1. Case Presentation
Staci Smith DO
April 17th, 2009

2. Differential Diagnosis
hematuria
proteinuria glomerulonephritis
red blood cell casts

3. Red Blood Cell Casts Glomerular hematuria Nephritic syndrome
Dysmorphic rbc’s
glomerular damage
rule out urologic causes
Nephritic syndrome
HTN
RBC casts
Proteinuria
Edema

4. Dysmorphic rbc
dysmorphic red cells
acanthocytes
ring form

5. Fatty Cast
fat droplets
nephrotic syndrome

6. Differential Diagnosis: Glomerulonephritis
Postinfectious GN
IgA nephropathy
Thin basement membrane
Henoch-Schönlein purpura
Mesangial proliferative GN
SLE
Goodpasture’s dz
Vasculitis
Wegener’s, Churg-Strauss
Cryoglobulinemia
HIV
Membranoproliferative glomerulonephritis
Rapidly progressive GN
Fibrillary glomerulonephritis
Focal glomerulosclerosis
Membranous nephropathy
Amyloidosis
Multiple Myeloma DM
HUS

7. Differential Diagnosis : Glomerulonephritis
UA with C and S
Cbc with differential
Renal panel
Urine Pr/Cr
Renal US
Renal Duplex
Cystography
Urine eosinophils
SPEP / UPEP with IFE

8. Differential Diagnosis of Glomerulonephritis
ANA, dsDNA
SLE
Cryoglobulins, RF
Cryoglobulinemia, HCV
Anti-GBM
Anti-GBM dz ,Goodpasture’s
ANCA’s
c-ANCA: Wegener’s
p-ANCA: PAN, Churg Strauss, MPA
Complements
C3, C4, CH50
ASO
Post Strept GN
Hepatitis profile
MPGN
HIV
HIV, FSGS
Renal Biopsy

9. Differential Diagnosis Low Complements
SLE
Endocarditis
MPGN
Post infectious GN
Atheroembolic dz
Urine eos

10. Pulmonary Renal Syndromes
Wegener’s granulomatosis
MPA
Churg-Strauss
Goodpasture’s syndrome
SLE

11. Vasculitis

12. Wegener's Granulomatosis
distinguished from other vasculitides by the pattern of organ involvement
histologic features of granulomatosis and necrotizing inflammation
primary involvement
upper and lower respiratory tracts
kidneys - glomerulonephritis

13. Wegener's Granulomatosis
pathogenesis is unknown
interplay of an initiating inflammatory event and a highly specific immune response
response is directed against neutrophil granule proteins
high titer autoantibodies known as anti-neutrophil cytoplasmic antibodies (ANCA)

14. Wegener’s Triad 1954- Goodman and Churg triad of pathological features
systemic necrotizing angiitis
necrotizing granulomatous inflammation of the respiratory tract
necrotizing glomerulonephritis

15. ACR Criteria for WG : Two of four
Were developed before ANCA testing was in widespread use
Nasal or oral inflammation
oral ulcers or purulent or bloody nasal discharge
Abnormal chest radiograph findings
nodules, fixed infiltrates, or cavities
Urinary sediment
microhematuria (>5 red blood cells per high-power field)
red blood cell casts
Granulomatous inflammation noted at biopsy

16. Wegener’s Granulomatosis
Organs most frequently affected by Wegener’s
Confirm with tissue bx

17. Homogenous Perinuclear Staining
p-ANCA
Microscopic polyangitis
Churg-Strauss syndrome
Polyarteritis nodosa

18. Granular Cytoplasmic Staining
C-ANCA
PR3
Wegener’s

19. ANCA Positive and ANCA Negative
90 to 95 % of patients
ANCA-positive
small subset of patients
who do not have ANCA
limited forms
up to 40 % of patients may be ANCA-negative

20. Clinical History ELK classification
broad spectrum of organ involvement
ears, nose, and throat or upper respiratory tract (E); lungs (L); and kidneys (K)

21. ELK Classification: Ears, nose, and throat
nasal obstruction with serosanguineous discharge
chronic sinusitis
deep central facial pain
saddle nose deformity
middle ear involvement -hearing loss
subglottic stenosis-hoarseness and stridor

22. Wegener’s Granulomatosis
Saddle nose deformity

23. ELK Classification Lungs
asymptomatic or may present with cough and occasional hemoptysis
progressive dyspnea and respiratory failure
massive pulmonary hemorrhage

24. Wegener’s Granulomatosis
nodules in the middle and lower lung fields bilaterally

25. ELK Classification
Patients with kidney involvement generally are asymptomatic, but some patients may notice mild hematuria.
Edema secondary to nephrotic syndrome may be present

26. Wegener’s Granulomatosis
Neurologic involvement
approximately one third of patients
peripheral neuropathy with mononeuritis multiplex
cranial neuropathy involving the second, sixth, and seventh cranial nerves

27. Wegener’s Granulomatosis
Skin
14% of patients with a purpuric rash over the lower extremities

28. Wegener’s Granulomatosis
Eye and orbit
29% of patients
present with red or swollen eyes
Joints
arthralgias
inflammatory joint involvement
not erosive or deforming

29. Limited form of Wegener’s
clinical findings isolated to the upper respiratory tract or the lungs
one-fourth of cases
up to 80 percent eventually develop glomerulonephritis
incompletely understood phenotypic differences
younger at disease onset
more likely to be women

30. Renal Involvement : Wegener’s
acute renal failure with red cells
red cell and other casts
proteinuria
rapidly progressing
renal biopsy
segmental necrotizing glomerulonephritis
with few or no immune deposits (pauci-immune) on immunofluorescence and electron microscopy

31. Wegener’s Granulomatosis
light micrograph
segmental necrotizing lesions
bright red fibrin deposition

32. Renal Involvement : Wegener’s
glomerular involvement
often accompanied by mononuclear tubulointerstitial infiltrates
small vessel involvement
venules, capillaries, arterioles
reoccurs in renal transplant

33. Renal Involvement : Wegener’s
may be severe enough to require dialysis
hypertension
mediated by ischemia-induced activation of the renin-angiotensin system
angiotensin converting enzyme inhibitors
risk of worsening renal function
removal of the angiotensin II effect on autoregulation and maintenance of the glomerular filtration rate

34. Treatment untreated systemic WG long-lasting remission poor prognosis
90% of patients dying within 2 years
from respiratory or renal failure
long-lasting remission
cyclophosphamide in combination with corticosteroids
90% of patients respond to cyclophosphamide

35. Treatment : Induction Methylprednisolone 7mg/kg/day IV for 3 days
followed by oral prednisone 1 mg/kg/day
tapered to every other day and stopped in 3-4mo
Cyclophosphamide
2 mg/kg/day oral or IV 0.5g/m2 per month
adjust upward to 1 g/m2
follow cbc

36. Maintenance Therapy Reduce toxicity after three to six months
Use for one year
MTX
mild–to–moderatedisease
no pulmonary hemorrhage or fulminant renal failure
If intolerable to Cytoxan
Azathioprine
Cellcept
Infliximab, Etanercept

37. Predicting Relapse
ANCA titers usually parallel the course of vasculitis, especially C-ANCA
decreasing titers of ANCA predict a lower risk for clinical relapse

38. Plasma Exchange role is controversial no real added benefits
may be beneficial if life threatening pulmonary hemorrhage especially if dialysis dependent

39. Key Points : Decreased Complements
SLE
Endocarditis
MPGN
Post infectious GN
Atheroembolic dz
Urine eos

40. Differential Diagnosis
hematuria
proteinuria glomerulonephritis
red blood cell casts

41. Differential Diagnosis Low Complements
SLE
Endocarditis
MPGN
Post infectious GN
Atheroembolic dz
Urine eos

42. Red Blood Cell Casts Glomerular hematuria Nephritic syndrome
Dysmorphic rbc’s
glomerular damage
rule out urologic causes
Nephritic syndrome
HTN
RBC casts
Proteinuria
Edema

43. Differential Diagnosis: Glomerulonephritis
Postinfectious GN
IgA nephropathy
Thin basement membrane
Henoch-Schönlein purpura
Mesangial proliferative GN
SLE
Goodpasture’s dz
Vasculitis
Wegener’s, Churg-Strauss
Cryoglobulinemia
HIV
Membranoproliferative glomerulonephritis
Rapidly progressive GN
Fibrillary glomerulonephritis
Focal glomerulosclerosis
Membranous nephropathy
Amyloidosis
Multiple Myeloma DM
HUS

44. Differential Diagnosis of Glomerulonephritis
ANA, dsDNA
SLE
Cryoglobulins, RF
Cryoglobulinemia, HCV
Anti-GBM
Anti-GBM dz ,Goodpasture’s
ANCA’s
c-ANCA: Wegener’s
p-ANCA: PAN, Churg Strauss, MPA
Complements
C3, C4, CH50
ASO
Post Strept GN
Hepatitis profile
MPGN
HIV
HIV, FSGS
Renal Biopsy

45. ACR Criteria for WG : Two of four
Were developed before ANCA testing was in widespread use
Nasal or oral inflammation
oral ulcers or purulent or bloody nasal discharge
Abnormal chest radiograph findings
nodules, fixed infiltrates, or cavities
Urinary sediment
microhematuria (>5 red blood cells per high-power field)
red blood cell casts
Granulomatous inflammation noted at biopsy

46. Renal Involvement : Wegener’s
acute renal failure with red cells
red cell and other casts
proteinuria
rapidly progressing
renal biopsy
segmental necrotizing glomerulonephritis
with few or no immune deposits (pauci-immune) on immunofluorescence and electron microscopy

47. Renal Involvement : Wegener’s
acute renal failure with red cells
red cell and other casts
proteinuria
rapidly progressing
renal biopsy
segmental necrotizing glomerulonephritis
with few or no immune deposits (pauci-immune) on immunofluorescence and electron microscopy

48. Wegener’s Granulomatosis
light micrograph
segmental necrotizing lesions
bright red fibrin deposition

49. Thank You

50. Reference
Duna, GF, Cotch, MF, Galperin, C, et al. Wegener's granulomatosis: Role of environmental exposures. Clin Exp Rheumatol 1998; 16:669.
Hoffman, GS, Kerr, GS, Leavitt, RY, et al. Wegener's granulomatosis: An analysis of 158 patients. Ann Intern Med 1992; 116:488.
Banerjee, A, McKane, W, Thiru, S, Farrington, K. Wegener's granulomatosis presenting as acute suppurative interstitial nephritis. J Clin Pathol 2001; 54:787.
Wen, YK, Chen, ML. Transformation from tubulointerstitial nephritis to crescentic glomerulonephritis: an unusual presentation of ANCA-associated renal vasculitis. Ren Fail 2006; 28:189