What Is Adult-Onset Still’s Disease?
Adult-onset Still's disease (AOSD) is a systemically inflammatory condition that mostly affects young individuals and has no recognized cause. Still's disease was named after George Still's description of 22 children with systemic-onset juvenile idiopathic arthritis (sIJA) in 1897. Following that, in 1971, Eric Bywaters described 14 adult patients with skin rash, fever, and polyarthritis whose clinical picture was strikingly similar to pediatric Still's disease, identifying AOSD. AOSD is still a multisystemic disorder with an unknown cause, challenging diagnosis, and little research compared to other rheumatic diseases, despite the bad outcomes in some individuals.
What Are the Clinical Features of AOSD?
The clinical triad of AOSD is characterized by rising fever, joint problems, and a maculopapular salmon-pink spectral skin rash.
Fever:
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Approximately 20 percent of flu symptoms with an unknown cause are caused by AOSD, and practically all patients have a high-spiking fever.
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AOSD fever is usually higher than 39 °C and lasts less than four hours. The maximum temperatures are usually reported either in the late afternoons or early evenings, following every day or twice daily pattern.
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The fever usually appears suddenly, similar to an infectious illness, and the temperature might sometimes return to normal without antipyretic treatment. Fever frequently precedes the start of other symptoms in AOSD.
Musculoskeletal Disease:
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Joint pain and inflammation, primarily affecting the wrists, knees, and ankles, are common signs of AOSD. These signs may be faint and intermittent during the onset of the disease.
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Patients may develop chronic destructive symmetrical polyarthritis as a result. After six months of infection, constriction of the precipitate or the carpometacarpal joint may occur, with probable progression to carpal ankylosis in the following years. In this situation, joint fluid aspiration has been reported to reveal an inflammatory fluid with a neutrophil concentration.
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Myalgias are another typical musculoskeletal AOSD symptom; they are usually generalized and concomitant with fever flare-ups.
Skin Disease:
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During febrile episodes, a high majority of AOSD patients may develop evanescent salmon-pink erythema that may be coupled with an erythematous maculopapular eruption, which appears largely on the trunk and proximate limbs. This eruption can last for weeks in some patients, usually with a more severe consequence.
Splenomegaly and Involvement of Lymph Nodes:
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In AOSD patients, splenomegaly and mild-to-severe enlargement of cervical lymph nodes (LNs) are common, and lymphoma should always be included in the differential diagnosis.
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Various patterns have been detected in histological examinations of LNs samples.
Involvement of Liver:
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Hepatomegaly (enlargement of the liver).
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Mild to severe cytolysis (cellular disintegration or pathological dissolution).
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Pseudo-angiocholitis (high blood ferritin levels and a decreased glycosylated ferritin percentage).
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Severe hepatitis.
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Hepatic failure.
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All patients have recovered completely from their hepatic involvement.
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Nonsteroidal anti-inflammatory medications (NSAIDs) use has been linked to liver impairment.
What Are the Other Signs and Symptoms of AOSD?
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AOSD can cause a variety of non-specific symptoms.
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Patients may experience sore throat symptoms early in the phase of the illness or during a flare-up. It has been claimed that it is linked to a viral infection (which causes the disease), inflammatory involvement of the crico-arytenoid joints, or aseptic non-exudative pharyngitis.
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Patients with AOSD may develop fibrosis, pericardial and pleural effusions, and other cardio-pulmonary symptoms.
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Interstitial nephritis, subacute glomerulitis, renal amyloidosis, and collapsing glomerulopathy have all been linked to AOSD.
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Neurological symptoms such as cranial nerve paralysis and seizures can also be identified.
What Are the Main Complications of AOSD
Macrophage Activation Syndrome:
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Non-remitting high fever.
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Hepatosplenomegaly.
Disseminated Intravascular Coagulopathy:
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Non-remitting high fever.
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Purpuric or petechial rash.
Thrombotic Thrombocytopenic Purpura:
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Microangiopathic Hemolytic Anemia: Anemia caused by physical damage to red blood cells resulting in fibrin formation or platelet aggregation occluding arterioles and capillaries.
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Thrombocytopenia: Decreased platelet count.
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Multiple Organ Failure: Failure of organs due to disseminated intravascular coagulation and thrombotic microangiopathies. They are dangerous conditions that occurs when the proteins that regulate blood clotting are overactive.
Diffuse Alveolar Hemorrhage:
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Hemoptysis: Spitting blood from lungs or bronchioles.
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Coughing.
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Progressive Dyspnoea: Breathlessness.
Pulmonary Hypertension:
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Shortness of breath.
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Chest pain.
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Swelling.
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Cyanosis (bluing of extremities due to the decreased oxygen level in the blood).
Aseptic Meningitis:
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Headache.
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Firm pain in the neck.
What Are the Laboratory Investigations for AOSD?
In AOSD, laboratory tests reveal signs that point to an inflammatory condition. The most common abnormalities in the laboratory tests include:
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An increase in erythrocyte sedimentation rate (ESR) which reveals inflammatory activity in the body.
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Leukocytosis (increased level of white blood cells [WBC]).
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Thrombocytopenia (decreased platelet count in the blood).
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Increased ferritin levels in the blood (this is the common finding in AOSD).
How to Diagnose AOSD?
Yamaguchi Criteria for the Diagnosis of AOSD:
At least five features are required for diagnosis, with at least two of these being major criteria.
Major Criteria:
- Fever of at least 39°C for at least a week.
- Arthralgia or arthritis for at least two weeks.
- Nonpruritic salmon-colored rash on trunk or extremities.
- Granulocytic leukocytosis (10,000/microL or greater).
Minor Criteria:
- Sore throat.
- Lymphadenopathy.
- Hepatomegaly or splenomegaly.
- Abnormal liver function tests.
- Negative tests for rheumatoid factors (RF) and antinuclear antibody (ANA).
AOSD is primarily an exclusionary diagnosis that should be evaluated only after ruling out various differential diagnoses. Among the various differentials, the following important disorders should be ruled out:
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Infectious diseases like infective endocarditis, tuberculosis (TB), and Lyme disease.
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Granulomatous diseases like Crohn’s disease, sarcoidosis, and idiopathic granulomatous hepatitis.
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Malignancies like lymphomas and leukemias.
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Connective tissue diseases such as systemic lupus erythematosus, mixed connective tissue disease, polyarteritis nodosa, Takayasu’s arteritis, and Wegener’s granulomatosis.
What Are the Various Disease Patterns of AOSD?
There are three different disease patterns of AOSD, they are:
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A monocyclic or self-limiting pattern is characterized by a single bout of systemic disease that lasts for a variable amount of time and is followed by complete remission.
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A polycyclic or intermittent pattern is characterized by two or more bouts of systemic disease that are separated by at least a two-month symptom-free remission phase.
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The chronic articular pattern is characterized by extensive articular symptoms that lead to the destruction of joints.
What Is the Prognosis of Patients With AOSD?
Patients with polyarticular origin, proximal joint inflammation, a previous episode in childhood, and a need for systemic steroids for further than two years have a bad prognosis. At the same time, individuals with monocyclic or polycyclic clinical manifestations, no arthritis at diagnosis, or an oligoarticular incidence and course demonstrated improved functional status.
How to Treat Patients With AOSD?
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First-line treatment is corticosteroids. It works for 60 percent of AOSD patients.
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Intra-articular steroid injection for a chronic articular pattern of AOSD.
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Disease-modifying antirheumatic drugs (DMARDs) for maintenance therapy.
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Sulfasalazine should be avoided as it causes severe adverse reactions such as abdominal pain, nausea, vomiting, and myelosuppression.
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Methotrexate is often used to prevent the worsening of arthritis.
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Cyclosporine for AOSD patients with macrophage activation syndrome (MAS).
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Anakinra for quick relief of systemic symptoms. Due to the short half-life, it is given subcutaneously once a day. If Anakinra does not provide enough of a response, Canakinumab and Rilonacept can be used instead as they have prolonged half-lives and, therefore, can be given every week or every eight weeks, respectively.
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Tocilizumab is used in the management of systemic-onset juvenile idiopathic arthritis and is usually administered as an intravenous infusion, once a month, or as a subcutaneous injection every one to two weeks.
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Intravenous immunoglobulins and exchange of plasma are other treatment options for refractory AOSD.
Conclusion:
AOSD has remained a diagnostic enigma for clinicians for the past four decades since it manifests as a collection of non-specific symptoms that could be produced by a wide range of disorders. The important thing to remember is that AOSD should be considered in the differential diagnosis for patients who have a prolonged and unexplained fever, musculoskeletal complaints, and a macular rash. Early diagnosis and management of the condition can help to avoid complications and provide a better prognosis and quality of life.