Juvenile idiopathic arthritis
Arthritis present for ≥6 weeks, in a child <16yrs. The ILAR classification
distinguishes immunogenetically distinct groups, with variations in regard to the
underlying pathogenesis, clinical phenotypes, treatment responses and outcomes.
There is an autosomal-recessive form of JIA/Still, caused by a mutation in the
gene LACC1, which encodes the protein FAMIN (fatty acid metabolism-immunity nexus),
a central regulator of immunometabolic function.
Types
1) Oligoarticular (subtype defined after 6 months)
i) Persistent oligoarticular
ii) Extended polyarticular
2) Polyarticular
i) seropositive
ii) seronegative
3) Systemic (Still’s disease)
4) Enthesitis-related arthritis (ERA)
5) Juvenile PsA
6) Undifferentiated
Epidemiology
-Oligoarticular (50%): female 3:1, peak 2-3yrs. 30% proceed to polyarticular.
-Polyarticular RF (-) (20-25%): female 3:1, peak 2-3yrs.
-ERA (10%): male predominance 2-3:1, peak >8yrs.
-Still (<10%): even sex distribution
-jPsA (<10%): late childhood
-Polyarticular RF (+) (<5%): peak >8yrs.
Genetic
Still’s has a genetic architecture that is distinct from other forms of JIA. Its characteristic
systemic inflammation has been associated with deregulation of innate immune
mechanisms, while oligoarticular and polyarticular have features of classical
autoimmune diseases, mediated by cells of the adaptive immune system and are
associated with specific HLA alleles.
Oligoarthritis and RF (-) polyarthritis have similar HLA associations: HLA-DRB1.
Specifically for oligoarticular, 3 HLA association have been found: 1) HLA-I, 2) HLA-
DR/DQ, 3) HLA-DP.
The shared epitope is associated only with RF (+) polyarticular JIA.
HLA-B27 (+) in 60-90% of ERA.
HLA variants, however, explain just 13% of the total variation in JIA susceptibility.
Clinical
, Extraarticular features differ among the various JIA categories. Whereas systemic
manifestations such as fever characterize Still’s, enthesitis is a distinguishing feature of
ERA and dactylitis is most commonly seen in jPsA.
A migratory pattern (resolving in ≤4wks) is characteristic of post-
streptococcal, ARF and gonococcal, while in JIA it’s additive pattern.
•Uveitis (10%): mainly (chronic) anterior uveitis, usually asymptomatic (in
contrast to SpA uveitis that’s acute, symptomatic and HLA-B27-related). Usually ANA (+).
Most frequently in oligoarthritis of the extended course type (5–30%), followed by ERA
(15-25%), persistent oligoarthritis (16–18%) and seronegative polyarthritis (4–14%) or
jPsA (10-12%). Uveitis does not always correlate with arthritis disease activity and may
manifest when the articular manifestations are in remission. It develops in about 90% of
cases within the first 4 years of JIA.
Screening (slit-lamp)
-high-risk patients (ANA [+], oligoarticular form): every 3 months for 4yrs, then every 6
months for 3yrs, then every year.
-low risk: every year
• Hip arthritis (20–63%), mainly in Still. Other inflammatory lesions include
bursitis, enthesitis and myositis. Destructive, irreversible lesions in the hip joint include
cysts, erosions, joint space narrowing, chondromalacia and ankylosis. Such joint
inflammation that interferes with bone growth may eventually lead to skeletal growth
disturbances and developmental disorders, such as bone remodeling. The majority of
children with hip involvement can develop irreversible changes within 5 years of
diagnosis and 25–45% will require a total hip replacement within the first 10 years of
disease onset, at least in the pre-bDMARD era. It may proceed to ANV of the femoral
head.
Oligoarticular (50%)
The most common type. Early childhood. May be further divided into persistent oligo- or
extended poly- according to the number of joints involved after the first 6 months. At
onset the knee is the most commonly affected Joint. >30% of patients develop extended
polyarticular disease during the disease course. Associated with chronic uveitis. ANA (+)
in 40-85%. Screen this group of patients for uveitis every 3 months.
Polyarticular
Symmetrical involvement. The TMJ and cervical spine are often affected and
occasionally torticollis. Hip and shoulder may be involved. Systemic features such as
fatigue, low-grade fevers, mild hepatosplenomegaly and anemia may occur.
-RF (-) (20-25%): mostly knees, wrists and ankles, can be asymmetric.
-RF (+) (<5%): teenage years. Involvement of small joints is typical,
resembles more adult-RA, can be CCP (+).
Still’s (10%)
Fever, rash, arthralgia/arthritis, elevated liver enzymes, lymphadenopathy,
hepatosplenomegaly, serositis. Hip is typically affected. 50% develop polyarthritis within
3-12 months. MAS in 5-40%.
ERA (10%)
Arthritis present for ≥6 weeks, in a child <16yrs. The ILAR classification
distinguishes immunogenetically distinct groups, with variations in regard to the
underlying pathogenesis, clinical phenotypes, treatment responses and outcomes.
There is an autosomal-recessive form of JIA/Still, caused by a mutation in the
gene LACC1, which encodes the protein FAMIN (fatty acid metabolism-immunity nexus),
a central regulator of immunometabolic function.
Types
1) Oligoarticular (subtype defined after 6 months)
i) Persistent oligoarticular
ii) Extended polyarticular
2) Polyarticular
i) seropositive
ii) seronegative
3) Systemic (Still’s disease)
4) Enthesitis-related arthritis (ERA)
5) Juvenile PsA
6) Undifferentiated
Epidemiology
-Oligoarticular (50%): female 3:1, peak 2-3yrs. 30% proceed to polyarticular.
-Polyarticular RF (-) (20-25%): female 3:1, peak 2-3yrs.
-ERA (10%): male predominance 2-3:1, peak >8yrs.
-Still (<10%): even sex distribution
-jPsA (<10%): late childhood
-Polyarticular RF (+) (<5%): peak >8yrs.
Genetic
Still’s has a genetic architecture that is distinct from other forms of JIA. Its characteristic
systemic inflammation has been associated with deregulation of innate immune
mechanisms, while oligoarticular and polyarticular have features of classical
autoimmune diseases, mediated by cells of the adaptive immune system and are
associated with specific HLA alleles.
Oligoarthritis and RF (-) polyarthritis have similar HLA associations: HLA-DRB1.
Specifically for oligoarticular, 3 HLA association have been found: 1) HLA-I, 2) HLA-
DR/DQ, 3) HLA-DP.
The shared epitope is associated only with RF (+) polyarticular JIA.
HLA-B27 (+) in 60-90% of ERA.
HLA variants, however, explain just 13% of the total variation in JIA susceptibility.
Clinical
, Extraarticular features differ among the various JIA categories. Whereas systemic
manifestations such as fever characterize Still’s, enthesitis is a distinguishing feature of
ERA and dactylitis is most commonly seen in jPsA.
A migratory pattern (resolving in ≤4wks) is characteristic of post-
streptococcal, ARF and gonococcal, while in JIA it’s additive pattern.
•Uveitis (10%): mainly (chronic) anterior uveitis, usually asymptomatic (in
contrast to SpA uveitis that’s acute, symptomatic and HLA-B27-related). Usually ANA (+).
Most frequently in oligoarthritis of the extended course type (5–30%), followed by ERA
(15-25%), persistent oligoarthritis (16–18%) and seronegative polyarthritis (4–14%) or
jPsA (10-12%). Uveitis does not always correlate with arthritis disease activity and may
manifest when the articular manifestations are in remission. It develops in about 90% of
cases within the first 4 years of JIA.
Screening (slit-lamp)
-high-risk patients (ANA [+], oligoarticular form): every 3 months for 4yrs, then every 6
months for 3yrs, then every year.
-low risk: every year
• Hip arthritis (20–63%), mainly in Still. Other inflammatory lesions include
bursitis, enthesitis and myositis. Destructive, irreversible lesions in the hip joint include
cysts, erosions, joint space narrowing, chondromalacia and ankylosis. Such joint
inflammation that interferes with bone growth may eventually lead to skeletal growth
disturbances and developmental disorders, such as bone remodeling. The majority of
children with hip involvement can develop irreversible changes within 5 years of
diagnosis and 25–45% will require a total hip replacement within the first 10 years of
disease onset, at least in the pre-bDMARD era. It may proceed to ANV of the femoral
head.
Oligoarticular (50%)
The most common type. Early childhood. May be further divided into persistent oligo- or
extended poly- according to the number of joints involved after the first 6 months. At
onset the knee is the most commonly affected Joint. >30% of patients develop extended
polyarticular disease during the disease course. Associated with chronic uveitis. ANA (+)
in 40-85%. Screen this group of patients for uveitis every 3 months.
Polyarticular
Symmetrical involvement. The TMJ and cervical spine are often affected and
occasionally torticollis. Hip and shoulder may be involved. Systemic features such as
fatigue, low-grade fevers, mild hepatosplenomegaly and anemia may occur.
-RF (-) (20-25%): mostly knees, wrists and ankles, can be asymmetric.
-RF (+) (<5%): teenage years. Involvement of small joints is typical,
resembles more adult-RA, can be CCP (+).
Still’s (10%)
Fever, rash, arthralgia/arthritis, elevated liver enzymes, lymphadenopathy,
hepatosplenomegaly, serositis. Hip is typically affected. 50% develop polyarthritis within
3-12 months. MAS in 5-40%.
ERA (10%)
