undifferentiated connective tissue disease
Introduction
Introduction to undifferentiated connective tissue disease In recent years, undifferentiated connective tissue disease (UCTD) has gradually been recognized. The disease has clinical manifestations of certain connective tissue diseases, but does not meet the diagnostic criteria for any particular disease. It may belong to an early stage or setback type of diffuse connective tissue disease, and may be an independent disease in some patients. So far, no clinical manifestations and specific laboratory indicators of UCTD have been found. . The diagnosis of UCTD mainly depends on clinical manifestations. Whether this disease is another connective tissue disease still needs further research in the academic community. basic knowledge The proportion of the disease: the incidence rate is about 0.001% -0.003% Susceptible people: no special people Mode of infection: non-infectious Complications: malnutrition, hypertension, vasculitis, renal artery stenosis, pleural effusion, pericardial effusion
Cause
Undifferentiated connective tissue disease etiology
Environmental factors (45%)
In 1998, Lacey et al. studied 205 patients with UCTD and 2095 normal controls. The results showed that 25% (52/205) of the 205 female UCTD patients had a clear history of exposure to chemical solvents, and 2095 controls matched for factors such as ethnic composition, education level, marital economic status, and alcohol and tobacco hobbies. Only 17% (364/2095) have a clear history of chemical solvent exposure. A detailed study of medical history found that chemical agents, beauty products, drugs, rubber products, paints and pigments were significantly associated with the onset of UCTD. Exposure to paint, cleaning agents and turpentine may also be associated with the onset of UCTD. Lacey et al.'s study further suggests that medical implants such as catheters, artificial joints, and metal-fixed stents for orthopedic surgery can also increase the risk of disease. All of the above studies suggest that environmental factors play an important role in the pathogenesis of UCTD.
Genetic factors (35%)
Like most connective tissue diseases, the occurrence of UCTD has a certain genetic basis. Some studies have shown that some patients have a family history of autoimmune diseases. In 1988, Ganczarczyk et al compared 22 HLA subtypes of UCTD patients and 211 SLE patients. The positive rate of HLA-B8 and HLA-DR3 subtypes in UCTD patients was significantly higher than that in normal people. The positive rate of HLA-DR1 subtypes in 7 patients who eventually progressed to SLE was significantly lower than that in normal subjects. It is suggested that the HLA-DR1 subtype may be an anti-UCTD gene.
Pathogenesis
Like most connective tissue diseases, the occurrence of UCTD has a certain genetic basis. Some studies have shown that some patients have a family history of autoimmune diseases. In 1988, Ganczarczzyk compared 22 HLA subtypes of UCTD patients and 211 SLE patients. The positive rate of HLA-B8 and HLA-DR3 subtypes in patients with UCTD was significantly higher than that in normal subjects, and the positive rate of HLA-DR1 subtypes in 7 patients who eventually progressed to SLE was significantly lower than that in normal subjects, similar to SLE patients. The HLA-DR1 subtype may be an anti-UCTD gene.
Recently, Mosca et al. found that UCTD patients had an increased recurrence rate during pregnancy. Of the 22 subjects, 6 (24%) had recurrence or aggravation during pregnancy, compared with only 7% of the patients in the control group. Repeated, therefore, changes in sex hormone levels or imbalance of estrogen and progesterone ratios may be related to the occurrence of this disease.
Prevention
Undifferentiated connective tissue disease prevention
1. Remove the inducement of the disease, pay attention to hygiene, strengthen physical exercise to improve immunity and prevent infection.
2. Early diagnosis and early treatment, do not give up treatment easily when the disease is relieved.
3. It is very important to maintain a good attitude, to maintain a good mood, to have an optimistic, open-minded spirit, and to be confident in the fight against disease. Don't be afraid, only in this way can you mobilize your subjective initiative and improve your body's immune function.
4. Appropriate nutrient supply, under today's living conditions, it is not appropriate to emphasize too much high sugar, high protein, high vitamin and low fat diet. However, the nutrition should be balanced, and the vegetarian diet should be accompanied by vegetables, fruits, meat, egg milk, etc. The intake is determined by the fatness of the person.
Complication
Undifferentiated connective tissue disease complications Complications, malnutrition, vasculitis, renal artery stenosis, pleural effusion, pericardial effusion
1. Renault phenomenon may occur frequently in patients with local soft tissue atrophy, necrosis and other malnutrition. In severe cases, limb bone resorption occurs. About 5% of patients may have hypertension, and important organ vasculitis such as heart vessels may also appear. Inflammation, renal artery stenosis, arteriovenous embolism, etc.
2. Pleural effusion, pericardial effusion or both concurrently.
3. Individual cases have a significant tendency to bleed and even cause death.
Symptom
Symptoms of undifferentiated connective tissue disease Common symptoms Kidney damage Protein urinary light allergy Low heat bleeding tendency Myalgia Pulmonary interstitial fibrosis Lymph node enlargement Lung texture thickening illusion
The disease often conceals onset, the average time from clinical symptoms to treatment is 2 to 3 years, an average of 38 months, the patient's clinical manifestations are often mild, fatigue, hypothermia, lymphadenopathy and other non-specific symptoms are common, some Large-scale clinical investigations have found that the most common symptoms are joint swelling and pain, Raynaud's phenomenon and skin mucosal damage, while important organs such as the kidney and central nervous system are rare. Table 1 summarizes the major UCTD studies to date. Common clinical manifestations and laboratory abnormalities in patients.
During the follow-up period, the clinical symptoms of the patients may fluctuate with the course of the disease and treatment, and tend to gradually relieve the trend, but overall the disease activity does not change much.
Skin mucosal lesion
Skin lesions are quite common, and the rash type is diverse. Some patients have a rash as the first symptom.
Discoid erythema is more common in patients with SLE, and occurs in about 34% of patients. It can be found in all ethnic groups. The incidence is higher in black patients, which is higher than the red color of the exposed parts of the body. The pimples are most common in the head and neck. The size of the rash varies, and the shape is different. There are many scales on the surface. The scar is often left after healing, and the local skin shrinks.
The incidence of erythema in the ankle is about 10%. It is a red maculopapular rash on the cheek. It can be a typical butterfly-like distribution, or it can be irregularly shaped. After the improvement, there is no scar.
The incidence of photoallergies is between 13% and 24%. About 18% of patients have dry mouth and dry eyes. The incidence of mucosal ulcers is lower than that of SLE, ranging from 3% to 13%. The hands are diffuse and subcutaneous. There are also reports in the festival.
2. Joint and muscle lesions
This lesion is more common, about 37% to 80% of patients may have joint pain or arthritis, the average incidence rate is 55%, and the average incidence of arthritis is 42%, mostly non-invasive polyarthritis. Few joint deformity deformities can occur, involving the joints of all sizes, including interphalangeal joints, metatarsophalangeal joints, mandibular joints, etc., but it is more common with arthritis, which may be associated with morning stiffness, but most of the time is shorter. Synovial fluid examination showed more inflammatory exudate, the number of cells was small, the protein content was yellow when the protein content was high, and the bacterial culture was negative.
Muscle involvement is more common, mostly manifested as myalgia and muscle weakness in the proximal muscles of the extremities. Individual reports may even have mild to moderate elevation of muscle enzymes, but no abnormal or mild myogenic damage to the EMG, no significant muscle biopsy. Abnormal, does not meet the diagnostic criteria for myositis or other connective tissue diseases.
3. Vasculitis
The Raynaud's phenomenon is one of the most common clinical manifestations of UCTD. It is found in about 50% of patients and may persist as the only clinical symptom for many years. It is characterized by pale puberty, bruising and flushing, with local pain or numbness. There are incentives such as cold or emotional agitation, and gradually relieve after a few minutes or tens of minutes. Small arteriospasm is the pathological basis. Long-term frequent authors may have local soft tissue atrophy, necrosis and other malnutrition, and severe bone resorption.
In addition, about 5% of patients may have hypertension, imaging examination of local vascular wall hyperplasia or stenosis, important organ vasculitis such as cardiac vasculitis, renal artery stenosis, arteriovenous embolism and other rare.
4. Lung and heart disease
Serositis is the most common, but the incidence is slightly lower than SLE, about 11%, can be expressed as pleural effusion, pericardial effusion or both, the severity of the disease varies, mild cases can have no obvious clinical manifestations, serious Cardiac tamponade may even occur, and serous puncture examination often indicates leakage, and antinuclear antibodies may be positive.
Other lung manifestations include pulmonary interstitial fibrosis and interstitial pneumonia. Rarely manifested as endogenous lipid pneumonia, pulmonary interstitial fibrosis and multiple onset of disease, manifested as progressive dyspnea, X-ray examination showed lung The texture is thickened, disordered, the lung function prompts the diffusion function, the motor function of the lungs and the chest high-resolution CT are sensitive, which can assist early diagnosis.
Heart disease can affect the whole heart layer, including pericarditis, myocarditis and endocarditis, clinical chest tightness, palpitations, dyspnea and other symptoms, ECG can have a variety of arrhythmia and ST-T changes.
5. Blood system lesions
About 20% of patients have this lesion, which can be expressed as white blood cells, thrombocytopenia and anemia. The majority of white blood cells are moderately reduced, and some patients have thrombocytopenia, which can be quite serious. Individual cases have obvious bleeding tendency and even death. Hemolysis anemia is rare, mostly chronic anemia and iron deficiency anemia, and complete blood cell reduction is also visible.
6. Kidney damage
The incidence of renal damage is about 11%. It is rare in patients with discoid erythema and ANA negative. The clinical manifestations may include edema, hypertension, proteinuria, hematuria and serum creatinine levels, but rarely cause severe renal function. Not complete.
7. Other
Neurological damage is rare, and can be manifested as migraine symptoms such as migraine, convulsions, behavioral abnormalities and hallucinations, as well as organic nervous system diseases such as peripheral neuritis, headache, hemianopia, sensory and activity disorders.
Other rare manifestations such as abnormal thyroid function have also been reported.
Examine
Examination of undifferentiated connective tissue disease
UCTD patients may have multiple laboratory abnormalities, but for each individual, most UCTD patients have only one of two test abnormalities, and the autoantibody profile is relatively simple.
Hematological examination shows leukopenia, thrombocytopenia or anemia, hemolytic anemia may be positive for Coombs test, partial thromboplastin time prolonged in patients with autoimmune thrombocytopenia, proteinuria, hematuria, etc. may appear in urine, and blood cell sedimentation rate may be accelerated. And -globulin increased, some patients have elevated transaminase, often suggesting autoimmune liver damage.
The ANA positive in serological examination is the most common, the positive rate is 55%100%, the average is about 58%, the fluorescent karyotype is the most common type, the homogenous type and the perinuclear type are rare, and the titer and SLE are rare. similar.
A small number of patients may have rheumatoid factor, anti-RNP antibody, anti-SSA or SSB antibody positive, anti-RNP antibody is often associated with Raynaud's phenomenon and arthritis, while anti-SSA antibody positive patients are often accompanied by dry mouth, anti-dsDNA antibody positive, The anti-Sm antibody was positive, the false positive and the complement reduction in the syphilis serum test were rare, and the results of the self-antibody spectrum of the UCTD patients are shown in Table 2.
In other auxiliary examinations, B-ultra-visible liver and spleen, lymphadenopathy, B-ultrasound and X-ray examination may also find pericardial or pleural effusion, abnormal lung function is rare.
Diagnosis
Diagnosis and differentiation of undifferentiated connective tissue disease
diagnosis
There is no unified UCTD diagnostic standard. Table 3 lists the names and diagnostic conditions of UCTD reported in recent years for reference in clinical and research work. According to foreign reports and analysis of 70 patients with UCTD in Peking University People's Hospital, UCTD The diagnosis should have more than one typical symptom or sign of rheumatism with more than one high titer autoantibody, with a course of more than two years, with the exception of any other CTD.
Analysis of limited cases in foreign countries and our hospital suggests that the clinical characteristics of UCTD are met, but patients with shorter course may have typical clinical manifestations or laboratory abnormalities of other CTD within a certain period of time. Patients with Raynaud's phenomenon and ANA positive may be present. In a year or two, even in the years after the diagnosis of UCTD, typical systemic lupus erythematosus or scleroderma appears. Such cases are not uncommon. Therefore, patients with a disease duration of less than two years should not easily diagnose the disease, even if the disease lasts longer. Patients with well-diagnosed cases should also be followed closely, paying attention to the possibility of developing other CTDs.
For patients with diffuse CTD disease with early use of immunosuppressive agents and glucocorticoids, due to partial control of the disease, clinical manifestations and laboratory abnormalities of other CTD may not be exhibited, and the diagnostic conditions of UCTD are met, and the condition of this treatment is "Frustration" itself is a reflection of effective treatment, but it is easy to ignore further examination and regular treatment of patients. Therefore, clinically, such patients should still be subjected to more systematic laboratory tests, such as those with suspected dermatomyositis. Muscle biopsy, suspected anti-nuclear antibodies in SLE, anti-ds-DNA antibody detection, etc., in order to correctly diagnose and promptly give regular treatment.
Differential diagnosis
Clinically, attention should be paid to distinguish undifferentiated connective tissue disease from overlap syndrome and mixed connective tissue disease (MCTD). Overlap syndrome refers to the clinical manifestations of two connective tissue diseases at the same time or in succession, and meets their respective Diagnostic criteria, mixed connective tissue disease has internationally recognized diagnostic criteria, may have clinical symptoms such as systemic lupus erythematosus, polymyositis or progressive systemic sclerosis, but does not meet its diagnostic criteria, and with Renault Phenomenon, swelling of the hands, lung involvement and high titers of nRNP antibodies are characteristic.
