This document presents a case of a 51-year-old male patient who presented with fever, facial puffiness, hematuria, and leg swelling for several days. Investigations revealed positive C-ANCA and renal biopsy showing focal segmental glomerulonephritis with focal necrosis. A final diagnosis of ANCA vasculitis involving the kidneys and upper respiratory tract, possibly Wegener's granulomatosis, was made. Treatment with cyclophosphamide and glucocorticoids achieved remission. The document discusses ANCA, Wegener's granulomatosis pathogenesis and clinical features, investigations, treatment including immunosuppression, and monitoring of disease activity.

1. An Interesting case from
Medicine Dept
Presented by : Dr Shaz Pamangadan
Govt Medical College kannur.

2. • 51/M, labourer, from kannur—————
• Presenting complaints
• Fever - 7 days
• Facial puffiness - 7 days
• Haematuria - 7 days – on and off
• B/L leg swelling - 3 days

3. - h/o fever for 7 days , 1 week 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. Past history
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
• Moderately built and nourished
• Periorbital puffiness +
• B/L pitting pedal edema + (minimal)
• Grade 1 clubbing +
• No pallor/icterus/cyanosis/lymphadenopathy/
Skin,hair,nails appears normal
• Bone & joints – normal . Eyes – normal
• No paranasal sinus tenderness

8. • Vital signs
• Pulse - 82/min,regular,normal volume;all periphera pulses equally
felt
• BP - 150/100 mmHg, Rt arm ,sitting position.—
• RR -16/min,abdominothoracic —
• Temp – Afebrile
• JVP – not elevated
• SYSTEMIC EXAMINATION : within normal limits.

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
• MCV--- 86
• MCH--- 29

11. • RFT 16/10 22/10
• RBS ---104
• UREA--- 50
• CREATININE--- 2.7
• Na--- 138
• K--- 3.8
• LFT
• T Bil ---1.0
• SGOT--- 22
• SGPT--- 19
• S ALBUMIN--- 4.4
• T CHOLESTEROL--- 160

12. • URINE ROUTINE & MICROSCOPY
• URINE R/E :
• SPECIFIC GRAVITY--- 1.020
• PH--- 5
• GLUCOSE ---NIL
• BILIRUBIN ---NIL
• KETONE ---NIL
• RBC--- 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. • 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. • ? Acute Glomerulonephritis
to do C3,C4,C ANCA,P ANCA .
To continue antibiotics

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

17. D/D
1.Wegeners granulomatosis
2.Microscopic polyangiitis
3.Idiopathic necrotising glomerulonephritis
4.CHURG strauss syndrome

18. • -PLAN :
CT chest
CT PNS
ENT opinion

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

20. • ENT opinion .
• L/E : Ear,nose,throat -normal
• DNE with biopsy

21. • Renal biopsy :
—Focal segmental glomerulonephritis ;focal necrosis + —No immune
deposition

22. • FINAL DIAGNOSIS
—ANCA vasculitis
renal & upper respiratory tract involvement
possibly Wegener’s granulomatosis

23. 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

24. 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

25. 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

26. 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

27. 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 ;

28. • 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

29. • 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%

30. • 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

31. • 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

32. • —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

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

34. • Lab diagnosis
• —General :
• - leucocytosis ,normochromic normocytic anemia ,
• thrombocytosis
• - raised ESR &CRP;
• Pathology : necrosis ; granulomatous changes ; vasculitis

35. • 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

36. • 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

37. • 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

38. 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

39. • THANK YOU