Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatic arthritis (82), is the most common rheumatic disease of childhood, affecting approxi­mately 16-150 in 100,000 (83).

Early arthritis may be manifested by swelling, warmth, and joint stiffness, typically worse at the beginning of the day then improving with activity. Symptoms usually fluctuate; uncontrolled inflamma­tion leads to joint damage. Younger children rarely complain of joint pain, but may instead become irrita­ble, stop walking or using an extremity, or regress in their behavior (87). Other symptoms include decreased appetite, malaise, inactivity, morning stiffness, night­time joint pains, and failure to thrive (87). Enuresis may occur in a recently toilet-trained child (88). Later disease presents with reduced range of motion (ROM), contractures, overgrowth or undergrowth of affected limbs, and resultant disability.

A characteristic feature of chronic arthritis in chil­dren is the effect the disease has on bone and joint development (89,90). Local growth disturbances at inflammation sites can lead to overgrowth (second­ary to possible inflammatory-mediated increased Vascularization and growth factor release) or under­growth (secondary to growth center damage or prema­ture fusion of epiphyseal plates).

The differential diagnosis of JIA is large (Table 14.1 provides a full differential diagnosis).

The assumption that JIA will universally resolve by adulthood is incorrect (92). Radiological joint damage occurs in children with systemic arthritis and polyar­ticular arthritis within two years, and in oligoarthritis within five years (93,94) Despite long-term persistence of disease activity in JIA, much improvement in functional outcomes has been made in the last decade (95,96). Indicators of poor outcome include greater severity or extension of arthritis at onset, symmetrical disease, early wrist or hip involvement, presence of RF, persis­tent active disease, and early radiographic changes (97).

Clinical Features of JIA Subtypes

Systemic JIA Systemic-onset JIA presents with many extra-articular features and represents 10% to 20% of all JIA (86). Diagnosis requires arthritis accompanied or preceded by quotidian fever (spikes >39 degrees Celsius once a day with return to normal between peaks) of at least two weeks' duration, plus one or more of the following: evanescent salmon-colored rash, gen­eralized lymphadenopathy, hepatomegaly, splenomeg­aly, or serositis.

About 5% to 8% of children with systemic JIA develop a life-threatening complication known as macrophage activation syndrome (98) with persistent fever, lymphadenopathy, and splenomegaly, and there is profound depression in one or more of the blood cell lines (often initially platelets) with raised liver func­tion enzymes and clotting abnormalities. Definitive bone marrow examination shows numerous well-dif­ferentiated macrophages actively phagocytizing hemo- poetic elements (99).

In one-half of children with systemic JIA, the course follows a relapsing-remitting course, with arthritis accompanying febrile episodes, then remis­sion once systemic features are controlled. Long-term outlook for these children is usually good. In the other half, the disease is unremitting, with resultant severe joint destruction, and is probably the most severe JIA subtype (83,100). Poor prognostic signs include the continued presence of systemic features and a platelet count exceeding 600,000/mm³ six months after onset (87). At least one-third of children will develop severe arthritis (101).

Oligoarthritis. Oligoarthritis is classified into two sub­types: persistent (affecting not more than four joints throughout the disease course) and extended (affect­ing more than four joints after the first six months of disease). Characteristically, there is an early onset before 6 years of age of an asymmetric arthritis, usu­ally in the lower limbs, and predominantly in females. Antinuclear antibodies (ANAs) are detected in sub­stantial titres in about 70% to 80%, and they represent a risk factor for iridocyclitis. Children with the oligoar­thritis subtype generally have the best outcome (83); however, sight-threatening, clinically silent uveitis develops in the first four years from diagnosis. Regular ophthalmology follow-up is essential (102).

Polyarthritis. Polyarthritis must affect five or more joints in the first six months of the disease. RF-positive pol­yarthritis mainly affects adolescent girls, with a sym­metrical pattern, and is the same as adult RF-positive disease (89). By five years from onset, severe deform­ing arthritis is generally present (90). RF-negative polyarthritis is a more heterogenous group with more

14.1

Differential Diagnosis of Juvenile Idiopathic Arthritis

Pediatric Rheumatic Diseases

Systemic lupus erythematosus

Juvenile dermatomyositis

Scleroderma

Localized (linear, morphea, etc.)

Generalized (systemic sclerosis, CREST, etc.)

Mixed connective tissue cisease (overlap syndrome)

Juvenile ankylosing spondylitis

Acute rheumatic fever

Reactive or postinfectious arthritis

Vasculitis

Kawasaki disease

Henoch-Schoenlein purpura

Behgets disease

Wegener granulomatosis

Polyarteritis nodosa

Autoinflammatory disorders

Tumor necrosis factor receptor-alpha associated periodic syndromes

Familial cold autoinflammatory syndrome

Neonatal onset multisystem inflammatory disease

Chronic infantile neurologic, cutaneous and articular syndrome

Periodic fever, adenitis, pharyngitis and apthous ulcer syndrome

Fibromyalgia

Complex regional pain syndrome, type II

Infectious Diseases

Bacterial arthritis

Viral arthritis

Fungal arthritis

Osteomyelitis

Fasciitis/myositis

Neoplastic Diseases

Leukemia

Lymphoma

Neuroblastoma

Primary bone neoplasms

Hematologic Diseases

Hemophilia

Sickle cell disease

Noninflammatory Disorders

Trauma

Overuse syndromes

Osteonecrosis syndromes

Avascular necrosis syndromes

Slipped capital femoral epiphysis

Toxic synovitis of the hip

Patellofemoral dysfunction (chondromalacia patellae) Diskitis

Miscellaneous Disorders

Inflammatory bowel disease

Sarcoidosis

Collagen disorders

Chronic recurrent multifocal osteomyelitis

Growing pains

Hypermobility syndromes

Foreign-body arthritis

Psychogenic arthralgias/arthritis (conversion reactions)

variable outcome.

Psoriatic Arthritis. Psoriatic arthritis accounts for about 5% of JIA and requires the simultaneous presence of arthritis and the typical psoriatic rash, or if the rash is absent, arthritis plus two of the following: positive family history of psoriasis in a first-degree relative, dactylitis, and nail pitting. Psoriatic disease in chil­dren before the age of 5 years appears to be more diffi­cult to control than in an older subset of children, with a median of 9.5 years (86).

Enthesitis-Related Arthritis. Enthesitis-related arthritis affects males after the age of 6 years (89, 90) and most children are HLA-B27-positive. The most common sites of enthesitis are the calcaneal insertion of the Achilles tendon, plantar fascia, and tarsal area. Arthritis commonly affects the joints of the lower extremities. Unlike other JIA subsets, hip involvement is common at disease presentation.

These children may progress to fulfill criteria for ankylosing spondylitis, reactive arthritis, or arthritis associated with inflammatory bowel disease. Uveitis is also a clinical problem in this subset, but it is usu­ally sudden in onset, symptomatic, and more unilat­eral than in children with other JIA subsets (86).

Juvenile ankylosing spondylitis, not considered part of the JIA subclassification; mainly affects ado­lescent boys; is strongly associated with HLA-B7; and manifests as an asymmetric, often episodic, oligoar­thritis in the lower limbs. Later on, bilateral sacro­iliac joints become involved, and progression of the disease can lead to the characteristic “bamboo” spine on radiographic images secondary to ankylosis of spinal joints. In children, peripheral arthritis and enthesitis present early in the disease, but sacroiliac and spine joints are not involved until many years later (104).

Inflammatory bowel-associated arthritis occurs in approximately 10% to 20% of children with ulcera­tive colitis and Crohn's disease. The arthritis usually affects a few joints and may be associated with spon­dylitis; erythema nodosum and growth failure may occur.

Undifferentiated Arthritis. This subset is not a separate entity, but is more of a catch-all category for those chil­dren who do not satisfy inclusion criteria for any cate­gory, or who meet criteria in more than one category.

Rehabilitation of the Child With JIA

Goals of treatment include controlling symptoms, pre­venting joint damage, achieving normal growth and development, and maintaining function and normal activity levels.

Treatment goals may vary during maintenance and acute flare-ups of the disease.

Resting a joint may be necessary during an acute flare-up to prevent aggravation of the disease process; activities that affect or excessively stress joints should be discouraged during acute flare-ups. Resting a joint may also be useful during the maintenance phase for joint protection. Rest periods may be necessary to reduce fatigue; resting in the prone position will help reduce hip and knee flexion contractures.

Splinting is used during a flare-up to provide alignment during a rest period. Functional splints may be used during flare-ups and maintenance phases if they provide joint relief and allow functional activities without stressing inflamed joints. Splinting can be used during the maintenance phase to promote local joint rest, support weakened structures, and assist function. To prevent flexion contractures, the upper extremity is splinted in a functional position as fol­lows: wrist 15-20 degrees of extension, some finger flexion, 25 degrees at the metacarpophalangeal (MCP) joint, and 5-10 degrees at the PIP joint, with the thumb in opposition.

Gentle ROM with passive extension greater than flexion two to three times a day is used to preserve joint ROM. Incorporating pain medication, progressive muscle relaxation, breathing exercises, biofeedback, massage, or doing the exercises in a nice, warm tub can greatly facilitate ROM exercises. Gentle ROM exer­cises should be done as tolerated during acute flare- ups to prevent flexion contractures.

Heat is an excellent modality in the maintenance phase to decrease stiffness, increase tissue elasticity, and decrease pain and muscle spasm. Hydrotherapy with temperatures 90-100 degrees Fahrenheit, fluido- therapy, paraffin, or moist heat can be used. Most chil­dren prefer heat to cold. Taking a hot bath or shower, sleeping in a sleeping bag, or using a hot pack (along with ROM exercises) may help relieve morning stiff­ness. Caution must be exercised in insensate areas to avoid burns. Ultrasound is contraindicated in children with open growth plates. Heat should not be used dur­ing an acute flare-up, as it increases the inflammatory response and causes further joint destruction.

Cold can be used during an acute flare-up for pain relief and to decrease swelling. It may also be benefi­cial during the maintenance phase for the same rea­sons. Cold should not be used over insensate areas or in those with Raynaud's phenomenon.

Adaptive strengthening exercises can be incor­porated into play and recreational activities. Some examples include throwing a ball (strengthens elbow and shoulder), riding a bike (promotes knee and hip extension), and swimming (decreases weight bearing on painful joints). Incorporating general aerobic con­ditioning is also important and may include activities such as swimming, dancing, noncontact karate, and tai chi. Isometric strengthening exercises are fine dur­ing an acute flare-up, but vigorous exercise should be held until the acute process is over. Hydrotherapy can be combined with land-based physiotherapy in treat­ing JIA (105).

Adaptive equipment can be used for joint protec­tion, rest, and to minimize further joint destruction during both phases. Examples include adaptive uten­sils, adaptive pens and computer access, table and desk modifications (to prevent excessive trunk and neck flexion), zipper pulls, dressing sticks, long-handled brushes, elastic waistbands, Velcro closures, and larger buttons. Children should actively participate in func­tional activities of daily living (ADL) training in order to choose acceptable devices and improve their use.

Activity and ambulation should be encouraged as much as possible. A posterior walker for upright posture (with decreased flexion) and a standing pro­gram may be useful for functional mobility training if wheelchair use cannot be avoided. In children with JIA, custom-made semirigid foot orthotics with shock­absorbing posts have been found to significantly improve pain, ambulation speed, self-rated activity, and functional ability levels compared to prefabricated off-the-shelf shoe inserts or supportive athletic shoes alone (106).

A presurgical joint rehabilitation program aims to strengthen the muscles needed for mobility in the postop period, train for future ambulation aids, and identify other joint involvement that may affect the rehabilitation process. Post-surgical rehabilitation ful­fills those goals set in the pre-surgical rehabilitation program. Ambulation aids such as the platform walker may be used to better distribute weight bearing pres­sure on affected upper extremity joints after knee or hip surgery. In children status post-hip prosthesis, the acetabular component should be checked for loosen­ing (as opposed to the femoral component in adults), especially if children are active.

Growth retardation can occur during periods of active disease; it may also be compounded by cortico­steroid use. Maximize growth by promoting optimal nutrition. Children with JIA should eat a balanced diet with supplemental multivitamins, calcium, vitamin D, and sunshine secondary to the high risk of osteope­nia. Plenty of (nonimpact) activity again should be encouraged.

Counseling for both the child with JIA and their family should be provided to maximize psychosocial and emotional well-being. Treatment goals also include addressing family, school, and vocation. Assisting in the preparation of a 504 plan for school accommoda­tions enables a child with joint disease opportunity for more complete participation in his or her school life and academic career. Summer camps are a prac­tical way of addressing peer support within adoles­cent rheumatology services; positive effects include increased control, self-esteem, physical fitness, inde­pendence from parents, self-management of health care, and an opportunity to meet others with a similar condition (107).

Specific Joints in JIA

Cervical Spine. Cervical spine involvement occurs more often in children with JIA than adults. Restriction of ROM, pain, and muscle spasms, which may present as torticollis, may be seen. A soft cervical collar to serve as a reminder for proper alignment and pro­vide warmth may be helpful in acute pain with mus­cle spasm. Minimizing time in flexion is important. If the transverse ligament becomes weakened, atlanto­axial subluxation can occur. If subluxation occurs, a firm cervical collar should be worn during automotive transport.

Temporomandibular Joint (TMJ). This joint is affected in almost two-thirds of children with JIA (108) by causing pain in chewing and opening the mouth, stiffness, and micrognathia. Younger children will not complain of jaw pain, but will instead choose to modify their diet to avoid pain. Progressive jaw ROM exercises and modalites may help treat pain and stiffness. If the lower jaw does not develop properly, it may create an over­bite, requiring orthodontist intervention and/or oral surgery. Mandibular and facial growth disturbances are more common in polyarticular types of JIA.

Upper Extremities. The shoulder is not commonly involved at the onset of disease. Approximately one-third of children with polyarticular or psoriatic disease may eventually develop shoulder involvement and loss of adduction and internal rotation affecting midline ADLs, such as grooming and toileting. The elbow requires at least 90 degrees of flexion range to per­form ADLs such as eating, grooming, and reaching. Loss of more than 45 degrees of elbow extension lim­its the use of arms as levers to rise from a seated posi­tion and makes toileting and lower extremity dressing difficult. Wrist involvement is common in children; there is early loss of wrist extension with progres­sive flexion contracture. A nighttime resting wrist splint can maintain the wrist in 15 to 20 degrees of extension with the fingers in a few degrees of flexion; ulnar deviation can also be built in as necessary. Strengthening of wrist extensors and radial deviators is necessary to reduce wrist flexion and ulnar devi­ation contractures. Moist heat to reduce spasm and improve tissue elasticity followed by serial casting for 48-72 hours as tolerated may help reduce contrac­tures by slowly increasing wrist extension as tolerated while controlling ulnar deviation and subluxation; commercially available dynamic splinting may also facilitate stretching. Should ankylosis be inevitable, the hand should be splinted in a neutral position for optimal function in self-cares.

Functional grasp may become limited as fingers lose both flexion and extension range. Flexion con­tractures of the metacarpal and proximal interpha- langeal joints are often seen. The use of ring splints in metal or plastic can help control proximal inter- phalangeal flexion and extension seen in boutonniere and swan neck deformities, respectively. Fingers can be strengthened through play with clay and various adaptive putties.

Lower Extremities. In the lower extremities, flexion contractures occur at the knee and hip. Painful ambu­lation can lead to increased sitting, which in turn leads to increased flexion contracture, deconditioning, weakness, atrophy, and osteoporosis. Hip flexion con­tractures in children occur with internal rotation and adduction, compared with adults who tend to develop external rotation and abduction. Prone lying greater than 20 minutes per day with the hips and knees extended and feet off the edge of the bed can help prevent these contractures. Other strategies include strengthening of the hip extensors, external rotators, abductors, and quadriceps, along with ROM exercises to stretch the hip flexors, internal rotators, adductors, and hamstrings. Hip extensors can be strengthened through swimming, aquatic therapy, and bicycling. Encouraging upright posture and ambulation, using a stander as necessary, is also helpful. Hip develop­ment may be assisted by the use of a stander; a prone stander can strengthen neck and hip extensors, while a supine stander maintains the knees in extension and allows upright weight bearing.

The knee is the most commonly affected joint in JIA; early involvement of the knee can cause quad­riceps weakness that may not resolve. Knee contrac­tures can lead to other joint contractures and further gait abnormalities. Bony overgrowth with resultant leg-length discrepancies are often seen. The knee can be maintained in extension using resting splints such as knee immobilizers and alternating legs nightly as needed to increase comfort and compliance. Dynamic splinting using an adjustable knee joint can be used to improve ROM and limit excessive flexion and valgus tendency. Because forced extension of the knee with a contracture can exacerbate posterior subluxation, cau­tion must be exercised in using bracing and splinting. Active quadriceps strengthening should be done post­brace removal and also maintained with knee exten­sion exercise or isometric exercises if too painful. Kicking, bicycling, and walking can also strengthen weak quadriceps muscles.

Multiple foot deformities can occur in JIA, includ­ing claw toe, valgus or varus hindfoot, and ankle plantarflexion contracture deformities. The midfoot is frequently affected, and can be quite painful and dif­ficult to treat. Tenosynovitis that is difficult to discern from joint disease may occur. Molded foot orthoses can be used to reduce pain at the metatarsal heads and heels with weight bearing. A University of California at Berkeley orthosis can prevent or control varus and valgus deformities. A posterior leaf-spring ankle foot orthosis (AFO) or nighttime resting splint may be helpful to reduce loss of ankle dorsiflexion range and control varus and valgus. Ankle rotation exercises, balancing exercises, and raising the heel on a step can strengthen ankle muscles. Footwear should be com­fortable and accommodate any foot deformities. High heels should generally be avoided, as they can help develop plantarflexion contractures and add to foot deformities. Flip-flops should also be avoided second­ary to their lack of adequate support.

Inflammation causing bony overgrowth at the distal femur can cause a true leg-length discrepancy (LLD), leading to pelvic asymmetry and scoliosis. The increased blood flow from inflammation may alterna­tively cause early epiphyseal closure and overall limb shortening.

Medical and Surgical Treatments of JIA

Children with JIA are treated with more of an induc­tion and maintenance approach, taking advantage of windows of opportunity to modify the disease course, usually under the guidance of a pediatric rheuma­tologist (109). Nonsteroidal anti-inflammatory drugs (NSAIDs) are used briefly in the initial phase (110).

Intra-articular steroid injections in affected joints using triamcinolone hexacetonide (preferred formula­tion in pediatric practice) (111) are frequently needed at disease onset or during the disease course. They may be substituted for NSAIDs in mono or oligoarthri­tis at times (83). Early use of intra-articular steroids in one or two affected joints may even have the potential to modify the course of JIA (87).

Methotrexate is used early on in the disease course as a second-line agent of choice for persistent, active arthritis (112), with improvement usually seen in 6 to 12 weeks. Parenteral methotrexate is supe­rior to oral, especially at higher doses. Leflunamide may also be used if methotrexate is ineffective (113). Recommendations vary from 6 to 24 months of remis­sion before tapering medications other than NSAIDs; the best method for tapering methotrexate is unknown (88). Approximately 70% to 75% of children with chronic arthritis achieve remissions with NSAIDs plus methotrexate (114).

The biologics (etanercept, infliximab, adali- mumab, anakinra, abatacept, and rituximab) have all been demonstrated to be effective in treating inflammatory arthritis (88). Tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) are now approved for use in children (115) and are used after methotrexate. Infliximab has an efficacy sim­ilar to etanercept (116). Abatacept, a T-cell blocker, has been recently approved by the Food and Drug Administration (FDA) for use in children with JIA, and has promise for the TNF inhibitor nonresponders. Special risks in treating children with biologics include increased risk for infections (especially var­icella), how and when to proceed with usual immu­nizations, long-term effects, and possibility of later malignancies or development of central nervous sys­tem demylinating disease (88). Early and aggressive treatment of JIA with newer agents holds unlimited promise for even better outcomes for children with JIA. Steroids are used as sparingly as possible to con­trol inflammation in order to avoid long-term side effects such as weight gain, poor growth, and risk of infection. There is no systemic evidence that steroids are disease-modifying (92).

Children with JIA are at high risk of developing osteopenia secondary to the disease itself, to steroid treatment of the primary disease, lack of physical activ­ity and weight bearing, limited sunshine exposure, and inadequate vitamin D and calcium. Calcium and vitamin D supplementation, sunshine, and encourage­ment of physical activity should be incorporated into the treatment plan.

Surgery is rarely used in the early course of the dis­ease; however, surgery can be used later in the course to relieve pain, release joint contractures, and replace a damaged joint. Older children whose growth is com­plete or almost complete and whose joints are badly damaged by arthritis may need joint replacement sur­gery to reduce pain and improve function. Soft tissue releases may be needed to reposition malaligned joints or release contractures.