Overview
Steele’s disease originally refers to the systemic onset of juvenile chronic arthritis, but similar disease can also occur in adults, called adult onset still’s disease AOSD. The disease was once called “allergic subseptic disease”, but since 1987 it has been unified as adult Still’s disease.
The cause of the disease is not known. The clinical features are fever, arthralgia and/or arthritis, rash, myalgia, sore throat, enlarged lymph nodes, neutrophilia and thrombocytosis, and in severe cases, systemic damage. Since there are no specific diagnostic methods or criteria, infections, tumors, and other connective tissue diseases need to be excluded before considering the diagnosis. In some patients, even if the diagnosis of adult Still’s disease is made, close follow-up during treatment is required to further exclude the possibility of these diseases. The prevalence of the disease is similar in men and women and is scattered throughout the world with no geographical differences. The age of prevalence is 16-35 years, but it can also be seen at an advanced age.
Clinical manifestations
1. Symptoms and signs
(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 themselves weeks or even months after the onset of fever. 80% of patients have typical flaccid fever (remittent fever), usually in the evening.
fever, usually with a sudden rise in body temperature in the evening, reaching 39°C or higher, with or without chills, but the temperature may drop to normal on its own the next morning without heat remission. Usually the temperature spike is once a day, but twice a day is rare.
(2) Rash is another major manifestation of the disease, seen in more than 85% of patients, the typical rash is orange-red macular rash or maculopapular rash, sometimes the rash form is variable, may be urticaria-like rash. The rash is mainly distributed on the trunk and extremities, but can also be seen on the face. The characteristic feature of the rash is that it often accompanies fever, often appearing in the evening when the fever begins and disappearing the next morning when the fever subsides. Another skin abnormality is the diffuse erythema and mild itching of the skin in the corresponding area due to mechanical stimulation such as folding of clothes, bedding, scratching or hot water bathing, a phenomenon known as Koebner’s phenomenon, seen in about 1/3 of patients.
(3) Joints and muscles Almost 100% of patients have joint pain and arthritis in more than 90%. 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 follicle hyperplasia in the posterior pharyngeal wall and tonsillar enlargement, negative pharyngeal swab culture, and ineffective antimicrobial treatment.
(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 renal, 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.
2.Laboratory tests
(1) Blood routine In the active stage of the disease, more than 90% of patients have increased neutrophils and about 80% of patients have blood leukocyte count ≥15×109/L. About 50% of patients have elevated platelet count and no change in eosinophils. Orthocytic orthochromic anemia may be combined. Blood sedimentation is increased in almost 100% of patients.
(2) Liver enzymes are mildly increased in some patients.
(3) Blood bacterial culture is negative.
(4) Rheumatoid factor and antinuclear antibodies are negative, and only a few may be positive in low titers. Blood complement levels are normal or high.
(5) Serum ferritin SF The SF level is increased in this disease and its level is positively correlated with the disease activity. Therefore, SF not only contributes to the diagnosis of the disease, but also has a certain significance in determining whether the disease is active and evaluating the effect of treatment.
(6) The synovial fluid and plasma cavity effusion have increased leukocytes, showing inflammatory changes, among which neutrophils are mainly increased.
3.Radiological manifestations
In patients with arthritis, there may be periarticular soft tissue swelling and osteoporosis at the ends of the joint bones. As the disease progresses, there may be destruction of articular cartilage and narrowing of the joint space, and such changes are most likely to occur in the wrist joint. The subchondral bone may also be destroyed, which may eventually lead to joint stiffness and deformity.
Diagnosis and differential diagnosis
1.Diagnostic points
The disease should be suspected if the following clinical manifestations and positive laboratory test results are present.
(1) Fever is the most prominent symptom of the disease and appears earliest. The typical fever pattern is flaccid fever, usually once a day.
(2) The rash is common on the trunk and extremities, but can also be seen on the face as an orange-red rash or maculopapular rash, usually accompanied by fever, and is transient.
(3) There is usually arthralgia and/or arthritis, with early oligoarthritis or polyarthritis developing. Myalgic symptoms are also common.
(4) Peripheral blood leukocytes are significantly elevated, mainly neutrophils, and blood cultures are negative.
(5) Serological tests: most patients are negative for rheumatoid factor and antinuclear antibodies.
(6) Multiple antimicrobial therapy is ineffective, while glucocorticoids are effective.
2.Diagnostic criteria
There is no specific diagnostic method for this disease, and many diagnostic or classification criteria have been developed at home and abroad, but there is still no unified and accepted standard. However, there is no unified standard yet. We recommend the American Cush criteria and Japanese criteria, which have been applied more frequently.
(1)Cush criteria
Necessary conditions
Fever ≥39℃
Arthralgia or arthritis
Rheumatoid factor <1:80
Antinuclear antibody <1:100
Any two of the following must also be present
Blood leukocytes ≥15×109/L
Skin rash
Pleurisy or pericarditis
Hepatomegaly or splenomegaly or lymph node enlargement
(2) Japanese preliminary diagnostic criteria
Main conditions
Fever ≥ 39°C and lasting for more than one week
Arthralgia lasting more than two weeks
Typical skin rash
White blood cells ≥15×109/L
Secondary conditions
Sore throat
Lymph nodes and/or splenomegaly
Abnormal liver function
Negative rheumatoid factor and antinuclear antibodies
This criterion requires exclusion of: infectious diseases, malignancies, other rheumatic diseases. A diagnosis can be made if five or more conditions (including at least two major conditions) are met.
3.Differential diagnosis
Care should be taken to exclude the following diseases before diagnosing adult Steele’s disease.
(1) Infectious diseases: viral infections (hepatitis B virus, rubella virus, microvirus, coxsackievirus, EB virus, cytomegalovirus, human immunodeficiency virus, etc.), subacute bacterial endocarditis, meningococcal bacteraemia, gonococcal bacteraemia and other bacteria causing bacteremia or sepsis, tuberculosis, Lyme disease (Lyme disease), syphilis and rheumatic fever.
(2) Malignant tumors: leukemia, lymphoma, etc.
(3) Connective tissue diseases: systemic lupus erythematosus, primary dry syndrome, mixed connective tissue diseases, etc.
(4) Vasculitis: polyarteritis nodosa, Wegener’s granulomatosis, thrombotic thrombocytopenic purpura, aortitis, etc.
(5) Other diseases: serum sickness, nodular disease, primary granulomatous hepatitis, Crohn’s disease (Crohn’s disease), etc.
【Treatment principles and programs】.
There is no cure for this disease, but if diagnosed early, reasonable treatment can control the attack and prevent recurrence, the medication method is the same as rheumatoid arthritis.
Commonly used drugs are non-steroidal anti-inflammatory drugs (NSAIDS), glucocorticoids, anti-rheumatic drugs to improve the condition (DMARDS), etc.
1 Non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs can be used first in the acute febrile inflammatory period, generally need to use larger doses, and should continue to be used for 1~3 months after remission, and then gradually reduce the dose. Regularly review liver and kidney function and blood count, and pay attention to adverse reactions. For details of commonly used NSAIDs, see Rheumatoid Arthritis.
About 1/4 of adult patients with Steele’s disease can have their symptoms controlled and their disease remitted with the reasonable use of NSAIDs, and usually these patients have a good prognosis.
2 Glucocorticoids
Glucocorticosteroids should be used for those who are ineffective with NSAIDs alone, whose symptoms are not well controlled, or who have relapsed with dose reduction, or who have systemic damage or severe disease. Prednisone 0.5~1mg/kg/d is commonly used, and the dose can be gradually reduced after 1 month of symptom control and disease stabilization, and then maintained with the minimum effective amount. In severe cases, high-dose hormone (prednisone ≥1.0mg/kg/d) is needed, and methylprednisolone shock therapy is also available, usually at a dose of 500-1000mg/time, slowly administered intravenously for 3 days. It can be repeated after 1-3 weeks if necessary, and oral prednisone is continued during the interval and after the shock. Long-term hormone users should pay attention to complications such as infection and osteoporosis. Timely supplementation of drugs related to the prevention and treatment of osteoporosis, such as diphosphonates and active vitamin D that inhibit osteoclasts.
3 Improve the condition anti-rheumatic drugs (DMARDs)
DMARDs should be added as soon as possible if fever is not controlled by hormones or if the hormone dose is reduced, or if arthritis is evident.
When using DMARDs, methotrexate (MTX) is preferred at a dose of 7.5-15 mg/week, and the dose can be increased in severe cases. In milder cases, hydroxychloroquine can be used. Azathioprine, cyclophosphamide and cyclosporine are used for recalcitrant cases. When using cyclophosphamide, there are shock therapy and small dose usage, compared to the two, shock therapy has less side effects. In clinical practice, other DMARDs can be used in combination with MTX, and when the chronic phase with arthritis is the main manifestation, the treatment can be referred to rheumatoid arthritis: MTX+SASP; MTX+HCQ; MTX+penicillamine; MTX+Gold, etc. If patients cannot tolerate MTX or the efficacy is not good, they can switch to Leflunomide (LEF), which can be combined with other DMARDs on top of LEF.
During the course of drug administration, the adverse effects of the drugs used should be closely observed, such as regular observation of blood picture, blood sedimentation, liver and kidney function. Ferritin (SF) can also be observed regularly. If clinical symptoms and signs disappear, blood picture is normal, blood sedimentation is normal, and SF drops to normal level, it indicates remission of the disease. After the remission of the disease, the hormone should be reduced first, but in order to continue to control the disease to prevent relapse, DMARDs should continue to be applied for a longer period of time, and the dose can be reduced as appropriate.
4 Botanical preparations
Some botanical preparations, such as rehmannia polysaccharide, cyanophylline, and total peony glycosides have been used in the treatment of various rheumatic diseases. In the chronic phase of the disease, arthritis is the main manifestation of the disease can also be used (see rheumatoid arthritis drugs).
Prognosis]
The heterogeneity of the disease is reflected in the diversity of the patient’s condition and disease course. A small number of patients have a self-limiting tendency to have no more episodes after one episode of remission. In contrast, most patients are prone to recurrent attacks after remission. There is also a chronic, persistent type of activity that eventually manifests as chronic arthritis with cartilage and bone destruction, similar to rheumatoid arthritis. It is important to emphasize that adult Still’s disease is an exclusionary disease and there are still no specific uniform diagnostic criteria. Even after the diagnosis is confirmed, medications must be adjusted during treatment and follow-up to improve the prognosis and frequent attention to exclude infections, tumors and other diseases, so that the diagnosis can be revised and the treatment plan changed.