Overview of the disease
A group of clinical syndromes characterized by high fever, rash, and arthralgia of unknown etiology.
It is characterized by high fever, characteristic rash, arthritis/arthralgia, and elevated white blood cell count.
The pathogenesis of the disease is still unclear, and is generally believed to be related to infection, genetics, and immune abnormalities.
Treatment is mainly pharmacologic, including non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and immunosuppressants.
Definition
Adult Still’s disease is a group of clinical syndromes of unknown etiology, characterized by high fever, characteristic rash, arthritis/arthralgia, sore throat, and elevated white blood cells, often accompanied by enlargement of the liver, spleen, and lymph nodes.
Incidence
It occurs at any age, with a high prevalence between 16 and 35 years of age, and is slightly more common in females than in males.
The incidence and prevalence are not consistent among different races, with a reported incidence of less than 1/100,000, which has not been reported in China [1].
Steele disease resolves spontaneously in 34% of adults, 24% of patients present with intermittent episodes, and 36% of patients become chronic [1].
Etiology
Causes of the disease
The etiology of adult Still’s disease is unclear and is generally thought to be caused by the following factors.
Infections
Although essentially adult Still’s disease is not an infection, the onset of the disease is related to infection. These include bacterial, viral and other infectious factors, with Mycoplasma and Chlamydia being more common. Through immunoreactive cell action, inflammatory cytokines and other stimuli lead to the patient to produce high fever and joint muscle pain and other symptoms.
Genetic factors
Genetic factors are one of the main factors in the development of the disease, and studies have shown that patients with a family history of the disease are relatively more likely to develop the disease.
Immune Abnormalities
It is believed that cellular and humoral immune abnormalities are associated with the development of adult Still’s disease. Cytokines produced by mononuclear macrophages have been found to be involved in the development of the disease, but the exact pathogenesis is unknown.
Predisposing factors
People at high risk for adult Still’s disease are those with a family history of the disease.
Symptoms
Main Symptoms
Fever
It is one of the most common symptoms of adult Still’s disease.
It presents as a flaccid fever type with a temperature ≥39°C, with large daily fluctuations of 2°C or more, and persists for more than 1 week.
Body temperature may drop to normal between febrile episodes, and the patient is irritable and unwell during the fever and recovers after the fever subsides.
Rash
The rash usually presents as a transient pruritic skin lesion, usually a reddish-orange macule or papule, and in a small number of patients, urticaria.
The rash is usually located on the trunk and extremities, and in a small percentage of patients the face may be present.
The lesions may appear with the onset of fever and dissipate as the fever subsides, showing a transient pattern.
Joint and Muscle Symptoms
Joint pain is present in 90% of patients and usually involves the larger joints, such as the knee, elbow, and hip.
Some patients may have joint swelling and pain, which usually flares up or worsens with fever.
80% of patients have muscle pain.
Enlarged lymph nodes
Often, enlargement of lymph nodes in superficial areas can be seen in the early stages of adult Still’s disease.
Enlarged lymph nodes can be palpated in the neck, armpits, and groin.
Involvement of the mesenteric lymph nodes can lead to acute abdominal pain, which is often misdiagnosed as acute abdomen.
Other symptoms
Sore throat
Sore throat usually appears in the early stage of the disease, worsened by fever and relieved by fever. Pharyngeal congestion, lymphoid follicular hyperplasia in the posterior pharyngeal wall, and enlarged tonsils may be seen.
Hepatosplenomegaly
Hepatosplenomegaly is present in more than half of the patients, which is soft and non-indurated, and may shrink after the fever subsides.
Cardiac lesions
Cardiac lesions are often characterized by pericarditis. Most are accompanied by pleurisy or polyplasmacythemia, and a few patients have myocarditis.
Renal lesions
Involvement of the kidneys is often accompanied by proteinuria and may be associated with interstitial nephritis, membranous glomerulonephritis, collapsing glomerulopathy, or secondary amyloidosis.
Severe patients can develop nephrotic syndrome or even uremia.
Neurologic lesions
Neurologic involvement can present with signs of meningeal irritation and encephalopathy.
Phagocytic syndrome
Life-threatening phagocytic syndrome occurs in a small number of adults with Still’s disease and can be triggered by disease activity or infection.
Be alert for phagocytic syndrome if there is persistent high fever, enlarged liver and spleen lymph nodes, severe hemopenia, abnormal liver function, progressive elevation of ferritin, decreased fibrinogen, and coagulation disorders.
Consultation
Department of Medicine
Rheumatology
If symptoms of unexplained joint or muscle pain occur, especially if accompanied by high fever, prompt medical attention is recommended.
Dermatology
For skin rashes such as maculopapular rash, urticaria, erythema, maculopapular rash, etc., it is recommended to consult a doctor promptly.
Preparation
Preparation for consultation: registration, preparation of documents, common problems
Tips for seeking medical treatment
As the skin lesions (rashes) of patients with this disease change rapidly, you can take photos of past skin lesions (rashes) with your cell phone, which may give your doctor more reference.
Do not wear make-up before your visit to the doctor if your face shows any abnormalities.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
What is the change of body temperature? Is there any symptom of high fever (temperature ≥39℃)? Is the fever resolving spontaneously?
Is there a rash? Is the rash accompanied by itching? Is it associated with fever?
Are there any symptoms of joint swelling and pain?
Medical History Checklist
Is there a family history of adult Steele’s disease?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood, blood biochemistry (including liver function, blood sedimentation, C-reactive protein, serum ferritin, glycosylated ferritin), autoantibodies (including rheumatoid factor, antinuclear antibody profile, antineutrophil cytoplasmic antibody, etc.), bone marrow examination.
Imaging tests: X-ray, CT.
List of medications
Medications used in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office
Hormonal drugs: e.g. prednisone, methylprednisolone.
Non-steroidal anti-inflammatory drugs: e.g. diclofenac sodium, celecoxib
Immunosuppressants: e.g. methotrexate.
Biological inhibitors: e.g. etanercept, infliximab, adalimumab, tolizumab.
Diagnosis
Diagnostic basis
There is no specific diagnostic method for this disease, and the correct diagnosis is mainly based on clinical judgment and full exclusion of other diseases. Once unexplained fever, characteristic rash, arthritis/arthralgia are detected, it is necessary to be alert to the possibility of this disease.
Medical History
Risk factors such as a family history of adult Steele’s disease.
Clinical manifestations
Presence of fever ≥39°C for more than 2 weeks.
A rash accompanied by fever, transient and dissipating after the fever subsides.
Pressure, pain and distension in large joints.
Lymph node enlargement throughout the body.
Accompanied by sore throat.
Accompanied by hepatosplenomegaly.
Accompanied by proteinuria.
Laboratory Tests
Blood tests
Routine blood tests are performed to determine the presence or absence of elevated white blood cells.
An increase in the total number of peripheral blood leukocytes (leukocytes greater than 10 x 109 /L), mainly granulocytosis, is one of the diagnostic criteria for adult Still’s disease.
Blood biochemistry
Including liver function, blood sedimentation, C-reactive protein, serum ferritin, glycosylated ferritin and so on.
Liver function is mainly to determine whether there is liver damage.
Blood sedimentation and C-reactive protein mainly assist in determining the degree of inflammation and help to assist in the diagnosis of the disease.
Serum ferritin and glycosylated ferritin can be significantly elevated in adults with Still’s disease, but are not specific diagnostic indicators. They may decrease as the disease improves.
Autoantibodies
Tests include rheumatoid factor, antinuclear antibody profile, and antineutrophil cytoplasmic antibodies, mainly to rule out other autoimmune diseases.
Negative autoantibodies such as rheumatoid factor and anti-nuclear antibody profile, anti-neutrophil cytoplasmic antibody, etc. are helpful in the diagnosis of adult Still’s disease.
Bone marrow examination
The purpose is to rule out hematopoietic disorders and is performed primarily by aspirating a certain amount of bone marrow.
Bone marrow examination shows proliferation of granulocytes with toxic granules and vacuoles in the cytoplasm, suggesting an infectious bone marrow picture, which can assist in the diagnosis of adult Still’s disease when infectious diseases are excluded.
Imaging
Joint X-ray
Can be used to look for trauma or tumors in the joints.
In patients with arthritis, there may be periarticular soft tissue swelling and osteoporosis of the bone ends of the joints. In patients with chronic arthritis, there may be destruction of articular cartilage and narrowing of the joint space.
CT
CT can be used to find out whether there are foci of infection in the chest and abdomen, and to observe whether there is enlargement of the liver and spleen and tumor occupancy.
If the examination finds hepatosplenomegaly, infected foci, occupation, etc., all of them are helpful in the early diagnosis and differential diagnosis of adult Steele’s disease.
Diagnostic criteria
Many diagnostic or classification criteria have been formulated at home and abroad, but there is still no recognized unified and specific diagnostic criteria. At present, there are mainly Japanese criteria, Cush’s criteria and Fautrel’s criteria. The Japanese Yamaguchi Criteria of 1992 is recommended for more applications.
Japanese standard (Yamaguchi standard)
Primary diagnostic criteria: fever ≥39℃ for more than 1 week; arthritis/joint pain for more than 2 weeks; typical rash; blood leukocytes ≥10×109/L and more than 80% polymorphonuclear leukocytes.
Secondary diagnostic criteria: sore throat; lymph nodes and/or splenomegaly; abnormal liver function; negative rheumatoid factor (RF) and antinuclear antibody (ANA).
Exclusion criteria: exclude neoplastic diseases, infectious diseases and other rheumatic diseases.
Adult Still’s disease may be considered if 5 or more diagnostic criteria (of which at least 2 of the major criteria must be met) are met, along with exclusion criteria.
Cush Criteria
Required: fever ≥39°C; joint pain/arthritis; rheumatoid factor (RF) <1:80; antinuclear antibody (ANA) <1:100.
In addition, 2 of the following: rash; blood leukocytes ≥15×109/L; pleurisy or pericarditis; hepatomegaly or splenomegaly or lymph node enlargement.
Fautrel Criteria
Primary criteria: fever ≥39°C; arthralgia; transient skin erythema; pharyngitis; polymorphonuclear leukocytes ≥80%; glycosylated ferritin ≤20%.
Secondary criteria: cutaneous maculopapular rash; blood leukocytes ≥10×109/L.
Consider the diagnosis of the disease when ≥4 major criteria are met, or 3 major criteria + 2 minor criteria.
Differential diagnosis
Sepsis
Similarities: both can present with fever, rash, etc.
Differences: Sepsis is an acute systemic infection that occurs when various pathogenic bacteria invade the circulation and produce toxins. Its rash is usually hemorrhagic, presenting as petechiae, and blood cultures can often detect the causative organisms, and antibiotic treatment against the causative organisms is effective. Adult STILL’s disease is an autoimmune disorder with no evidence of infection, and hormones are effective.
Systemic lupus erythematosus
Similarities: Both have fever, rash, joint symptoms.
Differences: SLE is mostly characterized by butterfly-shaped erythema on the face, which does not subside after the fever subsides. In contrast, the erythema of adult Steele’s disease usually occurs on the trunk and limbs, and is relieved by fever. SLE may test positive for antinuclear antibodies and anti-dsDNA, whereas adult Still’s disease is negative for serum antinuclear antibodies.
Lymphoma
Similarity: Both may present with enlarged lymph nodes, fever, and rash.
Differences: The lymph nodes in lymphoma are usually painlessly and progressively enlarged. In adult Still’s disease, the lymph nodes are usually not progressively enlarged and can be differentiated by lymph node pathology.
Treatment
The purpose of treatment: to terminate or inhibit the abnormal immune response in the patient’s body, to protect the function of various organs and systems, and to prevent the occurrence of complications.
Therapeutic principle: there is no cure for this disease, and the main treatment principle is to relieve the pain, alleviate the condition, control the attack, prevent complications and prevent recurrence. Treatment is mainly based on drug therapy.
Drug treatment
Non-steroidal anti-inflammatory drugs (NSAIDs)
In the absence of serious clinical symptoms, first-line treatment can rely on NSAIDs, which can be preferred for mild patients.
Clinically used drugs include diclofenac sodium and celecoxib.
Long-term use of NSAIDs should be periodically reviewed for liver and renal function, and adverse effects should be noted. They are currently contraindicated in patients with active gastroenteritis or ulcers, and in patients who are allergic to the drug.
Glucocorticoids
Hormones remain the foundation of adult Still’s disease treatment, with common drugs such as prednisone and methylprednisolone.
Glucocorticosteroids can be started when NSAIDs alone are not effective. Lower doses of glucocorticosteroids provide faster relief of symptoms such as fever, rash, and arthralgia, as well as a reduction in the rate of disease recurrence.
Patients taking hormones for a long period of time will develop hormone dependence or drug resistance, and are prone to infections, osteoporosis and other adverse reactions. Use with caution in people with peptic ulcers, blood clots, and high blood pressure.
Immunosuppressants
Available in cases of hormone dependence or resistance and ineffective treatment with NSAIDs, the most widely used immunosuppressant is methotrexate (MTX).
MTX improves systemic and chronic arthritic symptoms in adults with Still’s disease, helps patients reduce their hormone use, and helps reduce the rate of disease recurrence. Clinical studies have shown that MTX is more effective when used in combination with hormones.
MTX is susceptible to adverse reactions such as hepatic impairment. It is contraindicated in people with severe hepatic insufficiency and those who are allergic to the drug.
Biological agents
Targeted biologics may be used in patients with refractory adult Still’s disease who have not responded well to traditional disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids.
In current therapeutic practice, treatments such as tumor necrosis factor-α (TNF-α) blockers and IL-6 antagonists are used. The former include etanercept, infliximab, adalimumab, and tolizumab.
Adverse effects of biologics are some may increase the chance of respiratory infections.
Other treatments
Plasma exchange and immunosorbent therapy
Plasma exchange and immunosorbent therapy can remove the large amount of inflammatory cytokines and abnormal immunoglobulins produced in the body, and play a certain therapeutic role.
Prognosis
Cure
The course of adult Still’s disease is diverse, and most patients have a favorable prognosis.
Most patients, if seen within the first year of disease onset, have an effective remission with no recurrence; a few patients may relapse after remission, but most relapses are less severe than the initial symptoms.
In a few patients, the joints show chronic disease with persistent activity, and joint deformity may gradually appear.
Patients with important organ damage at the onset of the disease may develop organ insufficiency or even die.
Prognostic factors
The prognosis of adult Still’s disease is influenced by a number of factors, and the following factors often lead to a poor prognosis.
Hemophagocytic syndrome
Combination of respiratory distress syndrome, pneumonia.
Severe nephritis.
Combined liver failure.
Combined central neuropathy.
Combined with myocarditis, endocarditis, heart failure, and infarction.
Hazards
Symptoms of adult Still’s disease combined with hemophagocytic syndrome can be life-threatening. There is a risk of liver failure, central neuropathy, myocarditis, endocarditis, and pneumonia, which may lead to heart failure in severe cases, severely affecting the patient’s quality of life.
As a result of long-term disease distress, it can cause psychological stress and anxiety and other adverse emotions in patients.
Daily
Daily Management
Dietary management
Pay attention to light diet and balanced nutrition.
Patients with cerebrovascular disease need to pay attention to reducing fat intake.
Patients with hepatic impairment need to pay attention to the intake of high protein and low fat food.
For adults with other conditions, there are no special dietary requirements and a normal diet is sufficient.
Life management
Pay attention to the combination of work and rest, appropriate exercise, avoid strenuous exercise.
Psychological support
Some adults with Steele disease experience recurrent episodes, so patients may experience anxiety, depression and other negative emotions.
In case of emotional instability and depression, relatives and friends can provide enhanced support and guidance, and psychological intervention can be provided when necessary.
Disease Monitoring
Monitor and record blood pressure and temperature daily. Temperature can be monitored 4 times a day.
Observe whether the extent of the lesion becomes larger, such as the extent of the rash becomes larger and the color of the skin becomes darker.
Watch for changes in the color of the skin, whether it becomes yellow.
Note any changes in the color of the urine and the amount of urine.
Follow-up review
A small number of patients will present chronic disease activity state, can gradually appear joint deformity, and even accompanied by other organs damage, life-threatening, regular follow-up can effectively prevent joint deformity and organs damage.
Regular follow-ups are conducted according to medical advice, and the follow-up cycle is usually about 1 to 3 months.
Tests that may need to be done at the time of follow-up include routine blood tests, liver and kidney functions, and blood sedimentation tests.
Prevention
Prevention of disease
Preventive Measures
The cause of adult Still’s disease is unknown and generally cannot be effectively prevented, but the risk of developing the disease can be helped by a healthy lifestyle or behavior.
Prevent infection, it is currently believed that infection is the most common cause of adult Still’s disease, so pay attention to daily exercise to improve the body’s immunity.
Pay attention to your diet and eat more fruits and green leafy vegetables. Reduce the intake of animal fats, such as animal fats and oils, and desserts with a high fat content.
Maintain good living habits, keep a regular routine and avoid staying up late.
Take good care of your skin, pay attention to the hygiene of the rash area, do not scratch, and choose loose and soft cotton clothes.
Follow your doctor’s instructions, take your medication on time, and have regular checkups to minimize the occurrence of other systemic diseases.
Screening
Patients with a family history of adult Still’s disease who develop suspicious symptoms (e.g. high fever, rash, joint pain, etc.) need to be seen promptly for screening.