This talk was given by Dr. Hermine Brunner of Cincinnati Childrens Hospital to a group of patient families, at Systemic Juvenile Idiopathic Arthritis (or SJIA) Family Day on July 22nd, 2017.
Physiochemical properties of nanomaterials and its nanotoxicity.pptx
What is SJIA - How is it different than other diseases - Dr. Hermine Brunner
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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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
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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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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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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