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
THANK YOU
for your patient listening
-------------------------