Pulmonary Vasculitis | Jindal Chest Clinic

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PULMONARY VASCULITIS
S. K. Jindal Department of Pulmonary
Medicine Postgraduate Institute of Medical
Education and Research Chandigarh, India
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PULMONARY VASCULITIS

• Clinically diverse disorders of unknown (known)
  aetiologies characterized by inflammation (and
  necrosis) of different sized blood vessels (in
  the lungs)

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PATHOLOGY

• Inflammation and necrosis of all layers
  secondary thrombosis
• Inflammatory cells
• Leucocytoclastic Neutrophilic predominance
• Granulomatous Lymphocytic predominance
• Site Bronchocentric
• Angiocentric Involvement of vessels of all
  sizes

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PATHOGENESIS

• Unknown ? Ethnic predispositions
• Immunopathogenesis
• Pathogenic autoantibodies ANCARh factor,
  Cryoglobulinaemia
• Hyperglobulinaemia, Hypocomplementaemia
• Immune complex deposition Type III reaction
• Antigens ? Streptococcal M protein
• Hepatitis B surface antigen
  Mycotuberculosis
• Blood vessel predisposition
• Local vasodilatation
• Increased vascular permeability

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VASCULAR MANIFESTATIONS

• Medium/Large vessel involvement
• Infarction, Necrosis
• End Organ dysfunction
• Small vessel involvement (capillaries,
  arterioles, venules)
• Loss of vascular integrity
• Leakage of blood (DAH)

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Pulmonary VasculitisA proposed Classification

• Distinct Clinicomorphological syndromes of
  unknown etiology. Lung involvement invariable
• Wegeners Granulomatosis (WG) 6. Takayasus
  aortoarteritis
• Churg-Strauss Syndrome (CSS) 7. Sarcoidosis
• Lymphomatoid granulomatosis (LYG) 8.
  Goodpastures syndrome
• Necrotising sarcoid granulomatosis (NSG) 9.
  Primary pulmonary
• Bronchocentric granulomatosis (BG)
  hypertension
• B. Distinct Clinical Syndromes of Nonspecific
  arteritis, etiology unknown. Lung involvement
  variable
• Henoch-Schonlein purpura 6. Behcets disease
• Rheumatoid arthritis 7. Mixed cryoglobulinemia
• Systemic lupus erythematosus 8. Giant cell
  arteritis
• Progressive systemic sclerosis 9. Extrinsic
  alveolitis
• Sjogrens syndrome 10. Miscellaneous
• For complete list consult Strauss et al.

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Pulmonary VasculitisA proposed Classification

• Pulmonary vasculitis due to infection
• Cause identifiable at histology
• Bacterial Tuberculosis, syphilis, atypical
  mycobacteria
• Fungal Aspergillosis, mucormycosis,
  histoplasmosis, others
• Parasitic ascariasis, filariasis
• Nonspecific histology
• Bacterial (streptococcal, staphylococcal,
  gonococcal, meningococcal)
• Septicemia, infective endocarditis
• Overlap syndromes
• A and A, A and B, or B and B. Polyangiitis
  overlap syndrome
• Bronchocentric granulomatosis (BG) A and B or A
  and C
• Infection in either group A or B disease
• Group A or B disease developing in a patient with
  group C disease

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Infective vasculitis
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Fungal Pulmonary Vasculitis at Necropsy
Potential Predisposing Factors in 23 patients

• Aspergillosis 19
• Renal failures 8
• Crescentic nephritis 2
• Acute tubular necrosis 5
• Amyloidosis 1
• Hepatic failure 3
• Fulminant hepatitis 2
• Reyes syndrome 1
• Septicemia 2
• Colitis 4
• Ulcerative colitis 1
• Pseudomembranous 1
• Ischemic 1
• Shigellosis 1
• Neoplasia 2
• Immune deficiency 2
• Normal 2
• Mucormycosis 4
• Renal failure 3

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Pulmonary mucormycosis
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Severe Sepsis Purpura fulminans
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Community-acquired pneumonia
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Pulmonary vasculitides

• A. Lung as the major site
• WG, C-SS, NSG, LAG
• B. Lungs in disseminatd disease
• HSS, BD, GCA, SVV, PAN, Takayasu,
  Cryoglobulinemia
• C. Limited lung involvement
• CTD (RA, SLE, PSS), Sarcoidosis, Eosinophilic
  Pn., H. Pn., Drugs, IBD, Infectious syndromes

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ANCA Associated Vasculitides

• Wegeners Granulomatosis
• Allergic Granulomatosis and Angiitis
• - The Churg-Strauss Syndrome
• Microscopic Polyangiitis
• Pauci-immune Glomerulonephritis

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Non-ANCA Vasculitides

• Behcets Disease
• Takayasus Arteritis
• Sarcoidosis and Necrotizing
• Sarcoid Granulomatois

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SYMPTOMS SIGNS

• Leukocytoclastic vasculitis
• Fever, Malaise
• Arthralgia
• Skin lesions Purpura, Bullae
• Raynauds phenomenon
• Granulomatous vasculitis
• Dyspnoea, cough, haemoptysis
• Upper airways Nasal erosions
• Iritis
• Oral and genital ulcers

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DIAGNOSIS

• Clinical
• Haematological Raised ESR, Leucocytosis,
  Eosinophilia
• Serological Hyperimmunoglobulinaemia
• Decrease in complement/component
• Circulating immune complexes
• Rh factor, ANF, ANCA
• Radiological
• Pulmonary Function Tests
• Histological Biopsy of skin, kidney, lung,
  Temporal artery

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Wegeners Granulomatosis

• A clinical syndrome of necrotizing
• granulomatous vasculitis..
• Wegener 1936, (Klinger 1931)

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Pathology / Pathogenesis

• ANCA associated small vessel vasculitis with
  predilection for upper RT, lungs, kidneys
• Necrosis
• Granulomatous inflammation
• Vasculitis
• Micro abscesses
• Scattered MN giant cells in a highly inflam.
  background
• (Yi and Colby 2001)

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PATHOGENESIS

• ANCA
• Other auto antibodies
• Priming by inflam. cytokines
• Activation
• Leucocytes Monocytes
• Degranulation
• ROS, Cytokines
• Damage
• Endothelial Cells
• (Hewins et al 2000)

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Is WG and Autoimmune Disease?

• Strong and specific association with antibodies
  against proteinase 3
• AB titres correlate with clinical disease
  activity and predict relapse
• Favourable response to immuno-suppressive
  treatment
• (Hewins et al
  2000)

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Diagnosis

1. Clinical
2. Radiological
3. Bronchoscopy
4. C-ANCA positivity
5. Histopathology

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Organ involvement

• ELK syndrome
• Ear, nose, throat
• Lungs
• Kidneys
• Multisystem Joints, skin, eyes, CNS
• Limited WG Lungs
• Rare GIT, CVS

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Wegeners Granulomatosis Extent of Disease at
Diagnosis (ELK System) ()
Extent Deremee (n 50) Gross (n 46) Bambery (n 15)
E alone 28 59 0
L alone 16 13 0
EL 16 13 20
EK 8 4 7
LK 10 4 20
ELK 22 7 53
Bambery et al, 1991 Bambery et al, 1991 Bambery et al, 1991 Bambery et al, 1991
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Clinical Features NIH Cohort158 pts Followed
for 20 yrs.

• Upper Respir Tract Sinusitis, nasal obst, otitis
  media, deafness, oral lesions
• Lungs (85) Cough, haemoptysis, pleuritis
• Glomerulo nephritis (77)
• Eyes (52) Conjunctivitis, scleritis, dacryo
  cystitis, iritis, retinitis ,proptosis, diplopia,
  eye pain
• Nonspecific Arthralgias, myalgias, fever, wt.
  loss, skin lesions
• 
  (Hoffman et al 1992)

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Wegeners Granulomatosis in Indians Clinical
features and outcome in 15 patients
Pulmonary Other
Cough 80 Constitutional 86
Hemoptysis 46 Arthralgia 53
Pain 40 Nose 53
Consolidation 33 Sinuses 46
Effusion 33 Eye 46
Hemorrhage 13 Skin 46
Radiology Renal 40
Infiltrates 80 Ear 33
Cavities 60 Outcome
Nodules 60 Alive (32-78 months) 33
Consolidation 46 Dead 53
Pericardial effusion 20 Lost 14

Bambery et al, 1991 Bambery et al, 1991 Bambery et al, 1991 Bambery et al, 1991
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WG (India) Clinical Features

• Singh et al Bambery et al
• (13) (18)
• MF Ratio 1.1 1 1 1
• Age (Mean) Yrs 30.2 41.5
• Duration (Mean) Mo. 7.1 8.0
• Constitutional - 89
• Upper Resp. tract 100 55
• Ear 0 28
• Lungs 100 78
• Eye 44 39
• Kidneys 77 39
• Joints 100 55
• Skin 38 39
• CNS 23 28
• (JAPI 1992)

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Wegeners Granulomatosis Versus Tuberculosis
WG Tuberculosis
Clinical course at presentation
Long standing progressive
Short fulminant fatal (bleeding)
Clinical features
Fever, constitutional symptoms
Cough, sputum (hemoptysis) (frank) (streaky)
Consolidation Rare
Pleural effusion (large) -
Chest radiology
Infiltrates Mid zone Apical
Nodularity Large Small
Cavities Mid-lower zone Upper zone
Parenchymal nodules Common Rare
Shifting shadows -
Sinusitis, saddle nose, epistaxis Common Rare
Eye disease Common (50) Rare (2)
Proptosis, scleritis, vasculitis -
Uveitis
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Wegeners Granulomatosis Versus Tuberculosis
WG Tuberculosis

Nervous system Nerve palsies Meningitis
Skin vasculitis and gangrene -
Skin nodules
Lymphadenopathy Rare Common
Joint pains
Arthritis -
Heart Arteritis Pericarditis
Renal lesions Common, 40-80 Rare, 5
Glomerulonephritis -
Renal failure Common Very rare
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WG Unusual Presentations

• Gut Abd pain
• Heart Pericarditis
• Cardiac arteritis
• Blindness
• 
  (Watt RA 2000)

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Wegeners granulomatosis
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c-ANCA Positivity

• Active WG 80-90
• Limited active 55-66
• Most commonly against PR3
• Other conditions Systemic vasculitides
• - Autoimmune hepatitis
• - Sclerosing cholangitis
• - Infections, malignancies
• - IBD, rheumatic autoimmune dis.
• (Schnabel
  et al 1996)

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Other Vasculitides
Disorder Histology Clinical Features Clinical Features Clinical Features
Disorder Histology Respir Kidneys Others
1. Lymphomatoid Granulomatosis Angiocentric angiodestructive Lower Upper Rare CNS Lymphomas
2. AGA (Churg Strauss Synd) Granulomatosis extravasc. Necrotizing Lower Upper Rare Asthma Eosinophilia
3. Necrotizing sarcoid GM Confluent granu. Minimal necrotic vasculitis Lower Nil Benign
4. Bronchocentric Granulomatosis Infiltration, Ulceration Destruction Lower Nil Asthma Aspergilosis
5. Leukocytoclastic vasculitis Neutrophilic systemic dis. Poststreptococcal/MTB/Hepatitis B Frequent Rare Purpura, Eye, Joints, GIT, CNS
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CLINICAL FEATURES
WG CSS MPA
Asthma 0 4 0
Eosinophilia (blood, tissue) /- 4 0
Allergy history 0 4 0
UR Tract 3 2 0
LR Tract 3 3 1
G.N. 2 1 4
Skin lesion 2 3 2
Mononeuritis multiplex 2 3 1
Eye 2 0 1
Joints 2 2 2
Cardiac /- 2 /-
DeRemee (In Fishman 1998) DeRemee (In Fishman 1998) DeRemee (In Fishman 1998) DeRemee (In Fishman 1998)
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Churg-Strauss Syndrome
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Vasculitides Associated with Pulmonary Artery
Aneurysms

• Behcets disease
• Takayasus arteritis
• Giant cell arteritis
• Unclassified

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Diffuse Pulm (Alveolar) Haemorrhage

• Antibasement memb antibody dis (Goodpastures
  syndrome)
• ANCA mediated vasculitides
• Idiopathic rapidly progressive GN
• CTDs (SLE, PSS)
• Immunocompromise (AIDS, BMT)
• Exogenous agents/drugs (isocyanates,
  D-penicillamine, cocaine, anhydrides)

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Patchy GGO, ANF, ANCA, GBM negative Idiopathic
pulmonary hemosiderosis
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Isolated eosinophilic pleural effusion ANF,
ANCA- negative
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TREATMENT

• Leucocytoclastic Often self limiting
• Corticosteroids
• Allergic granulomatosis angiitis
• Necrotizing sarcoid granulomatosis
• Bronchocentric granulomatosis
• Eosinophilia-myalgia syndrome
• Giant cell arteritis
• Cytotoxic (with/without CS)
• Failure to respond to CS esp. when lung and
  renal involvement
• Wegeners granulomatosis
• PAN, CTDs and others

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TREATMENT

• Induction
• Corticosteroids Cyclophosphamide
• Cyclophosphamide alone
• Anti lymphocytic monoclonal antibodies
• Maintenance
• Methotrexate
• Azathioprine, others
• Trimethoprim sulphamethoxazole (Limited WG)

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Novel Therapies

• Transplant immunosuppressives (Cyclosporin,
  tacrolimus, mycophenolate)
• Plasmapheresis
• Anti lymphocytic monoclonal antibodies
• TNF inhibitor etanercept
• 
  (Thomas-Golbanov et al 2001)

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Osler-Weber-Rendu disease
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Pulmonary thromboembolism
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