Pediatric mixed connective tissue disease
Introduction
Introduction to mixed connective tissue disease in children Mixed connective tissue disease (MCTD) is a syndrome characterized by clinical manifestations of connective tissue disease such as systemic lupus erythematosus, polymyositis and systemic sclerosis, but not in line with it. A diagnosis of a disease, and an autoimmune disease of high titer anti-ribonucleoprotein (RNP) antibody in serum. basic knowledge The proportion of illness: 0.004% Susceptible people: children Mode of infection: non-infectious Complications: pericarditis, myocarditis, arrhythmia
Cause
Causes of mixed connective tissue disease in children
(1) Causes of the disease
The cause of MCTD is unknown. The pathogenesis may be related to immune disorders. The evidence is that high titers of anti-RNP antibodies persist in serum, significant polyclonal hypergammaglobulinemia, excessive B lymphocyte activity, inhibitory T cell defects, and active circulating immune complexes In 25% of patients with hypocomplementemia, IgG, IgM, IgA, and complement deposition were found in the vessel wall, muscle fiber membrane, glomerular basement membrane, and skin epidermal and dermal junctions. The relationship between this disease and HLA is under study. Some people think that it has a specific immunogenetic background, which is closely related to HLA-DR4 and -DR5, and considers MCTD as an independent disease.
(two) pathogenesis
The pathogenesis of MCTD is still unclear. The following evidence suggests that its pathogenesis may be related to immune mediated: circulating immune complexes in glomerular deposition, serum anti-RNP antibody positive, extensive infiltration of many lymphocytes and plasma cells, high gamma globulinemia and T cell inhibition. The antigenic site of the anti-RNP antibody is a nuclear RNA protein complex, and low molecular weight small ribonucleic acid proteins (SnRNPs) are involved in nuclear RNA synthesis. In addition to the SnRNPs antibody, MCTD patients also have other antibodies with high molecular weight linked to the nuclear matrix. It has been demonstrated that IgG anti-RNP antibodies are linked to the interior of the cell via Fc receptors, but the pathway by which the immune response is activated remains unclear.
Serum antibodies in SLE patients are different from MCTD, and the abnormal T lymphocyte subsets are also different. An increase in the number of MCTD immune complexes may be associated with impaired immune complex clearance in the reticuloendothelial system.
Genetic factors may be related to MCTD, but MCTD and SLE have different family-borne systems.
Prevention
Prevention of mixed connective tissue disease in children
The cause of death is mainly infection and other complications and adverse reactions of hormone therapy. Very few serious cases can die of renal failure and central nervous system diseases. Therefore, early diagnosis and reasonable and effective treatment of this disease can prevent complications. Extend survival. Early to strengthen warmth, avoid trauma, oral administration of corticosteroids and blood circulation and collaterals, timely to the hospital for treatment. Avoid cold, moist and irritating. In patients with connective tissue disease, in cold and humid environments, joint pain is often aggravated, and Raynaud's phenomenon or impotence in both hands and feet and increased pain are observed.
Complication
Complications of mixed connective tissue disease in children Complications pericarditis myocarditis arrhythmia
The causes of death were pulmonary disease, renal failure, myocarditis, myocardial infarction, heart failure, cerebral embolism, cerebral hemorrhage and generalized vasculitis, and colonic perforation. Children with mixed connective tissue disease are more serious, the central nervous system, heart and kidney are more involved than adults, arthritis is also common, and there may be severe thrombocytopenia. Can occur finger or toe ischemic ulcer or necrosis; a few complicated pleurisy, non-interstitial fibrosis, pulmonary hypertension; can be complicated by pericarditis, myocarditis, arrhythmia, heart valve disease, cardiac insufficiency, etc.; can be complicated by multiple nerves Inflammation, aseptic meningitis, epilepsy, etc. There are still swollen lymph nodes, a few hepatosplenomegaly.
Symptom
Symptoms of mixed connective tissue disease in children Common symptoms Fatigue and kidney damage Joint pain and extremities appear in the cock... Gastrointestinal symptoms Redness and swelling of the back of the hand telangiectasia
Although various connective tissue diseases can occur in children and even in old age, they are more common in adults and less in children. The age of onset ranged from 5 to 80 years old, with an average age of 37 years, and 80% of patients were women. Rheumatic fever, childhood rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, vasculitis, allergic purpura, mucocutaneous lymph node syndrome, infant polyarteritis, dermatomyositis, crust Sick and so on.
Early clinical manifestations
Early symptoms are mild, such as Raynaud's phenomenon, muscle pain, joint pain, fatigue, examination of hyperglobulinemia, suspicious positive antinuclear antibodies, and confirmed as typical performance after several months or years. The phenomenon of Raynaud's phenomenon, edema and thickening of the skin of hands and fingers can be displayed months or years before other manifestations appear. Myasthenia (with or without pain or tenderness) can be diagnosed as myositis. Pleuritis and pericarditis can also be early signs, such as fever, joint pain, and erythematous rash, which can be diagnosed as SLE. Early childhood kidney, heart involvement and thrombocytopenia are more common in adults than in adults. Early stage can also be manifested by pulmonary involvement in dyspnea, and lymphoma is diagnosed as lymphoma.
Main clinical manifestations:
1. Skin lesions:
Almost every MCTD patient has skin involvement. The most common is hand swelling, hand swelling accounted for 66% to 88%, especially the finger is a conical head-shaped sausage, the skin is tight, thickened and accompanied by significant edema, which is caused by increased skin collagen. But without obvious hardening, swelling but wrist, can be combined with telangiectasia. Lupus-like rash includes acute cheek rash; diffuse, non-skin, erythematous lesion; and/or chronic discoid skin lesion; reticular bluish. Other upper eyelids, including ganglion atrophic erythematous dermatomyositis, have purple erythema, disseminated non-scarring alopecia and pigment abnormalities, facial and hand palsy telangiectasia, and telangiectasia around the nail. About 3/4 of the patients have scleroderma-like skin changes.
2. Renault phenomenon:
Up to 90% to 100%, the limbs end up with pale, hair and flushing three-phase reactions, mostly in the upper limbs, bilateral symmetry, but also involving the lower limbs, or both upper and lower limbs, occasionally in the ears, nose, cheeks Department or collar. The child responded significantly to cold water and cold. A small number of severely ill children may develop ischemic ulcers or necrosis of the fingers.
3. Joint lesions:
87% to 100% of patients have significant arthritis and multiple joint pain. The joints are generally free of deformities, sometimes occasionally deformed like rheumatoid arthritis, and a few have joint erosion and deformity. However, it is limited to the hands, wrists or feet and may be accompanied by subcutaneous nodules.
4. Lung performance:
Some patients may have no respiratory symptoms in the clinic, and 70% of asymptomatic patients have abnormal lung function and/or X-ray examination. Can be associated with a small amount of pleural effusion, difficulty breathing, about 2 / 3 patients have pulmonary dysfunction, 1/2 patients with restrictive ventilatory dysfunction, a few pleurisy, non-interstitial fibrosis, pulmonary hypertension. Pulmonary function was measured in 3/4 cases, most commonly with carbon monoxide diffusion dysfunction and reduced vital capacity, restricted breathing, some with exercise dyspnea and pulmonary hypertension, the latter secondary to pulmonary fibrosis or pulmonary arterioles Membrane hyperplasia. X-ray films showed changes in the lung parenchyma of the basal nodules in the base of the lungs.
5. Digestive tract performance:
The digestive tract involvement accounted for 70%. It can be seen that the esophageal dilatation and the 2/3 peristalsis of the distal end of the esophagus are weakened, which may cause cyanosis and difficulty in swallowing after eating. Duodenal enlargement and large intestine diverticulum have been reported to have cystic gas accumulation in the intestine. Intestinal dysfunction causes painful spasm, flatulence, constipation and diarrhea alternation and malabsorption. There are also a wide range of gastrointestinal lesions.
6. Heart performance:
Pediatric heart involvement is more common in adults. Heart disease is about 30% with pericarditis. There are still myocarditis, arrhythmia, cardiac insufficiency, complete conduction block, rhythm disorder and heart failure. There may also be valvular lesions such as mitral valve. Insufficient atresia and stenosis, a case of aortic valve insufficiency has been reported to cause heart failure.
7. Kidney performance:
Kidney involvement is less, about 5% to 25%, renal puncture shows diffuse membranous hyperplasia, diffuse membranous nephritis, focal glomerulonephritis, glomerular vascular cell proliferation, cell infiltration, intimal proliferation And vascular occlusion. Renal damage manifested as proteinuria and hematuria, and 28% of patients had hematuria, proteinuria, tubular urine, severe renal failure and death from progressive renal failure.
8. Neuropathy:
About 10%, the most common trigeminal neuralgia, in addition to polyneuritis, aseptic meningitis, epilepsy, transverse myelitis, cauda equina syndrome, paroxysmal vascular headache and psychosis.
9. Blood system:
Moderate anemia, leukopenia, Coombe-positive hemolytic anemia and thrombocytopenia are rare, severe thrombocytopenia requires splenectomy, and can die from intracranial hemorrhage.
10. Other:
About 30% of cases have hepatosplenomegaly and superficial lymphadenopathy. Severe liver dysfunction is rare. In addition, it can be accompanied by Sjogren's syndrome (7% to 50%) or Hashimoto's thyroiditis (6%).
Examine
Examination of mixed connective tissue disease in children
Peripheral blood
During the activity period, there were moderate anemias, and the total number of white blood cells was different. Most of them increased or normal, especially the systemic type, up to 6 to 70,000/cm 3 , and even leukemia-like reactions. The erythrocyte sedimentation rate increased significantly, the C-reactive protein was mostly positive, the mucin measurement was increased, and the anti-streptolysin "O" was generally not high. Globulin, gamma globulin, and gamma globulin are significantly increased, while albumin is mostly reduced. Serum sarcoplasmic enzymes such as creatine phosphokinase, aldolase, lactate dehydrogenase, and aspartate aminotransferase may be elevated in active patients.
Serum immunology
MCTD is characterized by high concentrations of anti-RNP antibodies (>1:1000) in serum. The anti-RNP antibody has a high detection rate and a high titer in MCTD, and is a characteristic antibody of MCTD. In recent years, anti-RNP antibodies have also been found in SLE and other connective tissue diseases, but the detection rate and titer are low. Almost all MCTDs have serum ANA positive, and serum ANA positive diagnosis MCTD is not specific. The number of T lymphocytes in the blood circulation is reduced, and the function of inhibitory T lymphocytes is decreased. In 90% of cases, circulating immune complexes can be detected, and the concentration is parallel with the disease activity, and the complement reduction is less than 20%. The incidence of HLA-B7, HLA-DW1 and -BW55 is increased. Some scholars have suggested that MCTD patients have no correlation with HLA-A, -B antigen, but the frequency of antigens with -DR4 and -DR5 is significantly increased, reaching 61% and 57%, respectively.
1. Immunoblotting: The 68KD polypeptide antibody has a high positive rate of 78% and has certain characteristics.
2. Immunoprotein electrophoresis showed an increase in IgG, IgA and IgM. Positive for antinuclear antibodies.
3. Immunofluorescence: Direct immunofluorescence from normal non-exposed skin showed that the epidermal cell nucleus showed a spot-type fluorescence pattern, which was IgG deposition; about 30% of cases had immunoglobulin deposition at the dermal epithelial junction, and the vessel wall and muscle fiber IgG, IgM and complement deposition were also observed in the glomerular basement membrane.
4. Rheumatoid latex agglutination test: The positive rate of adult chronic rheumatoid arthritis is higher, up to 80%, while the positive rate of children is lower, about 10-20%. However, rheumatoid factor tests such as systemic lupus erythematosus and scleroderma may also be resistant in other connective tissue diseases. Therefore, the positive person should be combined with the clinical diagnosis, and the negative can not rule out the disease.
Film degree exam:
1. Electrocardiogram examination: ST-T changes can be seen on the electrocardiogram when there is a heart involvement.
2. Esophageal angiography: Visible peristalsis and dilatation of the lower esophagus.
3. Electromyography examination: abnormal electromyogram, muscle biopsy showed focal inflammatory myositis, interstitial and perivascular lymphocytes and plasma cells infiltration, muscle fiber degeneration.
4. X-ray film: sometimes visible small pieces of bone erosion, finger plexus erosion, calcification around the joints, aseptic osteonecrosis of the femoral head. Chest radiographs in 30% of patients showed irregular small patches of shadow.
5. A wrinkle capillary angioscopy common shrub-type capillary abnormalities.
Diagnosis
Diagnosis and diagnosis of mixed connective tissue disease in children
1. Overlapping syndrome refers to the overlap of two or more connective tissue diseases in the same patient at the same time or in succession, and thus is significantly different from MCTD. Although MCTD has multiple overlapping symptoms in clinical practice, it has its own diagnostic criteria and characteristics.
The clinical manifestations of overlap syndrome are two or more rheumatic diseases coexisting in the same period, such as systemic lupus erythematosus and nodular polyarteritis, systemic lupus erythematosus and systemic sclerosis coexist, juvenile rheumatoid arthritis In addition to severe arthritis and subcutaneous nodules, there are also antinuclear antibody positive and vasculitis, which coexists with systemic lupus erythematosus. In addition, systemic sclerosis can also be positive for anti-nuclear antibodies, severe arthritis, leukopenia, hemolytic anemia, and the like.
Overlap syndrome can also occur more than two types of rheumatic diseases, such as dermatomyositis for many years, there are two-finger arthritis, which can be seen as dermatomyositis and rheumatoid arthritis overlap. During the course of systemic lupus erythematosus, typical joint deformities of rheumatoid arthritis occur, which can be diagnosed as an overlap between systemic lupus erythematosus and rheumatoid arthritis.
The treatment of overlap syndrome is more difficult than treating a single disease. The application of the drug should depend on which rheumatic disease is predominant. The main drugs are adrenocortical hormones and immunological preparations. The dosage and usage refer to the relevant rheumatic diseases section.
The prognosis of this syndrome is worse than that of a single rheumatic disease. It also depends on which two diseases overlap. Compared with MCTD, the 5-year survival rate of MCTD was 93%, while the survival rate of overlap syndrome was only 53%.
2. Systemic lupus erythematosus, polymyositis, systemic sclerosis MCTD each have some of the characteristics of the three, but can not explain the performance of MCTD with a single disease.
