General Information
Juvenile idiopathic arthritis is an autoinflammatory disease of unknown etiology. It is the most common connective tissue disease in children, presenting mainly with the manifestation of arthritis.
Clinic:
All children with juvenile idiopathic arthritis have chronic joint involvement (arthritis lasting more than 6 weeks and not attributable to other known causes).
JIA diagnostic criteria:
1) Onset before age 16
2) Arthritis in one or more joints
- Swelling or effusion or presence of at least two of the following symptoms
a) Limitation of movement
b) Sensitivity or pain with movement
c) Heat increase
3) Disease duration longer than 6 weeks
4) According to joint involvement in the first 6 months after onset:
Polyarthritis: 5 joint involvement
· Oligoarthritis: p. 4 joint involvement
Systemic: Arthritis with rash and fever
5) Exclusion of other causes of arthritis
Jia Clinical Classification
Systemic Jia (Still's Disease)
• It is seen equally in girls and boys.
• These children classically present with a fever of ≥39°C (intermittent fever) once or twice a day lasting at least two weeks. Body temperature drops below 37°C between two fevers. If it remains high, another diagnosis should be considered. The fever rises in the evening.
• Fever is accompanied by an erythematous, nonpruritic pink (salmon}-colored, transient macular rash.
Associated Findings:
• Arthralgia, myalgia, neck pain, restlessness, generalized LAP, HSM, pericarditis and pleuritis may accompany.
• Anemia, leukocytosis and thrombocytosis
• Arthritis may not be present in the first weeks of the disease. In this period, differential diagnosis is made with infection, episodic fever syndromes and malignancy. The Koebner phenomenon may be positive.
• Rheumatoid factor (RF} and antinuclear antibody (ANA) are negative.
Poor Prognosis Criteria:
1. Polyarticular involvement
2. Fever lasting longer than three months
3. Elevated inflammatory markers (ESR, thrombocyte count) for more than 6 months
Polyarticular (RF-) JIA
• Bimodal onset (2-4 years and 10-14 years) is seen.
• Similar to the symmetrical involvement of adult rheumatoid arthritis.
• Arthritis is mild and rheumatoid nodules are rare.
• ANA can be (+).
• A large number of small and large joints are involved. Cervical spine (atlantoaxial subluxation), temporomandibular joint (may cause micrognathia) and hip joint are frequently involved.
Polyarticular (RF +) JIA
• It begins in late childhood. It is more common in girls over the age of nine.
• The disease usually keeps large joints symmetrical.
• It has the worst prognosis and causes loss of function.
• Arthritis is severe and rheumatoid nodules are encountered especially in the elbow and Achilles tendon.
• Morning stiffness is characteristic.
Poor Prognosis Criteria in Polyarticular JIA :
1- Early onset age
2- Rheumatoid factor (RF) positivity
3- Presence of rheumatoid nodules
4- Anti-cyclic citrulline peptide (anti CCP) antibody positivity (this antibody has high specificity and can be found positive before RF)
5- Having a large number of affected joints
Oligoarticular JIA
• It is the most common type. It is common in girls under 4 years of age.
• Arthritis is asymmetrical and mostly the large joints of the lower extremities are involved.
• Hip involvement alone is never expected.
• ANA (60%) is positive and poses a risk for anterior uveitis.
Enthesitis Associated Arthritis
• It is common in males after the age of eight. Arthritis is asymmetrical.
• Involvement of the knee, ankle and sacroiliac joint, especially the hip joint, is common.
• HLAB27 is 80% {+).
• Heel pain and Achilles tendinitis are common. There is severe pain (enthesitis) at the attachment site of the tendon to the bone.
• Acute iridocyclitis attacks are encountered in 10-20%.
Psoriatic Arthritis
The most common pattern of psoriatic arthritis; asymmetric oligoarthritis. This affects large and small joints in an asymmetrical pattern.
Symmetrical distal interphalangeal joint disease, which is rarely seen in patients with psoriatic arthritis, is diagnostic.
HLA-B27-associated sacroiliitis can be seen in 30% of cases, but the majority of patients are HLA-B27 negative and do not have arthritis in the sacroiliac joint or lumbosacral spine. Hip and sacroiliac joint involvement is more common in HLAB27 positive cases.
The presence of nail pitting, dactylitis, onycholysis, or a family history of psoriasis may suggest psoriatic arthritis in a girl with oligoarthritis or polyarthritis.
ANA positivity can be seen.
While the cases with pre-school onset are mostly female, ANA positive and at risk of asymptomatic eye involvement; adolescent cases are frequently seen in equal proportion of boys and girls.
Laboratory at JIA:
Patients have leukocytosis, thrombocytosis and anemia as indicators of chronic inflammatory response. Leukopenia and thrombocytopenia are the precursors of macrophage activation syndrome (MAS).
Ferritin is high and further elevated if MAS develops (> 10000 ng/mL)
RF with latex fixation is in IgM structure. It is positive in 5% to 1% of polyarticular JIA.
RF positivity in JIA indicates poor prognosis of joint involvement.
The association of ANA positivity with iridocyclitis is common in JIA.
Radiology at JIA
In the early period: There is soft tissue swelling around the joint, enlargement of the joint space, and periarticular osteoporosis. Periosteal new bone formation and enlargement of the phalanges are also seen.
In the late period: narrowing of the joint space, ankylosis in the carpal and tarsal bones, subluxation in the hip, fusion starting from the C2 and C3 apophyseal joints and progressing to the other vertebrae are typical findings.
Treatment in JIA
Oligoarticular JIA
First-line treatment is nonsteroidal anti-inflammatory drugs (NSAIDs).
The most preferred NSAIDs are naproxen, ibuprofen and meloxicam.
In oligoarticular JIA, if there is no response to NSAID treatment lasting 4-6 weeks, intra-articular corticosteroid is used, and in cases unresponsive to this treatment, methotrexate is used.
Polyarticular JIA
First-line treatment is methotrexate + NSAIDs.
TNF-alpha inhibitors etanercept or adalimumab or infliximab or abatacept, an anticytotoxic T-lymphocyte-associated antigen-4 immunoglobulin, can be given to patients who are unresponsive to methotrexate and have poor prognostic factors.
Antimetabolite drugs: Methotrexate, leflunomide, sulfasalazine
systemic JIA
Response to methotrexate and TNF alpha inhibitors is poor. Therefore, in cases with systemic symptoms, short-term systemic steroids are used initially, followed by iL-1 inhibitors (anakinra, rilonacept, canakinumab) or IL-6 receptor antagonist toclizumab.
Complications in JIA
Macrophage activation syndrome (hemophagocytosis): Among the connective tissue diseases, JIA is the most common cause of this condition in children.
Patients may have purpura, mucosal bleeding, increase in fibrin degradation products, PT and PTT prolongation.
Treatment:
High-dose methylprednisolone, cyclosporine, or anakinra
• Orthopedic complications: Scoliosis, fractures and joint deformities, shortening of leg length
• Osteopenia (due to increased IL-6 and TNF-alpha)
Differential Diagnosis in JIA:
Seronegative spondyloarthropathies
• Juvenile ankylosing spondylitis
• Inflammatory bowel diseases
• Psoriatic arthritis
• Reactive arthritis (associated with urethritis, iridocyclitis and mucocutaneous lesions)
Reactive Arthritis
Acute rheumatic fever
Reactive arthritis (Arthritis secondary to genitourinary or gastrointestinal tract infections caused by agents such as Shigella, Salmonella, Yersinia, Chlamydia or meningococci.
serum sickness
Toxic synovitis of the hip
Postimmunization
