What is adult Still?
It is thought to be an allergic disease between rheumatic fever and juvenile rheumatoid arthritis, and is very similar to the acute systemic form of juvenile rheumatoid arthritis (Still’s disease). It is also thought to be a clinical stage of rheumatoid arthritis or a clinical variant of it. It is also thought to be an independent disease that includes both adult-onset Still’s disease and continuous cases of Still’s disease that occurred in childhood and recurred in adulthood (pediatric adult Still’s disease).
However, after long-term observation, most patients do not have sequelae such as joint ankylosis and deformity. The onset of AOSD, the affected population, HLA typing, joint involvement characteristics, negative antinuclear antibody (ANA) and rheumatoid factor (RF), and the prognosis of the disease are now mostly considered to be significantly different from rheumatoid arthritis, and they are two different diseases. At present, the disease is still classified as rheumatology and immunology.
I. Etiology and pathogenesis
1, immune disorders AOSD patients have decreased T 4 helper cells, increased T 8 suppressor cells, decreased total T lymphocytes, increased neutrophils, eosinophils, monocytes are the main features of the disease, suggesting cellular immune disorders. In addition, decreased serum complement and increased immune complexes also reflect humoral immune disorders in patients.
2. Infection 70% of patients have pharyngitis and gingivitis at the same time, and most patients have increased anti-O titers, which many scholars believe is related to streptococcal infection. Some anti-viral antibodies have been isolated from a few patients, and it remains to be studied whether there is a viral infection.
3, genetic It is reported that the disease is associated with HLA-B 8, BW 35, BW 44 and DRB1 sequences and other histocompatibility antigen expression, suggesting that genetics and the patient’s susceptibility and disease expression related.
4, mental factors Some foreign studies have suggested that mental and work stress is definitely related to the development of the disease.
5, allergic reactions Most patients with AOSD have increased serum IgE levels, and low levels of specific IgE for different allergens can be detected, but IgE levels do not correlate significantly with the severity of the disease. This suggests that type I allergic reactions are involved in the pathogenesis of AOSD. There is a consensus that the disease is a post-infectious metaplasia, probably a combination of chronic infection and allergic or autoimmune reactions. In conclusion, there are many new academic views and theories on the etiology and pathogenesis of this disease, and the research on this has become a hot spot in the understanding of AOSD.
Clinical manifestations
The disease is mostly seen in young people, 18-32 years old, and the prevalence of men and women is basically equal. The clinical manifestations are complex and varied, often with multi-system involvement, mainly manifesting as fever, rash, arthralgias, followed by sore throat, lymph node enlargement, and hepatosplenomegaly.
① Fever – is the most common and earliest symptom of the disease. Other manifestations such as rash, joint and muscle symptoms, and increased peripheral blood leukocytes may manifest weeks or even months after the onset of fever. 80% of patients have a typical remittent fever, usually with a sudden rise in body temperature of 39°C or more in the evening, with or without chills, but the temperature may drop to normal on its own in the morning of the next day without heat remission. Usually the temperature spike is once a day, but twice a day is rare.
The typical rash is an orange-red rash or maculopapular rash, and sometimes the rash is variable and may appear as an urticaria-like rash. The rash is mainly distributed on the trunk and extremities, but can also be seen on the face. The rash is often accompanied by a fever, which often appears in the evening when the fever starts and disappears the next morning when the fever subsides.
Another skin abnormality is the diffuse erythema of the skin with mild itching due to mechanical stimulation such as folding of clothes, bedding, scratching or hot water baths, which is known as Koebner’s phenomenon and is seen in about 1/3 of patients.
(iii) Joints and muscles – almost 100% of patients have joint pain and arthritis in more than 90% of cases. The knee and wrist joints are most commonly involved, followed by the ankle, shoulder and elbow joints, and the proximal interphalangeal joints, metacarpophalangeal joints and distal interphalangeal joints can also be involved. The number of joints involved is small in the early stages of the disease, but may increase later to show polyarthritis. In many patients, the cartilage and bone tissue of the affected joints may be damaged by erosion, so joint stiffness and deformity may occur in the late stage. Muscle pain is common, accounting for more than 80% of cases. Most patients have varying degrees of muscle aches and pains with fever, and some patients have muscle weakness and mildly increased muscle enzymes.
④ Sore throat – Most patients have sore throat in the early stage of the disease, sometimes present throughout the course of the disease, and the sore throat appears or worsens during fever and relieves after the fever subsides. There may be pharyngeal congestion, lymphatic follicular hyperplasia in the posterior pharyngeal wall and tonsillar enlargement, negative pharyngeal swab culture, and ineffective antimicrobial therapy.
⑤ Other clinical manifestations – there may be peripheral lymph node enlargement, hepatosplenomegaly, abdominal pain (a few resemble acute abdomen), pleurisy, pericardial effusion, myocarditis, and pneumonia. Less common are kidney, central nervous abnormalities, and peripheral nerve damage. A few patients may develop acute respiratory failure, congestive heart failure, pericardial tamponade, constrictive pericarditis, diffuse intravascular coagulation (DIC), severe anemia, and necrotizing lymphadenopathy.
III. Diagnostic criteria for adult Still
There is no specific diagnostic method for this disease, and many diagnostic or classification indexes have been developed at home and abroad, but there is still no unified index that can be accepted. In recent years, some articles have reported that serum ferritin (SF) is significantly elevated during the active phase of the disease, exceeding the normal value by more than 5-10 times and paralleling the disease activity, which can be used as a reference indicator for the diagnosis of the disease and as a criterion for observing the disease activity and monitoring the efficacy of treatment. In terms of diagnostic criteria, the more commonly used American Cush criteria and Japanese criteria are recommended, and only the Cush criteria are recommended below: Required condition: fever ≥ 39°C
Arthritis/arthralgia
Rheumatoid factor <1:80
Antinuclear antibody <1:100
Any two of the following: blood leukocyte count ≥ 15×109/L
Skin rash
Pleurisy or pericarditis
Hepatomegaly or splenomegaly or generalized superficial lymph node enlargement
In addition, the disease is a clinical diagnosis or exclusion diagnosis, so other diseases associated with fever, rash, and arthritis must first be excluded at the time of diagnosis, including various infections (viral infections, bacterial endocarditis, sepsis, tuberculosis, syphilis, Lyme disease, etc.), malignancies (leukemia, lymphoma, etc.), immune diseases (systemic lupus erythematosus, mixed connective tissue disease, various vasculitis, reactive arthritis, rheumatic fever, erythema nodosum, etc.) and drug allergy, etc.
The condition was also closely observed during the treatment follow-up to further exclude possible occult diseases and rare diseases. There are reports of misdiagnosis of small liver abscess, malignant histiocytosis and retroperitoneal reticulocytic sarcoma as AOSD.
IV. Treatment
1.Glucocorticoid: Prednisone 1mg/(kg・d), after the symptoms improve, gradually reduce the dosage, the total course of treatment should not exceed 6 months. The total course of treatment should not exceed 6 months. Non-steroidal drugs can be added in the process of dose reduction to consolidate the efficacy. When the efficacy is not good, high-dose methylprednisolone shock treatment can be used.
2.Non-steroidal anti-inflammatory drugs: NSAIDs can be used alone in mild cases, such as naproxen 0.2g twice a day, indomethacin 25mg three times a day and fotarine 25-60mg three times a day.
3, slow-acting anti-rheumatic drugs: long-term poor control of the disease, glucocorticoids are not effective, the following drugs can be used. Methotrexate, Ryder, penicillamine, salazosulfapyridine and rheumatoid polysaccharide, etc., the dose of rheumatoid arthritis treatment.
(i) Acute phase
About 1/4 patients respond well to non-steroidal anti-inflammatory drugs (NSAIDs) and these patients tend to have a better prognosis. High-dose enteric aspirin and indomethacin were commonly used before the advent of selective cyclooxygenase-2 (COX-2) inhibitors. Side effects such as hepatotoxicity and intravascular coagulation need to be noted during the use of NSAIDs.
Systemic glucocorticoids are required in the following cases.
(1) NSAID is not effective or toxic side effects such as hepatic impairment or relapse after dose reduction;
②Severe conditions such as pericardial tamponade, myocarditis, severe pneumonia, intravascular coagulation and other serious organ damage. Usually the hormone dose is 0.5~1mg/Kg/d of prednisone, and a few critically ill patients need to use methylprednisolone shock therapy.
(II) Chronic phase
The main problem is arthritis. Palliative agents (including gold, hydroxychloroquine, salazosulfapyridine and penicillamine) help to control arthritis and other chronic systemic lesions. Immunosuppressive agents such as azathioprine, cyclophosphamide, and cyclophilin may be used in recalcitrant cases. After 10 years of disease onset, about half of the patients still require palliative medications, and 1/3 of them also require concomitant low-dose hormones.
V. Prognosis
Most of the patients have a good prognosis. 1/5 of the patients are in remission within 1 year and no recurrence afterwards. 1/3 of the patients are in complete remission after several recurrent episodes and the time of recurrence is variable, but the symptoms are often milder and shorter in recurrence than in the first episode. The rest of the patients have a chronic course, mainly chronic arthritis, and a few may progress to severe joint destruction, which may lead to joint ankylosis and even joint replacement.
Polyarthritis (≥4 joints involved) or involvement of the foot, shoulder and hip joints tend to become chronic. In addition, those with childhood onset requiring systemic hormone therapy for more than 2 years also tend to have a poor prognosis. Causes of death include acute liver failure, diffuse intravascular coagulation, secondary amyloidosis, and sepsis.