what is sjia - how is it different than other diseases - dr. hermine brunner
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What is SJIA - how is it different than other diseases
HERMINE BRUNNER, MD MSC MBA
PROFESSOR OF PEDIATRICS
CHIEF, DIVISION OF RHEUMATOLOGY
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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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7. Shenoi S, Wallace CA. J Pediatr. 2016;177:19-26.
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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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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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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. 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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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
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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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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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Pathogenetic ModelsPeter Nigrovic; ARTHRITIS & RHEUMATOLOGY; Vol. 66, No. 6, June 2014, pp 1405–1413
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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 diseasesPeter 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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Prognosis of SJIA
has markedly
improved with the
approval of IL1 and
IL6 blocking
medications
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0
10
20
30
4050
60
70
80
90
Persistent
Oligo
Extended
Oligo
Polyarthritis
(RF+)
Polyarthritis
(RF-)
Systemic
Disease Type
% o
f p
ati
en
ts
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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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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In the past: progressive joint destruction in approximately 1/3 of the childrenMore 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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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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Mortality
In SJIA mostly due to disease complications:
Infection
MAS
Myocarditis
Amyloidosis
Systemic
64%
Poly
18%
Pauci
12%
Other
6%
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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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Summary
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