Rheumatology



Rheumatology


Anne Griffin

Deepak Palakshappa

Catherine Aftandilian

Kavita B. Vyas

Smitha Chillambhi

Holly Rothermel



Juvenile Idiopathic Arthritis (JIA)


Definition

(Lancet 2007;369:767)



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


  • 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 W. European countries, polyarthritis in Costa Rica, India, New Zealand, and South Africa


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


Clinical Manifestations

(Lancet 2007;369:767)



  • Systemic arthritis: 10% of all cases of JIA



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


    • 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)


    • Polyarticular arthritis can develop late in disease course


    • 5%–8% develop Macrophage Activation Syndrome, life threatening; sudden onset sustained fever, pancytopenia, HSM, liver insuff, coagulopathy w/ hemorrhagic signs & neuro sx’s (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 and causing visual impairment; affects 30%, 5–7 yr after onset of arthritis)


    • Exclude if has psoriasis, FHx of psoriasis, HLA B27 assoc disease in 1st-degree relative, +RF, or occurs in a male >6 yr


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


    • Symmetric polyarthritis, affects small joints of hands and feet


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


    • Rheumatoid nodules in forearm and elbow occur in 1/3 of pts in 1st yr of disease


    • 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


    • Ddx: Spondyloarthropathies (HLA B27 assoc; Psoriatic, IBD, reactive arthritis): usually asymm, 6–14 yo, ♂ predom, affects large joints, assoc w/ enthesitis, sacroiliitis.



      • Psoriatic arthritis can lead to aortic stenosis as adults, but not always.


Etiology and Pathogenesis

(Lancet 2007;369:767)



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


  • Genome-wide scan of kids suggests several genes, at least 1 assoc w/ HLA region


Diagnostic Studies

(Lancet 2007;369:767)



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


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


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


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


  • Joint asp to r/o infxn only if 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



Prognosis and Outcome:

Studies have inconsistent results



  • Systemic arthritis: Variable course,



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


    • 50% unremitting, often systemic sx’s 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 postsynechiae, band keratopathy, cataract, and glaucoma


  • Polyarthritis: RF +: Progressive and diffuse involv, x-ray Δ’s early esp in hands and feet



    • RF– : Variable outcome


Management



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


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


  • NSAID’s 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


  • 2/3 children w/ persistently active joint dz require DMARDS or steroids. MTX most commonly prescribed w/ ∼70% responding. Biologic agents often used: Etanercept, adalimumab, infliximab. Abatacept recently approved.


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


Poststrep Reactive Arthritis



  • Distinct from arthritis assoc w/ rheumatic fever


  • At least 1–2 wk btw acute strep infxn and onset of poststrep reactive arthritis


  • 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


Reactive Arthritis


Definition

(Clin Microbiol Rev 2004;17:348)



  • Arthritis associated with a recent, prior, or coexisting extraarticular infection


  • Can refer to post infxn arthritis, urethritis, and conjunctivitis


Pathophysiology

(Curr Opin Rheumatol 1999;11:238)



  • Classic pathogens: Campylobacter, Chlamydia trach, Salmonella, Shigella, Yersinia


  • Bacterial antigens in synovium, trigger T-cell resp →immune-mediated synovitis



    • Chlamydial DNA and mRNA have been found in synovial membrane biopsies


    • Campylobacter, Salmonella, Shigella, Yersinia antigens present in synovial fluid


  • ↑ rate w/ HLA B27, perhaps because HLA B27 cells allow bacteria to persist


Epidemiology

(Clin Microbiol Rev 2004;17:348)



  • Uncommon disorder, estimated at 0.1% prevalence; 2nd to 4th decade of life


  • May be underdiagnosed because of asymptomatic prior infection


  • Following GU infxn (male to female 9:1) or enteric infection (male to female 1:1)


Clinical Manifestations

(Clin Microbiol Rev 2004;17:348)



  • Extra-articular findings include:



    • Conjunctivitis, often coincides with flares of arthritis, is mild, lasts 1–4 wk


    • Urethritis, usually painless, clear urethral discharge



























Symptoms Sens Spec Comments
Asym oligoarthritis 44% 95% Avg of 4 joints (knee, ankle, toes, wrist, fingers) Nondestructive
Sausage digit 27% 99% Occurs in 16% of pts
Heel pain 52% 92% A result of enthesitis
Low back pain 71% 77%  



Diagnostic Studies

(Clin Microbiol Rev 2004;17:348)



  • No established diagnostic criteria


  • 1996 Third International Workshop on Reactive Arthritis



    • Typical peripheral arthritis (predominantly lower limb, asym oligoarthritis)


    • Evidence of preceding infection



      • If diarrhea or urethritis laboratory confirmation is desired, but not essential


      • If no clinical infection, laboratory confirmation is necessary


      • Positive confirmatory testing includes: + stool cx; + chlamydia trachomatis


      • Pts w/ other causes (Lyme dz, septic arthritis, spondyloarthritis) are excluded


  • Routine HLA B27 screening is not helpful


  • Eval: X-rays of affected joints to r/o trauma, joint aspiration to r/o septic arthritis and gout, U/A to eval for urethritis, Chlamydia PCR, stool cx’s, Lyme serology, RF


Management

(Clin Microbiol Rev 2004;17:348)



  • NSAIDs (1st line Rx w/ 70%–75% response rate), intraarticular corticosteroids, DMARDs (2nd line for refractory arthritis)


  • No controlled data, but sulfasalazine, MTX, azathioprine have shown some efficacy


  • Antibiotics: Rx of urethritis can ↓ risk of reactive arthritis and ↓ relapse



    • Rx of enteric infections does not affect development of reactive arthritis


Complications

(Rheumatology 2000;39:117)



  • Generally benign course w/ most pts recovering wks–mo w/ no destructive Δ’s


  • Worse prognosis assoc w/: ♂ gender, FHx ankylosing spondylitis, presence HLA of B27, ESR >30, Poor response to NSAIDs, onset <16 yo. (Clin Microbiol Rev 2004;17:348)


Systemic Lupus Erythematosus

(Textbook of Pediatric Rheumatology, 5th ed. 2005. p 34).


Definition



  • Episodic, multisystem, AI dz affecting kids & adults w/ presence of antinuclear auto-Ab’s to ds-DNA & w/ widespread vascular & connective tissue inflamm


  • Neonatal lupus syndrome: Passively transferred AI dz in 1%–2% of neonates born to moms w/ AI dz (SLE, Sjögren), by transplacental passage of maternal anti-Ro or anti-La Ab’s; clinically w/ congenital heart block, rash, and rarely hepatobiliary or hematologic manifestations (anemia, thrombocytopenia)


  • “Drug-induced lupus” syndrome: Variant form of lupus that resolves w/i days to months after w/d of drug in pt w/ no underlying immune dysfxn. Most commonly w/ hydralazine, procainamide, quinidine, isoniazid, diltiazem, isoniazid, phenytoin, alpha-methyldopa, ethosuximide, trimethadione, and minocycline.


Epidemiology



  • Prevalence is 5000–10,000 children in the U.S.; median age onset 12 yo


  • Female predominance of 5:1 girls to boys


  • Incidence and severity vary: Asians, Hispanics, AA more commonly than Caucasian


Pathophysiology



  • Etiology is unknown


  • Autoreactive B and T cells → antigen-Ab complexes in circulation and deposit in tissues, such as renal glomerulus, dermal-epidermoid junction, and choroid plexus


  • Immune complexes activate complement system, resulting in hypocomplementemia during the active phase and presence of complement activation products


Clinical Manifestations

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Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Rheumatology

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