Juvenile Idiopathic Arthritis
Clinical Snapshot
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood: arthritis of unknown cause that begins before age 16 and persists for at least 6 weeks, diagnosed only after infection, malignancy, and other identifiable causes of joint inflammation have been excluded.[1] JIA is not a single disease — it is an umbrella term for 7 clinically distinct subtypes defined by the International League of Associations for Rheumatology (ILAR) classification system, and which subtype a child has genuinely changes both prognosis and treatment selection, unlike adult rheumatoid arthritis's comparatively uniform treat-to-target approach.[1] See the platform's Rheumatoid Arthritis chapter for the shared pharmacotherapy mechanisms (methotrexate, TNF inhibitors, and the broader biologic DMARD classes) that this chapter cross-references rather than re-explains in full; the content here focuses on what is genuinely different about the pediatric disease.
The 2 most distinctive pediatric-specific management points in this chapter. First, oligoarticular JIA — the most common subtype — carries a real and often entirely asymptomatic risk of chronic anterior uveitis that can cause silent, permanent vision damage before any eye symptom appears; regular, scheduled slit-lamp screening, not symptom-triggered care, is essential regardless of how well the joints are doing. Second, systemic JIA can be complicated by macrophage activation syndrome (MAS), a life-threatening hyperinflammatory emergency that every clinician caring for a child with systemic JIA must be able to recognize immediately. Both are covered in full depth in this chapter.
Recognize the Condition
Epidemiology
JIA is the most common chronic rheumatic disease of childhood. Population-based Canadian data from Manitoba show a prevalence of approximately 117 per 100,000 children and adolescents 18 years of age or younger, with an incidence that declined from 14.0 per 100,000 in 2000/2001 to 9.2 per 100,000 in 2010/2011; comparable Canadian provincial estimates are 98 per 100,000 in Saskatchewan and 80 per 100,000 in Quebec.[2] Oligoarticular JIA is the most common subtype, typically affecting toddlers and preschool-age girls; RF-positive polyarthritis more closely mirrors adult-onset disease and tends to present in adolescent girls; systemic JIA has no sex predominance and can begin at any age throughout childhood.[1]
The ILAR classification — the organizing framework for this entire chapter
Unlike adult RA, JIA is subdivided into 7 mutually exclusive categories based on the pattern of joint involvement in the first 6 months of disease, plus specific extra-articular features and serology. Getting the subtype right at diagnosis genuinely changes both prognosis and the treatment approach used throughout this chapter — it is not just a labelling exercise.[1]
The 7 ILAR subtypes
Oligoarthritis (most common subtype, roughly half of all JIA)
4 or fewer joints affected in the first 6 months of disease. Persistent oligoarthritis never exceeds 4 joints; extended oligoarthritis involves more than 4 joints after the first 6 months and behaves more like polyarthritis from that point forward. Typically affects young girls (peak onset ages 1-3 years), most often the knee. Carries the single highest risk of asymptomatic chronic anterior uveitis of any JIA subtype, especially when ANA-positive — see Monitoring & Follow-Up for the screening protocol.
Polyarthritis, RF-negative
5 or more joints affected in the first 6 months, rheumatoid factor negative. The most heterogeneous JIA category, ranging from a disease course resembling extended oligoarthritis to one resembling seropositive polyarthritis.
Polyarthritis, RF-positive
5 or more joints affected in the first 6 months, with rheumatoid factor positive on 2 occasions at least 3 months apart. Typically affects adolescent girls and behaves most similarly to adult-onset seropositive RA of any JIA subtype — often anti-CCP-positive as well, with a genuine risk of erosive, symmetric small-joint disease if undertreated.
Systemic JIA
A genuinely distinct autoinflammatory (not classically autoimmune) disease: arthritis accompanied by a documented quotidian fever (daily spiking to 39°C or higher, returning to baseline between spikes) for at least 2 weeks, plus at least 1 of an evanescent salmon-pink rash, generalized lymphadenopathy, hepatomegaly or splenomegaly, or serositis. Carries a real risk of macrophage activation syndrome, a life-threatening hyperinflammatory complication covered in full in Special Populations.
Enthesitis-related arthritis (ERA)
Arthritis and enthesitis together, or either alone plus at least 2 of: sacroiliac joint tenderness or inflammatory lumbosacral pain, HLA-B27 positivity, arthritis onset in a boy older than 6 years, acute (symptomatic) anterior uveitis, or a first-degree relative with ankylosing spondylitis, ERA, sacroiliitis with inflammatory bowel disease, reactive arthritis, or acute anterior uveitis. More common in boys; the uveitis associated with this subtype is typically acute and symptomatic (red, painful eye) rather than the silent, chronic uveitis of ANA-positive oligoarthritis.
Psoriatic JIA
Arthritis plus psoriasis, or arthritis plus at least 2 of: dactylitis, nail pitting or onycholysis, or a first-degree relative with psoriasis. A genuinely bimodal subtype — younger children often resemble ANA-positive oligoarthritis with uveitis risk, while older children more closely resemble adult psoriatic arthritis with enthesitis and axial involvement.
Undifferentiated arthritis
Arthritis that either fulfills the criteria for no single category above, or fulfills the criteria for more than 1 category simultaneously.
Clinical presentation
The hallmark is joint swelling, pain, and morning stiffness or "gelling" after periods of inactivity that improves with movement through the day — the same core pattern as adult RA. A genuinely pediatric-specific twist: young children very often cannot verbalize joint pain clearly, and may instead present with a limp, reluctance to use a limb, regression of previously acquired motor skills, or simple irritability rather than a clear complaint of pain — a presentation that is easy to miss or misattribute to a minor injury. Joint swelling is often more reliable than a pain history in this age group. Growth disturbance is a genuinely pediatric-specific complication of chronic inflammation, distinct from anything seen in adult RA: it can be localized (leg-length discrepancy from asymmetric knee involvement, or micrognathia from temporomandibular joint arthritis) or generalized (short stature from the combined effect of chronic systemic inflammation and corticosteroid exposure) — see Monitoring & Follow-Up.
Risk Factors
- Age under 16 years at onset — required by definition; oligoarthritis peaks at ages 1-3 years, while RF-positive polyarthritis more often begins in adolescence.
- Female sex for oligoarthritis and polyarthritis (both RF-positive and RF-negative); enthesitis-related arthritis is more common in boys.
- Genetic susceptibility, including HLA associations — HLA-B27 in particular for enthesitis-related arthritis, and various HLA-DR alleles for oligoarthritis and RF-negative polyarthritis.
- ANA positivity — not a risk factor for JIA itself, but the single most important risk stratifier for silent chronic anterior uveitis once JIA is diagnosed (see Monitoring & Follow-Up).
- Family history of JIA or another autoimmune/rheumatic disease; for enthesitis-related arthritis specifically, a first-degree relative with ankylosing spondylitis, inflammatory-bowel-disease-associated arthritis, reactive arthritis, or acute anterior uveitis.
- A preceding infectious or environmental trigger in a genetically susceptible child is suspected for most subtypes, but no single causative organism or exposure has been confirmed.
Red Flags & Refer
Any joint swelling or inflammatory joint pain persisting 6 weeks or longer in a child under 16 warrants pediatric rheumatology referral — treat this itself as a standing red flag, not only the items below.[1]
- Fever with rash and marked systemic illness in a child with known or suspected systemic JIA — evaluate urgently for macrophage activation syndrome (MAS), a life-threatening hyperinflammatory emergency. A falling platelet count in a previously thrombocytotic patient, or a falling ESR alongside a rising CRP (from consumptive hypofibrinogenemia), are subtle early clues that MAS can be worsening even as the fever pattern appears to be settling — see Special Populations for the full recognition and treatment pathway.[3]
- Any vision change or red eye in a child with JIA — refer for urgent ophthalmologic evaluation. Most JIA-associated chronic anterior uveitis is entirely asymptomatic until damage has already occurred, so do not wait for symptoms to trigger screening in the first place (see Monitoring & Follow-Up); a symptomatic red or painful eye, more typical of enthesitis-related arthritis, still needs urgent same-day assessment.[4]
- New joint swelling or pain in an infant or toddler presenting instead as a limp, refusal to bear weight, or regression of motor skills — evaluate promptly and do not dismiss as a minor injury without examination.
- Acute, severe, single-joint pain with fever, especially in a child without an established JIA diagnosis — evaluate urgently for septic arthritis or osteomyelitis, which require emergency orthopedic/infectious disease management rather than rheumatology referral.
- Signs suggesting malignancy (unexplained bruising, pallor, bone pain out of proportion to joint findings, night sweats, weight loss) — investigate for leukemia before starting any corticosteroid, which can mask or delay a malignancy diagnosis.
- Signs of progressive joint damage (new contracture, loss of range of motion, radiographic erosion) or growth disturbance (falling off the growth curve, leg-length discrepancy, micrognathia) — these indicate the current treatment plan needs escalation, not simply closer observation.
Assessment & Diagnosis
JIA is a clinical diagnosis of exclusion
There is no single confirmatory test for JIA. The diagnosis requires objective arthritis (joint swelling, or at least 2 of limited range of motion, tenderness/pain on motion, and warmth) in 1 or more joints, present for at least 6 weeks, with onset before age 16 — made only after excluding infection, malignancy, and other identifiable causes of childhood joint inflammation.[1]
Key differential diagnoses
| Feature | JIA | Septic arthritis / osteomyelitis | Leukemia | Reactive arthritis (post-infectious) | Mechanical/orthopedic (e.g., Perthes, slipped epiphysis) |
|---|---|---|---|---|---|
| Onset | Insidious, over weeks | Acute, over hours-days, often with fever | Variable; bone pain often out of proportion to exam findings | 1-4 weeks after a GI or genitourinary infection | Insidious or activity-related |
| Joint pattern | Persistent swelling, subtype-dependent distribution | Classically monoarticular, most often knee or hip | Can mimic any JIA pattern; migratory pain is a clue | Asymmetric, lower-limb predominant | Usually a single large joint (hip, knee) |
| Systemic features | Subtype-dependent (systemic JIA: quotidian fever, rash) | High fever, systemic illness, toxic-appearing | Pallor, bruising, fatigue, weight loss, lymphadenopathy | Preceding diarrheal or urethritis illness | None |
| Key investigations | Elevated ESR/CRP (may be normal, especially in oligoarthritis); ANA, RF, HLA-B27 for subtype classification | Markedly elevated ESR/CRP/WBC; joint aspirate positive on Gram stain/culture — a surgical emergency | Cytopenias, elevated LDH and uric acid, blasts on blood film or bone marrow | Positive stool/urethral culture or serology; self-limited over weeks | Normal inflammatory markers; characteristic radiographic findings |
Investigations
- ESR and CRP — support the diagnosis and help track disease activity, but a normal result does not exclude JIA, particularly oligoarthritis.
- ANA — not diagnostic of JIA itself, but the single most important test for uveitis risk stratification once JIA is confirmed (see Monitoring & Follow-Up).
- Rheumatoid factor and anti-CCP — define the RF-positive polyarthritis subtype; anti-CCP supports RF-positive disease and, like adult seropositive RA, associates with more erosive disease.
- HLA-B27 — supports (but is not required for) the enthesitis-related arthritis classification.
- CBC with differential/blood film, and LDH — screen for leukemia and other malignancy before starting any corticosteroid, since corticosteroids can transiently improve leukemic bone/joint pain and delay the correct diagnosis.
- Plain radiographs at baseline for the affected joint(s); MRI is increasingly used to detect subclinical synovitis and is particularly useful for the temporomandibular joint and sacroiliac joints (enthesitis-related arthritis) where clinical exam is less reliable.
Treatment Targets
- Achieve inactive disease or clinical remission, tracked with a validated composite disease-activity measure (e.g., the Juvenile Arthritis Disease Activity Score, JADAS) rather than symptoms alone.
- Treat early and adjust promptly against the defined target — a treat-to-target philosophy that genuinely parallels adult RA's own approach, applied here with pediatric-specific dosing and monitoring.
- Preserve joint function, and protect normal growth and pubertal development from the effects of both chronic inflammation and corticosteroid exposure.
- Prevent long-term joint damage, including growth disturbance (leg-length discrepancy, micrognathia) specific to a still-growing skeleton.
- Prevent the sight-threatening complications of JIA-associated uveitis through scheduled screening, not symptom-triggered care.
- Recognize and urgently treat macrophage activation syndrome in systemic JIA before it becomes life-threatening.
- Support a successful, well-planned transition to adult rheumatology care, since many JIA patients continue to have active disease into adulthood.
Choose Initial Treatment
Oligoarthritis, 1st line intra-articular corticosteroid injection (triamcinolone hexacetonide preferred) — strongly recommended as initial therapy and, for genuinely limited joint involvement, sometimes sufficient as sole therapy without any systemic DMARD.[5]
Oligoarthritis, inadequate response extending to more than 4 joints, recurring after injection, or an inadequate response — add methotrexate; dosing and folic acid co-administration follow the same principles as the Rheumatoid Arthritis chapter's methotrexate content, adapted to pediatric body-surface-area dosing (see Drug Tables).
Polyarthritis (RF-positive or RF-negative), 1st line start methotrexate promptly — a DMARD is strongly preferred over NSAID monotherapy, since NSAIDs alone do not adequately control persistent synovitis.[6]
Polyarthritis, high-risk features or inadequate response add a TNF inhibitor (adalimumab or etanercept preferred) after an inadequate 3-month methotrexate trial, or start it earlier alongside methotrexate for high-risk presentations — high disease activity at diagnosis, RF/anti-CCP positivity, or involvement of a high-risk joint such as the cervical spine, wrist, or hip — reflecting current evidence favoring earlier biologic use over an older, more prolonged step-up approach.[6]
Systemic JIA, 1st line start an IL-1 inhibitor (anakinra or canakinumab) or an IL-6 inhibitor (tocilizumab) early in the disease course — current evidence favors earlier biologic use targeting the distinct autoinflammatory pathophysiology of this subtype over the older approach of starting with NSAIDs, corticosteroids, and methotrexate alone.[5]
Systemic JIA with significant systemic features add a short systemic corticosteroid course for symptom bridging while the biologic takes effect, tapering as soon as disease activity allows.
Macrophage activation syndrome (any subtype, but overwhelmingly seen in systemic JIA) this is a medical emergency — do not manage with standard-dose adjunctive therapy; see Special Populations for the urgent treatment pathway.[3]
Non-Pharmacologic Treatment
- Multidisciplinary team care — pediatric rheumatology, ophthalmology, physical and occupational therapy, and, where growth or nutrition is affected, pediatric endocrinology and dietetics — improves outcomes beyond medication alone.[7]
- Regular physical activity is safe, beneficial, and belongs in every treatment plan — encourage normal participation in play, sport, and physical education rather than restricting activity because of joint disease, matching the same principle established for adult RA.
- Physical and occupational therapy for joint protection, range-of-motion preservation, and muscle strengthening around affected joints; splinting where indicated.
- School accommodations as needed — extra time between classes for joint stiffness, modified physical education, and staff awareness of the medication and monitoring schedule.
- Nutrition support and monitoring for a child with growth disturbance or on long-term corticosteroid therapy (see Monitoring & Follow-Up).
- Psychological support — chronic illness, visible joint changes, and a demanding treatment/monitoring schedule all carry a real psychosocial burden for the child and family.
- Caregiver and patient education — proactively explain that uveitis screening continues on schedule even when the joints are doing well and the eyes look and feel normal, since most JIA-associated uveitis is silent; this is one of the most common points of family confusion and missed follow-up.[4]
- For families of a child with systemic JIA, explicit education on the warning signs of macrophage activation syndrome (persistent high fever, new bruising/bleeding, lethargy) and to seek urgent care rather than waiting it out.
Special Populations
Macrophage activation syndrome — a life-threatening emergency in systemic JIA
MAS is a severe, potentially fatal hyperinflammatory syndrome — a secondary form of hemophagocytic lymphohistiocytosis — that complicates systemic JIA specifically, given its distinct autoinflammatory pathophysiology; it is rare in other JIA subtypes. Clinically overt MAS occurs in roughly 10% of systemic JIA patients, though subclinical, smoldering MAS may be considerably more common. Recognize it immediately — delayed treatment is the single biggest driver of mortality.[3]
Recognizing MAS
- Persistent high fever that may lose the typical quotidian (spiking-and-resolving) pattern of systemic JIA, instead becoming sustained.
- Hepatosplenomegaly, lymphadenopathy, and a purpuric or hemorrhagic rash (distinct from the evanescent salmon-pink rash of uncomplicated systemic JIA).
- CNS dysfunction (irritability, lethargy, seizure) and multiorgan involvement in severe cases.
- A falling platelet count in a patient whose systemic JIA had previously caused thrombocytosis is a genuinely important early clue, even when the platelet count is still technically within the normal range for age — a relative drop matters.
- A falling ESR with a rising or persistently high CRP — a classic and easily missed dissociation, caused by hypofibrinogenemia from disseminated intravascular coagulation artificially lowering the ESR. A "better-looking" ESR in a sicker-looking child is a red flag, not reassurance.
2016 EULAR/ACR/PRINTO classification criteria
In a febrile patient with known or suspected systemic JIA, MAS is classified by ferritin above 684 ng/mL (μg/L) plus at least 2 of the following 4 laboratory criteria: platelet count 181 × 10⁹/L or below; AST above 48 U/L; triglycerides above 156 mg/dL (1.76 mmol/L); or fibrinogen 360 mg/dL or below.[3] This is a classification tool intended for research case definition and is presented here as a teaching reference rather than an interactive calculator — clinical suspicion and urgent treatment should never wait for a complete criteria set to be confirmed.
Treatment — urgent, do not wait
Confirmed or strongly suspected MAS is treated as an emergency: IV pulse methylprednisolone plus an IL-1 inhibitor (anakinra, preferred for its short half-life and rapid titratability in a critically ill child) started together, with cyclosporine added as a steroid-sparing second agent for disease not rapidly responding to corticosteroid and anakinra alone. Supportive, often ICU-level, care is needed for multiorgan dysfunction.[3] See Drug Tables for dosing.
Transition to adult rheumatology care
Many JIA patients continue to have active disease into adulthood, making a well-planned transition genuinely important rather than a formality. Canadian CAPRI registry data show that at the final pediatric rheumatology visit around age 17, roughly one-third of patients (32%) still had active disease, 26% had clinically detected joint damage, 14% had a history of uveitis, and about three-quarters remained on medication (31% on a biologic DMARD).[8] Begin transition planning well before the actual transfer — confirm the adult rheumatology team has full records, including uveitis history and any joint damage, and do not assume disease control achieved in childhood will be self-evident to the new adult-care team without an explicit handoff.
Temporomandibular joint (TMJ) arthritis
TMJ involvement can be clinically silent while still causing progressive micrognathia and facial growth asymmetry in a growing child — a specific reason for a low threshold to image the TMJ (MRI) in a child with any JIA subtype, not only when jaw symptoms are reported. TMJ arthritis is also a specific anesthesia consideration: reduced jaw opening can complicate airway management and should be flagged before any procedure requiring intubation.[5]
Adolescents and reproductive planning
Discuss contraception and family planning with any adolescent of reproductive potential started on methotrexate or leflunomide, using the same preconception principles described in the Rheumatoid Arthritis chapter's Special Populations section (methotrexate discontinuation at least 3 months before attempting conception; leflunomide's washout protocol) — these do not change for a pediatric/adolescent patient once conception becomes a realistic possibility.
Monitoring & Follow-Up
Uveitis screening — one of the most important management points in this chapter
Most JIA-associated chronic anterior uveitis is entirely asymptomatic until damage has already occurred, which is exactly why screening is scheduled and risk-based rather than triggered by eye symptoms.[9] Every child with JIA needs a baseline slit-lamp ophthalmologic exam within 1-3 months of diagnosis, regardless of eye symptoms, followed by ongoing screening at a frequency determined by subtype, ANA status, age at onset, and disease duration.[4]
| Risk category | Criteria | Screening frequency |
|---|---|---|
| Highest risk | Oligoarthritis, RF-negative polyarthritis, psoriatic, or undifferentiated JIA, ANA-positive, onset age under 7 years, disease duration 4 years or less | Every 3 months |
| Intermediate risk | Same subtypes, but ANA-negative, onset age 7 or older, or disease duration over 4 years (any 1 factor differing from the highest-risk profile) | Every 6 months |
| Lower risk | RF-positive polyarthritis or systemic JIA | Every 12 months |
| Enthesitis-related arthritis | Uveitis in this subtype is typically acute and symptomatic (red, painful eye) rather than silent | Every 12 months routine, plus urgent same-day assessment for any eye symptom |
The Canadian Rheumatology Association's adaptation of this schedule specifies at least every 3 months for the first 4 years in the highest-risk group.[4] Screening continues for as long as meaningful risk persists — do not stop simply because the joints have been quiet for a period, since uveitis risk and joint disease activity do not track together.
Uveitis treatment threshold — a genuinely Canadian-specific adaptation
Topical prednisolone acetate 1% is first-line for active uveitis. The Canadian Rheumatology Association adapted the American College of Rheumatology's original threshold for adding systemic therapy — moving from needing more than 1-2 drops per day to needing more than 2 drops per day for 3 months or longer before escalating — reflecting Canadian-context shared decision-making about when topical therapy alone remains reasonable.[4] When systemic therapy for uveitis is needed, methotrexate is 1st-line, with adalimumab or infliximab preferred over etanercept specifically because etanercept is less effective for uveitis control despite being an entirely reasonable choice for joint disease alone.[9]
Growth and bone health monitoring — genuinely pediatric-specific
Chronic inflammation and corticosteroid exposure both impair growth independently, and their combined effect in an undertreated or long-term-corticosteroid-dependent child is a real, measurable risk distinct from anything in adult RA management.[1] Measure height, weight, and pubertal staging at every visit and plot on an age-appropriate growth curve; a child falling off their growth curve needs both treatment escalation (to control the underlying inflammation) and, where corticosteroid exposure is significant, specialist-directed evaluation for growth hormone therapy. Catch-up growth is genuinely possible once disease is controlled and corticosteroid exposure is minimized, so growth monitoring should continue for as long as active treatment continues, not just at diagnosis. Bone health monitoring (calcium and vitamin D intake, weight-bearing activity, and bone density assessment where corticosteroid exposure is prolonged or fracture risk is otherwise elevated) follows the same general principles as the Rheumatoid Arthritis chapter's corticosteroid-induced-osteoporosis content, adapted to pediatric dosing (see Drug Tables).
Disease activity measurement
The Juvenile Arthritis Disease Activity Score (JADAS) is the most widely used composite measure, combining an active joint count, physician and parent/patient global assessment, and ESR or CRP — analogous in concept to the DAS28 used in adult RA. Like the DAS28, it requires a hands-on joint examination and is a specialist-administered tool, presented here as reference only rather than a self-service calculator.
Drug monitoring
Methotrexate and biologic/tsDMARD pre-therapy and ongoing laboratory monitoring (CBC, LFTs, tuberculosis and hepatitis B/C screening before starting a biologic) follow the same principles detailed in the Rheumatoid Arthritis chapter's own Monitoring & Follow-Up section — apply them here with pediatric dosing and age-appropriate vaccination schedules. Live vaccines are avoided during biologic/tsDMARD therapy; inactivated vaccines remain recommended on schedule.[10]
Common Errors to Avoid
- Waiting for a child to report joint pain clearly before investigating — young children often present with a limp, reluctance to use a limb, or simple irritability instead.
- Treating oligoarthritis with NSAID monotherapy alone as if it were adequate disease control, rather than proceeding to intra-articular corticosteroid injection as genuine 1st-line therapy.
- Stopping or spacing out uveitis screening once the joints are well controlled — joint disease activity and uveitis risk do not track together, and most uveitis is silent until damage occurs.
- Waiting for eye symptoms before referring for ophthalmologic assessment in a child with oligoarthritis or RF-negative polyarthritis — the entire point of scheduled screening is that symptoms come too late.
- Choosing etanercept over adalimumab or infliximab specifically when uveitis is present — etanercept is less effective for uveitis control even though it remains a reasonable choice for joint disease alone.
- Missing early macrophage activation syndrome because the fever pattern looks reassuringly different from a typical systemic JIA flare, or because a falling ESR is misread as clinical improvement rather than recognized as a possible sign of consumptive hypofibrinogenemia.
- Starting a corticosteroid before excluding leukemia in a child with new joint pain, bone pain, or cytopenia — corticosteroids can transiently mask malignant disease and delay the correct diagnosis.
- Overlooking growth and pubertal staging at routine visits — growth disturbance is a genuinely pediatric-specific complication that is easy to miss without deliberately plotting a growth curve at every visit.
- Failing to plan the transition to adult rheumatology care early — many patients still have active disease and are on biologic therapy at the point of transfer, and an unplanned handoff risks a genuine gap in care.
- Treating an established biologic-class response principle from adult RA (e.g., switching mechanism rather than cycling within class after inadequate response) as though it does not apply in pediatrics — the same principle holds, adapted to pediatric dosing.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
NSAIDs — Symptom Control
Adjunctive symptom control across all subtypes; not disease-modifying and not sufficient as monotherapy for confirmed JIA.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Naproxen | Pediatric: 10-15 mg/kg/day PO divided twice daily, maximum 1000 mg/day | GI upset, GI ulceration with prolonged use, rare pseudoporphyria in fair-skinned, sun-exposed children | Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics | Weight-based pediatric dosing; reassess the need for a DMARD if used beyond a brief symptomatic trial. |
| Ibuprofen | Pediatric: 30-40 mg/kg/day PO divided 3-4 times daily, maximum approximately 2400 mg/day | GI upset, GI ulceration with prolonged use | Increased bleeding with anticoagulants; reduces antihypertensive efficacy of ACE inhibitors/ARBs/diuretics | Weight-based pediatric dosing. |
Intra-Articular Corticosteroid
1st-line therapy for oligoarthritis, and an adjunct for a flared joint in any subtype.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Triamcinolone (hexacetonide preferred) | Pediatric: Dose individualized to joint size, per product labelling | Local skin/subcutaneous atrophy at the injection site; transient post-injection flare; systemic corticosteroid effects with repeated use across multiple joints | Increased GI ulceration risk with concurrent NSAID use | Hexacetonide formulation preferred over acetonide for durability of effect; sedation or procedural support is often needed for the injection in a young child. |
Conventional Synthetic DMARDs
Methotrexate is the pediatric csDMARD backbone; dosing, folic acid co-administration, and monitoring principles mirror the Rheumatoid Arthritis chapter's methotrexate content, adapted to body-surface-area dosing.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Methotrexate | Pediatric: 10-15 mg/m² body-surface-area PO or SC once weekly, typically up to a 25 mg absolute weekly maximum | Nausea, malaise, oral ulcers, alopecia; rare bone marrow/liver toxicity, rare pneumonitis, immunosuppression | Avoid high-dose ASA and sulfonamides (e.g., high-dose trimethoprim/sulfamethoxazole) | Never dose more than once weekly. Give with folic acid to reduce toxicity. Baseline and periodic CBC, LFTs, creatinine — see the Rheumatoid Arthritis chapter for the full monitoring schedule. |
| Folic acid | Pediatric: 1 mg PO once daily, or 5 mg PO once weekly (typically the day after the methotrexate dose) | Well tolerated | None significant | Reduces methotrexate GI, hepatic, and mucosal toxicity without reducing efficacy. |
| Sulfasalazine | Pediatric: 30-50 mg/kg/day PO divided twice daily, maximum 2 g/day | Rash, bone marrow suppression, GI intolerance, photosensitivity | May decrease GI absorption of digoxin | Used mainly for enthesitis-related arthritis; avoid with sulfa allergy or G6PD deficiency; baseline and periodic CBC/LFTs. |
| Leflunomide | Pediatric: Weight-based, specialist-directed per current pediatric product monograph | Diarrhea, hepatotoxicity, hypertension, teratogenic | May decrease efficacy of oral contraceptives | Alternative when methotrexate is not tolerated; contraindicated in pregnancy — see the Rheumatoid Arthritis chapter's washout protocol for an adolescent planning conception. |
Tumor Necrosis Factor (TNF) Inhibitors
Adalimumab and infliximab are preferred over etanercept specifically when JIA-associated uveitis is present, since etanercept is less effective for uveitis control. Complete tuberculosis and hepatitis B/C screening before starting, as detailed in the Rheumatoid Arthritis chapter.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Adalimumab | Pediatric: Weight-tiered SC dosing per current pediatric product monograph | Injection-site reactions; infections including TB and opportunistic organisms; rare malignancy | None major beyond additive infection risk with other immunosuppressants | Approved from age 2 years; given alone or combined with methotrexate. |
| Etanercept | Pediatric: 0.8 mg/kg SC once weekly, maximum 50 mg | Injection-site reactions; infections; may increase risk of new-onset inflammatory bowel disease | None major beyond additive infection risk with other immunosuppressants | Approved from age 2 years; avoid preferring over adalimumab/infliximab when uveitis is present. |
| Infliximab | Pediatric: Weight-based IV dosing, specialist-directed | Infusion reactions; infections including TB and opportunistic organisms | None major beyond additive infection risk with other immunosuppressants | Always given with concomitant methotrexate to reduce immunogenicity; preferred TNF inhibitor for uveitis alongside adalimumab. |
| Golimumab | Pediatric: Weight-tiered dosing per current pediatric product monograph | Injection-site reactions; infections | None major beyond additive infection risk with other immunosuppressants | Alternative TNF inhibitor for polyarticular-course JIA. |
Other Biologic DMARDs
Alternatives for polyarthritis after TNF-inhibitor failure, or when a different mechanism of action is preferred.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Abatacept | Pediatric: Weight-tiered IV or SC dosing per current pediatric product monograph | Infusion/injection-site reactions; infection | None major beyond additive infection risk with other immunosuppressants | T-cell costimulation inhibitor; option for polyarthritis after inadequate response to a TNF inhibitor. |
| Tocilizumab | Pediatric: Weight-tiered IV or SC dosing per current pediatric product monograph, indication-specific | Neutropenia, elevated lipids/LFTs, infusion/injection reaction, rare GI perforation | May increase CYP450 enzyme activity as inflammation is controlled — monitor concurrent CYP450-metabolized drugs | IL-6 inhibitor; 1st-line biologic option for systemic JIA, alternative for polyarthritis; dosing differs between the systemic and polyarticular indications. |
Interleukin-1 (IL-1) Inhibitors — Systemic JIA and MAS
Target the distinct autoinflammatory pathophysiology of systemic JIA; anakinra's short half-life makes it the preferred agent when rapid dose titration may be needed.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Anakinra | Pediatric: 1-2 mg/kg SC once daily, up to 100 mg/day MAS (specialist-directed): Higher doses may be used, individualized to severity | Injection-site reactions (common, usually mild-moderate); infection; neutropenia | None major beyond additive infection risk with other immunosuppressants | 1st-line biologic for systemic JIA and preferred agent for suspected/confirmed macrophage activation syndrome given its short half-life. |
| Canakinumab | Pediatric: 4 mg/kg SC (maximum 300 mg) once every 4 weeks; age 2 years and older, weight 7.5 kg or more | Injection-site reactions, infection, headache | None major beyond additive infection risk with other immunosuppressants | Longer-acting IL-1 inhibitor alternative to anakinra for sustained systemic JIA control. |
Systemic Corticosteroids
Route and dose scale with acuity; use the lowest effective dose for the shortest duration given the direct, measurable effect of corticosteroid exposure on growth in a still-growing child.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Prednisolone | Pediatric: 0.5-2 mg/kg/day PO, maximum 60 mg/day | Growth suppression, hyperglycemia, osteoporosis, adrenal suppression, weight gain, mood change | Increased GI ulceration risk with NSAIDs | Bridging for severe systemic JIA features or a significant polyarthritis flare; taper as soon as disease activity allows. |
| Methylprednisolone sodium succinate (IV pulse) | Pediatric: 30 mg/kg IV once daily, maximum 1000 mg/dose, typically for 3 days | Hyperglycemia, hypertension, GI bleeding, adrenal suppression with repeated dosing | Increased GI ulceration risk with NSAIDs | 1st-line urgent therapy for confirmed macrophage activation syndrome, combined with an IL-1 inhibitor. |
Macrophage Activation Syndrome — Refractory Adjunct
Reserved for MAS not rapidly responding to IV pulse corticosteroid plus an IL-1 inhibitor.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Cyclosporine | Pediatric: 2-7 mg/kg/day PO divided twice daily, specialist-directed | Nephrotoxicity, hypertension, hirsutism, gingival hyperplasia | Numerous CYP3A4-mediated interactions; monitor renal function and blood pressure closely | Added as a steroid-sparing second agent for refractory MAS, specialist-directed, often given IV in severe disease. |
Bone Health Support
For a child with prolonged corticosteroid exposure or otherwise elevated fracture risk, adapted from the Rheumatoid Arthritis chapter's corticosteroid-induced-osteoporosis principles to pediatric intake targets.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Calcium carbonate | Pediatric: Individualized to reach an age-appropriate total elemental calcium intake | Constipation, GI upset | Reduces absorption of levothyroxine and some fluoroquinolones if co-administered — separate dosing by at least 2 hours | Aim for an age-appropriate total elemental calcium intake, preferably from diet with supplementation making up any gap. |
| Vitamin D3 | Pediatric: 400-1000 units PO daily, individualized to age and risk | Well tolerated at recommended doses; hypercalcemia with excessive doses | None significant at standard doses |
References
- International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001 — The Journal of Rheumatology (Petty RE, Southwood TR, Manners P, et al.). J Rheumatol 2004;31(2):390-392
- Trends in Population-Based Incidence and Prevalence of Juvenile Idiopathic Arthritis in Manitoba, Canada — Arthritis Care & Research (Shiff NJ, Oen K, Kroeker K, Lix LM). Arthritis Care Res (Hoboken) 2019;71(3):413-418
- 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A EULAR/ACR/PRINTO Collaborative Initiative — Arthritis & Rheumatology (Ravelli A, Minoia F, Davì S, et al.). Arthritis Rheumatol 2016;68(3):566-576
- Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis — The Journal of Rheumatology, Canadian Rheumatology Association (Berard R, et al.). J Rheumatol 2023;50(3):390-399
- 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis — Arthritis Care & Research, American College of Rheumatology (Onel KB, Horton DB, Lovell DJ, et al.). Arthritis Care Res (Hoboken) 2022;74(4):521-537
- 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis — Arthritis Care & Research, American College of Rheumatology (Ringold S, Angeles-Han ST, Beukelman T, et al.). Arthritis Care Res (Hoboken) 2019;71(6):717-734
- Management of Juvenile Idiopathic Arthritis 2015: A Position Statement from the Pediatric Committee of the Canadian Rheumatology Association — The Journal of Rheumatology, Canadian Rheumatology Association (Cellucci T, Guzman J, Petty RE, et al.). J Rheumatol 2016;43(10):1773-1776
- Clinical Characteristics of Adolescents with Juvenile Idiopathic Arthritis Transitioning to Adult Rheumatology Care in Canada: Results from the CAPRI Registry — The Journal of Rheumatology (Semalulu T, Berard R, Beattie K, et al.). J Rheumatol 2024;51(2)
- 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis — Arthritis Care & Research, American College of Rheumatology (Angeles-Han ST, Ringold S, Beukelman T, et al.). Arthritis Care Res (Hoboken) 2019;71(6):703-716
- 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging — Arthritis Care & Research, American College of Rheumatology (Onel KB, Horton DB, Lovell DJ, et al.). Arthritis Care Res (Hoboken) 2022;74(4):505-520
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.