Systemic Juvenile Idiopathic Arthritis  

What is Systemic Juvenile Idiopathic Arthritis  

• Systemic juvenile idiopathic arthritis (SJA) is defined as arthritis that occurs in children aged 16 yr or younger and is associated with a daily fever that persists for longer than 2 wk, a characteristic short-lived erythematous maculopapular rash, and at least one of the following associated features: lymphadenopathy, pericarditis, pleuritis, or hepatosplenomegaly.
• The International League of Associations for Rheumatology (ILAR) Diagnostic Criteria for Systemic juvenile idiopathic arthritis (SJA) is summarized below. 
• Systemic Juvenile Idiopathic Arthritis: International League of Associations for Rheumatology (ILAR) Diagnostic Criteria

Arthritis in any number of joints together with a fever of at least 2 wk duration that is documented to be daily (quotidian) for at least 3 days and is accompanied by one or more of the following:

• 1.Evanescent rash
• 2.Generalized lymphadenopathy
• 3.Enlargement of liver or spleen
• 4.Serositis

Exclusions:

• 1.Psoriasis or a history of psoriasis in the patient or a first-degree relative
• 2.Arthritis in a human leukocyte antigen (HLA)-B27–positive boy beginning after his sixth birthday
• 3.Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, reactive arthritis, or acute anterior uveitis or a history of one of these disorders in a first-degree relative
• 4.The presence of immunoglobulin (Ig)M rheumatoid factor (RF) on at least two occasions at least 3 months apart

The below describes the operational case definition for new-onset SJA adapted from CARRA Consensus Treatment Plans.

Operational Case Definition for New-Onset SJA Adapted from CARRA Consensus Treatment Plans

Patients should have:

• •Fever ^∗for at least 2 wk
• •Arthritis ^†‡in one or more joints for at least 10 days
• •At least one of the following:
  • 1.Evanescent erythematous rash
  • 2.Generalized lymphadenopathy
  • 3.Hepatomegaly and/or splenomegaly
  • 4.Pericarditis, pleuritis, and/or peritonitis

Patients should NOT have:

• •Infection that includes concomitant active or recurrent chronic bacterial, fungal, or viral infection at presentation and underlying infection, which may mimic initial presentation of sJIA ^‡
• •Malignancy ^‡

Synonyms

• SJA
• Stills Disease
• Systemic juvenile rheumatoid arthritis
• Systemic juvenile chronic arthritis

Epidemiology & demographics

Incidence

How common is Systemic Juvenile Idiopathic Arthritis?

6 to 100 per 100,000 children.

Predominant Gender and Age

• The incidence of SJA occurs equally among males and females and has a peak onset of 18 mo to 2 yr.

Genetics

• Multigenic/multifactorial.

What are the Physical findings & Clinical Presentation?

• SJA presents with a fever which typically exceeds 39° C and oscillates during a 24-h period.
• Typically, the peaks in fever are observed concomitantly with a transient salmon-colored maculopapular rash.
• The arthralgias observed can affect any joint, can be oligo- or polyarticular, and are usually symmetric in nature.
• Other systemic findings that can be observed are abdominal pain secondary to serositis, headaches, and pleuritis.
• The disease course is extremely variable and can include a fever and rash that last 2 to 3 wk and are followed by mild systemic symptoms vs. the onset of all the above symptoms at once.
• Macrophage activation syndrome (MAS) is a severe complication that can occur during SJA disease onset and is characterized by a persistent fever, atypical rash, coagulopathy, anemia, and hyperferritinemia.

What causes Systemic Juvenile Idiopathic Arthritis?

The etiology of SJA is currently unknown; however, there is data to suggest that interleukin-1 (IL-1) and IL-6 are primary contributors to the pathogenesis of the disease.

Differential Diagnosis

• Septic arthritis
• Reactive arthritis
• Acute rheumatic fever
• Systemic vasculitis
• Kawasaki disease
• Malignancy

Infections

• Bacterial endocarditis
• Acute rheumatic fever and other postinfectious reactive arthritis
• Cat scratch disease ( Bartonella )
• Brucellosis
• Mycoplasma
• Malaria
• Tuberculosis
• Many others

Malignancy (especially acute lymphoblastic leukemia)

Rheumatic and inflammatory diseases

• Systemic lupus erythematosus
• Dermatomyositis
• Polyarteritis nodosa
• Kawasaki disease
• Serum sickness
• Sarcoidosis, especially with onset at an early age
• Castleman disease
• Kikuchi Fujimoto disease

Inflammatory bowel disease

Autoinflammatory diseases

Familial Mediterranean fever

Mevalonate kinase deficiency (mevalonic aciduria/hyperimmunoglobulin D syndrome)

Tumor necrosis factor (TNF) receptor–associated periodic syndrome (TRAPS)

Muckle-Wells syndrome

Chronic infantile neurological cutaneous and articular syndrome (CINCA)/neonatal-onset multisystem inflammatory disease (NOMID)

Interferonopathies, such as chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperature (CANDLE) syndrome; STING-associated vasculopathy with onset in infancy (SAVI); Nod-like receptor family, caspase recruitment domain-containing 4 (NLRC4)-activating mutations; among many others

Workup

• A thorough history and physical exam are required to diagnose ERA.
• A focused history should include a history of joint and/or enthesitis, back pain, ocular symptoms, and bowel symptoms.
• One should ensure that the patient does not have a personal or family history of psoriasis as this would exclude the diagnosis of ERA.
• A focused physical exam should be performed to assess for the presence of spinal disease, sacroiliitis (SI) pain and or instability, joint pain, and enthesitis.

Laboratory Tests

• CBC, erythrocyte sedimentation rate, C-reactive protein
• Ferritin levels can occur in SJA even without the presence of MAS. Levels often exceed 1000 ng/ml
• Hepatic function panel, D-dimer, prothrombin time/international normalized ratio
  • 1.Minor elevations in aspartate aminotransferase and alanine transaminase, hypoalbuminemia are often present. However, markedly elevated hepatic enzyme abnormalities, prolonged clotting times, or an increase in D-dimers should prompt immediate consideration of MAS
• •Antinuclear antibodies, rheumatoid factor, and anticyclic citrullinated peptide Abs are all typically absent however are used to exclude other differential diagnoses
• •Urinary vanillylmandelic acids and bone marrow biopsy are necessary in the younger age groups to exclude neuroblastoma and leukemia

How is Systemic Juvenile Idiopathic Arthritis treated?

Non Pharmacologic Therapy

Physical therapy and occupational therapy

Acute General Treatment

• 24-hour NSAID coverage and high-dose corticosteroids are typically used initially to control the fevers and extraarticular manifestations of the disease
• In the presence of SJA associated MAS enteral ciclosporin A and corticosteroids have been demonstrated to be effective

Chronic Treatment

• Anti-tumor necrosis factor agents such as etanercept are typically less effective in treating SJA, however may be considered.
• Newer IL-6 (tocilizumab) and IL-1 (anakinra) blockade agents are currently being studied and may be effective when other treatments fail.

Referrals

• A multidisciplinary approach should be used to manage these patients.
• Referral to a rheumatologist is prudent. Referral to physical and occupation therapy should be given to ensure physical and educational progression that is age-appropriate.
• A referral to a psychologist should be considered to help the children and family cope with the daily demands in managing the disease.