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Official reprint from UpToDate www.uptodate.com ©2015 UpToDate

AuthorYukiko Kimura, MD

Section EditorMarisa Klein­Gitelman, MD, MPH

Deputy EditorElizabeth TePas, MD, MS

Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Sep 2015. | This topic last updated: Sep 09, 2014.

INTRODUCTION — Systemic juvenile idiopathic arthritis (sJIA, formerly called Still's disease or systemicjuvenile rheumatoid arthritis) is officially classified as a subset of juvenile idiopathic arthritis (JIA) that describespatients with intermittent fever, rash, and arthritis. It is termed "adult­onset Still's disease" when it occurs inpatients over the age of 16. sJIA accounts for about 10 to 20 percent of all cases of JIA. It typically affects bothsexes equally and may present in children as young as one year of age or younger. (See "Juvenile idiopathicarthritis: Epidemiology and immunopathogenesis".)

The clinical manifestations and diagnosis of sJIA are reviewed here (table 1). The management, complications,and prognosis of sJIA, as well as oligoarticular, polyarticular, enthesitis­related, and psoriatic JIA and generaltopics on JIA are discussed separately. (See "Systemic juvenile idiopathic arthritis: Treatment" and "Systemicjuvenile idiopathic arthritis: Course, prognosis, and complications" and "Oligoarticular juvenile idiopathic arthritis"and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations and diagnosis" and "Spondyloarthropathy inchildren" and "Psoriatic juvenile idiopathic arthritis: Pathogenesis, clinical manifestations, and diagnosis" and"Psoriatic juvenile idiopathic arthritis: Management and prognosis" and "Classification of juvenile arthritis" and"Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis".)

OVERVIEW — Patients with systemic juvenile idiopathic arthritis (sJIA) fall into the category of systemic arthritisin the 2004 proposed classification of the childhood arthritides [1]. Children with this illness comprise between 10and 20 percent of all cases of juvenile idiopathic arthritis (JIA). However, data suggest that this illness is a uniquecondition closer to the autoinflammatory family of diseases, with distinct manifestations and treatment responsesthat distinguish it from the other diseases categorized as JIA [2,3]. (See "Classification of juvenile arthritis" and"Periodic fever syndromes and other autoinflammatory diseases: An overview".)

This form of JIA may be the most difficult to diagnose and treat for the following reasons:

Some children who present with fever, rash, and diffuse joint pain do in fact have infections, leukemia, or otherserious conditions that are not sJIA. Thus, it is essential that clinicians thoroughly exclude other conditions beforemaking this diagnosis.

CLINICAL MANIFESTATIONS — Children with systemic juvenile idiopathic arthritis (sJIA) may present with avariety of articular and extraarticular signs and symptoms. In one large case series from a tertiary center, 136patients were diagnosed with sJIA from 1990 to 2005 [4]. The following manifestations at disease onset and

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Arthritis, although necessary to establish a definitive diagnosis, may not be evident early in the course of thedisease [1,4].

The systemic disease features may not be present in their typical forms initially, even though these typicalfeatures are also necessary to establish a definitive diagnosis [1,4].

There are no diagnostic tests for this disorder.

Affected children often appear quite ill with high spiking fevers, rashes, markedly elevated white blood cell(WBC) counts, and anemia. Most such children are initially thought to have an infection or malignancy, andthe correct diagnosis is only suspected after there has been no response to antibiotic therapy andmalignancy has been excluded.

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relative frequency were noted:

Articular manifestations — Arthralgias are common early in the course of sJIA, but arthritis is not alwaysprominent. Any number of joints may be involved when arthritis becomes apparent. Disease in the wrists, knees,and ankles is most typical, but the hands, hips, cervical spine, and temporomandibular joints are also sometimesaffected. Unlike the oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis (JIA), the arthritis ofsJIA may begin in the hips and may progress very rapidly, causing severe damage and dysfunction and need forearly joint replacement surgery as well as loss of growth potential in younger patients. (See "Systemic juvenileidiopathic arthritis: Course, prognosis, and complications", section on 'Growth retardation'.)

Micrognathia and cervical spine fusion are commonly present in children with longstanding sJIA, but do not appearuntil after the disease has been present for months to years (image 1) [5]. In the past, these abnormalities affectedas many as 50 percent of children with disease onset in the first decade of life. Earlier and more targetedtreatment has led to a decrease in these complications. (See "Systemic juvenile idiopathic arthritis: Treatment".)

Extraarticular manifestations — The most common extraarticular manifestations are quotidian fever and amacular, salmon pink rash.

Fever — Children with sJIA usually come to medical attention urgently because they typically present withhigh fevers. The key finding that suggests the diagnosis is the daily, but intermittent, nature of the fever. Thediagnosis is strongly in doubt if the patient's temperature does not spontaneously return to normal on a daily basis.This pattern of one high spike of fever a day with normal or subnormal temperatures during the rest of the 24­hourperiod is called quotidian fever. Some children have more than one spike of fever a day, but their temperaturereturns to normal in between the fever spikes. Affected children are characteristically ill­appearing when febrile, butseem to improve dramatically when their temperature is normal. If rash is present (see 'Rash' below), it also tendsto appear or worsen when the fever is present. These features, in addition to the lack of response to antibiotics,help to distinguish patients with sJIA from those with an infection. (See 'Differential diagnosis' below.)

Some children do not have this typical fever pattern initially and have continuous fevers, fever that does not occurdaily, or no fever at all. If untreated, however, most patients will eventually develop this highly specific feverpattern.

Rash — A macular, salmon pink rash is frequently present (picture 1). It usually consists of multiple round tooval macules that are slightly raised and are of differing sizes. The smaller ones have a slight pallor surroundingthem and the larger ones commonly exhibit central pallor. The rash is often difficult to detect or may not be noticedat all in dark­skinned individuals. The rash is brought out by heat and touch, and is often found in the axillae andaround the waist, but may be present anywhere on the body. It is most prominent when the child is febrile. Unlikeviral exanthems, which persist, the rash often fades as the temperature returns to normal, only to reappear withthe next fever spike. The rash also may appear following stroking of the skin or other minor trauma (Koebnerphenomenon) (picture 2). The rash can be intensely pruritic in some patients. It can become somewhat confluentand become urticarial in appearance, especially in those patients who scratch themselves because of the pruritus[6].

Other clinical findings — In addition, the following clinical features can be observed:

Fever – 98 percentArthritis – 88 percent (8 percent with monoarthritis, 45 percent with oligoarthritis, and 47 percent withpolyarthritis)

Rash – 81 percentLymphadenopathy – 31 percent

Hepatomegaly, splenomegaly, and lymphadenopathy are commonly found. This combination frequentlyraises suspicion of a malignancy, but lymph node biopsy shows benign reactive hyperplasia. (See'Malignancy' below.)

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LABORATORY FINDINGS — Characteristic patterns of laboratory abnormalities frequently are present andsuggestive of the disease, although there are no laboratory findings that are specific for the diagnosis:

Pericarditis and other forms of serositis are a feature of sJIA. A small pericardial effusion that is not usuallyclinically significant is often noted on echocardiogram. Large pericardial effusions are rare. Pericarditis mayresult in tamponade, in some cases with a fatal outcome [7].

Pulmonary manifestations include pleural effusion, which most often present during the acute phase of theillness in patients with serositis. Interstitial lung disease, alveolar proteinosis, and pulmonary hypertensionare rare, but are being reported with increased frequency [8].

Some children may initially present with features suggestive of Kawasaki disease (KD) or atypical KD,including coronary artery dilation on echocardiogram in some cases [9­11]. These patients are only diagnosedwith sJIA when they fail to respond to treatment for KD. (See "Kawasaki disease: Clinical features anddiagnosis" and "Incomplete (atypical) Kawasaki disease", section on 'Clinical presentation of typical versusincomplete KD'.)

White blood cell (WBC) counts in the 20,000 to 30,000/mm range are not uncommon, and at times theymay exceed 60,000 to 80,000. Granulocytes predominate [4].

3

There is usually a marked reactive thrombocytosis and the platelet count may exceed 1,000,000/mm [4].Thus, thrombocytopenia or even low normal platelet counts (eg, less than 200,000/mm ) should promptcareful evaluation for an alternative diagnosis (eg, bone marrow aspiration to exclude leukemia). A sudden,rapid drop in the platelet count may herald the development of macrophage activation syndrome (MAS), aform of hemophagocytic lymphohistiocytosis. (See 'Malignancy' below and "Clinical features and diagnosisof hemophagocytic lymphohistiocytosis", section on 'Rheumatologic disorders/MAS' and "Systemic juvenileidiopathic arthritis: Course, prognosis, and complications", section on 'Macrophage activation syndrome'.)

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Anemia is commonly present and often profound. It is primarily due to decreased synthesis and poorabsorption of oral iron rather than increased destruction [12]. The anemia can be exacerbated by chronicgastrointestinal blood loss induced by nonsteroidal antiinflammatory drugs (NSAIDs). Thus, children withsystemic juvenile idiopathic arthritis (sJIA) commonly become iron deficient over time, but oral ironsupplementation is often ineffective until the underlying inflammatory process has been corrected.Intravenous or intramuscular iron may be required in cases of severe iron deficiency [13]. Oral ironsupplementation is often necessary once systemic disease begins to come under control. (See "Irondeficiency in infants and young children: Treatment".)

The erythrocyte­sedimentation rate (ESR) is typically elevated in children with sJIA and may exceed 100mm/hour. A normal ESR is rare when the disease is active. The level of C­reactive protein (CRP), anotheracute­phase reactant, is usually elevated as well. The combination of a dramatic fall in the ESR and adramatic fall in the platelet count may herald the onset of MAS in an unwell child rather than clinicalimprovement. Careful evaluation of children with this combination of findings is essential. A dramatic rise inthe serum ferritin level or in fibrin split products (D­dimers) also strongly suggests the onset of MAS, and aferritin/ESR ratio of 80 is a proposed biomarker of MAS [14]. (See "Clinical features and diagnosis ofhemophagocytic lymphohistiocytosis", section on 'Rheumatologic disorders/MAS' and "Systemic juvenileidiopathic arthritis: Course, prognosis, and complications", section on 'Macrophage activation syndrome'.)

Extreme hyperferritinemia (often greater than 1000 or even 50,000 ng/mL) is also common in children withactive sJIA, even if overt MAS is not present. It can be useful in raising suspicion for the diagnosis of sJIA,since very few other illnesses are associated with such extreme elevations in ferritin levels [3,15]. (See"Clinical features and diagnosis of hemophagocytic lymphohistiocytosis", section on 'Rheumatologicdisorders/MAS'.)

Minor elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hypoalbuminemia,

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DIAGNOSIS — Systemic juvenile idiopathic arthritis (sJIA) is a diagnosis of exclusion. The hallmark of sJIA isthe combination of intermittent but daily fevers greater than 38.5ºC (quotidian fever pattern) and arthritis [1]. Thefever must be present for at least two weeks and the arthritis for at least six weeks in order to make a definitivediagnosis according to the International League of Associations for Rheumatology (ILAR) criteria, since many viraland other postinfectious forms of arthritis are associated with fever, as are malignancies. However, thesediseases often lack the characteristic intermittent spiking fever pattern of sJIA. (See "Specific viruses that causearthritis".)

There may be a prolonged delay between the onset of fever and the development of arthritis, but a definitivediagnosis of sJIA cannot be made until arthritis is present and is shown to be persistent [4]. In the presence of acharacteristic fever pattern, rash, and arthritis, a tentative diagnosis of sJIA can be made and appropriate therapybegun before two weeks have elapsed [17]. (See "Systemic juvenile idiopathic arthritis: Treatment".)

By definition, sJIA cannot be diagnosed if symptoms occur after the age of 16 years. A similar and probablyidentical illness has been described in adults and is called adult­onset Still's disease [18]. Recurrent disease afterthe age of 16 is not adult­onset Still's disease, but simply a continuation of sJIA. (See "Clinical manifestations anddiagnosis of adult Still's disease".)

DIFFERENTIAL DIAGNOSIS — Systemic juvenile idiopathic arthritis (sJIA) can be confused with a number ofother disorders, including viral or postinfectious arthritis, other rheumatic or autoinflammatory diseases,malignancy, or malaria.

Viral and postinfectious arthritis — Postinfectious and viral arthritis often present with fever that is notintermittent, rash that differs in appearance from that of sJIA, and transient arthritis. Parvovirus B19 is one of themost commonly confused viral infections that cause arthritis [19]. The mistaken diagnosis of these self­limitedconditions as sJIA is in large part responsible for the incorrect notion that the latter disorder often resolvescompletely without aggressive therapy. (See "Pathogenesis and diagnosis of viral arthritis".)

Reactive arthritis may also follow a variety of bacterial infections. Those typically associated with fever, rash, andarthritis include neisserial and streptococcal infections. Subacute bacterial endocarditis may present with thesesymptoms and may be associated with a positive test for rheumatoid factor (RF). These entities can usually be

increased globulin levels, and low­grade D­dimer positivity are often present. However, markedly elevatedhepatic enzyme abnormalities, prolonged clotting times, or an increase in D­dimers should prompt immediateconsideration of diffuse intravascular coagulation (DIC) or MAS. (See "Systemic juvenile idiopathic arthritis:Course, prognosis, and complications", section on 'Macrophage activation syndrome'.)

The urinalysis is typically normal in children with sJIA. Some children manifest low­grade proteinuria whenfebrile, but significant proteinuria or hematuria are almost never seen in patients with sJIA. Secondaryamyloidosis resulting in proteinuria that can reach the nephrotic range has been reported in the Europeanliterature, but is exceedingly rare [16]. Thus, the presence of hematuria or significant proteinuria incombination with fever, arthritis, and rash should prompt consideration of another diagnosis, such assystemic lupus erythematosus or a systemic vasculitis rather than juvenile idiopathic arthritis (JIA). (See"Systemic lupus erythematosus (SLE) in children: Clinical manifestations and diagnosis" and "Vasculitis inchildren: Classification and incidence" and "Vasculitis in children: Evaluation" and "Vasculitis in children:Management overview".)

Antinuclear antibodies (ANA) and rheumatoid factor (RF) rarely are seen in sJIA. Their presence shouldprompt consideration of alternative diagnoses. A positive RF, for example, may be associated with RF­positive polyarticular JIA, Sjögren's syndrome, or the early onset of adult type rheumatoid arthritis (RA) inteenagers. Both RF and ANA may be present in children with mixed connective tissue disease (MCTD).However, these conditions rarely mimic sJIA. (See "Polyarticular juvenile idiopathic arthritis: Clinicalmanifestations and diagnosis" and "Diagnosis and classification of Sjögren's syndrome" and "Clinicalmanifestations of rheumatoid arthritis".)

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differentiated by their clinical picture, appropriate cultures, and the response to antibiotics. Reactive arthritisfollowing enteric infection may be also mistakenly diagnosed as sJIA. The key differential features pointing awayfrom a diagnosis of sJIA include gastrointestinal complaints, ocular findings, and lack of the classic salmon pinkrash. (See "Clinical manifestations and diagnosis of acute rheumatic fever" and "Reactive arthritis" and "Clinicalmanifestations and diagnosis of infective endocarditis".)

Other autoimmune and autoinflammatory diseases — Arthritis with fever and rash may be the presentingmanifestations in systemic lupus erythematosus, polyarteritis nodosa, mixed connective tissue disease (MCTD),dermatomyositis, sarcoidosis, neonatal onset multisystem inflammatory disease, and other autoinflammatorydiseases. These illnesses can be excluded by the clinical picture and appropriate laboratory evaluations. As anexample, abdominal pain is common in polyarteritis nodosa and should prompt consideration of this illness onceother causes have been excluded. Chronic abdominal pain in a child with suspected sJIA should not be ascribedto benign conditions, such as "mesenteric adenitis," without thorough investigation to exclude other possiblediagnoses, especially vasculitis and inflammatory bowel disease. (See "Systemic lupus erythematosus (SLE) inchildren: Clinical manifestations and diagnosis" and "Vasculitis in children: Classification and incidence", sectionon 'Polyarteritis nodosa' and "Pathogenesis and clinical manifestations of juvenile dermatomyositis andpolymyositis" and "Extrapulmonary manifestations of sarcoidosis", section on 'Musculoskeletal' and "Cryopyrin­associated periodic syndromes and related disorders" and "Periodic fever syndromes and other autoinflammatorydiseases: An overview".)

Malignancy — Every pediatric rheumatology center reports the referral of children thought to have sJIA who werefound to have leukemia, lymphoma, or other malignancies. Clinician awareness is the key to proper diagnosis.sJIA is not associated with thrombocytopenia, lymphocytosis, neutropenia, or bone pain. Children with sJIA areuncomfortable and may have swollen joints, but they rarely cry out from pain even when their joints aremanipulated [20]. By comparison, children with leukemia or other malignancies may be exquisitely uncomfortableand often complain of pain when the shaft of a long bone is compressed away from any joints (eg, mid­humerus ormid­femur). The pain in leukemia can change and be fleeting, as opposed to the pain of chronic arthritis, whichmay involve several joints, but usually does not move from place to place. Refusal to weight bear is another signof bone pain that may be indicative of a malignancy. (See "Evaluation of the child with joint pain or swelling" and"Clinical assessment of the child with suspected cancer".)

Malaria — Malaria may have a diurnal fever pattern identical to that of sJIA and is also associated with chills, jointpains, and evidence of systemic illness. Malaria is extremely rare in nonendemic countries, but appropriate thickblood smears to exclude this diagnosis should be performed if the patient gives a history of residence in or travelto such areas. (See "Clinical manifestations of malaria".)

Other — Marrow infiltrative diseases, such as Langerhans cell histiocytosis, and inherited conditions, such asGaucher disease and Hunter and Hurler syndromes, also may present with fever, joint pain, and rash. However,none of these illnesses manifest the typical laboratory findings, the fever pattern, or the salmon pink rash of sJIA.(See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Gaucherdisease: Pathogenesis, clinical manifestations, and diagnosis" and "Mucopolysaccharidoses: Clinical features anddiagnosis", section on 'Hurler syndrome' and "Mucopolysaccharidoses: Clinical features and diagnosis", sectionon 'MPS type II (Hunter syndrome)'.)

SUMMARY

Systemic juvenile idiopathic arthritis (sJIA, formerly called Still's disease or systemic juvenile rheumatoidarthritis) is officially a subset of juvenile idiopathic arthritis (JIA) that describes patients with intermittentfever, rash, and arthritis. However, sJIA is probably an autoinflammatory disorder rather than an autoimmunedisorder. (See 'Introduction' above and 'Overview' above.)

sJIA is the most difficult form of JIA to diagnosis because there are no specific diagnostic tests, andarthritis, which is necessary for definite diagnosis, is often not evident early in the course of the disease. Inaddition, infection and malignancies must be considered prior to the diagnosis of sJIA in these cases,

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ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Thomas JA Lehman, MD,who contributed to an earlier version of this topic review.

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REFERENCES

1. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatologyclassification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31:390.

2. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet 2011; 377:2138.3. Nigrovic PA. Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis?

Arthritis Rheumatol 2014; 66:1405.4. Behrens EM, Beukelman T, Gallo L, et al. Evaluation of the presentation of systemic onset juvenile

rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR). JRheumatol 2008; 35:343.

5. Hensinger RN, DeVito PD, Ragsdale CG. Changes in the cervical spine in juvenile rheumatoid arthritis. JBone Joint Surg Am 1986; 68:189.

6. Prendiville JS, Tucker LB, Cabral DA, Crawford RI. A pruritic linear urticarial rash, fever, and systemicinflammatory disease in five adolescents: adult­onset still disease or systemic juvenile idiopathic arthritissine arthritis? Pediatr Dermatol 2004; 21:580.

7. Parvez N, Carpenter JL. Cardiac tamponade in Still disease: a review of the literature. South Med J 2009;102:832.

8. Kimura Y, Weiss JE, Haroldson KL, et al. Pulmonary hypertension and other potentially fatal pulmonarycomplications in systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2013; 65:745.

9. Dogra S, Gehlot A, Suri D, et al. Incomplete Kawasaki disease followed by systemic onset juvenileidiopathic arthritis­ the diagnostic dilemma. Indian J Pediatr 2013; 80:783.

10. Kumar S, Vaidyanathan B, Gayathri S, Rajam L. Systemic onset juvenile idiopathic arthritis withmacrophage activation syndrome misdiagnosed as Kawasaki disease: case report and literature review.Rheumatol Int 2013; 33:1065.

11. Binstadt BA, Levine JC, Nigrovic PA, et al. Coronary artery dilation among patients presenting withsystemic­onset juvenile idiopathic arthritis. Pediatrics 2005; 116:e89.

12. Harvey AR, Pippard MJ, Ansell BM. Microcytic anaemia in juvenile chronic arthritis. Scand J Rheumatol1987; 16:53.

13. Martini A, Ravelli A, Di Fuccia G, et al. Intravenous iron therapy for severe anaemia in systemic­onsetjuvenile chronic arthritis. Lancet 1994; 344:1052.

14. Gorelik M, Fall N, Altaye M, et al. Follistatin­like protein 1 and the ferritin/erythrocyte sedimentation rate ratioare potential biomarkers for dysregulated gene expression and macrophage activation syndrome in systemic

because patients can initially appear quite ill with high spiking fever, rash, and often havehepatosplenomegaly or lymphadenopathy, and elevated white blood cell (WBC) counts prior to thepresentation of arthritis. (See 'Overview' above and 'Clinical manifestations' above and 'Laboratory findings'above and 'Diagnosis' above and 'Differential diagnosis' above.)

The diagnosis is made clinically and is based upon the presence of intermittent daily high spiking fevers(quotidian fever) for at least two weeks and arthritis. There are no laboratory findings that are specific for thediagnosis of sJIA, but granulocyte predominant leukocytosis, elevated acute­phase reactants, andhyperferritinemia should raise suspicion for this disorder. A salmon pink rash is also suggestive of thediagnosis, particularly when other clinical features are present. (See 'Diagnosis' above and 'Laboratoryfindings' above and 'Clinical manifestations' above.)

The differential diagnosis includes arthritis associated with infections, other autoimmune andautoinflammatory disorders, malignancy, and malaria. (See 'Differential diagnosis' above.)

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juvenile idiopathic arthritis. J Rheumatol 2013; 40:1191.15. Pelkonen P, Swanljung K, Siimes MA. Ferritinemia as an indicator of systemic disease activity in children

with systemic juvenile rheumatoid arthritis. Acta Paediatr Scand 1986; 75:64.16. Cassidy JT, Petty RE. Juvenile rheumatoid arthritis. In: Textbook of Pediatric Rheumatology, 4th ed,

Cassidy JT, Petty RE (Eds), WB Saunders Company, Philadelphia 2001. p.218.17. DeWitt EM, Kimura Y, Beukelman T, et al. Consensus treatment plans for new­onset systemic juvenile

idiopathic arthritis. Arthritis Care Res (Hoboken) 2012; 64:1001.18. Cush JJ, Medsger TA Jr, Christy WC, et al. Adult­onset Still's disease. Clinical course and outcome.

Arthritis Rheum 1987; 30:186.19. Nocton JJ, Miller LC, Tucker LB, Schaller JG. Human parvovirus B19­associated arthritis in children. J

Pediatr 1993; 122:186.20. Cabral DA, Tucker LB. Malignancies in children who initially present with rheumatic complaints. J Pediatr

1999; 134:53.

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GRAPHICS

Features of three of the major subtypes of juvenile idiopathicarthritis (JIA)

Systemic JIAOligoarticular

JIAPolyarticular

JIA

Percent of JIApatients

10 to 15 50 30 to 40

Sex F = M F>M F>M

Age Any <17 years Peak 2 to 3 years, rare>10

Peaks 2 to 5, 10 to 14years

Joints Any number and anyjoint

Large joints, but rarelyhips

Any, usuallysymmetrical and rareto start in hips

Fever, rash,lymphadenopathy,hepatosplenomegaly

Yes No No

Uveitis Rare 20%, most commonin patients who areANA positive

Less frequently seenthan in oligoarticularJIA

Laboratory abnormalities

­ Leukocytosis Marked No No

­ Anemia Marked No Mild

­ Elevated ESR Marked Mild Mild

­ ANA Absent Low titer common Low titer common inyounger

­ Rheumatoid factor Rare Absent 10 to 20% in those >10years

­ Elevated ferritin Marked No Mild

Destructive arthritis >50% Rare >50%

Disease­modifyingand biologic drugs

Commonly used Rarely used Commonly used

F: female; M: male; ANA: antinuclear antibody; ESR: erythrocyte­sedimentation rate.

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Cervical spine fusion in systemic juvenileidiopathic arthritis

Fusion of the cervical spine may affect up to 50 percent of childrenwith systemic juvenile idiopathic arthritis in the first decade of life.Apophyseal joint space narrowing and bony ankylosis occur,especially at C2­C3. These changes are not usually present elsewherein the spine.

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Systemic juvenile idiopathic arthritis rash

A salmon­pink rash is characteristic of this juvenile idiopathic arthritis(JIA) subtype. The rash is brought out by heat and often can be foundin the axillae and around the waist, but may be present anywhere onthe body.

Courtesy of Robert Sundel, MD.

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Systemic juvenile idiopathic arthritis rash with Koebnerphenomenon

Systemic juvenile idiopathic arthritis rash on a patient's back is shown in Panel A, with aclose­up view in Panel B. The rash usually consists of multiple round to oval, salmon­pink macules that are slightly raised and are of differing sizes. The rash can appearfollowing stroking of the skin or other minor trauma (Koebner phenomenon).

Courtesy of Yukiko Kimura, MD.

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Disclosures: Yukiko Kimura, MD Grant/Research/Clinical Trial Support: Novartis [Systemic JIA (Canakinumab)]. Consultant/AdvisoryBoards: Novartis [Systemic JIA, polyarticular JIA (Canakinumab)]; SOBI [Systemic JIA, polyarticular JIA (Anakinra)]; Regeneron[Systemic JIA, polyarticular JIA (Sarilimumab)]. Marisa Klein­Gitelman, MD, MPH Nothing to disclose. Elizabeth TePas, MD, MSNothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti­level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures