Juvenile idiopathic arthritis

Juvenile Idiopathic Arthritis

Anas Bahnassi PhD CDM CDE

4 Week

Definition:

• JIA usually begins before the age of 16 and must present with objective signs of joint inflammation (e.g., swelling, pain, limited ROM, warmth, erythema) for at least 6 weeks in at least one joint or at least two of the following: tenderness, pain with movement, joint warmth, or limited motion.

• Other conditions causing arthritis such as infectious arthritis and malignancy must be excluded.

• The onset of disease is rare before 6 months of age, and the peak age of onset ranges from 1 to 3 years. However, new cases are seen throughout childhood.

Signs and Symptoms:

1. JIA begins with synovial inflammation. 2. Morning stiffness and joint pain probably occur in JIA as frequently as in RA;

however, children should be observed carefully for symptoms because they often cannot articulate complaints.

3. Morning stiffness and joint pain may manifest as increased irritability, guarding of involved joints, or refusal to walk.

4. Fatigue and low-grade fever, anorexia, weight loss, and failure to grow are other manifestations.

5. JIA can be divided into several subsets based on characteristic signs and symptoms during the first 4 to 6 months of disease:

a) Polyarticular b) pauciarticular or oligoarthritic, c) systemic arthritis, d) enthesitis related, e) psoriatic, f) other

More common in

children under 5

More common in

children over 8

Seropositive ( RF positive 5-10% of all JIA

patients)

Seronegative ( RF negative

20%–25% of all JIA patients)

Polyarticular

JIA Patterns of Onset:

Both common in girls more than boys

Temporomandibular joint injury is

common leading to limited bite & micrognathia

Onset can be acute but

mostly insidious

Large fast growing joints

are mostly affected

Polyarticular


Systemic manifestations rare: fever,

slight hepatosplenomegaly, lymphadenopathy,

pericarditis, and chronic uveitis

Mostly boys over 8 years

of age

Mostly girls between 1-5 years

old

Early childhood onset

More common

Late childhood onset

Oligoarthritic or

Pauciarticular 40-60%


3. Joints commonly affected: knees, ankles, hands,

feet, and wrists. 4. No hip involved

1. Test negative for ANA

2. No extra articular manifestation

1. 20%-30% develop iridocyclitis

(uvititis) 2. Test positive for

ANA

Oligoarthritic or

Pauciarticular


3. Hip involvement.

Children with early

onset

Children with late

onset

Sacroiliac joint

tenderness

Inflammatory spinal pain

Enthesitis-related JIA should have two of these

six reds:

Family history of enthesitis-related JIA

HLA B27 positivity

Onset of polyarthritis

/oligoarthritis in a boy >8

years of age

Acute anterior uveitis


Family history of psoriasis

Dactylitis: Finger or toe inflammation

Psoriatic JIA should have two of the

three reds:

Onycholysis: Nail pitting

All are HLA B27 positive


• J.R., a 4-year-old girl, is hospitalized for high fever and arthritis. • Several weeks before admission, J.R. developed a daily fever ranging from 103°F to 106°F. • One week before admission, her knees became painful and swollen. • J.R. is listless and irritable during her physical examination. • The rectal temperature is 102.4°F. She refuses to walk.

• The right hip is tender and the right wrist and both knees are warm, red, and swollen.

• Minimal generalized lymphadenopathy and splenomegaly are present.

• The Westergren ESR is 82 mm/hour, the WBC count 37,000 cells/mm3 with a mild left shift, and Hct 33%.

• Cultures of the throat, urine, stool, and blood are negative. • An intermediate-strength purified protein derivative,

antistreptolysin-O titer, ANA titer, and RF titer all are normal.

• Radiographs of the chest and involved joints all are normal. • An electrocardiogram reveals only tachycardia. • After hospitalization and withholding aspirin, an evanescent

rash becomes apparent in conjunction with fever spikes.

What signs and symptoms of JIA does J.R. manifest?

• The signs and symptoms (i.e., the spiking fever episodes, evanescent rash, arthritis, lymphadenopathy, splenomegaly) that J.R. experienced are characteristic of systemic-onset JIA.

• These children also may have a normocytic, hypochromic anemia, elevated ESR, thrombocytosis, and leukocytosis.

• Leukocytosis is common and a WBC count of 30,000 to 50,000 cells/mm3 is seen occasionally.

• A positive RF titer is uncommon in JIA and is present in only 5% to 10% of all cases.

• The ANA titer more often is positive and is most prevalent in young girls and children with early-onset pauciarticular arthritis and uveitis.

What is the goal of therapy for J.R?

The goal of JIA treatment is to: • Minimize the destructive effects of

inflammation. • Control pain • Preserve or restore movement. • Promote development and growth, to

facilitate an acceptable quality of life.

What is the initial drug therapy for JIA?

• NSAID therapy is the treatment of choice. • At least two different NSAIDs should be tried before ruling

out this group. • Failure to respond to an NSAID in a particular chemical class

does not rule out the efficacy of others in the same class. • Naproxen is the most prescribed dosed at 10 to 15 mg/kg/day

(maximum, 750 mg) in two daily divided doses. • Oxaprozin can be administered once daily as a 600-mg dose if

weight is between 22 and 31 kg, 900 mg if weight is between 32 and 54 kg, and 1,200 mg if weight is >55 kg.

• Nabumetone is also frequently used for JIA because of convenient once daily dosing.

• Ibuprofen doses should not exceed 40 to 50 mg/kg/day. • Tolmetin usually is dosed at 20 mg/kg/day in three to four

divided doses.

Should aspirin be discontinued in a JIA patient who experiences chickenpox because of the potential for causing Reye syndrome?

• Reye syndrome occurs in association with the use of aspirin as an antipyretic in children during the prodromal phase of viral illnesses such as influenza and chickenpox.

• Reye syndrome is characterized by fatty vacuolization of the liver producing hepatic injury, vomiting, hypoglycemia, and progressive encephalopathy.

• Aspirin should not be given to febrile children who are at risk for Reye syndrome by virtue of possible infection with either influenza virus or chickenpox.

• Patients with JIA should avoid salicylate ingestion during febrile illnesses that represent possible infection with either influenza or chickenpox.

When should DMARDs be used in JIA? • Most children with JIA improve significantly with NSAID treatment, especially pauciarticular disease. • Patients with polyarticular, RF-positive disease and patients with early-

onset polyarthritis in association with systemic-onset disease both have poor prognosis in terms of ultimate joint function and should receive early consideration for DMARD therapy.

• Children with polyarticular-onset, RF-negative disease generally have a better prognosis than patients with polyarticular involvement and may wait considerably longer before introducing a DMARD for these patients.

• Most DMARDs used for adult RA are not effective for JIA. • MTX is clearly the DMARD of choice for polyarthritic JIA.

• The recommended dose of MTX for JIA treatment is 5 to 15 mg/m2 (0.15–0.5 mg/kg) orally or subcutaneously each week.

• Pediatric patients are often prescribed the injectable form of MTX for oral consumption via a suspension.

• Food reduces the bioavailability of MTX, so MTX should be administered on an empty stomach or parentrally if bioavailability is an issue parenteral preparations should be used.

When should DMARDs be used in JIA?

• Children tolerate MTX therapy well and generally experience few serious or troublesome adverse effects (e.g., transient liver enzyme elevations, nausea, vomiting, oral ulcerations).

• These adverse effects are reduced with daily folic acid therapy(1 mg) or weekly folinic acid (the day after MTX dosing).

• The combination of MTX and other DMARDs has not been fully evaluated.

• If MTX is not tolerated or is ineffective, SSZ is often the next DMARD selected.

• SSZ (30–50 mg/kg/per day in two divided doses with a maximum of 2 g/day) is effective for pauciarticular and polyarticular JIA, but numerous adverse effects (e.g., liver enzyme elevations, leukopenia, hypoimmunoglobulinemia, hematomas, diarrhea, anorexia) lead to discontinuation of therapy in about 30% of patients.

• HCQ may be considered if SSZ fails, but efficacy data from well-designed randomized controlled trials are not available.

What biological agents are effective in JIA?

• Etanercept (Enbrel), the only FDA-approved biological agent for the treatment of JIA, is indicated for patients 4 years of age and older whose conditions have failed to respond to one or more DMARDs.

• The recommended dose is 0.4 mg/kg (maximum, 25 mg) subcutaneously twice weekly.

• Etanercept monotherapy at this dose would be expected to yield about a 76% response rate.

• Safety of etanercept in children is comparable to adults with the exception of significantly more abdominal pain vomiting.

• JIA patients should be current on immunizations before initiation of etanercept therapy because the effect of etanercept on vaccine response is unknown.

• Safety and efficacy data reflecting up to 8 years of treatment support the long-term use of etanercept for JIA.

What is the evidence supporting the use of intra-articular corticosteroid therapy in JIA?

• Intra-articular corticosteroid therapy seems to be highly efficacious in JIA.

• Full disease remission of injected joints lasting longer than 6 months can be expected in 84% of patients with JIA, and 60% of patients could be expected to be able to discontinue all oral medications, with even greater success in patients with pauciarticular JIA.

• Long-term negative effects of corticosteroid therapy (e.g., joint stability, osteonecrosis, soft tissue atrophy) are not usually encountered.

• Intra-articular corticosteroid therapy seems to be a safe and effective option for JIA, particularly in pauciarticular disease limited to a few troublesome joints.

J.R. is scheduled to be seen by an ophthalmologist every 6 months to screen for uveitis. How should her uveitis be managed?

• Uveitis associated with JIA (Iridocyclitis) is a nongranulomatous inflammation involving the iris and ciliary body.

• The posterior uveal tract, or choroid, rarely is affected. • Chronic uveitis can progress, leading to cataracts, glaucoma, and

blindness. • Careful screening and early detection are effective at preventing

these conditions. • Uveitis is most common in ANA-positive oligoarthritis JIA and usually

occurs within 4 to 7 years of JIA diagnosis. • Fewer than 1% of patients with systemic JIA develop uveitis. • Uveitis rarely presents with symptoms, and even if symptoms occur,

children may have difficulty recognizing them (e.g., ocular pain, decreased vision, headaches, red eye, unequal pupils).


• Prevention of uveitis relies on compliance with regularly scheduled slit-lamp examinations performed by an ophthalmologist.

• Direct ophthalmoscopy cannot detect uveitis. • All JIA patients must have a baseline slit-lamp examination within 1

month of diagnosis. • The highest-risk JIA patients for uveitis (e.g., ANA-positive

oligoarthritis or polyarthritis, ≤6 years of age at JIA onset and ≤4 years JIA duration) require slit-lamp examination every 3 months.

• At the opposite extreme, low-risk oligoarthritis or polyarthritis patients (i.e., >7 years JIA duration, >6 years of age at JIA onset and >4 years JID duration, ≤6 years of age at JIA onset and >4 years JIA duration who are ANA negative, >6 years of age at JIA onset and ANA negative) and systemic JIA patients require slit-lamp examination once a year.

• If detected early, the prognosis for uveitis is very good.


• The initial drug of choice is a topical corticosteroid (e.g., dexamethasone, prednisolone), which usually reduces ocular inflammation rapidly.

• More severe and chronic uveitis may require a 1- to 3-day course of intravenous methylprednisolone (30 mg/kg once daily, maximum 1 g/dose).

• Uveitis that responds poorly to corticosteroids should be treated with systemic NSAIDs, followed by serial trials of by MTX and anti-TNF agents if responses are inadequate

Pharmacottherapy Anas Bahnassi PhD CDM CDE

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Health & Medicine

Juvenile idiopathic arthritis