if intestinal gastrointestinal barium examination finds intestinal fistula, adhesion, small intestine Short circuit, etc., will help the identification of this disease.
2. Primary malabsorption syndrome
Compared with the primary malabsorption syndrome, the disease is similar in terms of refractory gastrointestinal symptoms, nutritional deficiencies due to malabsorption, and insufficient vitamins, but the primary malabsorption syndrome has no lymphadenopathy. Arthritis, fever and cardiopulmonary changes, small intestinal mucosal biopsy specimens without HPS positive PAS staining macrophages, gastrointestinal barium meal examination also has significant differences.
3. Lymphoma
When lymphoma manifests as fever, swollen lymph nodes, diarrhea and joint symptoms, it is easy to be confused with Whipple's disease, but the former small intestinal mucosal biopsy specimen has no PAS-positive macrophages, and the gastrointestinal barium meal examination has no X-ray of HP. Performance, it is easy to distinguish the two.
4. Systemic sclerosis
Sometimes the main clinical manifestations of malabsorption, diarrhea, abdominal pain, like Hewlett-Packard disease, but no pigmentation, no response to antibiotic treatment, skin pathological changes are typical features of scleroderma, small intestinal mucosa and lymph node biopsy specimens also have no PAS Staining positive macrophages.
5. Addison's disease
When there is secondary adrenal insufficiency in Whipple's disease, attention should be paid to the differentiation of primary Addison's disease. Although both have pigmentation, hypotension, electrolyte imbalance, the latter have no digestive symptoms, no former. Characteristic pathological changes and small bowel X-ray abnormalities, no arthritis, lymphadenopathy and cardiopulmonary manifestations.
