This document describes the case of a 51-year-old male labourer admitted with fever, facial puffiness, haematuria, epistaxis and leg swelling for 3-7 days. Investigations revealed cANCA positivity and renal involvement. A renal biopsy showed focal segmental glomerulonephritis with necrosis, consistent with ANCA vasculitis. A diagnosis of Wegener's granulomatosis was made based on renal and upper respiratory tract involvement. The patient was started on steroids and cyclophosphamide for treatment.

1. Dr Teffy
M4 unit
Prof Dr G Elangovan’s unit

2. Panjatcharam, 51/M, labourer, from Vyasarpadi
Admitted with ,
 Fever - 7 days ,1 wk back
 Facial puffiness - 7 days
 Haematuria - 7 days,on& off
 Epistaxis - 3 days
 B/L leg swelling - 3 days

3. H/o fever for 7 days, I wk back
- high grade,intermittent,not associated with
chills/rigor
- cough with minimal mucoid expectoration +;
no hemoptysis
H/o facial puffiness - 7days,
- periorbital,early morning
H/o haematuria - 7days
- painless,early morning

4. • H/o epistaxis – 3 days
- on &off,minimal bleed ,subsides spontaneously
• H/o B/L leg swelling – 3 days
- minimal,progressive,
No H/o abdominal distension/breathlessness/
decreased urine output
No H/o loin pain/abdominal pain/dysuria/pyuria
No H/o chest pain/palpitation/giddiness/syncope
No H/o jaundice/nausea/vomiting

5. No h/o head ache/facial pain/rhinitis
No h/o other bleeding tendencies
No h/o sore throat/skin lesions /jointpains/
rashes/ulcers/drug or native medicine intake
No h/o trauma

6. Recently detected to be hypertensive one week back
No h/o DM/CAD/TB/CKD
Personal history: alcoholic & smoker – 30 yrs
Family history : non contributary

7. • ON EXAMINATION :
• conscious , oriented to time,place&person
• comfortable at rest
• Hydration fair
• Periorbital puffiness +
• B/L pitting pedal edema + (minimal)
• Grade 1 clubbing +
• No pallor/icterus/cyanosis/lymphadenopathy/
skin lesions
• Bone & joints – normal; Eyes – normal
• No paranasal sinus tenderness

8. Vital signs :
Pulse - 82/min,regular,normal volume;all peripheral
pulses equally felt
BP - 150/100 mmHg, Rt arm ,sitting
RR -16/min,abdominothoracic
Temp – Normal
JVP – not elevated
SYSTEMIC EXAMINATION : within normal limit

9. Possibility of a renal disorder
– ? Acute glomerulonephritis

10. INVESTIGATIONS
COMPLETE BLOOD COUNT
Hb 13
PCV 40
TC 9,800
DC N 60 L38 E2
Platelet count 3,00,000/mm3
ESR 30/64
MCV 86
MCH 29

11. RFT 16/10 22/10
RBS 104 98
UREA 50 48
CREATININE 1.7 1.6
Na 138 137
K 3.8 3.9
LFT
T Bil 1.0
SGOT 22
SGPT 19
S ALBUMIN 4.4
T CHOLESTEROL 160

12. URINE ROUTINE & MICROSCOPY
SPECIFIC GRAVITY 1.020
PH 5
GLUCOSE -
BILIRUBIN -
KETONE -
BLOOD 3+
PROTEIN 3+
RBC CASTS +
24 Hr URINE PROTEIN 400 MG/DAY
URINE C/S NO GROWTH

13. USG ABDOMEN & PELVIS: NORMAL STUDY
RK- 10.3;LK – 10.9
Normal PCS,Echoes, CMD+
• ECG : NSR;WNL
• ECHO:Normal
• Peripheral smear study : normal

14. OTHER INVESTIGATIONS :
CRP 25
ASO titre negative
Rheumatoid factor negative
ANA negative
HIV 1&2 Negative
HBs Ag Negative
Anti HCV Negative
S CALCIUM 10.2
S PHOSPOROUS 4.3
S URIC ACID 5.1

15. NEPHROLOGY OPINION :
16/10 – ? Acute Glomerulonephritis
- to do C3,C4,C ANCA,P ANCA
- continue antibiotics

16. C 3 121(90-180)
C4 23.45(10-40)
C ANCA POSITIVE ( IFA)
P ANCA Negative

17. ANCA vasculitis with epistaxis
? Wegener’s Granulomatosis
-PLAN :
CT chest
CT PNS
ENT opinion

18. CHEST X RAY PA VIEW : WNL
CT CHEST : WNL
CT PNS : B/L PANSINUSITIS
–mucosal thickening +;no bony
erosions/expansion/fluid level

19. Chest X ray

20. CT Chest

21. X ray PNS

23. ENT opinion(23/10) :
L/E : Ear,nose,throat -normal
DNE with biopsy

24. NEPHROLOGY REVIEW :
24/10 – C/O ANCA Vasculitis;
Epistaxis
B/L Pansinusitis
- ? Wegener’s Granulomatosis
PLAN : Renal biopsy
: To start IV methyl prednisolone followed by
oral prednisolone

25. Renal biopsy
Focal segmental glomerulonephritis ;focal necrosis +
No immune deposition

26. Sinus mucosal biopsy
- results pending

27. FINAL DIAGNOSIS
 ANCA vasculitis
-renal & upper respiratory tract involvement ;
D/D
1.Wegeners granulomatosis
2.Microscopic polyangiitis
3.Idiopathic necrotising glomerulonephritis
4.CHURG strauss syndrome
possibly Wegener’s granulomatosis

28. TREATMENT given
INJ Cefotaxime 1g IV BD
INJ Ranitidine 50 mg IV BD
INJ Frusemide 20 mg IV BD , 2 days
INJ Methyl prednisolone 1 g in 100 ml NS IV infusion
over 1 hr , 3 days followed by
Tab Prednisolone 60 mg/day ( 1 mg/kg bw)

29. ANCA
1982 –Davies & colleagues first described ANCA ;
Two types – c ANCA & p ANCA (IFA);
Antigens associated are
-- proteinase 3-PR3 – c ANCA
--myeloperoxidase –MPO-p ANCA
• ANCA positivity by IFA should be confirmed by antigen
specific testing for both PR3 & MPO

30. DISEASE ASSOCIATIONS
Vasculitis :-
: small vessel vasculitis – WG,MPA,CSS
: idiopathic necrotising crescentic glomerulonephritis
Sensitivity of ANCA -50 to 90 %
-Negative test does not rule out diagnosis in
patients with high pretest probability
Specificity of ANCA ;
: If IFA results are combined with antigen specific assays,the
specificity of both PR3-ANCA & MPO-ANCA is exceedingly high.
• Influences disease phenotype
-- PR3 – WG; MPO - MPA
-- PR3 positive patients -> more relapse
->more granuloma
-> more extrarenal

31. others..
Rheumatoid arthritis ,SLE, myositis
Cystic fibrosis , endocarditis ,& HIV
Inflammatory bowel disease :UC > crohn’s
Sclerosing cholangitis ,autoimmune heaptitis
Drugs :
Hydralazine ,propylthiouracil high MPO-
D penicillamine ,minocycline ANCA

32. Wegener’s granulomatosis
• First described in 1931 by Heinz Klinger ;
• Classic triad-Granulomatous necrotising vasculitis affecting the
upper & lower respiratory tract and the kidneys;
• Prevalence – 3/1,00,000 persons
• Affects both sexes equally ;
• Affects all ages –( mean age 41 yrs );
• More common in Caucasians

33. Pathogenesis
Exact cause unknown;
HLA-DR1 & HLA-DQw7 association has been reported ;
PR3-ANCA antibodies are highly specific for Wegener’s
(90-97%);
ANCA s cause neutrophil degranulation & also cause
endothelial damage ;
Evidence of T cell involvement is less direct ;

34. Clinical features
Predilection for upper,lower respiratory tract & the
kidneys ;
Mild forms of wegener’s without renal involvement
have been described ;
Indolent or rapidly progressive course ;
Unexplained constitutional symptoms like fever and
weight loss in one fourth of the patients

35. Upper airway features
Most common presenting feature
In 70 % of the patients at onset ,ultimately developing in
>90%
Sinusitis(MC) initial presentation in 50 -67%;in85 %
during the course of the disease
Secondary infection-S. aureus is predominant organism;
Epistaxis -11-32%
Biopsy - granulomatous inflammation with necrosis ;
vasculitis+/-
- complete diagnostic triad in 3 – 16%

36. Renal manifestations
Presence or absence of renal disease defines generalised or
limited wegener’s ;
Early disease mey be clinically silent
Extrarenal manifestations may precede renal disease
11-18% at presentation & 80% over the course
 mild focal & segmental glomerulonephritis with minimal
haematuria & little dimunition of GFR
tofulminant,diffuse,necrotizing &crescentic
glomerulonephritis(RPGN) leading within days to wks to
oligoanuria &dialysis

37. If untreated mean survival is 5 months ;
Chronic renal failure in 42% despite treatment ;
Urine microscopy most useful tool ;
Presence of RBC casts 100% positive predictive value
for glomerulonephritis ;
Fulminant WG - can manifest as pulmonary renal
syndrome ( alveolar haemorrhage & RPGN)
Accounts directly or indirectly for most of the
mortality in this disease

38. PATHOLOGY:
Focal ,segmental glomerulonephritis
Fibrinoid necrosis & proliferative changes
Epiithelial crescents
Sclerotic lesions
Vasculitis – focal in 5-10%
Granulomatous changes –only in 3-20%
Immune complex deposition unusual (pauci
immune)
The degree of renal failure & serum creatinine do not
always correlate with pathological features

39. picture

40. Frequency of Clinical features In 158 pts ; Studied at NIH
MANIFESTATION AT DISEASE ONSET DURING THE COURSE
KIDNEY
Glomerulonephritis 18 77
EAR/NOSE/THROAT 73 92
Sinusitis 51 85
Nasal disease 36 68
Otitis media 25 44
Hearing loss 14 42
Subglottic stenosis 1 16
Ear pain 9 14
Oral lesions 3 10
LUNG 45 85
Pulmonary infiltrates 25 66
Pulmonary nodules 24 58
Hemoptysis 12 30
Pleuritis 10 28

41. EYES
Conjunctivitis 5 18
Scleritis 6 16
Proptosis 2 15
Visual loss 8
Corneal/retinal lesions,iritis
OTHERS
Arthralgias/arthritis 32 67
fever 23 50
cough 19 46
Skin abnormalities 13 46
Wt loss 15 35
Peripheral neuropathy 1 15
CNS disease 8
Pericarditis 2 6
Venous thromboembolism,
Accelarated atherosclerosis

42. ACR criteria(1990) : WG : atleast 2/4 criteria
1. Nasal/oral inflammation
2. Abnormal chest radiograph
3. Microhaematuria
4. Biopsy

43. Lab diagnosis
General :
- leucocytosis ,normochromic normocytic anemia ,
thrombocytosis
- raised ESR &CRP;
• Pathology : necrosis ; granulomatous changes ;
vasculitis
: open lung biopsies – 90 %

44. ANCA & WG :
1985 – Vander woude & colleagues – first to suggest
an association between ANCA & wegener’s
Most likely to be positive in pts with triad disease
that is active & untreated
 - PR3 ANCA -sensitivity –active disease – 90%
remission -40%
-specificity - > 95%
High titre ANCA + PR3/MPO specific assay
with high pretest probability is sufficient to diagnose
even in the absence of tissue confirmation

45. Regarding monitoring disease activity,
A substantial no of pts with rise in ANCA titre did not
flare;hence rise in ANCA titre should not be the sole
basis for therapeutic decision making
It was rare to see a flare in the absence of increased
ANCA-strong negative predictive value

46. TREATMENT
CYCLOPHOSPHAMIDE + GLUCOCORTICOIDS :
complete remission in 75 % of patients
Cyclophosphamide
– oral ; 2mg/kg/d
- monitor leucocyte count (>3,000)/µl
- S/e – haemorrhagic cystitis(30%);bladder
cancer(6%);myelodysplasia(2%); infertility
-comtinued for 1 yr after the induction of complete
remission ,taper &discontinue

47. Glucocorticoids :
-Oral;prednisone 1 mg/kg/d initially(1mth);then
alternate day schedule ;taper&discontinue
- S/E –
diabetes,cataract,infections,osteoporosis;cushingoid
features
- IV pulse methyl prednisolone (1g/d for 3 days )
especially for severe cases
• 50% of remissions are later associated with one or
more relapses

48. Maintenance
Methotrexate – start at 0.3mg/kg single weekly dose
- till 2 yrs past remission
Azathioprine- 2mg/kg/day
Mycophenolate mofetil – 1000mg twice a day

49. OTHERS:
Methotrexate induction for non severe disease
Rituximab
TMP-SMX(upper airway disease)
Organ specific treatment
- isolated sinus or joint or skin disease
- subglottic stenosis & endobronchial stenosis

50. Case reports :
1. Unusual renal manifestation of Wegener’s -60 yr old female presented
with glomerulonephritis & ,mononeuritis multiplex 2 yrs before
development of classic necrotizing granulomatous inflammation of
sinuses & nose along with pulmonary nodules
The American Journal of medicine
vol64,issue5,may 1978
2. Upper respiratory tract (maxillary & ethmoidal sinusitis) , renal
involvement(pauci immune crescentic glomerulonephritis),vasculitis
in a 15 yr old girl;c ANCA positive; responded well to steroids &
cyclophosphamide
Journal of clinical medicine research
vol 2,no 4,august 2010

51. REFERENCES
1. Kellys textbook of Rheumatology
2.Oxford textbook of Rheumatology
3.Harrison’s Internal Medicine
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