Steele’s disease originally refers to juvenile arthritis with a systemic origin, but a similar disease can also occur in adults and is called adult Steele’s disease. The disease was once called “allergic subsepsis,” but since 1987 it has been referred to 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. Because there are no specific diagnostic methods or criteria, it is often necessary to exclude infections and tumors before considering its diagnosis. In some patients, even if the diagnosis of adult Sclerosis is made, close follow-up during treatment is required to further exclude the development of infections and/or tumors. The disease occurs similarly 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 be seen at advanced ages.
Clinical manifestations
1. Symptoms and signs
(1) Fever: It 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 appear weeks or even months after the onset of fever. 80% or more of patients have a typical spiking fever, usually with a sudden rise in body temperature in the evening, with or without chills, reaching 39°C or higher, but the temperature may drop to normal on its own in the morning of the next day without heat remission. Usually peak fever is once a day, but twice a day is rare.
(2) Rash: This 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, can 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 starts and disappearing the next morning when the fever subsides. Another skin abnormality is that about 1/3 of the patients have diffuse erythema and mild pruritus in the skin due to mechanical stimulation such as folding of clothes, bedding, scratching or hot water baths, which is known as Koebner’s phenomenon.
(3) Joints and muscles: almost 100% of patients have joint pain, arthritis in more than 90%. The knee and wrist joints, followed by the ankle, shoulder, and elbow joints are most susceptible to involvement. Proximal interphalangeal joints, metacarpophalangeal joints and distal interphalangeal joints can also be involved. In the early stages of the disease, few joints are involved, but later the number of joints involved increases and becomes polyarthritic. In many patients, the cartilage and bone tissue of the affected joints can be eroded and destroyed, so the joints may become stiff and deformed 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 sore throat appears or worsens during fever and relieves after the fever subsides. There is hemorrhage in the pharynx, lymphatic follicle hyperplasia in the posterior pharyngeal wall, enlarged tonsils, negative pharyngeal swab culture, and antimicrobial therapy is ineffective in sore throat.
(5) Other clinical manifestations: such as peripheral lymph node enlargement, hepatosplenomegaly, abdominal pain (a few resemble acute abdomen), pleurisy, pericardial effusion, myocarditis, 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, more than 90% of patients have increased neutrophils, 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) Negative rheumatoid factor and antinuclear antibodies, only a few patients may have low positive titers. Blood complement level is normal or high.
(5) Serum ferritin (SF). SF level is increased in this disease and its level correlates with disease activity. Therefore, SF not only contributes to the diagnosis of the disease, but also has some significance in observing whether the disease is active and determining the effect of treatment.
(6) Synovial fluid and plasma fluid leukocytes are elevated, showing inflammatory changes, among which neutrophils are mainly elevated.
3.Radiological manifestations
In arthritis, there may be swelling of the soft tissue around the joint and osteoporosis of the joint bone ends. As the disease progresses, the articular cartilage may be destroyed and the joint space narrowed, which is most likely to be seen in the wrist joint. The subchondral bone may also be destroyed, eventually leading to joint stiffness and deformity.
Diagnosis and differential diagnosis
1.Diagnostic points
The disease should be suspected when the following clinical manifestations and related tests are present.
(1) Fever is the most prominent symptom of the disease and appears at the earliest, with a typical fever pattern of peak 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 examination: 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. The American Cush criteria and Japanese criteria are recommended.
This criterion needs to exclude: infectious diseases, malignant tumors, and other rheumatic diseases. The diagnosis can be made if five or more conditions (including at least two major conditions) are met.
3.Differential diagnosis
The following diseases should be differentiated prior to the diagnosis of adult Steele’s disease.
(1) Infectious diseases: viral infections (hepatitis B virus, rubella, microvirus, coxsackievirus, EBV, cytomegalovirus, human immunodeficiency virus, etc.), subacute bacterial endocarditis, meningococcal bacteremia, gonococcal bacteremia and other bacterial-induced bacteremia or sepsis, tuberculosis, Lyme disease (Lyme disease), syphilis and rheumatic fever, etc.
(2) Malignant neoplasm: leukemia, lymphoma, immunoblast lymphadenopathy.
(3) Connective tissue diseases: systemic lupus erythematosus, primary dry syndrome, mixed connective tissue disease, 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, etc.
Treatment principles and protocols
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)
Acute fever and inflammation period can first use NSAIDs, generally need to use a larger dose, the disease should continue to use 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 (refer to rheumatoid arthritis medication).
About 1/4 of adult patients with Still’s disease can have their symptoms controlled and in remission with reasonable use of NSAIDs, and usually these patients have a good prognosis.
2. Glucocorticoids
Glucocorticosteroids should be used for those who do not have effect with NSAIDs alone, whose symptoms are not well controlled, or who have relapsed with dose reduction, or who have systemic damage and are in serious condition. 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)
Those whose fever is still not controlled by hormones or whose relapse is immediate by hormone reduction; or whose arthritic manifestations are obvious should be added with DMARDs as early as possible.
Nausea and vomiting are common, and bone marrow suppression. Carcinogenic effect (related to the total dose and course of treatment, but in recent years, some people think that if no serious toxic side effects do not limit the total amount), hemorrhagic cystitis and bladder cancer (less common in China), liver damage, jaundice, hair loss. Infection, herpes zoster, teratogenicity and sterility. Hypertension, hepatic and renal toxicity, neurological damage, secondary infections, tumor and gastrointestinal reactions, gingival hyperplasia, hirsutism, etc.
When using DMARDs, methotrexate (MTX) is preferred at a dose of 7.5-15 mg/week, and the dose can be increased if the disease is severe. 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 fewer side effects. In clinical practice, other DMARDs can be used in combination with MTX according to the condition, and when the chronic phase is characterized by arthritis, the combination of rheumatoid arthritis DMARDs such as MTX+SASP; MTX+HCQ; MTX+penicillamine; MTX+Gold can be used. If the patient cannot tolerate MTX or the efficacy is not good, Leflunomide (LEF) can be used instead, and it 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. After the remission of the disease, the hormone should be stopped 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, but the dose can be reduced.
4.Botanical preparations
Some botanical preparations, such as Radix Polygoni, Cyanidin, and Paeoniflorin, have been used in the treatment of various rheumatic diseases. The chronic phase of the disease, arthritis as the main manifestation can also be observed when using (see rheumatoid arthritis drugs).
Prognosis
The patient’s condition and course are diverse, reflecting the heterogeneity of the disease. A small number of patients have a tendency to have self-limiting attacks after a remission. Most patients are prone to recurrent attacks after remission. There are also chronically active types that eventually develop chronic arthritis with cartilage and bone destruction, similar to rheumatoid arthritis.
It is important to emphasize that adult Steele’s disease is a disease of exclusion and there are still no specific uniform diagnostic criteria. Even after the diagnosis is confirmed, medications must be adjusted at any time 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.