JIA and Other Rheumatic Diseases in Children. Norma Liburd, RN-BC, MN
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1 JIA and Other Rheumatic Diseases in Children Norma Liburd, RN-BC, MN
2 Define Juvenile Idiopathic Arthritis (JIA) and discuss the diagnostic criteria. Objectives Identify the subtypes of JIA and discuss characteristics of each. Name at least one NSAID, one biologic and one DMARD used in the treatment of JIA.
3 A few more Objectives Discuss three school related problems students with JIA have and intervention strategies for each. Identify the criteria for classification of systemic lupus erythematosus. Name the most common type of juvenile localized scleroderma. Discuss the criteria for diagnosis of juvenile dermatomyositis, and treatment approaches
4 Overview of JIA New classification criteria proposed by the Pediatric Task Force of the International League of Associations for Rheumatology (ILAR) in 1997 Chronic arthritis in childhood one of the more frequent chronic illnesses of childhood. An important cause of short and long-term disability
5 Chronic arthritis in childhood: JIA It s not a single disease, but a group of related, genetically heterogeneous, phenotypically diverse immunoinflammatory disorders affecting joints and other structures, possibly activated by contact with an external antigen or antigens.
6 JRA - Incidence/Prevalence. Published series are difficult to interpret due to classification, methodologies, heterogeneity Incidence: (per year) 1/100,000 in Japan 20/100,000 in Norway Prevalence: 10 /100,000 in France 400/100,000 in Australia 113/ 100,000 Arthritis Foundation: 300,000 children in the US have chronic arthritis.
7 JRA Classification Criteria JRA American College of Rheumatology 1970 three types of onset: oligo (pauciarticular), polyarticular, & systemic in the first 6 months of onset JCA Juvenile Chronic Arthritis (European League Against Rheumatism) 1977 JIA Juvenile Idiopathic Arthritis proposed by the Pediatric Task force of the International League of Associations for Rheumatology ILAR (1993) developed to achieve homogeneity within disease and categories.
8 Sex Ratio All types of JIA: Girls: Boys 2:1 Oligo JIA: Girls: Boys 3:1 JIA with uveitis Girls: Boys 5-6:1 Poly JRA: Girls: Boys 3:1 Systemic JRA: Girls: Boys approx. 1:1
9 JIA outcomes: Mortality Disease associated death rate is < 1% in Europe < 0.3% in North America These numbers represent a 4 Fold to 14 fold Increase in Mortality Rate Compared with General Population Causes are cardiac, infection & macrophage activation syndrome
10 JRA outcome: functional abilities Author Year Published Followup in years (mean) Bunim % Laaksonen 1966 >16 48% Ansell 1976 >15 23% Hill 1976 (14.5) 33% Hanson (10) 28% Stoeber (15) 41% Levinson % Zak % Poor Function
11 Classification Criteria for JIA Age at onset <16 years Duration of Arthritis: 6 weeks Arthritis in one or more joints defined as swelling or effusion, or presence of two or more of the following signs: (in 1 or more joints) Limitation of ROM Tenderness or pain on motion Increased heat Exclusion of other diseases
12 Diagnostic Studies
13 Diagnostic Tests There is no lab test that diagnoses JIA The H&P should determine the labs, not the reverse CBC Rheumatoid factor Antinuclear Antibody (ANA) with titer ESR or CRP Anti-CCP (anti-cyclic citrullinated protein)
14 Radiologic Studies X-rays Soft tissue swelling Osteoporosis Periosteal new bone formation Epiphyseal overgrowth Marginal erosions Narrowing of cartilaginous space Joint subluxation Bony fusion Dexascans Osteopenia Osteoporosis
15 Etiology Immune mediated disease Abnormal immunoregulation Abnormal cytokine production in the inflammatory pathway (TNF, IL-6, IL-2R, IL-1alpha) Complex genetic predispositions HLA associations Environmental triggers Infections Trauma Stress
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19 Synovial lining is a thin membrane enclosing the joint space. The joint space contains fluid that bathes the joint and reduces friction on motion.
20 With onset of inflammation, the synovial lining thickens and secretes more fluid, which may remain in the joint and cause swelling. The inflamed lining produces warmth, swelling, and pain. As inflammation progresses, the synovial lining grows over the cartilage and starts to erode it. As inflammation continues, changes include marked erosion of cartilage, cystic changes and thinning of the bone.
21 Classification Criteria 1. Systemic 2. Oligoarthritis a. Persistent b. Extended 3. Polyarthritis (rheumatoid factor negative) 4. Polyarthritis (rheumatoid factor positive) 5. Psoriatic arthritis 6. Enthesitis-related arthritis 7. Undifferentiated arthritis a. Fits no other category b. Fits more than one category From Petty RE, Southwood TR, Baum J et al: Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997, J Rheumatol 25: , 1998.
22 JIA Subtypes Systemic Onset (5-15%) Polyarticular Onset (20%) Rheumatoid Factor Positive Rheumatoid Factor Negative (85%) Oligoarthritis (50-80%) Juvenile psoriatic arthritis (7%) Enthesitis related arthritis Undifferentiated
23 Definition: Systemic JIA Arthritis with, or preceded by, daily fever of at least 2 weeks duration Fevers are quotidian (daily) for at least 3 days and is accompanied by one or more of the following: Evanescent, non-fixed, erythematous rash Generalized lymph node enlargement Hepatomegaly and/or splenomegaly Serositis
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26 Quotidian fever Intermittent fever of systemic JIA in a 3- year-old girl. The fever spikes usually occurred daily in the late evening to early morning (quotidian pattern), returned to normal or below normal, and were accompanied by severe malaise, tachycardia, and rash.
27 Rash - Salmon colored Maculopapular flat to slightly raised Trunk and extremities Migratory Pruritic 5% Fleeting Persistent with fever spike Systemic JRA
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29 Overview of Systemic JIA 10-15% of all JRA patients Broad peak of onset 1-5 years M:F 1:1 Variable number of joints Il-6 is elevated and correlates with disease activity Extraarticular symptoms: Fever 100 % Rash 95% Hepatosplenomegaly, 85% Lymphadenopathy 70% Pericarditis 35% Pleuritis 20%
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31 Macrophage Activation Syndrome Rare devastating complication of systemic JIA. Etiology is uncertain. Demonstration of macrophages ingesting other hematopoietic cells in marrow is diagnostic Early recognition is life-saving Looks somewhat like a flare up of systemic JRA but is different enough to allow for early recognition) Associated with CMV, EBV, changes in meds Mortality 10-20%
32 Macrophage Activation Syndrome Acute onset of fever with Bruising, purpura, mucosal bleeding Enlarged lymph nodes, liver, spleen Elevated AST, ALT, PT, PTT, fibrin D-dimer Elevated ferritin & triglycerides Abrupt fall in WBC & platelets Fall in ESR Fall in fibrinogen, clotting factors Often progresses to fatal DIC, hepatic failure, encephalopathy Treatment: IV steroids, cyclosporin
33 Polyarticular JIA - RF negative Five or more joints in the first 6 months of disease Asymmetric joint involvement Large joints of knees, wrists, elbows and ankles often affected Morning stiffness, joint pain Intermittent low-grade fever
34 Polyarticular - RF positive Arthritis affecting 5 or more joints in the first 6 months of disease. Similar to adult RA Females with onset in adolescence Rheumatoid nodules Early onset of erosive synovitis Symmetric joint involvement Small joints of hands or feet are affected TMJ: micronathia Cervical spine may be affected
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37 Rheumatoid Nodules Occur in 5-10% of children with JIA Most frequently on elbow Pressure points, digital flexor tendon sheaths, Achilles tendons, bridge of nose in child who wears glasses Firm or hard, usually mobile, nontender. Solitary or multiple, may change in size, may last months to years.
38 Oligoarticular JIA Arthritis in 1 to 4 joints during the first 6 months of disease Girls 1 to 4 years Knees, ankles, elbows Painless swelling of joints is common Uveitis: insidious, subacute 15-20% have uveitis
39 JIA: Oligo persistent No more than 4 joints affected throughout the disease course JIA: Oligo - extended Affects a total of more than 4 joints after the first 6 months of disease. At least 1/3 of children with Oligoarticular arthritis fall into this category Outcome is more typical of RF+ polyarticular disease
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41 Intraocular inflammation affects iris and ciliary body Usually insidious and may be asymptomatic Activity of eye does not parallel joint disease Slit lamp exam detects anterior chamber inflammation Girls, ANA + and onset before age 7 at higher risk Uveitis in JIA
42 Prognosis of Uveitis in JIA Very good in 25% of cases 25% may require surgery for cataracts and/or glaucoma 50% require prolonged treatment for moderate to severe chronic inflammation; however, the prognosis is generally good Complications: cataracts 20%, glaucoma 20%, band keratopathy 16% (end stage scarring)
43 Uveitis in JIA Usually occurs after onset of arthritis. Highest risk is within 2 years of onset of arthritis. Majority develop eye disease within 5-7 years after onset 65% have bilateral involvement, unilateral may progress to bilateral Treatment includes topical steroids, SQ Methotrexate, IV Remicade; SQ Humira and Enbrel.
44 Slit Lamp Exam JIA Guidelines Rheumatology & Ophthalmology sections of the American Academy of Pediatrics, 1993 Oligoarticular ANA+ <7 years at Dx Oligoarticular ANA+ 7 or older at Dx Oligoarticular ANA - <7 years at Dx Oligoarticular ANA <7 years at Dx Systemic Q 3-4 months for 7 years, then yearly. Q 4-6 months for 7 yrs, then yearly. Q 4-6 months for 4 yrs, then yearly. Yearly.
45 Guidelines for ophthalmological screening of children with JIA JIA Onset ANA Onset < 7 yrs Onset 7 years Oligo Positive Every 3-4 months Every 4-6 months Oligo Negative Every 4-6 months Every 4-6 months Polyarthritis Positive Every 3-4 months Every 4-6 months Polyarthritis Negative Every 4-6 months Every 4-6 months Systemic Neg or pos Every 12 months Every 12 months High risk screen every 3 months Moderate risk screen every 4-6 months Low risk: screen every 12 months All patients considered to be at low risk 7 yr after onset of arthritis; should have yearly ophthalmological exams indefinitely. All patients are considered to be at low risk 4 years after onset of arthritis, should have yearly ophthalmological exams indefinitely. All high risk patients are considered to be at medium risk 4 years after onset of arthritis. Modified from Yancy C, et.al, The Guidelines of the Rheumatology and ophthalmology sections of the AAP. Pediatrics 92: , 2003.
46 JIA: Psoriatic Arthritis Arthritis and psoriasis or Arthritis with 2 of the following: Dactylitis - sausage like swelling of toe or finger Nail pitting Psoriasis in a first degree relative (parents, siblings) Slightly more females Symmetrical involving large and small joints
47 JRA: Spondyloarthropathy JIA: Enthesitis related arthritis Arthritis and enthesitis Arthritis or enthesitis with at least 2 of the following: Sacroiliac joint tenderness and/or inflammatory lumbosacral pain Presence of HLA-B27 Onset of arthritis in a male after age 6 years Ankylosing spondylitis, Enthesitis Related Arthritis, Sacroiliitis with inflammatory bowel disease, Reiter s syndrome or acute anterior uveitis in a first-degree relative.
48 JRA: Spondyloarthropathy JIA: Enthesitis related arthritis Primarily affects boys 8 years and older Affects large joints of lower extremities Heel pain and Achilles tendonitis Sacroiliitis (90% of cases) Iritis (20% of cases) generally acute process Low grade fevers Decreased appetite
49 Medications NSAIDs DMARDs: Methotrexate, Plaquenil, Sulfasalazine Biologic response modifiers Glucocorticosteroids Miscellaneous
50 NSAIDS FDA approved for pediatric use Aspirin Tolmetin Naproxen Ibuprofen Indomethacin Meloxicam (Mobic) Celebrex
51 Common NSAIDS in JIA mg/kg/day Max Naproxen Ibuprofen Indomethacin Tolmetin Meloxican Piroxicam Celecoxib Nabumetone (Relafen) ASA
52 Methotrexate Standard dose: mg/m2 or mg/kg/week, subq Improvement seen in 6-8 weeks, but may take up to 6 months. Labs every 6 weeks: CBC, CMP No alcohol Used for treatment of uveitis (4-6 months to determine efficacy)
53 Meds: Targeting inflammation
54 Meds: Biologic Agents: Target against cytokines involved in inflammation: TNF, IL-1Ra, IL-6 Enbrel (Etanercept): approved for JRA 0.4 mg/kg twice per week SQ injections Improvement by third to fourth dose Hold for suspected bacterial infection, varicella Site reactions Binds to TNF
55 Biologic Agents: Remicade (Infliximab) - infusion, risk of anaphylaxis, dose may need to be increased depending on response, used in refractory uveitis as well 3 mg/kg IV weeks 0, 2 and 6 (may dose to 10 mg/kg) Improvement can be seen after first dose Labs every 4-8 weeks (CBC, CMP) Not approved for children
56 Biologic Agents: Anakinra (Kineret) (blocks IL-1 which stimulates synoviocytes and chondrocytes to produce small inflammatory mediators leading to cartilage destruction and bone erosions. Used in systemic JRA (but not approved) Daily, very painful, SQ injections, rotation of sites is important
57 Biologics Actemra (Tocilizumab) 8 mg/kg ACTEMRA is indicated for the treatment of active systemic juvenile idiopathic arthritis in patients 2 years of age and older who have responded inadequately to previously therapy with NSAIDS and steroids. --Given every 2 weeks by IV, over one hour. --Dosing interval can be shortened to every week if condition warrants.
58 Biologics Humira (adalimumab) TNF blocker: approved for children ages 4 to 17 Dose: 15mg (33 lbs) to <30 kg (66 lbs): 20 mg every other week Dose: 30kg or more: 40 mg every other week Humira pen or prefilled syringe Painful injections, but can add lidocaine to buffer the pain (Hershey study). Can shorten interval to weekly (with auth)
59 Biologics Orencia (Abatacept) T-lymphocyte modulator IV over 30 minutes: at 0, 2 4 weeks, then every 4 weeks Approved for children 6 and older as monotherapy or with methotrexate <75 Kg: 10 mg/kg If over 75 Kg: follow adult dosing Approved for adults: weekly SQ self injection
60 Glucocorticosteroids IV Solumedrol and daily oral Prednisone systemic flares ~ pericarditis or persistent Sx temporary measure until DMARD is effective Joint injections - usually under sedation Triamcinolone hexacetonide (Aristaspan) long acting steroid Works best with large joints
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62 Miscellaneous Treatment Thalidomide: 2 mg/kg/day Mechanism of action probably by effects on TNF and other inflammatory cytokines Very rigorous patient monitoring Bone Marrow Transplant Experimental for severe autoimmune disease unresponsive to conventional therapy Autologous stem cell transplant being evaluated in small number of children Infections ~ very risky high death rate
63 PT/OT - Overall goals Maintain or restore functional ROM in joints Strengthen muscles surrounding affected joints - to enable joints to remain in a functional position Assist child to perform activities in ways as close to normal as possible so they do not feel different from peers.
64 PT/OT - Management in JIA Splint fabrication
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