Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and...
-
Upload
caroline-mackay -
Category
Documents
-
view
220 -
download
3
Transcript of Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and...
![Page 1: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/1.jpg)
Aysin Bakkaloglu, M.D.
Hacettepe University Faculty of MedicinePediatric Nephrology and Rheumatology
Ankara, TURKIYE
ESPN 2008 Lyon, FRANCE
TREATING DIFFICULT PATIENTS OF RENAL VASCULITIS
TREATING DIFFICULT PATIENTS OF RENAL VASCULITIS
![Page 2: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/2.jpg)
Plan of the talkPlan of the talk
Treatment of difficult patients of renal
vasculitis
– ANCA associated vasculitis
- Wegener granulamatosis
- Microscopic polyangiitis
– Classic polyarteritis nodosa
– Takayasu arteritis
![Page 3: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/3.jpg)
ANCA ASSOCIATED VASCULITISANCA ASSOCIATED VASCULITIS
Wegener’s granulomatosis
Microscopic polyangiitis
Renal limited vasculitis
Churg-Strauss syndrome
Histologic similarities
Potential contribution of ANCA to theirpathogenesis
Similar responses toimmunosuppressive therapy
Nat Clin Rheumatol 2006; 2: 661-670
![Page 4: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/4.jpg)
GOALS of TREATMENT in ANCA ASSOCIATED VASCULITIS
GOALS of TREATMENT in ANCA ASSOCIATED VASCULITIS
Patient survival
Induce remission of active state
Reduce disease relapse
Minimize therapeutic toxicity– Least toxic and most effective therapy – Prevent and monitor toxicity
![Page 5: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/5.jpg)
CHALLENGES in TREATING ANCA ASSOCIATED VASCULITIS
CHALLENGES in TREATING ANCA ASSOCIATED VASCULITIS
Rarety of ANCA associated vasculitis in children
High morbidity and mortality
Definitions of – disease stages
– activity stages
– outcome measures
Duration of treatment
![Page 6: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/6.jpg)
CASE 1 CASE 1
![Page 7: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/7.jpg)
12 year old girl
Weakness, periumblical abdominal pain
Loss of appetite
Nausea, vomiting
Pallor
Decreased urine output with hematuria
Besbas N et al. Pediatr Nephrol 2003;18: 696-699
![Page 8: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/8.jpg)
Laboratory TestsLaboratory Tests
Hb : 7.8 g/dl
WBC : 7300 /mm3
Platelet : 240 x103 /mm3
CRP : 10.2 mg/dl
ESR : 120 mm/hr
BUN : 51 mg/dl
Cre : 5.84 mg/dl
T. prot : 7.3 g/dl
Alb : 3.2 g/dl
Urinary pH : 6.5 density : 1020 protein : 4 +
7-8 RBC / hpf
Urinary protein : 87.5 mg/m2/hr
GFR : 18 ml/min/ 1.73 m2
ANA : Negative
Anti ds-DNA : Negative
ANCA:
– p-ANCA: strong positive (IFA)
– MPO-ANCA: 250 EU/ml (ELISA)
Anti-GBM: positive
Besbas N et al. Pediatr Nephrol 2003;18: 696-699
![Page 9: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/9.jpg)
Renal BiopsyRenal Biopsy
Besbas N et al. Pediatr Nephrol 2003;18: 696-699
![Page 10: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/10.jpg)
1 mo 2 mo 3 mo 4 mo 5 mo 6 mo 9 mo 12 mo 15 mo 18 mo 21 mo 24 mo
0.5 mg/kg/d prednisone0.5 mg/kg/d prednisone
MP
ZM
PZ
2 mg/kg/d cyclophosphamide
2 mg/kg/d azathiopurine
Plasma exchangePlasma exchange
MMFMMF
EtanerceptRituximabEtanerceptRituximab
Ser
um
cre
atin
ine
(mg
/dl)
![Page 11: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/11.jpg)
Nine years after successful renal transplantation– Cre: 0.98 mg/dl– GFR: 112 ml/min/1.73 m2
![Page 12: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/12.jpg)
CASE 2CASE 2
![Page 13: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/13.jpg)
Necrotic tissue (soft palate, digits and uvula)
Arthritis
Myalgia
Limitation of motion
URTI
Hoarseness, swollen edematous tongue, speech abnormality,
wt loss
URTI
Hoarseness, swollen edematous tongue, speech abnormality,
wt loss
Fatigue, worsening of the symptoms and myalgia
Fatigue, worsening of the symptoms and myalgia
Glossitis, iv penicilinGlossitis, iv penicilin
Fever
Subcutaneous nodules (fingertips, nose)
Generalized maculopapular rash
Necrotic lesions (right foot sole)
Generalized edema
Fever
Subcutaneous nodules (fingertips, nose)
Generalized maculopapular rash
Necrotic lesions (right foot sole)
Generalized edema
Ceftriaxone and clindamicin ivCeftriaxone and clindamicin iv Iloprost, Pentoxiphyllin
Amlodipine, Captopril
Piperacillin-Tazobactam, Vancomycin,
Rifampicin, Fluconazole
Iloprost, Pentoxiphyllin
Amlodipine, Captopril
Piperacillin-Tazobactam, Vancomycin,
Rifampicin, Fluconazole
daysdays0022
4466
10 year old, girl10 year old, girl
![Page 14: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/14.jpg)
Physical ExaminationPhysical Examination
BP: 130/60 mmHg
Pulse: 92 /min
BW: 40 kg (75p)
Height: 146 cm (50-75p)
BP: 130/60 mmHg
Pulse: 92 /min
BW: 40 kg (75p)
Height: 146 cm (50-75p)
Maculopapular rash
Edema (pretibial and dorsum of hand)
Tongue atrophy and tissue loss
Necrotic lesions
![Page 15: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/15.jpg)
Laboratory TestsLaboratory Tests
Hb : 7.4 g/dl
WBC : 20100 /mm3
Platelet: 550x103 /mm3
CRP : 14.9 mg/dl
ESR : 90 mm/hr
BUN : 8 mg/dl
T. prot : 6.17 g/dl
Alb : 2.39 g/dl
Urinary ph: 6.5 density:1020 protein: - , 1-2 RBC
IgA : 158 mg/dl (68-378)
IgM : 144 mg/dl (50-250)
IgG : 2050 mg/dl (650-1600)
ANA : Negative
Anti-DNA : Negative
c-ANCA : Mild staining at IIFNegative for MPO, PR3
Thrombotic panel including ACLs all (-)
MEFV : V726A/-
![Page 16: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/16.jpg)
Paranasal CT
![Page 17: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/17.jpg)
Necrotizing VasculitisNecrotizing Vasculitis
![Page 18: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/18.jpg)
Ora
l p
red
nis
on
e (2
mg
/kg
/day
)
Ora
l cy
clo
ph
osp
ham
ide
(2 m
g/k
g/d
ay)
Ora
l p
red
nis
on
e (2
mg
/kg
/day
)
Ora
l cy
clo
ph
osp
ham
ide
(2 m
g/k
g/d
ay)
daysdays1515
Pu
lse
ster
oid
Pu
lse
ster
oid
1717
Pla
sma
exch
ang
eP
lasm
a ex
chan
ge
1919
Pla
sma
exch
ang
eP
lasm
a ex
chan
ge
2121
Pla
sma
exch
ang
eP
lasm
a ex
chan
ge
2323P
lasm
a ex
chan
ge
Pla
sma
exch
ang
e2525
Pla
sma
exch
ang
eP
lasm
a ex
chan
ge
60603232
Pla
sma
exch
ang
eP
lasm
a ex
chan
ge
Hem
atu
ria,
p
rote
inu
ria,
dys
pn
eaH
emat
uri
a,
pro
tein
uri
a, d
ysp
nea
1414
![Page 19: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/19.jpg)
Classification of a child as WG:
3 of the following six should be present:
1. Abnormal urinalysis* 2. Granulomatous
inflammation on biopsy*3. Nasal-sinus inflammation*4. Subglottic, tracheal or
endobronchial stenosis5. Abnormal chest x-ray or CT*6. PR3 ANCA or C-ANCA
staining
Classification of a child as C-PAN:
Biopsy showing small and/or mid-size artery necrotizing vasculitis and/or angiographic abnormalities+2 out of the following 7 criteria
1. Skin involvement* 2. Myalgia or muscle tenderness*3. Systemic hypertension 4. Mononeuropathy or polyneuropathy5. Abnormal urinalysis and/or impaired
renal function*6. Testicular pain or tenderness7. Signs or symptoms suggesting
vasculitis of any other major organ system (gastrointestinal, cardiac, pulmonary, or CNS)*
EULAR/PRES Criteria. Ann Rheum Dis; 2006
![Page 20: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/20.jpg)
Prednisolone– oral 2 mg/kg – IV 15 mg/kg/dose
CYC– Oral 2 mg/kg– 500 mg/m2
Cre (> 500 mmol/l )
Vital organ involvementplasma exchange
• AZA: 1-2 mg/kg/d• CS: 0.25 mg/kg/alternate day
Risk factors for ERSD and relapse:
• Upper or lower respiratory tract disease
• Proteinase-3 ANCA seropositivity
• Severe kidney disease
• Female sex
3-6 months
12 months or longer
Bakkaloglu A et al. Arch Dis Clin 2001; 85: 427-430.Besbas N et al. Pediatr Nephrol 2000; 14: 325-327.
![Page 21: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/21.jpg)
INDUCTION THERAPYINDUCTION THERAPY
Prednisone ( 1-2 mg/kg/day) ± MP ( 3 pulses)Cyclophosphamide ( 2 mg/kg/day) or iv pulses
3 - 6 mo.
NORAM: MTX vs CYCMEPEX: PE vs MPCYCLOPS: CYC iv vs oralWEGET: Etanercept vs placeboSOLUTION: ATG
Maintenance therapyNORAM: MTX vs CYCCYCAZAREM: AZA vs CYCIMPROVE: AZA vs MMFREMAIN: AZA, 24 mo vs 48 mo
![Page 22: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/22.jpg)
Rituximab (RITUXVAS): – Several, uncontrolled studies (refractory)
Many reports observed disease remissions in relapsing and refractory patients with ANCA associated or other vasculitides
LeflunomideDeoxypergualinAnti CD52: – Predominantly leads to T-lymphocyte depletion– Its use has been complicated by a high frequency of
infection
Anti-thymocyte globulin (ATG):– Should be reserved for severe refractory WG
Recent Alternative Therapies
![Page 23: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/23.jpg)
CASE 3CASE 3
![Page 24: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/24.jpg)
3 year old girl
Poor appetite, fatigue, weight loss for one month
Over the past five days– Severe and frequent vomiting– Subsequently developed drowsiness and unconsciousness
– High blood pressure– Subarachnoid hemorrhage
Topaloglu R et al. Pediatr Nephrol 2005 Jul; 20 (7): 1011-5.
![Page 25: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/25.jpg)
Physical examinationPhysical examination
Body temperature: 36.6 CPulse rate: 104 /min
Respiratory rate: 20 /min
Blood pressure: – 180/110 mm Hg (left arm)– 175/105 mm Hg (right arm)
She was unconscious
Mydriasis
Diminished light reaction in the right eye
Right third nerve and left six nerve palsies
Left hemiparesis
Deep tendon reflexes were all diminished
Topaloglu R et al. Pediatr Nephrol 2005 Jul; 20 (7): 1011-5.
![Page 26: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/26.jpg)
Laboratory TestsLaboratory Tests
Hb : 9.9 g/dl
WBC : 22100 /mm3
Platelet: 675x103 /mm3
CRP : 10.2 mg/dl
ESR : 60 mm/hr
BUN : 8 mg/dl
Cre : 0.5 mg/dl
Urinary pH: 6.5 density: 1011 protein: protein- , 1-2 WBC /hpf
IgA : 168 mg/dl (68-378)
IgM : 1220 mg/dl (50-250)
IgG : 1450 mg/dl (650-1600)
ANA : Negative
Anti-DNA : Negative
ANCA : Negative
HBsAg : Negative
Anti-HCV: Negative
![Page 27: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/27.jpg)
CT/MRI CT/MRI
Topaloglu R et al. Pediatr Nephrol 2005; 20: 1011-1015.
![Page 28: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/28.jpg)
Angiography Angiography
Topaloglu R et al. Pediatr Nephrol 2005; 20: 1011-1015.
![Page 29: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/29.jpg)
CLASSIC POLYARTERITIS NODOSACLASSIC POLYARTERITIS NODOSA
Hypertensive emergency
Subarachnoidal hemorrhage
Angiography: Diffuse aneurysmal changes
Steroid intravenous, followed by p.o. route
Cyclophosphamide 2 mg/kg, p.o., 6 mo.
Azathiopurine (12 mo.)
MMF (12 mo.)
Low dose steroid (alternate day continuing)
![Page 30: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/30.jpg)
CASE 4CASE 4
![Page 31: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/31.jpg)
12 year old girl
Abdominal pain, myalgia
Nausea
Fever
Rash on extremities
Recurrent abdominal pain and fever- FMF?
Blood pressure: 150/90 mmHg
![Page 32: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/32.jpg)
Laboratory TestsLaboratory Tests
Hb : 11.7 g/dl
WBC : 12400 /mm3
Platelet: 558 x103 /mm3
CRP : 18 mg/dl
ESR : 55 mm/hr
BUN : 12 mg/dl
Cre : 0.6 mg/dl
Urinary pH: 6.5 density: 1018 protein: +++
10-15 RBC/hpf
IgA : 184 mg/dl (68-378)
IgM : 770 mg/dl (50-250)
IgG : 1850 mg/dl (650-1600)
ANA : Negative
Anti-DNA : Negative
ANCA :
– c-ANCA: positive (IFA)PR-3 ANCA : positive (ELISA)
HBsAg : Positive
HBV DNA: 330 pg/ml (0-5)
MEFV: M694 V/-
![Page 33: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/33.jpg)
![Page 34: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/34.jpg)
Renal AngiographyRenal Angiography
![Page 35: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/35.jpg)
Liver biopsy-Chronic hepatit B infection grade 1
– Lamuvidine therapy (1 year)
Polyarteritis nodosa
– 1 mg/kg/day oral prednisone
– 4 months later steroids tapered and stopped
FMF
– More inflammation, more vasculitis among FMF patients
– Increased MEFV mutations among vasculitis patients
– 0.03 mg/kg colchicum dispert
8 years follow up, BP (normal), renal function test (normal)
Medicine (Baltimore). 2005; 84: 1-11.
![Page 36: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/36.jpg)
CASE 5CASE 5
![Page 37: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/37.jpg)
9 month old girlFever and irritabilityMother-carrier for HBs AgBlood pressure: 180/100 mmHgESH: 70 mm/hrUrinalysis: protein +++Angiogram: Renal and mesenteric microaneurysmsHBs Ag (+)HBe Ag (+) HBV DNA > 2000 pg/ml
Duzova A et al. Eur J Pediatr 2001; 160: 519-520
![Page 38: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/38.jpg)
+ + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + + + + + + + + + + + + + + + HBV DNA pg/ml
HBs AgHBe Ag
Antihypertensive drugs
Prednisolone (2 mg/kg)
Cyclophosphamide (2 mg/kg)
Interferon
>2000 >2000 >2000 >2000 714
Months
302220181686420
Blo
od
pre
ssu
re (
mm
Hg)
200
180
160
140
120
100
80
60
40
Diastolic BP
Systolic BP
*
Figure 1: Time course of blood pressure, treatment and virological parameters
5x106 U/m2 10x106 U/m2
Duzova A et al. Eur J Pediatr 2001; 160: 519-520
*: anaemia and leukocytopenia
![Page 39: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/39.jpg)
CASE 6 & 7CASE 6 & 7
![Page 40: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/40.jpg)
Patient 6Patient 6
Age at diagnosis: 12 y
Headache
BP: 150/100 mm Hg
ESR: 44 mm/hr
ppd: positive
Urinalysis: Proteinuria
Angiography
RRA: Normal
LRA: Stenosis
Entire thoracic and abdominal artery involvement, presence of aneurysms
![Page 41: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/41.jpg)
![Page 42: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/42.jpg)
Medical treatment
– Prednisolone (bolus, po)
– CYC (po)
– MTX (po/sc)
– Anti-hypertensive
• CCB
• Alpha-blocker
• Beta-blocker
Anti-tbc treatment
Surgical treatment
– Left nephrectomy
Duration of follow up: 10 years
Low dose steroid
TREATMENTTREATMENT
![Page 43: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/43.jpg)
Patient 7Patient 7
Age at diagnosis: 16 y
Arthralgia
MEFV : E148Q/-
FMF? 4 years
Headache
BP: 180/100 mm Hg
ESR: 16 mm/hr
Angiography
RRA: stenosis at the origin
LRA: stenosis at the origin
Involvement of SMA and suprarenal abdominal aorta
![Page 44: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/44.jpg)
![Page 45: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/45.jpg)
TREATMENTTREATMENT
Medical treatment– Prednisone (po)– MTX (po)– Anti-hypertensive
• CCB• Beta blocker
Surgical treatment• Thoraco-abdominal by pass, left aorta renal
by pass• Right aorta renal by pass
Duration of follow up: 1 yearLow dose steroid and MTX
![Page 46: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/46.jpg)
![Page 47: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/47.jpg)
Takayasu ArteritisTakayasu Arteritis
Mainstay of the treatment is to attenuate inflammatory process and control HTN
Corticosteroids: Therapy is continued until patients achieve remission
Cyclophosphamide (1-2 mg/kg/d)
Azathioprine (1-2 mg/kg)
Methotrexate (0.3 mg/kg/wk)
Anti-TNF
Ozen S et al. J Pediatr 2007; 150: 72-76Hoffman et al. Arthritis Rheum 2004; 50: 2296-2304
![Page 48: Aysin Bakkaloglu, M.D. Hacettepe University Faculty of Medicine Pediatric Nephrology and Rheumatology Ankara, TURKIYE ESPN 2008 Lyon, FRANCE TREATING DIFFICULT.](https://reader034.fdocuments.in/reader034/viewer/2022052504/551610c8550346cf6f8b624c/html5/thumbnails/48.jpg)
SummarySummary
Vasculitis should be excluded in any patient with renal or extrarenal symptoms and: – Elevated acute phase reactants– Constitutional symptoms– Organ involvement
Diagnosis is typically delayed 3 mo.; and the absence of extra-renal disease is associated with a longer delay.Longterm outcomes are closely related to the severity of organ dysfunction at diagnosisANCA testing enables earlier identification.In last 3 decades: MP+CYC therapy enables 75-90% remission at 6 mo. A variety of treatment options now available for AAV.Balance should be made between disease suppression and treatment toxicity.