Pediatrics

Management of Juvenile Idiopathic Arthritis in

Adolescents
Donald E Greydanus*, Mary D Moore**

Abstract
Many terms are used to describe juvenile rheumatoid arthritis and the term most used today is JIA or juvenile idiopathic
arthritis. JIA is the most common rheumatoid disorder occurring in 0.5-2.0/1,000 children and adolescents. It is typically
divided into oligoarticular, polyarticular (RF-positive and RF-negative) and systemic-onset (Stills disease). The laboratory
testing is nonspecific and there is no single test or combination of tests that are pathognomonic for JIA. This discussion
focuses on management of JIA that centers on nondrug treatment and drug treatment. JIA pharmacology centers on NSAIDs,
corticosteroids, DMARDs (especially methotrexate) and if available various cytotoxic agents and biologic response modifiers.
The proper use of nonpharmacologic and pharmacologic management can control pain, reduce inflammation as well as joint
damage and improve the quality-of-life for adolescents with JIA.
Keywords: Arthritis, rheumatoid disorder, children

R
heumatoid diseases are disorders with
inflammation and pain in connective tissues
and supporting body structures - ligaments,
joints, tendons and muscles.1,2 There is joint pain,
swelling and stiffness (particularly morning stiffness)
that leads to a myriad of disabilities with underlying
autoimmune dysfunction. Rheumatoid diseases cause
more activity limitation than diabetes mellitus, heart
disease and cancer. The most common rheumatic
disorders are juvenile idiopathic arthritis (JIA) and
spondyloarthropathies; these are found in 0.5-2.0/1,000
children and adolescents. This discussion focuses on
JIA and its management in adolescents.
Definition
A number terms have been used to describe chronic
inflammatory arthritis that have their onset prior
to 16 years of age.3,4 These terms include juvenile
rheumatoid arthritis (JRA) juvenile chronic arthritis
(JCA), juvenile arthritis (JA) and the term often used
today - JIA.
JIA refers to arthritis that remains for over six weeks
and involves joint swelling and/or painful joint
*Professor, Dept. of Pediatrics and Human Development
**Pediatrics Program
Michigan State University/Kalamazoo Center for Medical Studies
Kalamazoo, Michigan, USA
Address for correspondence
E-mail: moore@kcms.msu.edu
restricted movement.5 It is in contrast to arthralgia in
which there is joint pain with or without inflammation.
JIA is more common in females than males.
JIA Types
Table 1 lists disorders that may present with arthritis.1,4
Historically, three JIA have been identified by
rheumatologists: Oligoarticular (former: Pauciarticular),
polyarticular (rheumatoid factor [RF]-positive and
RF-negative) and systemic-onset (Stills disease).6-8
The International League of Associations for
Rheumatology (ILAR) classification for JIA also
includes enthesitis-related arthritis, psoriatic arthritis,
and undifferentiated arthritis. The evaluation rules
out other causes of arthritis including post infectious
arthritis, Lyme arthritis, septic arthritis, reactive
arthritis and others.9
JIA usually presents in a child or adolescent with
stiffness after a prolonged rest, whether developing
after a night’s sleep, prolonged day-time nap or
other prolonged period of inactivity. The stiffness is
accompanied by usually mild aching with joint swelling
that varies greatly in amount. It is important to note
that severe pain is not typical for JIA. Those with
oligoarticular JIA are at increased risk of developing
uveitis (iritis), which is gradual, insidious and often only
found when specifically looked for on eye examination.
Sometimes, the adolescent will present with overt eye
symptoms such as eye redness, pain, photophobia

750 Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013
 Pediatrics

Table 1. Disorders that can Present as Arthritis JIA Laboratory Testing

Acute monoarthritis Polyarthritis Lab testing in JIA is either normal or mildly elevated.
Enthesitis-related arthritis Spondyloarthropathies For example, the RF is negative in over 90% or
Hemophilia Enthesitis-related arthritis more of JIA youth, while the antinuclear antibodies
Leukemia Arthritis with inflammatory (ANA) titer is positive, usually in low titers, in upto
Neuroblastoma bowel disease 90%.11 There is no test nor combination of lab tests
Oligoarthritis Juvenile idiopathic that are pathognomonic for JIA to differentiate it
polyarthritis
Psoriatic arthritis
Lyme disease (usually from other rheumatoid disorders or arthritides
Reactive arthritis monoarticular) (Table 1). It is important to rule out such causes as
Septic arthritis Malignancies malignancy or septic arthritis. Joint aspiration is very
Trauma Periodic fever syndromes helpful in this regard and includes a Gram stain,
Chronic monoarthritis Polyarthritis related to culture, cell count, fluid glucose, fungal or acid-fast
Enthesitis-related arthritis infection bacillus, cytology and crystal examination, where
Episodic fever syndromes Psoriatic JIA indicated.
Hemophilia Reactive arthritis
Hemangioma Rheumatic fever (migratory JIA Complications
joint involvement)
JIA
Sarcoidosis It is important to diagnose JIA as early as possible and
Juvenile psoriatic arthritis
Serum sickness to provide comprehensive management to reduce the
Lyme arthritis
Systemic juvenile idiopathic potential complications of this chronic and recalcitrant
Oligoarthritis arthritis
Sarcoidosis rheumatoid disorder.12 These possible complications
Systemic lupus erythematosis
Synovial chondromatosis include inhibition of growth with shorted height,
Vasculitis
Tuberculosis variable joint destruction, bony overgrowth,
Viral arthritis
Villonodular synovitis contractures, spinal cord compression that includes the
*Modified with permission from: Patel DR, Moore MD: Concepts of cervical spine, chronic eye disease and even death.13
Rheumatology Ch. 25. In: Handbook of Clinical Pediatrics: An Update for
Eye complications include cataracts, secondary
the Ambulatory Pediatrician. Greydanus DE, Patel DR, Reddy VN,
Feinberg AN, Omar HA. (Eds.), World Scientific, New Jersey 2010:p.702. glaucoma, band keratopathy, posterior synechiae with
papillary complications, vision compromise and even
blindness.14 As noted the eye disease can be insidious
and/or changes in vision. Youth with polyarthritis are and thus, all patients with JIA should have regular eye
at reduced risk for chronic uveitis. screening by ophthalmologists to reduce the chances
The patient with oligoarthritis develops a nonpainful for development of severe, progressive eye disease.
limp and swelling of four or less joints within 6 months These ophthalmologists should identify and manage
of disease onset that is usually under eight years of the eye disease seen with JIA.
age. In polyarticular JIA, the joint swelling is found
Death from JIA may occur because of complications
in five or more joints within 6 months of disease
from potentially toxic drugs used to control JIA,
onset and two classic age ranges are noted: 1-6 years
infections, traumatic C-spine injury and the rare
of age and 11-16 years of age. Two classic subtypes of
polyarticular arthritis are described: RF-negative and macrophage activation syndrome (MAS).
RF-position. In the latter, there is 2 or more positive RF MAS is a type of hemophagocytic lymphohistiocytosis
tests during the first six months of disease-onset that syndrome stimulated by medications or viral
are 3 months or more apart. infections.15,16 MAS can arise with fever, lymph-
In systemic-onset JIA, there is arthritis in one or more adenopathy, petechiae, bleeding, pancytopenia and
joints that develops or is preceded by fever with organomegaly; the erythrocyte sedimentation rate can
high spikes of two weeks or more duration, which is lower very quickly and the ferritin levels can become
classically quotidian (daily) for 3 days or more.10 elevated. Improvement may be seen with treatment
One or more of these findings are noted as well: that includes high-dose corticosteroids, cyclosporine,
Hepatosplenomegaly (one or both), generalized rash, and tumor necrosis factor inhibitors. The death rate
recurrent rash (erythematous, evanescent) and/or can be over 30%. MAS is most common in systemic-
serositis (peritonitis and/or pleuritis and/or pericarditis). onset JIA.

Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013 751
Pediatrics
JIA Management
General
Adolescents with JIA require an individualized plan
managed by a clinician with training and skill in the
management of this condition seeking to improve
the quality of care for these patients.17-21 A number
of conservative measures can be utilized to help with
JIA pain, such as use of moist heat, rest, appropriate
physical activity and individualized joint support
(i.e, splints, casts, canes or crutches). Non-narcotic
analgesics are beneficial and narcotics should be
used only very cautiously (if at all) for this chronic
disorder. There remains no scientific evidence for
the use of nutritional supplements in the treatment
of JIA in children and adolescents. This includes
such agents as chondroitin sulfate, glucosamine,
S-adenosylmethionine (SAM-e) dehydroepiandro-
sterone (DHEA) or hyaluronic acid substitutes.
A number of nonpharmacologic modalities are available
and very useful, such as physical therapy, occupational
therapy, hydrotherapy, heat and cold applications,
transcutaneous electrical nerve stimulation (TENS)
and others. Steroid intra-articular injections are helpful
in those with only a few joints that are involved.
Consultation with surgeons is important to provide
needed arthroscopic surgery, osteotomy, bone fusion
and arthroplasty. It is also important to provide
appropriate management for potential comorbid
conditions, such as mood disorders, anxiety disorders
or sleep problems. Youth may find considerable help
from online chat rooms.
Rheumatoid Arthritis Drugs
Drugs for JIA are typically prescribed to control
pain, reduce inflammation as well as joint damage
and decrease JIA symptoms in addition to reducing
functional decline.1,4,22,23 These medications can slow
the course of the JIA and/or limit or prevent ongoing
destruction of joints or other body tissues. Cure is not
possible by any medication despite claims made in
various media or unscrupulous ‘experts.’ Cure may
occur in some rheumatoid diseases such as by use of
the correct antibiotics in infectious arthritis or Lyme
arthritis.
NSAIDs
The most commonly prescribed medications for JIA
around the world are the nonsteroidal anti-inflam-
matory drugs (NSAIDs).10,20 They have become very
popular analgesics since ibuprofen was introduced to
752 Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013
the drug market in the 1960s. The classic NSAIDs include
ibuprofen, tolmetin sodium, naproxen, indomethacin,
acetylsalicylic acid, sulindac and others.20
Commonly used NSAIDs are noted in Table 2 and
potential adverse effects in Table 3. It is important to
note that these medications do not affect the long-
term outcome of JIA but are very helpful to control
important JIA symptoms - pain, stiffness, swelling and
fever. Thus, they are very beneficial for these youth if
adverse effects do not restrict their use. A number of
topical agents are also available in various formulations
in different countries. However, some youth do not
tolerate their texture or the burning sensation that they
may cause.
NSAIDs approved by the US Food and Drugs
Administration (FDA) for use in children include
aspirin, ibuprofen, naproxen, indomethacin, oxaprozin,
meloxicam etodolac SR and celecoxib. Acetylsalicyclic
acid (aspirin) has been of historical use as an analgesic
in management of JIA but has been replaced by more
traditional NSAIDs. Clinicians are concerned with
the small but well-known risk of Reye syndrome and
salicylates should be avoided in those who have an
active infection with influenza or varicella. Salicylates
(especially ASA) are the only NSAIDs that leads to
less platelet aggregation with clinical relevance lasting
4-6 days from a small a dose as 80 mg. Salicylates have
an increased adverse effect profile and more toxicity
from an overdose in contrast to other NSAIDs.
NSAIDs can also cause dizziness, lethargy and
headaches that tend to cease with cessation of
the specific drug.20 These medications are useful
because they nonselectively inhibit cyclooxygenase
1 and 2 (COX-1 and COX-2) enzymes; however, this
property also leads to various side effects since the
COX-1 enzyme is expressed in the renal, hematologic
(i.e., platelets), and gastrointestinal (GI) systems. The
specific adverse effects depend on various factors such
as the specific drug used, dosage, degree of COX-1
inhibition, co-morbid conditions and contribution of
other prescribed medications. NSAID GI toxicity can
be reduced by adding misoprostol or proton pump
inhibitors and is especially useful for those at high-
risk for GI side effects, such as those with a history
of GI disorders or those also taking corticosteroids.
Asthmatic youth who are aspirin-sensitive should not
be taking NSAIDs.
More recent selective COX-2 inhibitors (i.e., rofecoxib,
celecoxib and valdecoxib) lead to less GI effects but
 Pediatrics

Table 2. Systemic Analgesics and Anti-inflammatory Drugs*

Generic name Adult dosage Pediatric dosage
Diclofenac sodium 100-200 mg daily 2-3 mg/kg/day
(2-4 divided doses) (2-4 divided doses)
*ER given 1-2x daily*
Diclofenac potassium 100-200 mg daily 2-3 mg/kg/day
(2-4 divided doses) (2-4 divided doses)
Diclofenac epolamine 180 mg patch every 12 hour N/A
Etodolac 600-1,000 mg daily 20-30 kg: 400 mg daily
(2-3 divided doses) 31-45 kg: 600 mg daily
46-60 kg: 800 mg daily
>60 kg: 1,000 mg daily
*Age 6-16 years*
*Based on ER product*
Fenoprofen calcium 200-600 mg 3-4x/day N/A
Max. 3,200 mg/day
Flurbiprofen 200-300 mg daily N/A
(2-4 divided doses)
Ibuprofen 1,200-3,200 mg daily 4-10 mg/kg/dose 3-4x/day
(3-4 divided doses) Max. 40 mg/kg/day
Indomethacin 50-200 mg daily 1-2 mg/kg/day
(2-3 divided doses) (2-4 divided doses)
Max. 4 mg/kg/day, NTE: 150-200 mg/day
*Age >2 years*
Ketoprofen IR: 150-300 mg daily N/A
(3-4 divided doses)
ER: 100-200 mg daily
Ketorolac tromethamine 20 mg initially, 10 mg 4x/day N/A
Max. 5-day duration
Meclofenamate sodium 200-400 mg daily N/A
(3-4 divided doses)
Mefenamic acid 500 mg initially, 250 mg every 6 hour as N/A
needed
(NTE: 1 week)
Meloxicam 7.5-15 mg daily 0.125 mg/kg/day
Max. 7.5 mg daily
*Age ≥2 years*
Nabumetone 500-2,000 mg daily N/A
(1-2 divided doses)
Naproxen Naproxen: 250-500 mg 2x/day *Analgesia: 5-7 mg/kg/dose every 8-12 hours
Naproxen sodium: 200-500 mg 2x/day *Inflammatory disease: 10-15 mg/kg/day
Naproxen DR: 375-500 mg 2x/day (2 divided doses)
Max 1,000 mg/day
*Age >2 years*

Cont’d...

Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013 753
Pediatrics

...Cont’d
Generic name Adult dosage Pediatric dosage
Oxaprozin 600-1,200 mg daily 22-31 kg: 600 mg daily
Max. 1,800 mg daily (in divided doses) 32-54 kg: 900 mg daily
≥55 kg: 1200 mg daily
*Age 6-16 years*
Piroxicam 10-20 mg daily 0.2-0.3 mg/kg/day
Max. 15 mg daily
Sulindac 150-200 mg 2x/day 2-4 mg/kg/day
(2 divided doses)
Max. 6 mg/kg/day, NTE: 400 mg/day
Tolmetin sodium 600-1,800 mg daily *Analagesia: 5-7 mg/kg/dose every 6-8 hours
(3 divided doses) *Inflammatory disease: 15-30 mg/kg/day
Max. 2,000 mg daily (3-4 divided doses)
NTE: 1,800 mg/day
*Age ≥2 years*
Celecoxib 100-400 mg daily 10-25 kg: 50 mg 2x/day
(1-2 divided doses) >25 kg: 100 mg 2x/day
*Age ≥2 years*
Diflunisal 500-1,000 mg daily N/A
(2-3 divided doses)
Max. 1,500 mg daily
Magnesium salicylate Novosal: 600 mg 3-4x day N/A
Max 4,800 mg daily
Doan’s: 934 mg every 6-hour as needed
Salsalate 3,000 mg daily N/A
(2-4 divided doses)
Choline magnesium trisalicylate 500-1,500 mg 2-3x/day 30-60 mg/kg/day
(3-4 divided doses)
IR = Immediate-release; ER = Extended-release; DR = Delayed-release, NTE = Not to exceed.
*Used with permission from: Greydanus DE, Moore MD, Feucht C. Concepts of rheumatoid disorders (Chapter 11). In: Adolescent Medicine:
Pharmacotherapeutics in Medical Disorders. Greydanus DE, Patel DR, Feucht C, Omar HA, Merrick J. (Eds.) 2012:p.333-55.

increase cardiovascular toxicity risks. Rofecoxib and
valdecoxib have been removed from the market because
of these cardiovascular adverse effects; celecoxib has
been approved by the FDA in the United States for use
in JIA. Selective COX-2 inhibitors do not reversibly
inhibit platelet aggregation.
Leukopenia may develop, which is usually mild and
resolves with medication cessation; however, rarely it
can be severe and chronic. Potential dermatologic
adverse effects of NSAIDs are myriad and range
from urticaria to Stevens-Johnson syndrome.
Pseudoporphyria is a photosensitive rash particularly
noted in fair complexioned individuals on chronic
naproxen use and this may lead to chronic scarring.
Approximately 3% of those taking NSAIDs (5% of
those on chronic salicylate use) develop increased
liver transaminases; overt liver toxicity is rare but
can be fatal. Renal toxicity may develop and include
proteinuria, hyperkalemia and interstitial nephritis.
Aseptic meningitis has been reported while on NSAIDs,
especially in those with systemic lupus erythematosus;
medications in this regard include ibuprofen, naproxen,
diclofenac, ketoprofen, tolmetin, sulindac and rofecoxib.
A trial and error method is needed to see which NSAID
provides the most benefit with the least or acceptable
side effect profile for an adolescent with JIA.20 One that
is taken once or twice a day is best for most to minimize
problems in taking the medication in school and also

754 Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013

to improve overall compliance. Some NSAIDs are
prepared in a liquid form and these include ibuprofen,
naproxen, indomethacin, meloxicam and various
salicylate preparations. Ketorolac and indomethacin are
available as parenteral formulations while diclofenac is
made in patch and topical gel forms.
Youth taking chronic NSAIDs should get periodic
(i.e. every 3 months) screening for GI, renal and
hematopoietic toxicity. The clinician should screen
for melena and abdominal pain and add a proton-
pump inhibitor if needed. Serum NSAID levels are not
clinically helpful except when monitoring salicylate
levels in those on chronic salicylate therapy.
Corticosteroids
Corticosteroids have become a very powerful tool
in pharmacologic management of many disorders
since the discovery of cortisone in 1949 by Edward
Kendall, an American chemist at the Mayo Clinic
(Rochester, Minnesota, USA) and physician Philip
Hench.24 These drugs (i.e. prednisone, cortisone,
hydrocortisone, methylprednisolone, others) are
powerful anti-inflammatory agents that also suppress
the immune system to help adolescents with JIA. They
can be given in various forms: orally, intra-articularly,
intramuscularly, intravenously or as topical agents.
As noted with other powerful drugs, corticosteroids
have much potential benefit but also many serious side
effects and so must be used carefully and judiciously.
Thus, they are used in youth with JIA with severe
disease and used when disease complications arise,
such as anemia or pericarditis. The lowest effective dose
should be used and a typical manner of application is
an alternative day schedule to reduce adverse effects
(Tables 3 and 4). Oral doses can range from 0.5 to 3
mg/kg day; it should be tapered as rapidly as possible.
Intra-articular corticosteroid injections are very helpful
in youth with minimal joint disease and may keep the
patient off regular systemic steroids as well as chronic
NSAID therapy. The steroid dose varies with the
size of the joint being injected and synovitis may be
well-controlled for months after the steroid injection.
Fluoroscopy or ultrasound assistance is suggested
for injection of a large joint, such as the hip. Youth
having considerable anxiety over this procedure may
need a short-acting sedative and general anesthesia is
suggested if several joints are being injected. It is best
that an experienced clinician perform this procedure
since it can be difficult because of such problems as
local fibrosis, bony changes or infection. The presence of
major synovial hypertrophy may limit the penetration
Pediatrics
Table 3. Potential Side Effects of NSAIDs
Headache
Dizziness
Bronchospasm
Gastrointestinal
Nausea, vomiting (indigestion, heartburn)
Gastritis; peptic ulcer disease
Gastrointestinal ulceration and bleeding
Hepatotoxicity
Rash
Bruising
Photosensitivity
Hypersensitivity reactions
Anaphylaxis
Tinnitus
Fluid retention or peripheral edema
Hyperkalemia
Suppression of bone marrow
Acute renal insufficiency (interstitial nephritis)
Increased risk of cardiovascular thrombotic events, myocardial infarction
and stroke.
Table 4. Potential Acute (Reversible) Effects of
Corticosteroids
Swelling (sodium and fluid retention)
Weight gain with moon facies; Cushinoid appearance
Emotional instability
Increased appetite
Sleep dysfunction
Steroid acne
Psycyhosis (rare)
Muscle weakness (severe; rare)
of steroid into the inflamed joint. Some atrophied
changes may occur along the needle tract because of
steroid leakage.
Infections are potential side effects of steroid use
and these include typical or common bacteria to
increased incidence of a myriad of opportunistic
infections as well as Mycobacterium tuberculosis.
An adolescent taking corticosteroids on a chronic
basis should be prescribed calcium and vitamin D
supplementation in addition to counseling about the
need for weight-bearing exercise. Clinician usually
obtain annual bone density studies and may recommend
bisphosphonates for prevention of osteoporosis in
adolescents taking chronic steroids for JIA.
Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013 755
Pediatrics
Disease-modifying Antirheumatic Drugs
Disease-modifiying antirheumatic drugs (DMARDs)
are another class of drugs for JIA with potential benefit
but also considerable side effects for youth with JIA.
They do not cause reversal of existing damage but can
result in reduced joint swelling, pain and destruction
in JIA patients. The agent most frequently used by
rheumatology experts is methotrexate, a drug first used
by the famous Boston pediatric pathologist, Dr Sidney
Farber, in the late 1940s to improve the high mortality
rate of children with leukemia.
It was approved by the US FDA in 1953, as an anticancer
agent and has since been used in various serious
illnesses, including JIA who have polyarthritis,
oligoarticular disease that is resistant to other
treatments, and also chronic, severe uveitis that is
steroid-refractory.20,25 Other DMARDs that are used
by experts include gold salts (intramuscular),
sulfasalazine, hydroxychloroquine, D-penicillamine
and leflunomide (Table 5). Gold salts are not used
often due to severe toxicity. Leflunomide is also not
used very often in adolescent females because of its
long half-life and significant risk for teratogeneis.
Methotrexate is used in moderate dosages in com-
bination with other medications, such as hydroxy-
chloroquine, sulfasalazine or biologic response
modifiers (Table 6). Such combinations achieve better
reduction in joint inflammation and destruction in
dosages best determined by experts in this disease.
Cytotoxic Agents
These drugs are utilized occasionally to attempt
treatment of rheumatoid disorders that have been
resistant to other agents already discussed. They
include azathioprine, chlorambucil and cyclophos-
phamide; sometimes they are part of treatment
protocols for autologous bone marrow transplantation.
Agents also used in such refractory situations include
mycophenolate mofetil and cyclosporine. Reasons
for not using these drugs more often include the
availability of other drugs with normally good efficacy
and also the high incidence of significant side effects
to cytotoxic agents. It is important to avoid use of
live vaccines in those taking cytotoxic agents; these
attenuated ‘live’ viral vaccines include the measles
vaccine, mumps vaccine, rubella vaccine, varicella
vaccine, yellow fever vaccine nasal-spray influenza
vaccine, rabies vaccine and others. Cytotoxic agents
should only be used by experts in rheumatoid diseases.26
Cyclophosphamide is a nitrogen mustard alkylating
agent, which can lead to nausea, emesis, anorexia,
756 Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013
Table 5. Potential Effects from Chronic
Corticosteroids (Can be Irreversible)
Hyperglycemia
Infections
Osteoporosis
Osteonecrosis of hips (2% for most; upto 25% in SLE)
Hirsuitism
Hypertension
Pseudotumor cerebri
Striae
Growth failure
Accelerated atherogenesis
Dyslipidemias
Cataracts
Arterial damage
lethargy, diarrhea, rash, weakness, hair loss, bone
marrow suppression, hemorrhagic cystitis, hematuria,
proteinuria, amenorrhea, pigmentation (skin and
nail), anaphylaxis, teratogencity and other side effects.
Chlorambucil can lead to agitation, bone marrow
suppression, tremor, confusion, hepatotoxicity, fertility
impairment, teratogenicity and others.
Azathioprine can lead to similar side effects including
acute pancreatitis, increase risk for cancer, fertility
impairment, teratogenicity and increased risk for
serious infections. Cyclosporine can induce abdominal
pain, headache, tremor, dizziness, acne, nephrotoxicity,
hepatotoxicity, hypertension, malignancy, encephalo-
pathy and others. Finally, mycophenolate can lead to
cough, headache, back pain, rash, increased infection
risk, reactivation of latent viral infections, anorexia,
nausea, emesis, weakness, possible increased risk for
lymphoma and other cancers, leukopenia, pure red
cell aplasia and teratogenicity. There can be multiple
drug interactions including decreased efficacy of oral
contraceptives.
Biologic Response Modifiers
Biologic response modifiers or biologics are
medications that are genetically engineered to block
various immune system pathways that are implicated
in the rheumatoid disease inflammatory processes.4,27-29
They can be particularly beneficial to adolescents
with rheumatoid diseases with inflammatory joint
disease as well as inflammatory bowel disease. They
include medications such as rituximab, adalimumab,
certolizumab pegol, tocilizumab, infliximab, abatacept,
etanercept and golimumab. A potential severe adverse

Table 6. DMARDs for Rheumatoid Disorders*
Generic name Adult dosage
Methotrexate 10-15/week; usually given IM
or orally
Add folic acid 1 mg daily
Leflunomide Initial: 100 mg/day for 3 days
Maintenance: 10-20 mg/day
Add folic acid 1 mg daily
Hydroxy- 400-600 mg/day; maintenance
chloroquine is 200-400/per day; also used as
antimalaria drug
Gold salts IM: 10 mg as an initial dose,
Gold sodium followed by 25 mg on Week 2,
thiomalate then 25-50 mg weekly until 1 g
total dose achieved
Maintenance: 25-50 mg every 2-4 ‘Nitroid’ reaction: Flushing, fainting, sweating
weeks and dizziness within 30 minutes of injection
Sulfasalazine 500 mg daily increasing to a
maximum daily dose of 3,000 mg
(in 2 divided doses)
Consider adding folic acid 1 mg
daily. Also used for inflammatory
bowel disease
D-penicillamine Initial: 125-250 mg/day, increase
by 125-250 mg/day at 1-3 month
intervals.
Maintenance: 500-750 mg/day.
Consider addition of pyridoxine
25 mg/day
Also used to treat Wilson’s
disease, cystinuria, arsenic
poisoning
LFTs = Liver function tests; CBC = Complete blood count; SCr = Serum creatinine; CrCl = Creatinine clearance; G6PD = Glucose-6-phosphate
dehydrogenase.
*Used with permission from: Greydanus DE, Moore MD, Feucht C. Concepts of rheumatoid disorders (Chapter 11). In: Adolescent Medicine:
Pharmacotherapeutics in Medical Disorders. Greydanus DE, Patel DR, Feucht C, Omar HA, Merrick J. (Eds.), 2012:p.333-5.
Pediatrics
Adverse effects Monitoring
Anorexia, nausea, emesis, abdominal cramps, LFTs, hepatitis B and C
hepatotoxicity, hepatic fibrosis, bone marrow serologies for those with
suppression, allergic pneumonitis, opportunistic risk factors for infection,
infections CBC with platelets, SCr
Teratogenic; abortifacient; avoid with renal
insufficiency (CrCl <30 ml/min); increased
toxicity if given with NSAIDs, trimethoprim,
sulfamethoxazole/trimethoprim
Diarrhea, nausea, reversible hair loss, rash, LFTs, CBC with platelets
bone marrow suppression, hepatotoxicity, Drug elimination
interstitial lung disease, peripheral neuropathy, procedure: Stop
anaphylaxis, severe dermatological reactions, leflunomide and administer
weight loss cholestyramine 8 g 3x/day
Teratogenic for 11 days
Verify plasma level is
<0.02 mg/l
Dermatological reactions including skin and Ophthalmic exams, CBC
mucosal pigmentation (blue/black), nausea, with platelets, G6PD
epigastric pain, retinal damage, blurred vision,
keratopathy, central nervous system toxicity,
hemolysis with G6PD deficiency
Nausea, diarrhea, stomatitis, decreased CBC with platelets,
appetite, exfoliative dermatitis, proteinuria, urinalysis
hepatitis, interstitial pneumonitis, enterocolitis,
blood dyscrasias with bone marrow suppression
Nausea, anorexia (use enteric coated form CBC with platelets, LFTs,
to reduce), rash, headache, hepatitis, bone urinalysis, G6PD
marrow suppression, hemolytic anemia with
G6PD deficiency, oligospermia (reversible),
aplastic anemia, hypersensitivity reactions,
renal toxicity
Aplastic anemia, lupus-like syndrome, CBC with platelets,
pruritus/rash, proteinuria, membranous urinalysis, LFTs
glomerulonephritis, elastosis perforans
serpiginosa, myasthenic syndrome, bone
marrow suppression, drug fever, mouth
ulcers, GI distress, altered taste, neuropathy,
intrahepatic cholestasis
Contraindicated during pregnancy
Avoid in renal insufficiency
Avoid concomitant use with gold therapy,
antimalarial and cytotoxic agents
Do not coadminister with antacids, iron or food
Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013 757
Pediatrics
effect of the immune blocking powers of these drugs is
the stimulation of hepatitis B or reactivation of latent
M. tuberculosis infection as well as post-drug increase
in lymphoma and others cancers.30
These agents are used alone or in combination
with DMARDs, especially methotrexate, for
those with refractory disease including DMARDs. It is
not recommended to use more than one biologic agent
due to the failure of additive effect and the high-risk
for severe side effects. A lower response rate to the
agent may occur because of the development of
antibodies to the drug. Patients on these agents should
avoid use of attenuated, ‘live’ vaccines. These drugs
are given as infusions in clinics or even injection in the
patient’s home. Guidelines for their use are published
by the American College of Rheumatology and these
recommendations are based on various factors, such
as disease duration, overall disease activity, and
the presence or absence of factors indicating a poor
outcome.2,3 They should be only be used by experts in
rheumatology and they are extremely expensive in the
United States healthcare system.
CONCLUSION
JIA is the most common rheumatoid disorder in
children and adolescents. The term, ‘juvenile’ refers
to the onset of symptoms before age 16 years.
A number of nondrug treatments are helpful including
physical therapy, occupational therapy, rest, moist
heat, individualized joint support (i.e., splints, casts,
canes or crutches) and others. Pain relief utilizes
NSAIDs and corticosteroids (oral, topical, intra-
articular, intramuscular, intravenous). Some adolescents
need additional medications including DMARDs,
especially methotrexate. Refractory situations may also
benefit from various cytotoxic agents (azathioprine,
cyclophosphamide, chlorambucil, mycophenolate
mofetil and cyclosporine. Finally, resistant cases
may respond to a new class of drugs called biologic
response modifiers or biologics. These agents have
considerable potential for severe side effects and
should be managed by a clinician with training in this
area. Much progress has been accomplished in
management of JIA in adolescents and yet, many
questions remain in the care of adolescents with JIA.31
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■■■■

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“Disease” Tag Prompts Parents to want Tx for Healthy Babies

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won’t work, researchers found. (Source: Medpage Today)

Indian Journal of Clinical Practice, Vol. 23, No. 11, April 2013 759