Adult Still's disease (ADS) is a multisystem autoinflammatory disease characterized by uncontrolled inflammatory symptoms that affect a person's joints and internal organs. The frequency of development of this pathology may vary among representatives of different nations, but it is known that most often the disease occurs in women aged 16 to 35 years. This disease is classified as incurable, but treatment is necessary. Only timely and correct diagnosis and therapy will allow the patient to achieve remission and maintain it for a long time.
Something in this style
“Among fevers of unknown origin, or diseases accompanied by fever, Still’s disease in adults occupies a special place in rheumatology. It is this that represents an important problem of differential diagnosis for rheumatologists. The insidiousness of the disease lies not only in the fact that it is not easy to diagnose due to the lack of specific tests, but also in the fact that it can lead to life-threatening complications,” emphasizes Evgeniy Nasonov, Academician of the Russian Academy of Sciences, chief freelance rheumatologist of the Ministry of Health of the Russian Federation .
Although Still's disease has a number of characteristic symptoms, each patient experiences it differently. Symptoms are most often very individual, which, of course, complicates the diagnosis. And delaying treatment is dangerous, since in about a third of patients, Still's disease can lead to disability if it is not diagnosed in a timely manner. A fatal outcome is also possible, its risk ranges from 2.3% to 14%. Life-threatening complications of this disease include macrophage activation syndrome - the same “cytokine storm” that many are now well aware of in connection with the coronavirus. That is, the patient can be killed by his own immune system.
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The main symptoms of Still's disease are:
- systemic (daily) fever with a rise in body temperature above 39 °C;
- joint pain (arthralgia and arthritis);
- a sore throat;
- salmon-colored skin rash;
- changes in blood tests with signs of inflammation (>10,000/ml leukocytes and >80% neutrophils).
Pathogenesis
The main mechanism of the pathogenesis of the disease is considered to be increased production of pro-inflammatory cytokines due to the high activity of T-helper type 1 and low suppressive activity of T-helper type 2, which leads to the release of tumor necrosis factor, which stimulates the synthesis of interleukins (IL) IL-1 and IL-6 , acting on the thermoregulatory center in the hypothalamus. Under the influence of IL-1, there is an increase in hematopoiesis, the production of acute phase proteins in the liver and endothelial proliferation, and under the influence of IL-6, osteoclast activation occurs [1]. The main forms of EFS are self-limiting (monocyclic), intermittent (polycyclic) and chronic articular [2].
School of Rheumatology
“When we talk about rare diseases, issues of differential diagnosis always come to the fore, because it is often extremely difficult to give the patient the correct diagnosis during the initial examination,” notes Professor, Director of the Federal State Budgetary Institution NIIR. V. A. Nasonova, Doctor of Medical Sciences Alexander Lila.
The expert explains that such care can only be provided to patients in an institution with a multidisciplinary team, where there are all the capabilities to carry out diagnostics and provide high-tech medical care within the same walls.
“If we talk about the Russian Federation as a whole, then specialists from the regions are often in dire need of advice to determine the algorithm for managing patients with Still’s disease. It will now be easier to obtain it thanks to the opening of a reference center for autoinflammatory diseases on the website of our institution,” says Lila. “Now a doctor of any specialty can receive correspondence consultation from federal experts if EFS is suspected in patients over 18 years of age.”
Clinical and laboratory signs of Still's disease in adults
One of the primary manifestations of the disease may be pharyngitis, which is not typical for rheumatic diseases. Joint damage manifests itself as monoarthritis, which later develops into destructive symmetrical polyarthritis. Symmetrical lesions of the metacarpophalangeal and distal interphalangeal joints are often detected. The rash with BSV is maculopapular, orange-pink in color, quickly passing, localized in places of mechanical irritation, on the trunk, face and limbs. Febrile fever, which manifests itself sharply in most patients, appears in the evening hours and resolves on its own within a few hours. Liver damage is manifested by its increase in size and increased levels of transaminases. Lymphadenopathy is characterized by enlargement of the cervical and submandibular lymph nodes. Splenomegaly is detected in 1/3 of patients. Damage to the cardiovascular and respiratory systems is manifested by pericarditis (very rarely myocarditis) and pleurisy. It is extremely rare to develop bilateral pulmonary infiltrates that resemble alveolitis or pneumonitis. Other rare manifestations of the disease include moderate abdominal pain, damage to the central nervous system (transient extrapyramidal disorders, pathological Babinski reflexes, epileptiform seizures, sensory neuropathy), kidney damage (during fever, proteinuria and microhematuria), eyes (conjunctivitis, iritis, keratoconjunctivitis sicca) .
Laboratory signs of the disease include: increased ESR, neutrophilic leukocytosis (>15×109/l), increased C-reactive protein, transaminases (ALT, AST) and alkaline phosphatase levels more than 3 times compared to the upper limit of normal, increased levels serum ferritin, decreased concentration of the glycosylated fraction of ferritin, increased serum IL-18; at the same time, RF, ACCP and antinuclear factor (ANF), as a rule, are not detected [2, 3]. The histological picture of bone marrow punctate is hyperplasia of granulocyte precursors, hemophagocytosis [2].
Tips for patients
1. Follow your doctor's orders
.
If the doctor has prescribed you to take anti-inflammatory drugs over a long course, then they should be taken until the end of the course, without missing a dose. Even when you feel good. Controlling inflammation means preventing complications.
2. Enrich your diet
.
If you have been prescribed high doses of corticosteroids (methylprednisilone, etc.), discuss additional vitamin D and calcium intake with your doctor. This will help prevent osteoporosis. Another option is to eat foods rich in vitamin D (such as cod liver) and calcium (dairy products).
3. Move more
.
You may find yourself craving exercise because of joint pain. But exercise will help you maintain the mobility of your limbs, so you need to warm up, but in accordance with your doctor’s recommendations.
Differential diagnosis
To exclude malignant tumor lesions of the lymph nodes, they are punctured with collection and subsequent cytological and histological examination of tissue samples.
If cardiopulmonary symptoms occur, additional consultation with specialists in the field of cardiology and pulmonology is required, as well as an ultrasound scan of the chest and electrocardiogram study.
Pathologies for which differential diagnosis is carried out:
systemic vasculitis;- arthritis (rheumatoid and psoriatic);
- granulomatous hepatitis;
- lymphoma;
- sarcoidosis;
- tuberculosis;
- dermatomyositis;
- endocarditis of infectious origin.
Affected Populations
The adult form of Still's disease affects men and women in equal numbers. Some medical literature suggests that the disorder affects women slightly more often than men. This primarily concerns young people aged 16 to 35 years. The incidence of the disease in adults is still unknown. Due to the highly variable symptoms and rarity of the disorder, it is often underdiagnosed or misdiagnosed, making it difficult to determine its true incidence in the general population.
Prevention
To date, no preventive measures have been developed specifically designed to prevent the development of Still's disease.
You can reduce the likelihood of getting sick by following these general recommendations:
- maintaining a healthy and moderately active lifestyle;
- avoiding joint injuries and stressful situations;
- minimizing the effects of high or low temperatures on the body;
- timely detection and elimination of bacterial or viral diseases, especially those that arise during pregnancy;
- undergoing annual full preventive examinations at the clinic with visits to all specialists.
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Treatment of Still's disease in adults
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat EFS, although more than 80% of patients fail to achieve remission with these drugs; in addition, approximately 20% develop adverse reactions. NSAIDs can be used during the diagnostic period, with a monocyclic clinical course of the disease or in cases of isolated and mild arthritis. The first-line drugs in the treatment of EFS, regardless of the clinical picture, are glucocorticoids. They should be prescribed immediately after confirmation of the diagnosis. The usual starting dose of glucocorticoids is 0.5–1 mg/kg/day. Pulse therapy with high doses of methylprednisolone can also be performed, especially in cases of severe damage to internal organs. Response to glucocorticoid treatment should be expected within hours to days. A reduction in the dose of glucocorticoids is possible after 4–6 weeks. from the start of therapy, when the symptoms of the disease disappear and normalization of laboratory parameters is achieved. It is possible to achieve control over EFS activity during glucocorticoid therapy in approximately 60% of patients. In cases of ineffectiveness of this group of drugs or the development of steroid dependence, disease-modifying anti-inflammatory drugs (DMARDs), primarily methotrexate, should be prescribed. The use of methotrexate at a dose of 7.5–20 mg per week leads to remission in 70% of patients and contributes to a significant reduction in the dose of glucocorticoids. Elevated levels of liver enzymes are not a contraindication for its use, but require careful monitoring. If methotrexate is insufficiently effective, other DMARDs (cyclosporine A, leflunomide, azathioprine, plaquenil) are prescribed. Resistance to treatment with glucocorticoids and DMARDs is a hallmark of refractory EFS, which more often occurs in the form of a polycyclic or chronic clinical variant and requires the use of genetically engineered biological drugs (GEBD). TNF-α inhibitors (infliximab, etanercept, adalimumab) were the first DMARDs used to treat refractory EFS. In a series of clinical observations of refractory EFS, the IL-6 receptor blocker tocilizumab was also effective. Cases of effective use of rituximab have been described [1].
Forecast
The result of treatment may be recovery or the pathology becoming chronic. Only a third of patients recover completely. 2/3 suffer from a recurrent form for life, in which exacerbations occur quite rarely.
In a small percentage of patients, Still's syndrome develops into a cyclically relapsing form with frequent repeated attacks of the pathology.
In the most advanced cases, severe polyarthritis is added to Still's syndrome, which is characterized by severe limitation of joint mobility.
Reasons for development
Despite the long-term study of Still's disease, the etiology of the disease has not yet been fully elucidated. The sudden onset of the disease, accompanied by high fever, leukocytosis and lymphadenopathy, indicates the infectious nature of the disease, but the infectious agent of the disease has not been identified.
According to the infectious theory, the occurrence of Still's disease is associated with the body's reaction to infection by viruses or bacterial microorganisms.
Isolated cases of disease associated with the virus have been identified:
- rubella;
- cytomegalovirus;
- parainfluenza;
- Epstein-Barr virus.
Sometimes the disease is associated with the presence of bacteria (mycoplasma, Escherichia).
Since the HLA B35 antigen was detected in patients, there is a hypothesis about the genetic nature of Still's disease, but definitive data on the relationship of the disease with HLA loci are lacking.
The hypothesis about the autoimmune nature of Still's disease is also not fully confirmed - the CICs (circulating immune complexes) that cause the development of allergic vasculitis are detected only in some patients.