1. Challenging issues about vasculitis
News on an old problem
Nephrology view
Dr. Oğuz Söylemezoğlu
Gazi University Pediatric Nephrology
Ankara,Turkey

2. Vasculitis Inflammation and damage to vessel wall
Independent of size or vessel type
Localized vs. systemic disease
Diverse symptoms and overlap
Difficult classification

3. Pathophysiology of Vasculitis
Pathogenic immune complex formation and/or deposition
Pathogenic T-lymphocyte responses and granuloma formation
Non-endothelial structures of the vessel wall are involved in controlling the inflammatory process, eg acting as antigen presenting cells and contributing pro-inflammatory mediators.
Pathogenetic role of ANCA ??

4. 2006
Eular/Pres Ozen, Dillon et al
2007
Dedeoglu,Sundel . Rheum Dis P Clin N Am

6. Turkish survey of paediatric vasculitis (Vasculitis study group
Turkish survey of paediatric vasculitis (Vasculitis study group. Clin Rheum 2007)

9. Overview : ANCA Associated Vasculitis
What are the challenges
Non toxic effective treatments
Earlier diagnosis at 1st presentation and relapse
Animal models
A move towards designer biologic therapies
Targeting B cells
Targeting T cells

13. The stages of the management of the disease

14. Very few studies in childhood

15. Wegener’s Granulomatosis
General
necrotizing granulomas of upper airway, lower airway, kidney
bilateral pneumonitis 95%
chonic sinusitis 90%
mucosal ulceration of nasopharynx 75%
renal disease 50-80%
hallmark pathologic lesion
necrotizing granulomatous vasculitis

24. IV pulse vs daily oral Cyclophosphamide ??

28. Strategies to reduce relapses ?? How to treat resistant disese ??
Leflunomide
Remission maintenance in WG
Infliximab and etanercept (TNF blockade)
WGET (70% remission , high rate relaps )
Infliximab induced 88% remission
IVIG
Antithymocyte Globulin
SOLUTION study in refractory WG
Deoxyspergualin
Blocks the Transcriptional activation of  L chain expression B Cell
Blocks the development of cytotoxic T cells
Trials underway

30. Blocking B lyS Campath 1(Alemtuzumab) anti-CD 52
Belimumab (Lymphostat-B)
In phase lll clinical trials in SLE
Atacicept:TACI Bloker(Phase ll)
BR3-Fc: BAFF Bloker

31. Part mouse , part human
Originally
used
for lymph
cancer , RA
Knocks
out
B cells
Rituximab
Usually given 2 injections,
2w apart

37. Abatacept (Orencia)
Only targets T cells that are activated to cause damage and makes them ‘anergic’
Potential to be highly selective therapy
Currently undergoing phase lll therapy
ABAVAS (BMS)

40. Chan AT,Autoimmunity Rev. 2006

41. Hypothetical events in the pathogenesis of ANCA small vessel vasculitis
Jennette JC,Falk RJ. Curr Op Rheum 2008

42. Microscopic polyangiitis: the future
Differences between MPA and WG
The role of respiratory epithelium in the induction
ANCA –negative vasculitis and vasculitis affecting different sizes of vessels
Molecular approches to classification will address
Therapeutics will have reduced steroids
Newer targets :Improve the speed and quality of remission
intracellular regulators of cytokines
Complement components
Antioxidants (N –acetyl cysteine

44. BEHCET’S DISEASE

45. Behcet’s Disease
Vasculitis with triad
oral, genital ulcers,
uveitis or iritis

46. Renal Involvement in BD ?
The frequency of renal problems vary between 0% to 55%.
Amyloidosis
glomerulonephritis
renal vascular disease,
interstitial nephritis
Akpolat .T et al Semin Arthritis Rheum. 2008

47. What are the news in BD?
TNF--1031 C allele was associated with disease susceptibility
Akman A,et al Br J Dermatol 2006
T helper type 1 immune reaction in active disease
Yanagihori et alJ Invest Dermatol,2006
IL-12 B heterozygocity is associated with BD
E-NOS gene polymorphism (Glu 298Asp) associated with BD
Oksel et al. Clin Exp Rheumatol 2006
IL-18 levels were high in BD and correlated with activity
Musabak et al, Rheumatol Int 2006
Anti-SBP(Sleneium Binding protein) positive with uveitis
Okunuki et al Exp Eye Res 2007
Therapy
Anti-TNF agents
Topical G-CSF for ulcers
Granulocytopheresis for refractory uveoretinitis

48. Conclusions
Childhood forms of vasculitis are in similar spectrum to adult disease
Long term treatment is similar
Emphasis on KD,HSP less WG and MPA
Large controlled trials of infliximab and rituximab are required
Therapy still depends on conventional drugs
Effects of disease and treatment on growth and development need to be addressed in children