Presented by Dr. Radhika Ghongane KMC Manipal

1. Pulmonary vasculitis
BY –
Dr. Radhika Ghongane
Junior Resident
KMC, Manipal

2. Introduction
• Usually a manifestation of a systemic disorder
• Inflammation of vessels of different sizes by a
variety of immunological mechanisms
• Types- primary and secondary

3. 2012 Chapel Hill nomenclature

4. ANCA = Anti-Neutrophil Cytoplasmic Antibodies
• Proteinase 3 (PR3) and Myeloperoxidase (MPO) are
present in granules of neutrophils/monocytes.
• ANCA are auto-antibodies against these antigens
C-ANCA: Diffuse, granular staining
PR3 Abs
P-ANCA: Perinuclear staining
MPO Abs

5. Granulomatosis with Polyangiitis
• Necrotizing granulomatous
inflammation+necrotizing vasculitis
• Most frequently involved sites-upper airways,
lungs, and kidneys
• Two forms- Limited or Severe

6. Clinical presentation

7. Radiology
• Nodules +/- cavitation
• Air-space opacities- pulmonary haemorrhage
or peripheral wedge-like consolidation
• Reticulonodular pattern
• Pleural effusions

9. Multiple, bilateral nodules, some with cavitation
and small bilateral pleural effusions

10. Histopathology
• Earliest lesion - Small necrotizing
microabscesses
• Necrotizing granulomatous inflammation +
small vessel vasculitis
• mixed cellular infiltrate containing
lymphocytes, plasma cells, scattered giant
cells, and eosinophils

11. Glomerulonephritis
• Kidneys are affected in 80% of
patients
• Microscopic hematuria and
red cell casts, proteinuria and
declining renal function
• Renal biopsy - segmental,
necrotizing inflammation and
cellular crescents

12. Microscopic Polyangiitis
• Histopathologically indistinguishable from GPA
• All organ systems may be involved
• Kidneys are most commonly affected (80%)
• Diffuse alveolar hemorrhage (10% to 30%)
• Most frequent cause of pulmonary renal
syndrome

13. Clinical presentation
• Palpable purpura
• Arthralgias and myalgias
• Gastrointestinal involvement occurs in about
1/3rd of patients – rarely seen in GPA
• Sinusitis and asthma are rarely found

14. Diagnosis
• 40% to 80% cases have p-ANCA
• Histopathological diagnosis may be necessary to
confirm the diagnosis
• Renal biopsy - pauci-immune focal segmental
necrotizing glomerulonephritis, with crescents
• Granulomatous inflammation is not a feature of MPA

15. Eosinophilic Granulomatosis with
Polyangiitis
• Necrotizing granulomatous inflammation and
vasculitis + Asthma + Eosinophilia
• Usually p-ANCA +
• ANCA status appears to correlate with disease
activity

16. Phases of the disease
PHASES CHARACTERISTIC
FEATURE
DURATION
1. Prodromal
allergic phase
Asthma Number of years
2. Eosinophilic
phase
Prominent
peripheral and
tissue
eosinophilia
Number of years
And the
manifestations
may remit and
recur
3. Vasculitic
phase
Systemic
vasculitis
Life threatening
Prognosis is better than that of GPA and MPA
Most deaths are secondary to cardiac involvement

17. Clinical presentation
• Pulmonary parenchymal involvement occurs in
38% of patients
• Alveolar hemorrhage is exceedingly rare
• Renal involvement is less prominent
• Peripheral nerve involvement, typically in the
form of mononeuritis multiplex, is more frequent

18. Radiology
• Transient alveolar-
type infiltrates are
most common
• Predominantly
peripheral distribution
• Nodular lesions
occasionally

19. Histopathology
• Necrotizing vasculitis
• Eosinophilic tissue
infiltration
• Extravascular granulomas

20. Pathophysiology of ANCA-Associated
Vasculitis
• Etiology of ANCA-associated vasculitis remains
unknown
• Causes of the production and persistence of ANCA
remain poorly understood
• ANCA production maybe the result of molecular
mimicry
• Many clinical observations suggest that the presence
and type of ANCA defines the disease phenotype

21. Goals of treatment in GPA/MPA
1. Induce early remission of active disease
2. Reduce disease relapse
3. Minimize therapeutic toxicity
4. Surgical interventions to repair damage

22. Remission Induction Therapy
• According to degree of disease severity, extent
and acuity.
1. Indolent GPA localized to the upper and/or
lower airways, ANCA negative –
Trimethoprim/Sulfamethoxazole at a dose of
160/800 mg twice daily

23. 2. Limited or non-severe or early-systemic –
• oral prednisone - 0.5 to 1 mg/kg per day
(generally not to exceed 80 mg/d)
• in combination with methotrexate with a
target dose of 20 to 25 mg once a week, orally
or subcutaneously

24. 3. Severe disease (generalized or organ-
threatening disease) –
a) oral prednisone in combination with oral
cyclophosphamide at a dose of 2 mg/kg daily
for 3 to 6 months

25. b) Rituximab - once-weekly doses (375 mg/m2
of body surface) for 18 months
c) daily oral cyclophosphamide followed by
azathioprine for 18 months
• 90% of patients attain remission with either of
these 3 regimens

26. 4. Rapidly progressive fulminant disease –
• Intravenous methy-lprednisolone, 1000
mg/day for 3 to 5 days
• Plasma exchange

27. Remission Maintenance Therapy
• Prednisone - tapered over 5-6 months with
the goal of complete discontinuation
• Limited disease -methotrexate
• Patients with cyclophosphamide for induction
should be switched to methotrexate or
azathioprine

28. • Azathioprine is preferred in patients with any
degree of renal insufficiency
• Alternative - Mycophenolate mofetil
• Duration of emission maintenance - at least 12
months, longer in relapse cases
• Early discontinuation of immunosuppressive
therapy is associated with an unduly high relapse
rate

29. Treatment of Patients Refractory to
Standard Therapy
• 10% cases are refractory
• Rituximab - standard of care for refractory
GPA
• Anti–TNF-α agents has been tried

30. Treatment of EGPA
• Systemic glucocorticoids are the cornerstone
of therapy
• Cyclophosphamide added to glucocorticoids
for remission induction
• Refractory disease - interferon-α therapy

31. GPA
EGPAMPA
Necrotizing Granuloma
Hypereosinophilia
•Sinusitis
•Subglottic stenosis
•Pulmonary nodules
•Orbital pseudotumor
•Glomerulonephritis
•c-ANCA +
•Asthma
•Pulmonary infiltrates
•Mononeuritis multiplex
•Myocarditis
•p-ANCA +
•Pulmonary capillaritis
•Glomerulonephritis
•Gastrointestinal involvement
•Asthma and sinusitis are rare

32. THANK YOU !