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What is SJIA - How is it different than other diseases - Dr. Hermine Brunner

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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.

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What is SJIA - How is it different than other diseases - Dr. Hermine Brunner

  1. 1. What is SJIA - how is it different than other diseases HERMINE BRUNNER, MD MSC MBA PROFESSOR OF PEDIATRICS CHIEF, DIVISION OF RHEUMATOLOGY
  2. 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 2
  3. 3. 7. Shenoi S, Wallace CA. J Pediatr. 2016;177:19-26. 3
  4. 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 4
  5. 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. 5
  6. 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. 6
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  8. 8. 7. Shenoi S, Wallace CA. J Pediatr. 2016;177:19-26. 8. Petty RE et al. J Rheumatol. 2004;31:390-392. 8
  9. 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. 9 SJIA is mostly a disease starting in childhood
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  12. 12. 12 Why do children get Systemic JIA ? Overactive immune system Environmental triggers Genetic factors Other
  13. 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 13
  14. 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. 14
  15. 15. Pathogenetic Models Peter Nigrovic; ARTHRITIS & RHEUMATOLOGY; Vol. 66, No. 6, June 2014, pp 1405–1413 15
  16. 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 16
  17. 17. Prognosis of SJIA has markedly improved with the approval of IL1 and IL6 blocking medications 17
  18. 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 18
  19. 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 19
  20. 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 20
  21. 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 22
  22. 22. Mortality In SJIA mostly due to disease complications:  Infection  MAS  Myocarditis  Amyloidosis Systemic 64% Poly 18% Pauci 12% Other 6% 23
  23. 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 24
  24. 24. Summary 25

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