Pocket Pediatrics: The Massachusetts General Hospital for Children Handbook of Pediatrics (Pocket Notebook Series), 2 Ed.

JUVENILE IDIOPATHIC ARTHRITIS (JIA)

Definition (Lancet 2011;377:2138; Lancet 2007;369:767)

• Dx of exclusion; previously JRA, now JIA per Internat League of Assoc for Rheum(ILAR)

• Includes all forms of arthritis (swelling or limitation of motion of joint w/ heat or pain) <16 yo, >6-wk duration and of unknown cause (Pediatr Clin North Am 2005:413)

• Must exclude infectious and postinfectious etiology, hematologic and neoplastic dz, connective tissue disease, vasculitis, and other inflammatory conditions

Epidemiology (Lancet 2007;369:767)

• Most common chronic rheumatic dz in children, prevalence 16–150 per 100,000

• Oligoarthritis most common in the US, W. European countries, polyarthritis in Costa Rica, India, New Zealand, and South Africa

• Occurs as frequently as juvenile DM, 4× more freq than CF & sickle cell anemia, & 10× more than ALL, hemophilia or musc dystrophy (Pediatr Rev 2006;27:e24)

Clinical Manifestations (BMJ 2010;341:c6434; Lancet 2007;369:767)

• Systemic arthritis: 10% of all cases of JIA; polygenic autoinflam syndrome w/ ↑ IL1 & 6

• Arthritis + quotidian fever of at least 2 wk duration + ≥1 of the following: Classic transient blanching macular or maculopapular rash, HSM, generalized LAD, or serositis. Fever and/or rash may precede arthritis by wks to mos

• Fever peak (usually >102.2°F in evening or morning) may coincide w/ appearance of rash, occ assoc w/ abd pain, myalgias (Pediatr Rev 2006;27:e24)

• Systemic sx often abate, polyarticular arthritis can develop late in disease course

• 2 types based on resp to anti-IL-1 Rx; one w/ complete resp, other resistant/interm

• 5–8% develop macrophage activation syndrome(MAS) which is life-threatening; sudden onset sustained fever, pancytopenia, HSM, liver insuff, coagulopathy w/ hemorrhagic signs & neuro sx (labs: Paradoxically ↓ ESR, ↑ Trigs, ↓ Na, ↑ ferritin, ↑ PT/PTT)

• Oligoarthritis: 40% of all cases JIA; ≤4 joints during 1st 6 mo of disease

• Asym arthritis, onset <6 yo,  predilection, often +ANA, w/ ↑ risk iridocyclitis (chronic, nongranulomatous, anter uveitis affects iris and ciliary body can cause visual impairment; affects 30%, flare/onset do not follow arthritis course

• Exclude if w/ psoriasis, FHx psoriasis, HLA B27 assoc dz in 1st-degree relative, +RF, or occurs in a male >6 yo (consider psoriatic or enthesitis-related arthritis)

• Usually knee > ankles, 30–50% 1 joint at presentation

• Often w/ swollen warm joint, limp worse in AM, after nap (Pediatr Rev 2006;27:e24)

• 50% w/ upper limb joint involved and ↑ ESR at onset predicts more severe outcome

• Can have leg-length discrepancy, initially sustained ↑ blood flow to growth plate w/ ↑ growth, then chronic inflamm w/ early epiphyseal closure

• Polyarticular onset: 25% of all cases of JIA, divided into RF+ and RF−

• RF+ (5%) affects ≥5 joints in 1st 6 mo of dz and +IgM RF, also assoc w/ +anti-CCP, at least 2× >3 mo apart; same as adult RF + RA and seen mainly in adolescent 

• Symmetric polyarthritis, affects small joints of hands & feet, unlike adult RA in that often w/ growth retardation or accelerated growth at affected joint

• Large joints, usually knees and ankles, can be affected, but usually w/ small joints

• Rheumatoid may occur, often extensor surfaces of joint

• RF neg: Heterogenous subtype affects ≥5 joints in 1st 6 mo of dz and IgM RF neg

• Can be asymmetric, early age at onset, female predominance, frequently +ANA, ↑ risk of iridocyclitis and assoc w/ HLA DRB1*0801

• Can be overt symmetric synovitis of large and small joints, onset in school age, ↑ ESR, neg ANA, variable outcome

• Can have dry synovitis (min joint swelling), stiffness, flexion contractures nml–↑ ESR

• Spondyloarthropathies (HLA B27 assoc; psoriatic, IBD, reactive arthritis): Usually asymm, 6–14 yo,  predom, affects large joints, assoc w/ enthesitis, sacroiliitis

• Psoriatic arthritis can occasionally lead to aortic stenosis as adults

Etiology and Pathogenesis (Lancet 2011;377:2138)

• Unknown; autoimmune, possible infectious trigger. Heterog group of disorders

• Genome-wide scan of kids suggests several genes, also HLA A2, B27, DRB1, & DP

Diagnostic Studies (Lancet 2011;377:2138; Lancet 2007;369:767)

• Eval is dependent on history (associated symptoms and signs) and physical exam (PE)

• PE sens 64% & spec 86%; screen w/ U/S for subclin dz (J Rheumatol 2011;38:2671)

• Systemic arthritis labs: ↑ WBC w/ ↑ PMNs, ↑ ESR, ↑ CRP, thrombocytosis, ↑ ferritin, ↑ vWFag

• Oligoarthritis labs: Acute phase labs nml–↑, + ANA (70–80%; risk for iridocyclitis)

• Polyarthritis lab features: RF+/− variable as above

• Radiographic eval w/ U/S & MRI often beneficial (↑ sens)

• Joint asp to r/o infxn only if it appears septic. Crystal dz very rare. If WBC >100 × 103mL (100 × 109/L) and 90% polys, infxn likely. Send fluid for cx, consider Lyme PCR

Management (BMJ 2010;341:c6434)

• Combo of drugs, physical and occupational Rx, and psychosocial support

• Periodic x-rays of affected joints to document progression of erosive disease

• Oligoarticular–intraarticular steroids can be very beneficial

• Classic use of NSAIDs w/ delayed DMARDs/steroids; new data favor DMARDs early

• NSAIDs mainstay of Rx: Avg time to sx improv 1 mo, up to 25% w/ no improv until 8–12 wk; approx 50% w/ improv to 1st NSAID, 50% w/ relief w/ next NSAID

• ⅔ children w/ persistently active joint dz require DMARDs or steroids. MTX most commonly prescribed w/ ∼70% responding. Biologic agents used: Etanercept, adalimumab, infliximab, golimumab, rituximab, abatacept, anti-IL-1 & anti-IL-6 used for systemics (anakinra, tocilizumab)

• ∼1/3 w/ excellent resp (inactive dz or remission) w/ etanercept (JAMA 2011;306:2340)

• Other agents, sulfasalazine, leflunomide, cyclosporine, cyclophosphamide, hydroxychloroquine, thalidomide, intraarticular steroids often helpful

Prognosis and Outcome: Studies have inconsistent results

• Systemic arthritis: Variable course

• 50% monocyclic or intermittent; w/ fever, remits when systemic sx controlled

• 50% unremitting, often systemic sx resolve and pt has chronic arthritis; severe w/ joint destruct. Rx w/ steroids can cause growth retard and osteoporosis

• Oligoarthritis: Best outcomes, joint erosion more freq in pts w/ polyartic course

• If w/ iridocyclitis at risk for post-synechiae, band keratopathy, cataract, and glaucoma

• Polyarthritis: RF+: Progressive and diffuse involv; x-ray Δs early esp in hands and feet

• RF−: Variable outcome

• JIA pts w/ 2–4× inc risk malig; ? 2/2 MTX/anti-TNF rx (Nat Rev Rheumatol 2011;7:6)

Poststrep Reactive Arthritis

• Distinct from arthritis assoc w/ rheumatic fever

• At least 1–2 wk btw acute strep infxn and onset + anti-DNAse B/ASLO titer/cx

• Response to aspirin and NSAIDs is poor

• Modified Jones criteria usually not met and there is no evidence of carditis

• Duration prolonged or recurrent and of ↑ severity and w/ tenosynovitis and renal abn

• No clear definition or Rx guidelines: No consensus on prophy PCN

Arthritis in Rheumatic Fever

• Most freq and least specific sx of rheumatic fever

• Migratory arthritis: Usually affects large joints, lower, then the upper extremities

• Joint involvement early in illness, more common and severe in adol and young adults

• Polyarthritis painful, but transient, inflammation lasts 2–3 d in each joint and 2 wk total

• X-ray may show slight effusion but otherwise normal

• Self-limited, resolves without sequelae and responds well to NSAIDs