1. What is SJIA - how is it different
than other diseases
HERMINE BRUNNER, MD MSC MBA
PROFESSOR OF PEDIATRICS
CHIEF, DIVISION OF RHEUMATOLOGY

2. Sir George Frederic Stills
(27 February 1868 – 28 June 1941)
 England’s first professor of childhood medicine
 First described 22 children with SJIA in 1897
 …also the first to describe attention deficit hyperactivity disorder
Still G F. On a form of
chronic joint disease in
children.Med-Chir Trans
1897; 80: 47-59.
Systemic-onset
juvenile chronic
arthritis
Systemic-onset
juvenile rheumatoid
arthritis
Systemic juvenile
idiopathic arthritis
Still’s disease
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3. 7. Shenoi S, Wallace CA. J Pediatr. 2016;177:19-26.
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4. Rash
 Nonpruritic, evanescent, urticarial-like,
maculopapular, salmon colored
 Koebner phenomenon
 Histologic evidence of sparse: Cellular
perivascular infiltrate
 Just as in other inflammatory processes (such as psoriasis,
lichen planus, cutaneous lupus or wound healing)
 Activated keratinocytes expressing proinflammatory S100-
proteins
M. Frosch, et al., “Expression of myeloidrelated proteins 8 and
14 in SJRA. A&R vol. 48, no. 9, pp. 2622–2626, 2003
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5.  Pericardial effusion > pleural effusion > peritoneal fluid
 Pericarditis
 Typical anterior chest pain, shortness of breath, friction
rub on auscultation
 Diagnosed by x-ray, EKG, echocardiography
 Myocarditis much less common
 4% in one study
Serositis
J. et al., “Symptomatic cardiac involvement in juvenile
rheumatoid arthritis,” International Journal of Cardiology, vol. 34,
no. 1, pp. 57–62, 1992.
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6. Fever
 (Double) quotidian fever
 (2) fever spike(s) per day, not induced by antipyretic medications
 About the same time every day
 DD: Malaria, Leishmaniasis
 The classic pattern with 1 spike in the evening is only
seen in 37% of the patients during initial presentation
 Morning fevers (12%),
 Twice daily fevers (15%)
 Intermittent fevers (27%)
 Unremitting fevers (5%)
E. M. Behrens et al: Evaluation of the presentation of sJRA . J Rheumatol, vol. 35, no. 2, pp. 343–348, 2008.
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7. 7

8. 7. Shenoi S, Wallace CA. J Pediatr. 2016;177:19-26.
8. Petty RE et al. J Rheumatol. 2004;31:390-392.
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9. SJIA – One of the Types of juvenile
idiopathic Arthritis
Group of Diseases
 Shared features
 Chronic Arthritis of unknown etiology
 Presentation by 16th birthday
Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P: International League of Associations for
Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004, 31(2):390–392. Stoll, Matthew L., and Randy Q. Cron. "Treatment of juvenile idiopathic arthritis:
a revolution in care." Pediatric rheumatology 12.1 (2014): 13.
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SJIA is mostly a disease
starting in childhood

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Why do
children
get
Systemic
JIA ?
Overactive
immune
system
Environmental
triggers
Genetic
factors
Other

13. Systemic JIA – Not A Single Gene
Disease
 More than a monogenic inflammatory disease
SJIA rarely runs in families
 Polygenic auto-inflammatory disease
1. No auto-reactive T cells or antibodies at onset
2. No strong human leucocyte antigen (HLA) associations
3. Microarray studies innate immune activity involving a cellular
structures called “inflammasomes”
S. Vastert, B. Prakken 232 / Best Practice & Research Clinical Rheumatology 28 (2014) 229-246
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14. Non-systemic Forms of JIA – Adaptive
Immune System Activation
 T cell subsets (Th17) and different Treg cells are very important
for the development/course of other JIA forms
 RNA-containing immune complexes (IC) against citrullinated peptide
antigens (collagen, fibrinogen) induce netosis
 B cell activation perpetuates IC formation
 Downstream ↑ Syk signaling, esp. with certain genetic mutations (e.g.
Zap-70, low affinity Fc receptor)
S. Vastert, B. Prakken 232 / Best Practice & Research Clinical Rheumatology 28 (2014)
Chauhan AK, Moore TL, Bi Y, Chen C. J Biol Chem (2016) 291:1368–86.
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15. Pathogenetic Models
Peter Nigrovic; ARTHRITIS & RHEUMATOLOGY; Vol. 66, No. 6, June 2014, pp 1405–1413
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16. Window of Opportunity – Basic
Science Evidence
 High IL-1, IL6, TNF levels facilitate differentiation of
pathogenic Th17 cells
 Esp. with genetic (environment) predisposition
 Shift to chronicity of Th17 response with sJIA (and other
forms of JIA)
 Th17 cell pool expands with arthritis progression
 Th17 depleted arthritis mice do not get joint diseases
Peter Nigrovic; ARTHRITIS & RHEUMATOLOGY; Vol. 66, No. 6, June 2014, pp 1405–1413;
S. Vastert, B. Prakken 232 / Best Practice & Research Clinical Rheumatology 28 (2014) 229-246
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17. Prognosis of SJIA
has markedly
improved with the
approval of IL1 and
IL6 blocking
medications
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18. 0
10
20
30
40
50
60
70
80
90
Persistent
Oligo
Extended
Oligo
Polyarthritis
(RF+)
Polyarthritis
(RF-)
Systemic
Disease Type
%ofpatients
CRM CR
Course of Disease & Clinical Remission on/off Medications
 Monocyclic, polycyclic, persistent
 40-50% active disease for at least 10
years
 Duration of CR off medications
 44% (196) patients achieved CR
 28% - CR lasted one year
 18% - CR lasted two years
 3% - CR lasted five years
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19. SJIA Poor prognostic Clinical Indicators
 Early age at onset
 Cumulative active disease
 Platelets > 600K at 6 months,
 Hip involvement by 6 months
 Generalized lymphadenopathy
Toronto Cohort
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20. In the past: progressive joint destruction in approximately 1/3 of the
children
More common in patients with polyarthritis
 Ankylosis in cervical spine, carpal &tarsal areas
 Joint space narrowing & erosions
Apophyseal fusion of
C2-C4 and undergrowth
of adjacent vertebrae
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21. Growth Delay
 Generalized - Localized
 Intensified by corticosteroid therapy
 Likely due to IL-6 effects
 Growth hormone therapy possible
in some patients
 Need to control inflammation
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22. Mortality
In SJIA mostly due to disease
complications:
 Infection
 MAS
 Myocarditis
 Amyloidosis
Systemic
64%
Poly
18%
Pauci
12%
Other
6%
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23. Amyloidosis
Very rare in North America
Biopsy required for diagnosis
 Deposited in kidneys, liver, gastro-
intestinal tract, heart, peripheral nerves
Proteinuria, diarrhea, hepato-
splenomegaly, unexplained anemia
Amyloid A deposition in kidneys detected by
staining with Congo Red dye
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24. Summary
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