The document discusses various types of vasculitis affecting the lungs, including large, medium, and small vessel vasculitis, detailing classification, clinical features, diagnosis, and management strategies. It emphasizes autoimmune conditions like Granulomatosis with Polyangiitis, Churg-Strauss Syndrome, Anti-GBM disease, and other related pulmonary eosinophilia syndromes. Key clinical manifestations include respiratory issues, renal failure, and systemic symptoms, along with treatment options ranging from immunosuppression to plasmapheresis.

1. Vasculitis and Lungs
Dr P Mayurathan
MBBS (Jaffna), MD in Medicine (Colombo), MRCP (UK), FRCP (London), FRCP (Edinburgh)
Senior Lecturer in Medicine, FHCS
Consultant Physician in Internal Medicine

2. • Defined as inflammation of blood vessel
• Multisystem disorders

3. 1. Large vessel vasculitis
2. Medium vessel vasculitis
3. Small vessel vasculitis
– ANCA positive vasculitis
– ANCA negative vasculitis
Classification of Vasculitis

4. Classification of Vasculitis
Small vessel vasculitis

6. ANCA (AntiNeutrophil Cytoplasmic Antibody )
• ANCAs are autoantibodies directed against proteins in the
cytoplasmic granules of neutrophils
• Targeting mainly at proteinase 3 (PR3) and myeloperoxidase (MPO)
expressed by innate immune cells
• c-ANCA (cytoplasmic antineutrophil cytoplasmic antibody)
– directed against PR3
• p-ANCA (perinuclear staining antineutrophil cytoplasmic antibody)
– specific for myeloperoxidase (MPO)

8. Wegener’s Granulomatosis (WG) OR
Granulomatosis with Polyangiitis (GPA)
• Systemic autoimmune disorder of unknown etiology
• Involves the formation of necrotizing granulomas and inflammation
of blood vessels (vasculitis)
• The vasculitis affects small- and medium-size vessels in many organs
• Most commonly affects the upper respiratory tract, lungs and
kidneys

10. Clinical Features
Non-specific constitutional complaints:
• Fevers
• Night sweats
• Fatigue (lethargy)
• Loss of appetite
• Weight loss

11. Respiratory Manifestations:
• Rhinitis
• Epistaxis
• Recurrent sinusitis
• Cough
• Pulmonary infiltrates (Migratory)
• Hemoptysis
• Chest discomfort
• Dyspnea
• Diffuse alveolar hemorrhage due to alveolar capillaritis
Clinical Features
Recurrent URT symptoms

12. Renal manifestations:
• Haematuria
• Proteinuria
• Crescentic necrotizing glomerulonephritis (RPGN – Rapidly
proliferative glomerulonepritis)
• Renal failure
Clinical Features

13. Clinical Features
Ophthalmic manifestations:
• Conjunctivitis
• Episcleritis
• Uveitis
• Optic nerve vasculitis
• Retinal artery occlusion

14. Neurological Manifestations:
• Mononeuritis multiplex
• Sensorimotor polyneuropathy
• Cranial nerve palsies
Clinical Features

15. Musculoskeletal:
• Myalgia
• Arthralgia
• Arthritis
Clinical Features

16. Cutaneous findings:
• Palpable purpura or skin ulcers
• Ulcerations may resemble pyoderma gangrenosum
• Petechiae
• Vesicles
• Pustules
• Hemorrhagic bullae
• Livedo reticularis
Clinical Features

17. Diagnosis
• Abnormal kidney function tests and urinalysis (high BU, Cr,
Haematuria, proteinuria and red cell cast)
• Elevated inflammatory markers (ESR, CRP)
• c-ANCA directed against PR3 is most specific for GPA (Some patients
with GPA can have positive p-ANCA)
• CXR and CT scanning
– The most common radiologic findings are single or multiple
nodules and masses
– Nodules are typically diffuse, and approximately 50% are
cavitatory lesions
– The shadows may be migratory in nature

18. • Sinus CT scanning: To evaluate sinus disease
• Spirometry – Restrictive lung disease with high DLCO commonly due
to pulmonary haemorrhage
• Bronchoscopy: Helpful in the evaluation of alveolar hemorrhage,
infection, airway disease, and endobronchial lesions
• Biopsy: The diagnosis of GPA is generally confirmed with tissue
biopsy from a site of active disease; renal and lung biopsies are most
specific for GPA
Diagnosis

19. Management
• Steroids – Prednisolone
• Cyclophosphamide
• Rituximab
• Methotrexate
• Plasma exchange may be considered in patients with RPGN

20. Churg-Strauss Syndrome (CSS) OR
Eosinophilic Granulomatosis with Polyangiitis (EGPA)

21. Churg-Strauss Syndrome (CSS) OR
Eosinophilic Granulomatosis with Polyangiitis (EGPA)
• Characterized by necrotizing vasculitis of small and medium-sized
systemic blood vessels
• Same type of vasculitis can be seen in granulomatosis with polyangiitis
(GPA), microscopic polyangiitis (MPA) and polyarteritis nodosa (PAN)
• The classic distinction of CSS/EGPA from the other diseases in the
category is the coexistence of asthma, rhinosinusitis and presence of
peripheral eosinophilia

22. Diagnostic Criteria
• 4 out of 6 features needed for confirmation
1. Asthma
2. Migratory infiltrates in lung
3. Paranasal sinus abnormalities
4. Mono or polyneuropathy
5. Peripheral blood eosinophilia (greater than 10% total
leucocyte count)
6. Eosinophilic tissue infiltrates in the biopsy

23. Pathophysiology
• Exact cause is unknown
• Production of p-ANCA, that attack host tissues because of
molecular mimicry or some other abnormality of immune
tolerance
• An independent or adjuvant role in this activation may be played
by tumor necrosis factor (TNF)

25. Investigations
• Eosinophilia (> 1500/µL or > 10% of total peripheral WBCs)
• Elevations of ANCA titers
– Found in 40% of cases
– Predominantly pANCAs directed against myeloperoxidase epitopes
• High ESR
• CXR/CT
– Normal or can have infiltrates
• Biopsy
– Specimens of skin, lymph nodes, lung parenchyma, or peripheral
nerve
– Demonstrate the characteristic vasculitis
– Kidney biopsy sample may show segmental necrotizing
glomerulonephritis with crescent formation in RPGN

26. Treatment
• Immunosuppression
• Plasma exchange

27. Anti-glomerular basement membrane (anti-GBM) disease
• Anti-GBM disease is an autoimmune disorder
• It is a rare disease associated with small vessel vasculitis that typically
affects the capillaries of kidneys
• Patients can develop rapidly progressive glomerulonephritis (RPGN)
• It is caused by the deposition in glomerular basement membrane of
circulating autoantibodies directed against antigens intrinsic to the
basement membrane
• The exact mechanism that induces the formation of autoantibodies is
unknown, but probably environmental factors, infections or direct damage
to kidneys and lungs
• ANCA is negative
• Goodpasture syndrome is one of the classical examples of anti-GBM
disease where kidneys and lungs are predominantly affected

28. Goodpasture Syndrome (GPS)

29. Goodpasture Syndrome
• Clinical entity of
– diffuse pulmonary hemorrhage and
– acute or rapidly progressive glomerulonephritis and
– the presence of circulating anti–glomerular basement membrane
(anti-GBM) antibodies

30. Pathophysiology
• Goodpasture syndrome is an autoimmune disorder
• Characterized by autoantibodies directed against the
glomerular/alveolar basement membrane
• The autoantibodies bind to their reactive epitopes in the basement
membranes and activate the complement cascade, resulting in tissue
injury
• The principal component of basement membrane is type IV collagen

31. Pathophysiology
alveolar basement
membrane
OR

32. Clinical Features
• Constitutional symptoms
– Malaise
– Chills
– Fever
– Arthralgias
• May precede or develop concurrently with pulmonary or renal
manifestations

33. Clinical Features
Respiratory manifestations:
• Hemoptysis
– Presenting symptom when the disease affects the lungs
– The level of hemoptysis may vary and may be absent
• Cough
• Shortness of breath
• Massive pulmonary hemorrhage leading to respiratory failure may
occur
• Pleuritic chest pain is present in less than half of the patients

34. Clinical Features
Renal manifestations:
• Hematuria
• Proteinuria
• Oedema
• High blood pressure
• Uremia

35. Investigations
• Urinalysis - low-grade proteinuria, gross or microscopic hematuria, and red
blood cell casts
• FBC
– Anemia (iron deficiency caused by intrapulmonary bleeding)
– Leukocytosis is common
• Elevated blood urea and serum creatinine levels
• Elevation of ESR
• Anti–GBM Antibody
– Useful to confirm the diagnosis and monitor the efficacy of treatment
– ELISA for anti-GBM antibodies are highly sensitive (>95%) and specific (>97%)

36. • CXR
– Patchy parenchymal consolidations, which are usually bilateral,
symmetric perihilar and bibasal
• Spirometry
– May reveal evidence of restriction
– DLCO is elevated secondary to pulmonary hemorrhage
• Biopsy
– Renal biopsy
Investigations

37. Management
• Plasmapheresis (therapeutic plasma exchange – TPE)
– Rapidly remove circulating antibody
• Stop further production of antibodies using immunosuppression
with medications

38. Non-Vasculitic Lung conditions

39. Pulmonary Eosinophilia
• Pulmonary diseases associated with tissue and/or blood eosinophilia
• Extrinsic or intrinsic in origin (some syndromes may overlap)
• Inhaled or ingested extrinsic factors
– Medications
– Infectious agents (eg, parasites, fungi, mycobacteria)
• Intrinsic pulmonary eosinophilic syndromes are generally idiopathic in nature
– Trophical Pulmonary Eosinophilia (TPE)
– Churg-Strauss Syndrome (CSS)
– Chronic Eosinophilic Pneumonia (CEP)
– Idiopathic Hypereosinophilic Syndrome (IHES)
– Eosinophilic granuloma (eg, pulmonary histiocytosis X or Langerhans cell
granulomatosis)
• Eosinophilia and pulmonary infiltrates have been reported in patients with AIDS,
lymphoma, a variety of inflammatory lung diseases and collagen vascular diseases
• Asthma may manifest with eosinophilia without infiltrates

40. Tropical Pulmonary Eosinophilia (TPE)
• Characterized by coughing, asthmatic attacks, and an enlarged spleen
• It occurs most frequently in tropical and subtropical areas like India and Southeast
Asia
• Tropical pulmonary eosinophilia is a rare, but well recognized
• Syndrome characterized by pulmonary interstitial infiltrates and marked peripheral
eosinophilia
• In non-endemic countries, patients are commonly thought to have bronchial
asthma
• The syndrome is caused by a distinct hypersensitive immunological reaction to
microfilariae of Wuchereria bancrofti and Brugia malayi

41. Microfilariae
Wuchereria bancrofti Brugia malayi

42. Clinical Presentation
• Persistent or recurrent cough that gets aggravated at night
• Rarely haemoptysis
• Wheeze
• Weakness
• Weight loss
• Low fever
• Enlarged lymph nodes in the neck and elsewhere
• Splenomegaly

43. Diagnosis
• The diagnostic criteria
– a history supportive of exposure to lymphatic filariasis
– a peripheral eosinophilia count greater than 3 × 109/L)
– an elevated serum IgE levels (> 1000 kU/L);
– increased titers of antifilarial antibodies
– peripheral blood negative for microfilariae
– a clinical response to diethylcarbamazine (DEC)

44. • High antifilarial IgG titers to microfilariae often result in cross
reactivity with other non-filarial helminth antigens (strongyloides and
schistosoma antigens)
• It is important to exclude other parasitic infections before tropical
pulmonary eosinophilia is diagnosed by serological tests
• Radiological findings are nonspecific (normal CXR in up to 20%)
• Lung biopsy is not part of the routine diagnostic investigation
Diagnosis

45. Treatment
• The dramatic response to Diethylcarbamazine (6 mg/kg/day in 3
divided doses for 21 days)
• The eosinophil count often falls dramatically within 7–10 days of
starting treatment