Adult-onset Still's disease overview

Adult-onset Still's disease
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Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Adult-onset Still’s Disease from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Adult-onset Still's disease (AOSD) is an inflammatory condition characterized by high spiking fever, rash, sore throat, and joint pain. In 1896, an English doctor named George Frederick Still, described the condition in children and the disease is named after him. In 1971, EG Bywaters described the term "adult Still's disease" which was later used for adults who had a condition similar to systemic onset JRA. Adult-onset Stiil's disease (AOSD) may be classified based on the predominant clinical picture with which the patient presents into systemic sub-type and chronic arthritis sub-type. The sub-types differ based on the cytokine profile, clinical course and response to treatment. It is an autoimmune inflammatory arthritis that typically affects adolescents and adults ranging from age 16-40 years. Major etiological mechanisms behind cause a dysfunction of the innate and cellular immunity (limited) leading to activation of effector cells of the disease. Although the pathogenesis of adult-onset Still's disease is largely knwon to be idiopathic. Triggers of AOSD lead to activation of toll-like receptors (TLR) and activation of immune system. Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) play an important role in the etiopathogenesis of AOSD. They lead to release of various cytokines in the body such as interleukin-1 beta (IL-1), interleukin-6 (IL-6), interleukin-17, interleukin-18, interferon-alpha (IFN-alpha) and tumor necrosis factor (TNF-alpha). On gross examination, the involved joints may exhibit soft tissue swelling, cartilage loss, jointerosions and carpal ankylosis (late during the disease process). On microscopic examination of the joint fluid, typical features associated with inflammatory joint disease may be observed. There is a dearth of data regarding the incidence and prevalence of adult-onset Still's disease (AOSD). In the Japanese and the European populations, the reported prevalence rates range from 10 to 340 cases per 100,000 individuals. The disease occurs worldwide and usually affects young adults (age 16-35 years). If left untreated, adult-onset Still's disease (AOSD) follows a relapsing and remitting course. Initial presentation of AOSD may be between 16 to 35 years of age. Symptoms usually evolve over weeks to months. Life-threatening complications known to be associated with AOSD include, macrophage activating syndrome (MAS), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), diffuse alveolar hemorrhage, pulmonary arterial hypertension (PAH), pericardial tamponade and myocarditis. The prognosis of adult-onset Still's disease depends upon the clinical course of the disease. The chronic articular form of the disease is associated with worse prognosis. The diagnosis of adult-onset Still's disease (AOSD) is made clinically along with supporting laboratory abnormalities and exclusion of other rheumatologic disorders, malignancy and infections. Three diagnostic criteria have been established in order to aid in the diagnosis of AOSD. Yamaguchi criteria is widely adopted. A patient suffering from AOSD may present with a fever greater than equal to 39 degrees celcius (102.2 degrees Fahrenheit) for greater than equal to 1 week along with associated arthralgia/arthritis for greater than equal to 2 weeks. There may be a maculopapular non-pruritic rash on the trunk or limbs. Patients may also complain of sore throat and lymphadenopathy. The symptoms of AOSD evolve over a period of weeks. On x-ray of the affected joints, soft tissue swelling and joint effusions may be seen during early course of the disease. Intercarpal and carpometacarpal joint space narrowing (JSN) and ankylosis may be observed. MRI is more sensitive than x-ray in detecting bony erosions. It can detect synovitis, inflammation of the lining of the joints and tendon abnormalities. Medical therapy in adult-onset Still's disease (AOSD) is guided by disease activity and severity. Corticosteroids are the first line therapy; Disease modifying anti-rheumatic drugs (DMARDs) as monotherapy or in combination with other agents may be used in refractory or complicated cases.

Historical Perspective

Adult-onset Still's disease (AOSD) is an inflammatory condition characterized by high spiking fever, rash, sore throat, and joint pain. In 1896, an English doctor named George Frederick Still, described the condition in children and the disease is named after him. In 1971, EG Bywaters described the term "adult Still's disease" which was later used for adults who had a condition similar to systemic onset JRA. There's no cure for adult-onset Still's disease; however, symptomatic treatment using corticosteroids, anti-interleukinagents and disease modifying anti-rheumatic drugs (DMARDs) may provide relief, and aid in remission.

Classification

Adult-onset Stiil's disease (AOSD) may be classified based on the predominant clinical picture with which the patient presents into systemic sub-type and chronic arthritis sub-type. The sub-types differ based on the cytokine profile, clinical course and response to treatment.

Pathophysiology

Adult-onset Still's disease (AOSD) is an autoimmune inflammatory arthritis that typically affects adolescents and adults ranging from age 16-40 years. Major etiological mechanisms behind cause a dysfunction of the innate and cellular immunity (limited) leading to activation of effector cells of the disease. Although the pathogenesis of adult-onset Still's disease is largely knwon to be idiopathic. Triggers of AOSD lead to activation of toll-like receptors (TLR) and activation of immune system. Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) play an important role in the etiopathogenesis of AOSD. They lead to release of various cytokines in the body such as interleukin-1 beta (IL-1), interleukin-6 (IL-6), interleukin-17, interleukin-18, interferon-alpha (IFN-alpha) and tumor necrosis factor (TNF-alpha) . These cytokines play major roles in modifying the normal working of the body and produce the typical clinical pictiure associated with AOSD. Some distinct HLA alleles have been shown to be associated with AOSD such as HLA-DR4, HLA-Bw35 (associated with good prognosis), HLA-DRB1, HLA-DRw6 (joint root involvement), HLA-B17, HLA-B35 and HLA-DR2. On gross examination, the involved joints may exhibit soft tissue swelling, cartilage loss, jointerosions and carpal ankylosis (late during the disease process). On microscopic examination of the joint fluid, typical features associated with inflammatory joint disease may be observed.

Causes

The cause of adult-onset Still's disease (AOSD) is unknown.

Differentiating Adult-onset Still's disease from Other Diseases

Adult-onset Still's disease (AOSD) is a diagnosis of exclusion and other conditions presenting with fever, fatigue, arthralgia, myalgia, rash and soft tissue swelling should be excluded if a diagnosis of AOSD is suspected clinically.

Epidemiology and Demographics

There is a dearth of data regarding the incidence and prevalence of adult-onset Still's disease (AOSD). In the Japanese and the European populations, the reported prevalence rates range from 10 to 340 cases per 100,000 individuals. The disease occurs worldwide and usually affects young adults (age 16-35 years). Adult-onset Still's disease (AOSD) affects females more than males. Aging adults affected by adult-onset Still's disease (AOSD) have a higher rate of development of complications related to AOSD and a higher mortality rate compared to younger individuals.

Risk Factors

The cause of adult-onset Still's disease (AOSD) remain unknown but stress are known to be associated with an increased risk of developing AOSD.

Screening

There is insufficient evidence to recommend routine screening of AOSD.

Natural History, Complications and Prognosis

If left untreated, adult-onset Still's disease (AOSD) follows a relapsing and remitting course. Initial presentation of AOSD may be between 16 to 35 years of age. Symptoms usually evolve over weeks to months. Life-threatening complications known to be associated with AOSD include, macrophage activating syndrome (MAS), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), diffuse alveolar hemorrhage, pulmonary arterial hypertension (PAH), pericardial tamponade and myocarditis. The prognosis of adult-onset Still's disease depends upon the clinical course of the disease. The chronic articular form of the disease is associated with worse prognosis. Other indicators of poor prognosis of AOSD include, presence of polyarthritis, interestitial pneumonia, pleuritis, joint erosions, Still's rash (salmon-colored maculopapular rash) and development of secondary complications.

Diagnosis

Diagnostic study of choice

The diagnosis of adult-onset Still's disease (AOSD) is made clinically along with supporting laboratory abnormalities and exclusion of other rheumatologic disorders, malignancy and infections. Three diagnostic criteria have been established in order to aid in the diagnosis of AOSD. Yamaguchi criteria is widely adopted.

History and symptoms

Obtaining a comprehensive history is an integral part of diagnosing adult-onset Still's disease (AOSD). The typical age of onset of adult-onset Still's disease (AOSD) is between 16 to 35 years of age. A patient suffering from AOSD may present with a fever greater than equal to 39 degrees celcius (102.2 degrees Fahrenheit) for greater than equal to 1 week along with associated arthralgia/arthritis for greater than equal to 2 weeks. There may be a maculopapular non-pruritic rash on the trunk or limbs. Patients may also complain of sore throat and lymphadenopathy. The symptoms of AOSD evolve over a period of weeks.

Physical examination

On physical examination, a patient suffering from adult-onset Still's disease (AOSD) may appear fatigued, has a high grade fever (spiking fever), tachycardia, salmon colored maculopapular rash on trunk and/or extremities, lymphadenopathy, hepatosplenomegaly, pleural and pericardial friction rub (due to underlying pleuritis and pericarditis).

Laboratory findings

Adult-onset Still's disease (AOSD) is diagnosed based on clinical presentation and history findings. However, due to underlying inflammatory process, inflammatory marker such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated. Complete blood count may show leukocytosis with a left shift (increased neutrophils), anemia, thrombocytosis or pancytopenia (in cases of hemophagocytic syndrome).

Electrocardiogram

There are no specific EKG findings associated with adult-onset Still's disease (AOSD), however, in cases complicated by pericarditis, cardiac tamponade or myocarditis EKG abnormalities may be observed.

X-ray

On x-ray of the affected joints, soft tissue swelling and joint effusions may be seen during early course of the disease. Intercarpal and carpometacarpal joint space narrowing (JSN) and ankylosis may be observed.

CT scan

On CT scan of the abdomen, patients suffering from Still's disease may have hepatomegaly and splenomegaly.

MRI

MRI is more sensitive than x-ray in detecting bony erosions. It can detect synovitis, inflammation of the lining of the joints and tendon abnormalities.

Other imaging findings

Bone scan (bone scinitgraphy) may be used for early detection of articular erosions in adult-onset Still's disease (AOSD).

Other diagnostic studies

There are no other diagnostic studies associated with adult-onset Still's disease (AOSD).

Treatment

Medical therapy

Medical therapy in adult-onset Still's disease (AOSD) is guided by disease activity and severity. Corticosteroids are the first line therapy; Disease modifying anti-rheumatic drugs (DMARDs) as monotherapy or in combination with other agents may be used in refractory or complicated cases.

Surgery

Surgery is not the mainstay of treatment of adult-onset Stills' disease (AOSD).

Primary prevention

There is no primary prevention for adult-onset Still's disease (AOSD)

Secondary prevention

Secondary prevention of adult-onset Still's disease (AOSD) is aimed at preventing relapses of the disease. Tocilizumab may be used to prevent relapses associated with AOSD.