sicca syndrome
Overview of diseases
Sjogren's syndrome (Sjogren's syndrome) is an autoimmune disease, characterized by dry mouth and dry eyes, which can involve many systems such as kidney, lung, nervous system and digestive system, and cause systemic organ involvement. It is characterized by muscle weakness, body aches, dry cough, chest tightness, epilepsy, flaccid paralysis, unexplained hepatitis, liver cirrhosis, chronic diarrhea and so on. Sjogren's syndrome is common in postmenopausal women or women aged 30-40, and the incidence rate is about 0.3-0.4%, which is as high as 0.77% in the elderly population. However, due to the variety of clinical manifestations, it is easy to be ignored or misdiagnosed. If people have the following symptoms, it may be a signal of Sjogren's syndrome, so they should go to the rheumatology immunology department in time.
Sjogren's syndrome (SS) is a chronic systemic inflammatory disease with unknown etiology. It is characterized by dry mucous membranes such as mouth and eyes, and is often accompanied by rheumatism (such as RA, scleroderma and SLE) with some autoimmune characteristics. Lymphocyte infiltration can be seen in the affected tissues. The incidence of Sjogren's syndrome is as high as 0.4-0.7%, and it can be as high as 3-4% in the elderly, especially middle-aged and elderly women. If the disease has systemic damage, if it is not treated properly, it can make the internal environment disorder and cause serious consequences.
1. Dry mouth and nose, difficulty swallowing steamed bread and other foods, dry tongue surface, ulcer or smooth as a mirror.
2. Dry eyes, less tears, foreign body sensation, repeated purulent infection of eyelids, and even decreased vision.
3. Multiple uncontrollable dental caries, black teeth and small pieces falling off.
4. Repeated swelling and pain of parotid gland and submandibular gland.
5. General weakness, low fever, muscle joint pain and myasthenia.
6. Vagina, dry skin, itching, purpura-like rash, erythema nodosum.
This disease is an autoimmune disease with a good prognosis, and only a few patients are at risk of lymphoma. Most patients with visceral injury can be relieved by proper treatment. Early detection and correct treatment can prevent the damage of dry mouth, dry eyes and long-term dryness to kidneys, lungs, liver and other organs.
Disease classification
Department of endocrinology, department of rheumatology and immunology
Disease description
Sjogren's syndrome (SS) is a systemic connective tissue disease that mainly invades exocrine glands. Dry mouth and dry eyes are the common manifestations. It can be divided into primary and secondary. The former has dry mouth and dry eyes, and there are many other system damages. The latter coexists with another definite connective tissue disease, the most common is rheumatoid arthritis, followed by systemic lupus erythematosus, and the latter coexists with another definite connective tissue disease. Domestic surveys have confirmed that the prevalence of rheumatism in the population is 0.29%-0.77%, and the prevalence of rheumatism in western countries ranks second, with women accounting for more than 90%, mostly after middle age.
Symptoms and signs
Slow onset, fatigue, and even fever.
1, dry mouth, dry mouth, drinking, serious people have difficulty eating dry food. Because of saliva theory, it is easy to have dental caries, and 63% of patients with primary SS have dental caries. 40% of patients have swollen salivary glands, and the surface is symmetrical, smooth and not hard. Glandular enlargement can persist and recur, and there are few secondary infections. If the glands are hard and nodular, be alert to malignant transformation.
2. Patients with dry eye have foreign body sensation or no tears, and the lacrimal gland is generally not swollen or slightly swollen.
3, skin mucous membrane skin dry, itching, common rash is purpura, but also urticaria-like rash, showing polymorphic, nodular erythema. I have chapped lips, oral ulcer, dry nasal cavity and vaginal mucosa.
4.70%-80% of joints and muscles have joint pain, even arthritis, but destructive arthritis is rare. Muscle weakness may occur, and myositis may occur in 5%.
5. Nearly half of the kidneys are complicated with renal damage, and the most common site involved is the distal renal tubule. The clinical manifestation is symptomatic or subclinical renal tubular acidosis. The former shows that the blood pH value is low and the urine cannot be acidified (pH > 6). Amine chloride load test can detect subclinical type. Complications of renal tubular acidosis: (1) periodic hypokalemic paralysis; (2) Renal chondrosis; (3) Renal urine collapse and proximal tubular involvement are manifested as amino acid urine, phosphourine, glycosuria and β 2 microsphere proteinuria. Glomerular involvement is rare, but the prognosis is poor.
6. 17% lung patients have dry cough, but there is no recurrent lung infection. There are too many inflammatory cells in bronchoalveolar lavage fluid in 50% patients, which indicates alveolar inflammation, and only a few patients have diffuse pulmonary interstitial fibrosis. Pulmonary function tests often show decreased function, but most of them have no clinical symptoms.
7, digestive system (1) atrophic gastritis, low gastric acid secretion function, gastric acid deficiency; (2) intestinal malabsorption; (3) The exocrine function of pancreas is low; (4) Hepatomegaly, elevated serum transaminase, and liver biopsy in patients with jaundice often showed chronic active hepatitis changes, and such patients responded well to adrenocortical hormone.
8. Due to vasculitis in different parts, the central nervous system is damaged to varying degrees. Symptoms include epilepsy, hemiplegia, hemianopia, myelitis, cranial neuritis and peripheral neuritis. The latter mainly involves sensory fibers.
9. The hemogram showed leukopenia and thrombocytopenia from 1/4 to 1/5, with only a small amount of bleeding.
10, lymphoproliferative 5%- 10% patients have lymphadenopathy. At least 50% patients have a large number of lymphocytes infiltration in internal organs during the course of the disease. More importantly, the incidence of lymphoma in patients with this disease is 44 times higher than that in normal people. During the follow-up of 50 SS cases in China/KLOC-0, 2 cases developed lymphoma. SS before lymphoma may have macroglobulinemia or monoglobulinemia. After lymphoma occurs, the level of blood immune protein can be reduced and autoantibodies disappear.
The cause of the disease
1. Heredity and sex HLA is related to SS. For example, in Europe and America, the frequency of DR3 and DR2 in SS patients is higher than that in normal people, and the frequency of DQA 1/DQB 1 in SS patients with anti-SSA and anti-SSB antibodies is higher. The high incidence of female indicates that the disease is related to sex hormones.
2. Virus
(1) Epstein-Barr virus Primary Epstein-Barr virus infection often invaded parotid gland, but SS did not occur at that time. However, Epstein-Barr virus can be cultured in parotid fluid of 50% SS patients (20% normal people). The increase of EB virus DNA in parotid gland indicates that the virus is activated, but this phenomenon also exists in other immune diseases, not unique to SS disease. Therefore, EB virus is not the direct cause of SSD, but as a polyclonal B cell activator, which may continue or aggravate the immune disorder of SS patients.
(2) HIV- 1 virus HIV- 1 infection can produce dry mouth and dry eyes, but it is different from SS in that the parotid gland is highly swollen, CD8 ++ but not CD4 ++ lymphocytes invade tissues, and the frequency of autoantibodies (RF, anti-SS-A antibody, anti-SS-B antibody and antinuclear antibody) does not increase, which is different from HLA.
(3) HTLV- 1 (human T lymphocyte virus) infection can lead to dry mouth, dry eyes and adult T lymphocyte leukemia.
3. A large number of lymphocytes infiltrated in the lobule of salivary gland in patients with immune abnormality, mainly CD4+T cells with DR antigen positive, and B cells accounted for 5%- 10%. T cells in glands produce IL-2, IL- 10 and IFN-γ, while B cells produce rheumatoid factor and immunoglobulin. Gland epithelial cells have strong HLA-II antigen body performance (which is not the case under normal circumstances), and secrete IL- 1 and IL-6. These phenomena indicate that there is a positive immune response in the gland and participate in the mechanism of tissue injury.
Etiological classification
Autoimmunity: A variety of autoantibodies such as antinuclear antibody, rheumatoid factor, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody and hyperglobulinemia were detected in patients with Sjogren's syndrome, which reflected the hyperactivity of B lymphocytes and the low inhibition of T lymphocytes. In addition, the change of T lymphocyte subsets in this disease, that is, the decrease of inhibitory T cells, reflects the abnormality of cellular immunity; Genetic basis: In the research and determination of immunogenetics, medical scientists found that HLA-DR3 and B8 in human leukocyte antigens are closely related to Sjogren's syndrome, and this correlation varies with different races, such as Western Europeans are related to HLA-B8, DR3 and DW52, and Japanese are related to HLA-DR53, indicating that Sjogren's syndrome has a genetic tendency; Virus infection: At present, it is believed that at least three viruses, such as EB virus, cytomegalovirus and HIV virus, are related to Sjogren's syndrome. Epstein-Barr virus can stimulate the proliferation of B cells and produce immunoglobulin. Some medical scientists have detected EB virus and its DNA gene in salivary gland, lacrimal gland and kidney samples of patients with primary Sjogren's syndrome.
physiopathology
Its etiology and pathogenesis are still unclear.
1. Heredity and sex HLA is related to SS. For example, in Europe and America, the frequency of DR3 and DR2 in SS patients is higher than that in normal people, and the frequency of DQA 1/DQB 1 in SS patients with anti-SSA and anti-SSB antibodies is higher. The high incidence of female indicates that the disease is related to sex hormones.
2. Virus
(1) Epstein-Barr virus Primary Epstein-Barr virus infection often invaded parotid gland, but SS did not occur at that time. However, Epstein-Barr virus can be cultured in parotid fluid of 50% SS patients (20% normal people). The increase of EB virus DNA in parotid gland indicates that the virus is activated, but this phenomenon also exists in other immune diseases, not unique to SS disease. Therefore, EB virus is not the direct cause of SSD, but as a polyclonal B cell activator, which may continue or aggravate the immune disorder of SS patients.
(2) HIV- 1 virus HIV- 1 infection can produce dry mouth and dry eyes, but it is different from SS in that the parotid gland is highly swollen, CD8 ++ but not CD4 ++ lymphocytes invade tissues, and the frequency of autoantibodies (RF, anti-SS-A antibody, anti-SS-B antibody and antinuclear antibody) does not increase, which is different from HLA.
(3) HTLV- 1 (human T lymphocyte virus) infection can lead to dry mouth, dry eyes and adult T lymphocyte leukemia.
3. A large number of lymphocytes infiltrated in the lobule of salivary gland in patients with immune abnormality, mainly CD4+T cells with DR antigen positive, and B cells accounted for 5%- 10%. T cells in glands produce IL-2, IL- 10 and IFN-γ, while B cells produce rheumatoid factor and immunoglobulin. Gland epithelial cells have strong HLA-II antigen body performance (which is not the case under normal circumstances), and secrete IL- 1 and IL-6. These phenomena indicate that there is a positive immune response in the gland and participate in the mechanism of tissue injury.
Diagnostic examination
1. Check
Routine blood, urine and stool examination, renal tubular acidification function examination, erythrocyte sedimentation rate, rheumatoid factor, antinuclear antibody, immunoglobulin, cryoglobulin and liver and kidney function determination, especially anti-SS-A(Ro) and SS-B(La) antibodies, were positive.
2. X-ray film, brain CT and magnetic resonance imaging of chest and affected joints.
B-ultrasound examination of kidney and abdomen and upper gastrointestinal endoscopy were performed when necessary.
3. Other inspections
Saliva velocity measurement, parotid radiography, lacrimal gland filter paper test and corneal staining. Biopsy of oral mucosa, lymph nodes, liver and kidney was performed when necessary.
4. Diagnostic criteria
(1) Diagnostic criteria of Sjogren's syndrome: There are at least two abnormalities in the following tests: ① Decreased flow rate of unstimulated saliva; ② The labial adenitis contains 1 or more focal lymphocyte infiltration; ③ Abnormal isotope contrast of salivary gland.
(2) Diagnostic criteria of keratoconjunctivitis sicca: ① Filter paper test, wet length ≤10 mm within 5 minutes; ② tear film rupture time < <10s; ; ③ Corneal staining spots > 10.
(3) Anti-SS-A(Ro) and SS-B(La) antibodies were positive. With the above three or two items, the diagnosis can be made, and other connective tissue diseases and lymphoma can be ruled out.
diagnostic criteria
1, dry keratitis
2, dry mouth disease
3. One of the following antibodies in serum is positive: anti-SS-A, anti-SS-B, ANA> 1:20, RF > 1: 20. Those who have the above three antibodies and exclude other diseases can be diagnosed.
Traditional therapy
At present, there is no specific medicine in western medicine, and 0.5% methyl cellulose can be used to improve symptoms. Corticosteroids (hormones), immunosuppressants, plasma exchange and other methods should be used when there is no systemic damage or other autoimmune diseases.
therapeutic regimen
1. Carry out routine nursing according to general nursing of internal medicine.
2. Quit smoking and drinking, and avoid using anticholinergic drugs.
3. Keep your mouth clean and rinse your mouth frequently.
4. Drop artificial tears into eyes and protect cornea with eye ointment before going to bed.
5. Nasal Ping Shu 48 mg/d, taken three times.
6. Potassium supplementation is suitable for patients with renal tubular acidosis and hypokalemic paralysis. According to the blood potassium, 6 ~ 9g of potassium chloride can be infused intravenously every day, and citric acid mixture containing potassium can be taken after it is stable.
7. Glucocorticoid is suitable for patients with nervous system, glomerulonephritis, interstitial pneumonia, liver injury, cytopenia and myositis. Prednisone1.0 mg/(kg d) gradually decreased after the symptoms were relieved.
8. Immunosuppressants such as cyclophosphamide1~ 2.5 mg/(kg d), oral or intravenous, azathioprine1~ 2 mg/(kg d), oral. During taking the medicine, check the blood routine twice a week and ask the patient to drink more water.
9. Combined chemotherapy is suitable for lymphoma patients.
Safety tips
Sjogren's syndrome is a chronic inflammatory autoimmune disease that mainly invades saliva and lacrimal gland. It is important to pay attention to details in daily life.
1. Keep a good mood, follow the doctor's advice and check regularly.
2. Diet: Eat more foods that nourish yin, clear away heat and promote fluid production, including loofah, celery, day lily, lotus root and yam. And avoid spicy, fried, salty and sour food. In general, nutrition should not be restricted too strictly.
3. Drugs that should be avoided as much as possible: Drugs that can reduce the secretion of exocrine glands and cause dry mouth include:
(1) anticholinergic drugs;
(2) Antihypertensive drugs: α -blockers (clonidine) and β -blockers (propranolol);
(3) diuretics;
(4) Antidepressants: amitriptyline, noramitriptyline, etc.
(5) Muscular spasm drugs: Aminobenzene heptene, Meso Ba Maw;
(6) Urological drugs: uracil and hydroxyDing Ning;
(7) Parkinson's drug therapy: carbidopa, levodopa;
(8) decongestants: chlorpheniramine, levoephedrine, etc.
4. Pay attention to oral hygiene: people with dry mouth, little saliva, dental caries and cracked tongue should pay attention to oral hygiene to prevent oral bacteria from multiplying, and those with dental caries should be repaired in time. Brush your teeth at least twice every morning and evening. It is recommended to choose a soft toothbrush and rinse your mouth after meals.
5. Avoid alcohol and tobacco and reduce the stimulation of physical factors. On weekdays, Ophiopogon japonicus, Adenophora adenophora, Glycyrrhiza uralensis and other traditional Chinese medicines are used to soak in water instead of making tea to keep the mouth moist.
6. Protect your eyes: Less tears make your eyes dry and your defense function decline, which can cause eye diseases such as corneal injury, bacterial infection and decreased vision. Care should be taken to prevent dry eyes. Artificial tears can be applied to the eyes, but the action time is short; In severe cases, cortisone eye drops can quickly relieve symptoms, but it is easy to relapse after stopping taking drugs, so it can not be used for a long time to avoid corneal thinning and perforation. People with eye irritation should use 2% acetylcysteine eye drops 3-4 times a day. In addition, 1% cyclosporine eye drops, 2-3 times a day, can significantly increase tear secretion.