Systemic-onset juvenile idiopathic arthritis (or the juvenile onset form of Still's disease) is a type of

juvenile idiopathic arthritis Juvenile idiopathic arthritis (JIA) is the most common, chronic rheumatic disease of childhood, affecting approximately one per 1,000 children. ''Juvenile'', in this context, refers to disease onset before 16 years of age, while ''idiopathic'' r ...

(JIA) with extra-articular manifestations like fever and rash apart from

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

. It was originally called systemic-onset juvenile rheumatoid arthritis or Still's disease. Predominantly extra-articular manifestations like high

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

s, rheumatic rash, enlargement of the liver and spleen, enlargement of the lymph nodes, and

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

. Other manifestations include inflammation of the pleura, inflammation of the pericardium, inflammation of the heart's muscular tissue, and inflammation of the peritoneum are also seen. It is sometimes called "juvenile-onset Still's disease" to distinguish it from

adult-onset Still's disease Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnos ...

. However, there is some evidence that the main difference between two conditions is the age of onset.

Presentation

Systemic JIA is characterized by arthritis,

, which typically is higher than the low-grade fever associated with polyarticular and a salmon pink

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

. It accounts for 10-20% of JIA and affects males and females equally, unlike the other two subtypes of JIA, and affects adolescents. It generally involves both large and small joints. Systemic JIA can be challenging to diagnose because the fever and rash come and go. Fever can occur at the same time every day or twice a day (often in late afternoon or evening) with a spontaneous rapid return to baseline (vs. continuous fever of

septic arthritis Acute septic arthritis, infectious arthritis, suppurative arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, hea ...

). The rash often occurs with fever. It is a discrete, salmon-pink macules of different sizes. It migrates to different locations on skin, rarely persisting in one location more than one hour. The rash is commonly seen on trunk and proximal extremities or over pressure areas. Arthritis is often absent in the first weeks or even 6–8 months into the illness. Systemic JIA may have

internal organ In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...

involvement such as hepatosplenomegaly, lymphadenopathy,

serositis Serositis refers to inflammation of the serous tissues of the body, the tissues lining the lungs (pleura), heart (pericardium), and the inner lining of the abdomen (peritoneum) and organs within. It is commonly found with fat wrapping or creeping ...

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

, or

tenosynovitis Tenosynovitis is the inflammation of the fluid-filled sheath (called the synovium) that surrounds a tendon, typically leading to joint pain, swelling, and stiffness. Tenosynovitis can be either infectious or noninfectious. Common clinical manifest ...

Cause

The cause is unknown but it's thought to be related to environmental, genetic, and hormonal factors. A polymorphism in

macrophage migration inhibitory factor Macrophage migration inhibitory factor (MIF), also known as glycosylation-inhibiting factor (GIF), L-dopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the ''MIF'' gene. MIF is an important regulator of i ...

has been associated with this condition.

Diagnosis

Rheumatoid factor Rheumatoid factor (RF) is the autoantibody that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG and different RFs can recognize different parts of the IgG-Fc. RF and IgG join to form immune com ...

and ANA tests are generally negative in systemic JIA. Lab findings:

anemia of chronic disease Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin product ...

(can also appear in non-systemic types),

neutrophilia Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosis ...

thrombocytosis Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...

, elevated

acute phase reactants Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute-p ...

( ESR, CRP,

ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ' ...

Treatment

Treatment with either

glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

anakinra Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modifi ...

, or

tocilizumab Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID19. It is a hu ...

has been examined.

Anakinra Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modifi ...

has been shown to resolve the clinical features of the disease in 87% of patients. It also induces remission in half of corticosteroid-resistant patients. The results of another study were similar, with half of the patients responding to treatment with Anakinra.

Canakinumab Canakinumab (International Nonproprietary Name, INN), sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis (SJIA) and active Still's disease, including adult-onset Still's disease (AOSD). ...

, an antibody to

interleukin-1 beta Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...

, is indicated for treatment in patients who respond poorly to other treatments.

Prognosis

25% of cases progress to severe destructive arthritis. In the United States, mortality is estimated at 4% and in Europe, mortality is estimated at 21.7%.

History

Still's disease is named after

English English usually refers to: * English language * English people English may also refer to: Peoples, culture, and language * ''English'', an adjective for something of, from, or related to England ** English national ide ...

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

Sir George Frederic Still Sir George Frederic Still, KCVO (27 February 1868 – 28 June 1941) was an English paediatrician, author of five medical textbooks, and publisher of hundreds of papers. Still first described a form of juvenile idiopathic arthritis as well ...

(1861–1941).G. F. Still. A special form of joint disease met with in children. Doctoral dissertation, Cambridge, 1896. It was characterized by EG Bywaters in 1971.

References

External links

{{Medical resources , DiseasesDB = 12430 , ICD10 = {{ICD10, M, 08, 2, m, 05 , ICD9 = {{ICD9, 714.30 , ICDO = , OMIM = 604302 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = , Orphanet = 85414 Arthritis Pediatrics Rheumatology Connective tissue diseases Inflammatory polyarthropathies Idiopathic diseases Rare diseases