Clinical Practice Guidelines for the Management of Juvenile Idiopathic Arthritis

Author: Juliann M. Trumpower FNP-S

Key Words: Juvenile Idiopathic Arthritis, management, practice guidelines, chronic pain, adolescents, functional disability

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BACKGROUNDJuvenile Idiopathic Arthritis (JIA) is the most common form of rheumatic disease in children, affecting more than 300,000 children in the United States. It is an autoimmune disorder thought to be brought on by a complex interplay of genetic and environmental factors. The disease includes a heterogeneous group of arthritic conditions that begin before the age of 16 and persist for more than 6 weeks (Seid, M., 2012).Joint and musculoskeletal pain is a common presenting complaint in primary care. Typically, the cause is benign and self-limiting, however, in other cases, such as with JIA, long term morbidity and mortality is negatively impacted when early detection and treatment is not initiated. Diagnosis and management of JIA has improved in recent years as a result of increased understanding of the subtypes and clinical presentation of the disease, along with newer medications and treatments. Despite these advancements, the response to treatment is as variable as the many subtypes, with some children achieving clinical remission, while others suffer profound functional disability, chronic pain, growth disturbances and deformity. (Cartwright, T., Fraser, E., Edmunds, S., Wilkinson, N. & Jacobs, K., 2014).

EPIDEMIOLOGYThe incidence of JIA in the United States is 45-50 children per 100,000 and 95-130 per 100,000 worldwide. JIA includes polyarticular, oligo articular, psoriatic, enthesitis,-related arthritis (ERA), systemic arthritis and undifferentiated arthritis. It does not spare any ethnic background but afflicts girls three times more than boys (Seid, M., 2012).

RISK FACTORS First degree relative with JIA- monozygotic twins and siblings of children with JIA have

a 15-30 fold increase risk for developing JIA than the general population Female (75% of children with JIA) Maternal smoking

Early life infection Recent infection (thought to initiate or augment JIA, much like with Type 1 diabetes)

Influenza, Rubella and Parovirus B19 have been associated with onset/exacerbation of JIA

Recent vaccination Stress (Ellis, J., Munro, J., & Ponsonby, A., 2009).

Medical History Obtain a comprehensive medical history, including growth and development. Obtain a thorough family medical history as JIA has been shown to have a

genetic/familial basis Previous and current medication Prior hospitalizations or surgeries? If so what and when? Any drug or environmental allergies? Any recent infections, trauma or stress? Any illicit drug, alcohol or tobacco use? What has been used to treat symptoms including

OTC drugs and creams? Any use of Complimentary Alternative Medications (CAM) including herbal supplements, yoga, acupuncture and hypnosis.

History of Chief Complaint Age of child? What are symptoms, when did they start and how long due symptoms last? Morning stiffness? If yes, how long does it last? What aggravates/alleviates symptoms? Any recent illness? Fever? If yes, is fever daily and at what time of day? Any joint pain and or swelling. Number of joints affected. Heat to joints or erythema

(arthritis rarely causes erythema and if present infectious source should be considered) Unusual fatigue Weight loss Growth disturbances in affected limb Limp present? In toddler, not pulling to stand on awakening from nap?

School attendance? (Sen, E., Clarke, S., & Ramanan, A., 2014)

Oligo arthritis - Arthritis affecting 1-4 joints in the first 6 months of disease -Often only one joint involved -Usually large weight bearing joints (knee/ankle) -Appear well -May have limp, limb length discrepancy, and/or muscle atrophy -Most common form of JIA accounting for up to 60% -Uveitis not uncommon especially if ANA positive

Polyarthritis -Arthritis in 5 or more joints in the first 6 months of disease -Accounts for 25-40% of JIA -May be Rheumatoid factor positive or negative

SUBTYPES OF JUVENILE IDIOPATHIC ARTHRITIS AND CLINICAL PRESENTATIONTable 1

-Uveitis uncommon -Joint contractures of proximal and distal interphalangeal joints -Deformities (Swan’s neck and Boutonniere deformities)

Systemic Onset -Arthritis with or proceeded by a fever -Fever may occur 1-2x a day at about the same time (predictable)

-Accounts for 10% of JIA -Child appears ill -Generalized myalgia and muscles tender to palpation -Salmon pink, macular rash often occurs with fever and non-pruritic -May develop serositis, pleural and/or pericardial effusions

-May complain of SOB or chest pain -High rate of morbidity and mortality

Psoriatic arthritis -Usually mild in children -Arthritis precedes psoriasis in 50% of children -Inflammation and swelling of an entire finger or toe -Nail pitting or splitting characteristic (70%)

-Mono-articular in 50%, DIP joint involvement 50% -Tenosynovitis in 30%

-May have disordered bone growth (Beukelman, T., et al., 2011)Enthesitis-related Arthritis (ERA)

-Arthritis and inflammation of an enthesitis site (the point at which a ligament, tendon, or joint capsule attaches to bone

-Arthritis or enthesitis with at least 2 of the following: 1) inflammation of the sacroiliac joints or pain and stiffness in the lumbosacral area; 2) positive blood test for HLA B27 gene; 3) onset of arthritis after age 6 in males; 4) first degree relative with Ankylosing spondylitis, ERA, IBD or uveitis

-May develop iritis with acute photophobia and conjunctivitis-High rate of pain and functional disability

-Symptoms worsen in evening and post-exercise -Complications include restrictive lung disease aortic insufficiency (Wwiss, P., Beukelmanm, T., Schanberg, L., Kimura, Y., & Colbert, R. 2012)Undifferentiated arthritis

-Arthritis manifestations that do not fulfill any 1 category -Arthritis manifestations that fulfill more than 1 categoryDiagnostic Studies

JIA is a clinical diagnosis with complete physical exam critical Rheumatoid Factor, ANA, HLA- B27 assay help define subtype but are not

diagnostic. Many patients will be negative for these and inflammatory markers including Sedimentation rate and C-reactive protein.

Radiologic studies including X-rays, MRI and Ultrasound may be useful in assessing and monitoring joint damage and effusions but are not diagnostic in early disease

CBC with differential (rule out infection or malignancy) Liver and kidney function should be checked prior to initiation of treatment Tuberculin skin test prior to immunosuppressive therapies

Serial eye exams are needed to prevent vision loss and assess for uveitis and other inflammatory eye conditions (Sen, E., Clarke, S., & Ramanan, A., 2014).

Differential Diagnosis Traumatic- fractures, soft tissue injury, non-accidental injury (child abuse) overuse

injury Orthopedic-hypermobility-associated, slipped upper femoral epiphysis (SUFE), Perthes’

disease, hip dysplasia, osteochondroses, for example, Osgood-Schlatter disease (tibial tuberosity), Sinding-Larsen syndrome (inferior patella) or Kohler disease (navicular). Osteochondritis dissecans, Scheuemann’s disease, spondylolisthesis

Infectious- Septic arthritis, osteomyelitis, discitis, soft tissue infections, psoas abscess, Lyme disease

Inflammatory- Transient synovitis of the hip, JIA, reactive arthritis, acute rheumatic fever, systemic lupus erythematosus (SLE), juvenile dermatomyositis, vasculitis such as Henoch-Schonlein purpura (HSP), and Mixed connective tissue disease (MCTD).

Neoplasia (benign)- bone cyst, chondroblastoma, osteoblastoma Neoplasia (malignant)- leukemia, lymphoma, neuroblastoma, Ewing’s sarcoma,

osteosarcoma, Langerhans cell histiocytosis Idiopathic pain- Growing pain/benign nocturnal limb pains (BNLP) of childhood,

diffuse idiopathic pain syndrome (juvenile fibromyalgia), Complex regional pain syndrome (CRPS)

Other- Rickets, sickle cell disease, fabricated or induced illness, celiac diseaseMultidisciplinary Management TeamMay include some or all of the following:

Primary Care Physician Pediatric Rheumatologist Orthopedic Physician Palliative Care Physical Therapy Occupational Therapy Social Work Educational Assistance including Individual Education Plan (IEP) Psychiatry/Psychology Music Therapist Child Life specialist Pastoral Care Inpatient Rehabilitation for severe pain/ functional deterioration

Goal of Treatment- -Control inflammation - prevent morbidity and mortality -prevent growth disturbances, joint contractures, joint destruction -prevent functional disability -control pain -Improve Health-related quality of life (HRQOL)-assess and treat anxiety/depression related to disease process

-develop adaptive coping mechanisms-support patient and family-treat insomnia-treat/prevent uveitis and other associated eye disorders-assess and treat medication side effects (i.e. folic acid deficiency from methotrexate) (Suresh, S., & Shah, R., 2011).Medications- See Table 2 for commonly prescribed pharmacological agents used to treat JIA

Nonsteroidal anti-inflammatory drugs (NSAIDS) Oral Corticosteroids Intra-articular corticosteroids Conventional Disease Modifying Rheumatic Drugs (DMARDs) Other DMARDs Biologics Pain management- lidocaine patches, opiates, etc.

Drug Dose Frequency Side effects MonitoringNSAIDSNaproxen 10mg/kg/dose BID GI bleed, upsetIbuprofen 5-10mg/kg/dose 3-4x a day aseptic meningitisIndomethacin 0.5- BID High side effects 1.0mg/kg/dose

DMARDsMethotrexate 1.0 mg/kg/dose Weekly Gastrointestinal, hepatic Renal Fx May be given PO/SQ bone marrow suppression, CBC, LFTs GI and mouth ulcers, alopecia 4-8 weekly

Sulfasalazine 40-60mg/kg/day BID GI, hepatic, rash, allergic CBC, LFT Reactions, Steven-Johnson’s Q 3 months Syndrome, assoc. with Reye’s Syndrome, contraindicated in G6PD deficiency

Other DMARDsCorticosteroids lowest dose possible immunosuppression, osteoporosis infection (0.3-0.5 mg/kg/day) Daily infection, hyperglycemia, weight May be given intraarticular gain, straie 1mg/kg for large joints

COMMON PHARMACOLOGICAL AGENTS FOR JIATable 2

Methylprednisone 30mg/kg IV infusion for severe hypertension, arrhythmia heart rate Disease flare BP Leflunomide, cyclosporine Used infrequently in JIAHydroxychloroquine, azathioprine BiologicsTumor necrosis factor Inhibitors

Etanercept (Enbrel) 0.4mg/kg Weekly rash, autoantibodies SQ Max 50mg increased infection

Infliximab 6mg/kg/IV 0,2 week, then headache, dizziness(Remicade) Q 4-6 weeks nasal and throat irritation

Adalimumab 24mg/m2 Q 14 days sepsis, opportunistic infection TB test(Humira) tuberculosis, lupus like reaction

Interleukin-1 Inhibitors (IL-1)Monoclonal antibodies

Tocilizumab (IL-6) 8mg/kg/IV every 14 days May take 3 months to work Rituximab 750mg/m2 weekly x 2 infusion reaction, infections

Costimulation blockerT cell and antigen presentingCell path blocking agent

Abatacept 10mg/kg 0,2 week, then Headache, URI, diarrhea,(Orencia) max 1 g every 4 weeks fever, pneumonia, Malignancies

(Beukelman, et. al, 2011)

Physical and Occupational Therapy Prevent contractures Provide stretching and disease specific exercises Return functional abilities Improve strength Orthotics and assistive technology (Apti, M., et al., 2014)

Psychosocial Interventions Psychotherapy-Depression, anxiety, and social withdrawal common. Psychological

therapies may include Cognitive behavioral therapy (CBT), Acceptance-based therapy (ACT), biofeedback, and hypnosis (Tilberg, A., Weiss, K., Harrison, D., & Bruce, B, 2014).

Assessment and treatment of sleep disturbances (Valrie, C., Bromberg, M., Palermo, T., & Schanberg, L. 2013).

Educational interventions (school absenteeism common) Financial resources- Families ability to maintain employment may be impacted by

child’s inability to consistently attend school. Medical care and therapies can be expensive and may not all be covered by insurance.

Complimentary Alternative Medicine (CAM)

Often based on biopsychological theory of disease (aims to treat mind, body and spirit) and includes such things as yoga, tai chi and hypnosis

Autoimmune disorders tend to flare in response to emotional stressors Families may not admit to CAM use for fear of judgement Essential oils, healing touch, herbal /mineral supplements and dietary changes

(Vinson, R., Yeh, G., Davis, R. B., & Logan, D., 2014).

Table 3. Domains of clinical evaluation of Juvenile Idiopathic ArthritisBiological Psychological Social

Pain characteristics Mood School attendance

Site/sites Anxiety Social functioning (peer/family)

Time features- onset, frequency, etc.

Depression Parental behaviors (protective responsiveness, overbearing, minimization

Descriptors Cognitions (attitudes, beliefs) pain catastrophizing

Parent characteristics- age, educational level, economic status

Intensity (0-10) NRS Sleep Cognitions (catastrophizing, expectancies

Radiation Behavioral problems Isolation

Precipitating factors Social isolation Inability to participate in sports and hobbies

Relieving factors loneliness Chronic illness in parent-Parent with chronic pain

Physical functioning hopelessness Community resources available

Level of disability Resilience factors Ability to participate in activities- outings, Band, support groups

Implication for Primary Care Providers

Early recognition and treatment of JIA can positively impact the overall morbidity and mortality associated with this condition. Primary care providers must carefully assess and evaluate complaints of joint and musculoskeletal pain for rheumatological causes and refer patients for timely evaluation and treatment. In addition, clinicians with patients with known JIA disease must be on the lookout for common complications including infection, effusions, uveitis, anxiety, depression and insomnia. As with any chronic condition, the provider may be

instrumental in coordinating care that provides for the physical, psychological, social, and educational needs of the patient.

References

Apti, M. D., Kasapcopur, O, Mengi, M., Ozturk, G., & Metin, G. (2014). Regular Aerobic Training Combined with Range of Motion Exercises in Juvenile Idiopathic Arthritis. BioMed Research International, 2014, 1-6. doi:10.1155/2014/748972

Beukelman, T., Patkar, N.M., Saag, K.G., Tolleson-Rinehart, S., Cron, R.Q., Dewitt, E. M…..Ruperto, N. 2011). 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic

Cartwright, T., Fraser, E., Edmunds, S., Wilkinson, N., & Jacobs, K. (2014). Journeys of adjustment: The experiences of adolescents living with juvenile idiopathic arthritis. Child: Care, Health and Development, 41 (5), 734-743. doi: 10.1111/cch.12206

Colebatch-Bourn, A., Edwards, C., Collado, P., D’agostino, M., Hemke, R., Jousse-Joulin, S…..Malattia, C. (2015). FR10503 Eular-Pres Points to Consider for the Use of Imaging in the Diagnosis and Management of Juvenile Idiopathic Arthritis in Clinical Practice. Annals of the Rheumatic Diseases Ann Rheum Dis, 74 (Suppl 2).

Ellis, J.A., Munro, J.E., & Ponsonby, A. (2009). Possible environmental determinants of juvenile idiopathic arthritis. Rheumatology, 49 (3), 411-425. doi:10.1093/rheumatology/kep383

Seid, M. (2012). Predictors of health-related quality of life in children and adolescents with juvenile idiopathic arthritis. Arthritis Care & Research, 64(5), 652-652. doi:10.1002/acr.21604

Sen, E., Clarke, S., & Ramanan, A. (2014). The child with joint pain in primary care. Best Practice & Research Clinical Rheumatology, 28(6), 888-906. doi:10.1016/j.berh.2015.04.008

Tseng, A. S., Weiss, K., Harrison, T., Hansen, D., & Bruce, B. (2014). Pain Relief as a PrimaryTreatment Goal: At What Point does Functioning and Well-Being Become more Important? ACase Study of an Adolescent with Debilitating Chronic Pain. Pain Research and Management,19(4), 219-223. doi:10.1155/2014/745458

Weiss, P.F., Beukelman, T., Schanberg, L.E., Kimura, Y., & Colbert, R.A. (2012). Enthesitis-related Arthritis is Associated with Higher Pain Intensity and Poorer Health Status in Comparison with Other Categories of Juvenile Idiopathic Arthritis: The Childhood Arthritis and Rheumatology Research Alliance Registry. The Journal of Rheumatology, 39(12), 2341-2351. doi:10.3899/jrheum.120642

Suresh, S., & Shah, R. (2011). Chronic pain management in children and adolescents. Essentialsof PainMedicine, 403-408. doi:10.1016/b978-1-4377-2242-0.00066-3

Valrie, C. R., Bromberg, M. H., Palermo, T., & Schanberg, L. E. (2013). A Systematic Review of Sleep in Pediatric Pain Populations. Journal of Developmental & amp; Behavioral

Vinson, R., Yeh, G., Davis, R. B., & Logan, D. (2014). Correlates of Complementary and

Alternative Medicine Use in a Pediatric Tertiary Pain Center. Academic Pediatrics, 14(5), 491-496. doi:10.1016/j.acap.2014.04.003

Figure 1.

Joint Pain

Clear Diagnosis of JIA

Unknown cause

Optimize Disease Specific Treatment (Rheumatology)

Pain persists

NO YES

Multidisciplinary Management

Continue disease specific Management

Pain education

Psychological TxSLEEP Medications

INTERVENTIONSAS APPROPRIATE

PT/OTCAM- herbs, hypnosis, yoga, etc.

Pain persists

Pediatric Pain Specialist

Inpatient or outpatient pain rehab