Adult Still's disease
Introduction
Introduction to Adult Still's Disease Still's disease is a seronegative polyarthritis that is a type of juvenile rheumatoid arthritis. It was first reported by Steele (1897), whose clinical features include long-term irregular fever, accompanied by liver, spleen, lymphadenopathy, anemia, leukocytosis, multiple large, medium and small arthritis, and muscle lesions. The disease is different in clinical manifestations and pathology from adult rheumatoid arthritis. Its systemic symptoms are more prominent, rheumatoid factor is mostly negative, and is associated with HLA-B27. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific people Mode of infection: non-infectious Complications: atelectasis, adult respiratory distress syndrome, peptic ulcer
Cause
Cause of adult Still's disease
Infection (30%):
Most patients have a history of upper respiratory tract infection before onset. There are pharyngitis and gingivitis on the onset of the disease. The serum anti-O is elevated in the laboratory test. Some patients have staphylococcal growth in the pharyngeal test, and the disease is relieved after the preparation of the self-vaccination. Still's disease is associated with streptococcal infection. In addition, antibodies against Yersinia, anti-Rubella virus antibodies and anti-mumps virus antibodies are found in the serum of some patients, and staphylococcal A immune complexes are present in some patients. Therefore, some people think that the incidence of adult Steel's disease has a certain relationship with infection, but in addition to the culture of the pharyngeal test, bacteria and viruses have never been isolated in other diseased tissues, so the role of infection in the pathogenesis cannot be determined.
Genetic factors (30%):
Adult Still's disease has been reported to be associated with class I and class II antigens in human leukocyte antigens, including HLAB8, Bw35, B44, DR4, DR5 and DR7, suggesting that the disease is genetically related.
Immune abnormality (25%):
Some studies have suggested that immune abnormalities are associated with this disease. Adult patients with Still's disease have abnormal cellular and humoral immunity, and 1 patient has tumor necrosis factor, interleukin-1, interleukin-2, and interleukin-2 receptor. And elevated levels of interleukin-6, decreased 2T helper cells, increased T suppressor cells, and decreased total number of T lymphocytes. T cell receptor- phenotype-positive T lymphocytes (TCR-gamma delta T cells) Increased and closely related to serum ferritin and C-reactive protein, T cell receptor- phenotype-positive T lymphocytes is a newly discovered T cell subset with the function of secreting various cytokines and Cytotoxic activity, some autoantibodies exist in some patients, such as anti-histone antibodies and anti-cardiolipin antibodies, and some patients have anti-erythrocyte antibodies and anti-platelet antibodies, 4 serum total complement, C3 and C4 Decreased, 5 circulating immune complexes are elevated, serum immunoglobulin is elevated, and hyperglobulinemia occurs during disease activity. Pregnancy and estrogen use may induce the disease. use.
The above studies suggest that adult Still's disease may be due to the excessive immune response of susceptible individuals to certain foreign antigens such as viral or bacterial infections, resulting in abnormal cellular and humoral immune regulation, resulting in fever rash, joint pain and elevated peripheral blood cells. A series of inflammatory clinical manifestations.
Pathogenesis
The pathogenesis of this disease is still unclear. There is no specific pathological change in this disease. The synovial membrane is characterized by non-specific synovitis, mild to moderate hyperplasia of synovial cells, vascular congestion, lymphocyte and plasma cell infiltration with follicular formation. The synovial lining cells were positive for IgG, IgM and rheumatoid factor, and the lymph nodes were non-specific inflammation. Some lymph nodes showed T-cell tumor-like immunogenic hyperplasia, sometimes with lymph node necrosis, and the skin showed skin collagen fiber edema around the blood vessels. Inflammatory cells infiltrate, muscles show muscle edema and non-specific inflammation, liver shows hepatocyte degeneration, necrosis, inflammatory cell infiltration in portal and portal areas, cardiac manifestations of interstitial myocarditis, cellulose exudative pericarditis and heart valves Inflammatory lesions, renal biopsy showed thickening of the glomerular basement membrane, tubular atrophy and interstitial cell infiltration.
Prevention
Adult Still's disease prevention
1. Pay attention to exercise, increase the body's ability to resist disease, do not fatigue, excessive consumption, quit smoking and alcohol.
2. Early detection and early diagnosis and early treatment, establish confidence in the fight against disease, adhere to treatment.
Complication
Adult Still's disease complications Complications, atelectasis, adult respiratory distress syndrome, peptic ulcer
Atelectasis, pulmonary hemorrhage, interstitial pneumonia and amyloidosis, or adult respiratory distress syndrome, as well as individual patients with peptic ulcer, appendicitis or pancreatitis.
Symptom
Symptoms of adult Still's disease Common symptoms Hepatosplenomegaly, sore throat, relaxation, heat, irregular heat, high fever, heat, chills, lymph node enlargement, thrombocytosis
The clinical manifestations of this disease are complex and diverse, often involving multiple systems, manifested as fever, rash, joint pain, followed by sore throat, swollen lymph nodes, liver, splenomegaly and serositis, etc., the performance and frequency of this disease.
1. Fever: fever is one of the important manifestations of this disease. It is almost seen in all patients, usually sudden high fever, one peak per day, and occasionally two peaks a day, mainly high fever, body temperature more than 39 ° C, usually in the afternoon Or reach the peak in the evening, after the body temperature lasts for 3 to 4 hours, there is no need to deal with self-sweating. In the morning, the body temperature drops to normal. Some patients start to have moderate to low heat. After 2 to 4 weeks, the patient has high fever. Some patients have irregular body temperature. High fever can occur at the time. The heat type is more common with relaxation heat. Others have irregular heat and heat retention. About half of the patients have chills before fever, but chills are rare. The heat course lasts for several days to several years. The rash, sore throat, muscle and joint pain symptoms worsen after fever, the rash can retreat after heat retreat, the above symptoms can be alleviated, although most patients have long-term fever, but the general condition is good, no obvious symptoms of poisoning.
2. Skin rash: The rash is another major manifestation of this disease. More than 85% of patients have a transient rash in the course of the disease. It is characterized by diffuse congestive red maculopapular rash, sometimes with mild itching, usually distributed in the neck. The department, the trunk and the extremities of the extremities can also appear in the palms and ankles. The shape of the rash is variable. Some patients may also have hives, nodular erythema or bleeding spots. The rash appears irregularly in time, and more often with fever in the evening. When it appears, and disappears with the heat in the early morning, that is, the characteristics of the night and night, it is transient, the rash disappears without leaving traces, but a few can have large patches of pigmentation, some patients are scratching, friction and other machinery After stimulation, the rash can be aggravated or manifested. It is called Koebner sign. The rash biopsy is swelling of skin collagen fibers and infiltration of inflammatory cells around the capillaries, and very few are non-specific panniculitis.
3. Joint and muscle symptoms: joint pain and arthritis are one of the main clinical manifestations of this disease, but they can be very light, so that they are easily overlooked. Generally, the onset is more insidious, mostly soft tissue pain around the joints and joints, swelling and tenderness. Any joint can be affected. The most frequently invaded joint is the knee joint, which accounts for about 85%. The second is the wrist joint, which accounts for about 74%. In addition, half of the patients have elbow, ankle, hip, shoulder and proximal interphalangeal joints. And the toe joint is involved, about one-third of patients have metacarpophalangeal joint involvement, about one-fifth of the patients affect the distal interphalangeal joint, initially affecting only a few joints, and then can develop into multiple joints, affected joints Appearance and distribution are similar to rheumatoid arthritis, but the synovitis of this disease is mild and transient, the joint fluid is inflammatory, and the neutrophils are elevated, generally ranging from 2.0×109/L to 75×109/L. Symptoms and signs of joints often relieve with the decrease of body temperature. Some patients show joint performance after fever or several months. In general, bone erosion and subluxation around the joints are rare. Most patients do not return after heat. Remaining joint deformities, a few more Chronic joint damage can also occur in joints of the joints and proximal interphalangeal joints. The wrist and wrist joints can be stiffened after many years. A few cervical vertebrae, temporomandibular joints and metatarsophalangeal joints can also develop joint stiffness. Most patients have fever. There were varying degrees of muscle soreness, and a small number of patients developed muscle weakness and a slight increase in muscle enzymes.
4. Sore throat: seen in 50% of patients, often in the early stages of the disease, sometimes in the entire course of the disease, sore throat appears or aggravated during fever, remission after heat withdrawal, pharyngeal examination can be seen pharyngeal congestion, posterior pharyngeal lymph Follicular hyperplasia, tonsil enlargement, throat swab culture negative, antibiotic treatment is not effective for this sore throat.
5. Lymph node enlargement: The early stage of the disease often has superficial lymph nodes, especially in the underarms and groin. It is symmetrically distributed, soft, with tenderness, no adhesion and different sizes. Some patients have lungs. Portal and mesenteric lymph nodes can cause non-fixed pain in the abdomen, mesenteric lymph node necrosis, can cause severe abdominal pain, and the enlarged lymph nodes shrink or disappear after normal body temperature.
6. Hepatosplenomegaly: About half of the patients have enlarged liver, generally mild, moderately swollen and soft. About 3/4 of the patients have abnormal liver function, alanine aminotransferase is elevated, and some patients have jaundice. However, alkaline phosphatase, -glutamyltranspeptidase, and creatine phosphokinase are generally normal. After the symptoms are relieved, the liver can return to normal. A small number of patients have sequestering bile, subacute severe hepatitis, acute liver failure. As a result of death, the spleen is mild to moderately swollen, soft, smooth, and can return to normal after the disease is relieved.
7. Heart damage: The heart damage of this disease is more common in pericardial lesions, followed by myocarditis, endocarditis is rare, clinical manifestations are palpitations, chest tightness, arrhythmia and congestive heart failure, etc., pericarditis is generally insidious, carefully Auscultation can be heard and pericardial friction sound, echocardiography can be seen in effusion, rare pericardial tamponade, some patients have pericardial constriction, myocardial lesions generally do not affect cardiac function.
8. Lung and pleural lesions: symptoms such as cough, cough, chest tightness and difficulty breathing, lung damage manifested as invasive inflammation, atelectasis, pulmonary hemorrhage, interstitial pneumonia and amyloidosis, or adult breathing Distress syndrome, pleural lesions are fibrinous pleurisy, pleural effusion and pleural hypertrophy, sputum culture and pleural effusion culture negative, some patients may have pulmonary bacterial infection or tuberculosis infection due to long-term application of hormones and immunosuppressive agents.
9. Abdominal pain: About 1/4 of patients have abdominal pain or total abdominal discomfort, nausea, vomiting and diarrhea, etc. Abdominal pain is often caused by mesenteric lymphadenitis, mechanical intestinal obstruction or peritonitis, and a small number of patients are mistaken for surgical urgency due to severe abdominal pain. Abdominal exploration and laparotomy.
10. Nervous system lesions: The disease of the nervous system is rare, involving the central and peripheral nervous system, meningeal irritation and encephalopathy, including headache, vomiting, epilepsy, meningoencephalitis, intracranial hypertension, cerebrospinal fluid examination, most normal, even There was a slight increase in protein content and negative culture of cerebrospinal fluid.
11. Other manifestations: kidney damage is less common, generally mild proteinuria, marked by fever, a small number of acute glomerulonephritis, nephrotic syndrome, interstitial nephritis and renal failure, etc., other damages include fatigue, Hair loss, oral ulcers, iridocyclitis, retinitis, keratitis, conjunctivitis, total ophthalmia, menopause and disseminated intravascular coagulation, etc., a small number of patients have recurrent episodes of amyloidosis for many years, in addition, patients with this disease Can be allergic to a variety of drugs and food, the emergence of a variety of drug eruptions, often caused by misdiagnosis.
The diagnosis of this disease is difficult, and it is necessary to exclude infectious diseases, rheumatic diseases, neoplastic diseases, iatrogenic diseases and allergic diseases before the diagnosis can be confirmed. There is no unified diagnostic standard for this disease, and a relatively unified understanding is in the presence of high fever. Transient porcine rash, arthritis and elevated white blood cells and neutrophils (often accompanied by other manifestations in Table 1) should be highly suspected of adult Still's disease, multiple blood cultures or negative for bone marrow culture and serum iron The abnormal increase of protein can be used as an important basis to support the diagnosis of this disease. Strict control of fever, rash, arthritis or pain is the key to preventing misdiagnosis. Several kinds of clinical diagnosis of adult Still's disease are now available. The criteria are listed below.
Examine
Adult Sill's disease check
1. The outstanding performance of this disease is that the total number of peripheral blood leukocytes in patients with more than 90% is increased, generally between 10×109/L and 20×109/L, and there are reports as high as 50×109/L, which is a leukemia-like reaction. High neutrophil increased, the classification is generally above 0.9, neutrophil nucleus left shift and eosinophils do not disappear, persistent and progressive anemia in the absence of gastrointestinal bleeding, mostly positive cells Positive pigmented anemia, can also be small cell hypohemolytic anemia or large cell positive pigment anemia, individual patients with hemolytic anemia, anemia is often associated with disease activity, more than half of patients with platelet counts up to 300 × 109 / L or more After the disease stabilizes, it returns to normal.
2. ESR is obviously increased, more than 100mm/h, C-reactive protein is mild or moderately elevated, and a few patients have low titer antinuclear antibodies. The positive rheumatoid factor often indicates that the patient may develop rheumatoid arthritis. , immunoglobulin and gamma globulin can be elevated, serum alanine aminotransferase, direct bilirubin and indirect bilirubin can be elevated, albumin is reduced, globulin is elevated, and even blood ammonia is elevated. When combined with myositis, creatine phosphokinase and lactate dehydrogenase are elevated.
3. Unless accompanied by secondary infection, blood culture and other bacteriological tests were negative, tuberculin pure protein derivative test was negative, and other microbiology cultures were also negative.
4. The bone marrow is often characterized by infectivity. The granulocyte system is proliferated actively, the nucleus is shifted to the left, the cytoplasm contains poisonous particles and vacuolar degeneration, and the bone marrow bacteria culture is negative.
5. It is worth mentioning that serum ferritin is significantly elevated in the active period of the disease, can be more than 10 times higher than the normal level, and parallel with the disease activity, can be used as a support point for the diagnosis of this disease, and can be used as an observation of disease activity and monitoring treatment. The indicator of the effect.
6. X-ray findings: X-ray findings of this disease are non-specific, early soft tissue swelling and osteoporosis near the joints, repeated or persistent arthritis can be seen in articular cartilage destruction and bone erosion, periosteum near the affected joint Common linear new bones, joint space stenosis, joint stiffness and joint subluxation in the late stage, often involving the wrist, knee and ankle joints, a small number of patients with cervical involvement report, the characteristic radiological changes are wrist Non-erosive stenosis of the palm and wrist joints can lead to bony rigidity. Compared with rheumatoid arthritis, the incidence is 6 times and 11 times higher. No infection or neoplastic lesions were found in various laboratory and imaging examinations. .
Diagnosis
Diagnosis and identification of adult Still's disease
Diagnostic criteria
1. American College of Rheumatology (ACR) diagnostic criteria for adult Still's disease
(1) Main conditions:
1 persistent or intermittent fever.
2 easy to disappear orange red rash or maculopapular rash.
3 arthritis.
4 increased white blood cells or neutrophils.
(2) Secondary conditions: sore throat, abnormal liver function, swollen lymph nodes, splenomegaly, other organs involved.
There are 4 main criteria to confirm the diagnosis, with fever, a major standard in the rash, plus more than one minor standard can suspect the disease.
2. Japanese Adult Still Research Committee on Diagnostic Criteria for Adult Still's Disease
(1) Main conditions:
1 fever 39 ° C, and lasted more than 1 week.
2 joint pain lasted for more than 2 weeks.
3 typical rashes.
4 leukocyte increase 10 × 109 / L, including neutrophils 80%.
(2) Secondary conditions:
1 sore throat.
2 lymph nodes and / or splenomegaly.
3 abnormal liver function.
4 types of rheumatoid factor and anti-nuclear antibodies were negative.
(3) Exclusion:
1 infectious diseases (especially sepsis and infectious mononucleosis).
2 malignant tumors (especially malignant lymphoma, leukemia).
3 rheumatism (especially polyarteritis, rheumatoid vasculitis with articular signs).
There are 5 or more of the above main conditions, 5 or more, and at least 2 main conditions, and exclude the diseases listed above, can be diagnosed.
3.Calabro standard
(1) Peak heat (39 ° C or higher) for no other reason, 1 to 2 peaks per day.
(2) Arthritis or joint pain or myalgia.
(3) Anti-nuclear antibodies and rheumatoid factor negative.
(4) Have at least the following two items: rheumatoid rash, systemic lymphadenopathy, hepatomegaly, splenomegaly, a cardiopulmonary manifestation (pleurisy, pericarditis, myocarditis) and an increase in neutrophils.
(5) Excluding other causes of high fever, rash, arthritis or joint pain with all the above 5 can be diagnosed.
Some scholars believe that the Japanese diagnostic criteria and the Calabro standard are specific and can be used for diagnosis and differential diagnosis to guide and clinical work. The American College of Rheumatology standard is simple, easy to remember, and widely used, and can be used as a preliminary diagnosis.
AOSD may have laboratory and imaging abnormalities and contribute to AOSD diagnosis, but there is no specific examination for this disease. When diagnosing AOSD, the following experiments can be taken: blood routine, liver function test, ESR, serum iron, ANA , RF and radiological examination of the affected joints.
Blood routine usually shows neutrophil-based leukocytosis, positive cell anemia, thrombocytosis, ESR usually rises, and inflammation is consistent, liver function test can find aminotransferase, alkaline phosphate Increased enzyme and LDH, serum iron levels will increase significantly, serum iron is consistent with the activity of the disease, so it can be used as a marker of treatment response, ANA and RF are usually negative, but in some patients, Can appear in low titers.
The radiological symptoms of AOSD are usually uncommon, and when present, symptoms consistent with AOSD diagnosis include non-invasive CMC and intra-wrist (no MCP joint) stenosis of the intercarpal space, sometimes leading to wrist stiffness.
Differential diagnosis
Because the disease is mainly clinically diagnosed and has no specific diagnostic indicators, other diseases with fever, rash and arthritis must be excluded at the time of diagnosis.
The following is the most confusing disease:
1. Septicemia This disease is mostly relaxation heat, more than 39 ° C at the peak of body temperature, there are obvious symptoms of chills before fever, such as chills, rash often have bleeding points, body temperature is still tired, weight loss and other consumption performance, by Careful examination can reveal the primary infection, blood culture or bone marrow culture is positive, antibiotic treatment is effective, the above can be identified.
2. Lymphoma This disease may have fever, anemia, painless lymphadenopathy, hepatosplenomegaly and skin changes, easily confused with adult Still's disease, characterized by progressive lymphadenopathy, quality and toughness, part Adhesion, heat stroke can be persistent fever or periodicity, heat type is uncertain; skin changes are often invasive plaques, nodules, etc.; bone marrow puncture and multi-site lymph nodes or skin biopsy can confirm the diagnosis.
3. Systemic lupus erythematosus This disease is mainly characterized by multiple system damage, more common in women, often fever, rash, arthritis, myalgia, hepatosplenomegaly and lymphadenopathy, pericarditis, proteinuria, etc., in the blood Leukopenia, there are a variety of autoantibodies, such as anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-Sm antibodies, anti-ribosomal antibodies, etc., total complement, C3, C4 decline, circulating immune complexes, elevated globulin, etc. Lymph node biopsy is mostly non-specific inflammation. If necessary, repeat autoantibody examination, pay attention to visceral damage to assist in diagnosis. After excluding other diseases, glucocorticoid treatment is effective and can also help diagnosis.
