Pulmonary Vasculitis | Jindal Chest Clinic

Overview on "Pulmonary Vasculitis" including its: symptoms, diagnosis, pathology, risk factors, management, treatment, etc. For more information, please contact us: 9779030507.

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

2. Clinicallydiversedisordersofunknown(known)
aetiologiescharacterizedbyinflammation(andnecrosis)
ofdifferentsizedbloodvessels(inthelungs)
PULMONARY VASCULITIS

3. PATHOLOGY
•Inflammationandnecrosisofalllayers–secondary
thrombosis
•Inflammatorycells
Leucocytoclastic–Neutrophilicpredominance
Granulomatous –Lymphocyticpredominance
•Site:Bronchocentric
Angiocentric–Involvementofvesselsofall
sizes

4. PATHOGENESIS
Unknown#?Ethnicpredispositions
A.Immunopathogenesis
•Pathogenicautoantibodies:ANCARhfactor,Cryoglobulinaemia
Hyperglobulinaemia,Hypocomplementaemia
•Immunecomplexdeposition–TypeIIIreaction
Antigens?:StreptococcalMprotein
HepatitisBsurfaceantigenMycotuberculosis
B.Bloodvesselpredisposition
•Localvasodilatation
•Increasedvascularpermeability

5. VASCULAR MANIFESTATIONS
A.Medium/Largevesselinvolvement
Infarction,Necrosis
EndOrgandysfunction
B.Smallvesselinvolvement(capillaries,arterioles,
venules)
Lossofvascularintegrity
Leakageofblood(DAH)

6. A.Distinct Clinicomorphologicalsyndromes of unknown etiology. Lung
involvement invariable
1.Wegener’s Granulomatosis(WG) 6. Takayasu’saortoarteritis
2.Churg-Strauss Syndrome (CSS) 7. Sarcoidosis
3.Lymphomatoidgranulomatosis(LYG) 8. Goodpasture’ssyndrome
4.Necrotisingsarcoidgranulomatosis(NSG)9. Primary pulmonary
5.Bronchocentricgranulomatosis(BG) hypertension
B. Distinct Clinical Syndromes of Nonspecific arteritis, etiology
unknown. Lung involvement variable
1.Henoch-Schonleinpurpura 6. Behcet’sdisease
2.Rheumatoid arthritis 7. Mixed cryoglobulinemia
3.Systemic lupus erythematosus 8. Giant cell arteritis
4.Progressive systemic sclerosis 9. Extrinsic alveolitis
5.Sjogren’ssyndrome 10. Miscellaneous*
*For complete list consult Strauss et al.
Pulmonary Vasculitis
A proposed Classification

7. Pulmonary Vasculitis
A proposed Classification
C.Pulmonaryvasculitisduetoinfection
1.Causeidentifiableathistology
•Bacterial:Tuberculosis,syphilis,atypicalmycobacteria
•Fungal:Aspergillosis,mucormycosis,histoplasmosis,others
•Parasitic:ascariasis,filariasis
2.Nonspecifichistology
•Bacterial (streptococcal,staphylococcal,gonococcal,
meningococcal)
•Septicemia,infectiveendocarditis
D.Overlapsyndromes
1.AandA,AandB,orBandB.Polyangiitisoverlapsyndrome
2.Bronchocentricgranulomatosis(BG)AandBorAandC
3.InfectionineithergroupAorBdisease
4.GroupAorBdiseasedevelopinginapatientwithgroupCdisease

8. Infective vasculitis

9. Fungal Pulmonary Vasculitis at Necropsy:
Potential Predisposing Factors in 23 patients
Aspergillosis 19
Renalfailures 8
Crescenticnephritis 2
Acutetubularnecrosis 5
Amyloidosis 1
Hepaticfailure 3
Fulminanthepatitis 2
Reye’ssyndrome 1
Septicemia 2
Colitis 4
Ulcerativecolitis 1
Pseudomembranous 1
Ischemic 1
Shigellosis 1
Neoplasia 2
Immunedeficiency 2
Normal 2
Mucormycosis 4
Renalfailure 3
Chronicnephritis 2
Amyloidosis 1
Normal 1
Bamberyetal1987

10. Pulmonary mucormycosis

11. Severe Sepsis
Purpura fulminans

13. Community-acquired
pneumonia

18. Pulmonary vasculitides
A.Lungasthemajorsite
WG,C-SS,NSG,LAG
B.Lungsindisseminatddisease
HSS,BD,GCA,SVV,PAN,Takayasu,
Cryoglobulinemia
C.Limitedlunginvolvement
CTD(RA,SLE,PSS),Sarcoidosis,EosinophilicPn.,
H.Pn.,Drugs,IBD,Infectioussyndromes

19. ANCA –Associated Vasculitides
•Wegener’sGranulomatosis
•AllergicGranulomatosisandAngiitis
-TheChurg-StraussSyndrome
•MicroscopicPolyangiitis
•Pauci-immuneGlomerulonephritis

20. Non-ANCA Vasculitides
•Behcet’sDisease
•Takayasu’sArteritis
•SarcoidosisandNecrotizing
•SarcoidGranulomatois

21. SYMPTOMS & SIGNS
A.Leukocytoclasticvasculitis
Fever,Malaise
Arthralgia
Skinlesions:Purpura,Bullae
Raynaud’sphenomenon
B.Granulomatousvasculitis
Dyspnoea,cough,haemoptysis
Upperairways:Nasalerosions
Iritis
Oralandgenitalulcers

22. DIAGNOSIS
1.Clinical
2.Haematological:RaisedESR,Leucocytosis,Eosinophilia
3.Serological:Hyperimmunoglobulinaemia
Decreaseincomplement/component
Circulatingimmunecomplexes
Rhfactor,ANF,ANCA
4.Radiological
5.PulmonaryFunctionTests
6.Histological:Biopsyofskin,kidney,lung,Temporalartery

23. Wegener’s Granulomatosis
Aclinicalsyndromeofnecrotizing
granulomatousvasculitis…..
Wegener1936,(Klinger1931)

24. Pathology / Pathogenesis
ANCAassociatedsmallvesselvasculitiswithpredilectionforupper
RT,lungs,kidneys
•Necrosis
•Granulomatousinflammation
•Vasculitis
•Microabscesses
•ScatteredMNgiantcellsinahighlyinflam.background
(YiandColby2001)

25. PATHOGENESIS
•ANCA
•Otherautoantibodies
Primingbyinflam.cytokines
Activation
Leucocytes&Monocytes
Degranulation
ROS,Cytokines
Damage
EndothelialCells
(Hewinsetal2000)

26. Is WG and Autoimmune Disease?
•Strongandspecificassociationwithantibodiesagainst
proteinase3
•ABtitrescorrelatewithclinicaldiseaseactivityand
predictrelapse
•Favourableresponsetoimmuno-suppressivetreatment
(Hewinsetal2000)

27. Diagnosis
1.Clinical
2.Radiological
3.Bronchoscopy
4.C-ANCApositivity
5.Histopathology

28. Organ involvement
•ELKsyndrome
Ear,nose,throat
Lungs
Kidneys
•Multisystem:Joints,skin,eyes,CNS
•“LimitedWG”:Lungs
•Rare:GIT,CVS

29. Wegener’s 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
Bamberyet al, 1991

30. Clinical Features: NIH Cohort
158 pts; Followed for 20 yrs.
1.UpperRespirTract:Sinusitis,nasalobst,otitismedia,deafness,
orallesions
2.Lungs(85%):Cough,haemoptysis,pleuritis
3.Glomerulonephritis(77%)
4.Eyes(52%):Conjunctivitis,scleritis,dacryocystitis,iritis,retinitis
,proptosis,diplopia,eyepain
5.Nonspecific:Arthralgias,myalgias,fever,wt.loss,skinlesions
(Hoffmanetal1992)

31. Wegener’s 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
Bamberyet al, 1991

32. WG (India): Clinical Features
Singhetal Bamberyetal
(13) (18)
M:FRatio 1.1:1 1:1
Age(Mean)Yrs 30.2 41.5
Duration(Mean)Mo. 7.1 8.0
Constitutional - 89%
UpperResp.tract 100% 55%
Ear 0 28%
Lungs 100% 78%
Eye 44% 39%
Kidneys 77% 39%
Joints 100% 55%
Skin 38% 39%
CNS 23% 28%
(JAPI1992)

34. Wegener’s Granulomatosis Versus Tuberculosis
WG Tuberculosis
Clinical course at presentation
Long standing progressive + +
Short fulminantfatal ++ (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 + +

35. Wegener’s Granulomatosis Versus Tuberculosis
WG Tuberculosis
Nervous system Nerve palsies Meningitis
Skin vasculitisand 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

36. WG: Unusual Presentations
•Gut: Abdpain
•Heart: Pericarditis
Cardiacarteritis
•Blindness
(WattRA2000)

40. Wegener’s granulomatosis

41. c-ANCA Positivity
•ActiveWG:80-90%
•Limitedactive: 55-66%
•MostcommonlyagainstPR3
•Otherconditions:Systemicvasculitides
-Autoimmunehepatitis
-Sclerosingcholangitis
-Infections,malignancies
-IBD,rheumaticautoimmunedis.
(Schnabeletal1996)

42. Other Vasculitides
Disorder Histology Clinical Features
Respir KidneysOthers
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 GMConfluent granu.
Minimal necrotic
vasculitis
Lower Nil Benign
4.Bronchocentric
Granulomatosis
Infiltration,
Ulceration
Destruction
Lower Nil Asthma
Aspergilosis
5.Leukocytoclastic
vasculitis
Neutrophilic
systemic dis.
Poststreptococcal/M
TB/Hepatitis B
FrequentRare Purpura, Eye,
Joints, GIT,
CNS

43. 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+
•Mononeuritismultiplex 2+ 3+ 1+
•Eye 2+ 0 1+
•Joints 2+ 2+ 2+
•Cardiac +/- 2+ +/-
DeRemee(In Fishman 1998)

44. Churg-Strauss Syndrome

45. Vasculitides Associated with
Pulmonary Artery Aneurysms
•Behcet’sdisease
•Takayasu’sarteritis
•Giantcellarteritis
•Unclassified

46. Diffuse Pulm (Alveolar) Haemorrhage
•Antibasementmembantibodydis(Goodpasture’ssyndrome)
•ANCAmediatedvasculitides
•IdiopathicrapidlyprogressiveGN
•CTDs(SLE,PSS)
•Immunocompromise(AIDS,BMT)
•Exogenousagents/drugs(isocyanates,D-penicillamine,cocaine,
anhydrides)

47. Patchy GGO, ANF, ANCA, GBM negative
Idiopathic pulmonary hemosiderosis

48. Isolated
eosinophilic
pleural effusion
ANF, ANCA-
negative

49. TREATMENT
•Leucocytoclastic–Oftenselflimiting
•Corticosteroids
Allergicgranulomatosis&angiitis
Necrotizingsarcoidgranulomatosis
Bronchocentricgranulomatosis
Eosinophilia-myalgiasyndrome
Giantcellarteritis
•Cytotoxic(with/withoutCS)
FailuretorespondtoCSesp.whenlungandrenalinvolvement
Wegener’sgranulomatosis
PAN,CTDsandothers

50. Induction
•Corticosteroids+Cyclophosphamide
•Cyclophosphamidealone
•Antilymphocyticmonoclonalantibodies
Maintenance
•Methotrexate
•Azathioprine,others
•Trimethoprim–sulphamethoxazole(LimitedWG)
TREATMENT

51. Novel Therapies
•Transplantimmunosuppressives (Cyclosporin,tacrolimus,
mycophenolate)
•Plasmapheresis
•Antilymphocyticmonoclonalantibodies
•TNFinhibitor:etanercept
(Thomas-Golbanovetal2001)

53. Osler-Weber-Rendu
disease

54. Pulmonary thromboembolism

55. THANK YOU