PulmonaryDiseaseinVasculitisAshley Henderson, MDAssociate ProfessorUNC Pulmonary/Critical Care

Vasculitides thatfrequentlyaffectthelung(Large vessels: aorta &  its largest branches)Medium‐sized vessels: main visceral arteries (eg, renal, hepatic, coronary, mesenteric);Small vessels: capillaries, venules, & arterioles.

Castaner, E et al, Radiographics 2010; 30:33‐53

CASE 1

27 y/o female with no past medical history presents with 1 month history of leg pain, a rash, and fatigue; now with a 2d history of hemoptysis

Exam95% on 5L O2Diffuse bilateral lung cracklesSkin with non‐blanching erythematous 

papular lesions on LE, abdomen, flank, some UE

1 month ago presentation

Creatinine 1.55 2.1

Hgb ?  9.68.4

PT/PTT 12/24.5

U/A 2+ prot, 3+ blood, 81 RBCs

ESR 41

ANCA PR3‐ANCA+

Labs

Patient’s Chest Xray Normal Chest Xray

Patient’sChest CT

• DAH (Diffuse alveolar hemorrhage) Pulmonary renal 

syndromes Coagulopathies Heart Failure DAD/ARDS Connective Tissue Dz Emboli Malignancies Drugs Radiation

• Pneumonia/Abscess• Pulmonary Embolism• Airway lesions• Bronchiectasis• Malignancy• Foreign Body• Trauma• Drugs• Connective Tissue Disease

WhatCausesHemoptysis?

Pulmonary Renal Syndrome

Renal failure with respiratory failure, associated with glomerulonephritis and diffuse alveolar hemorrhage secondary to an underlying autoimmune process

DIFFERENTIAL DIAGNOSIS OF PRS

• Pulmonary edema with CHF on anticoagulants• Malignant hypertension with renal and cardiac failure• Infectious diseases• Sepsis from pneumonia and subsequent renal impairment• Drug‐induced (cocaine)

Postgrad Med J 2013: 89: 274‐283

Case 2

60 y/o female with history of vocal cord dysfunction, anxiety• Presents with progressive dyspnea

CASE 2

Physical Exam• O2 saturations 96% on RA• Stridor on exam• No rashes, No edema

Case 2

Case 2

Case 2

LABS/DATA• MPO‐ANCA +

• CBC, Chemistries normal• Normal urine sediment• PFTs obstructed

Case 2

LABS/DATA—4mo after presentations/p cyclophosphamide and prednisone

Cr 0.71 (up from 0.5)Urine dip 2+ bloodMicroscopic exam with 5‐10 RBCs/hpf

15% dysmorphic

PFTs still obstructed

How Small Vessel Vasculitis Presents Radiologically

Nodules (all sizes)

Masses and Consolidation

Cavitary Lesions

Alveolar Infiltrates

Pleural effusions

Am J Roentgenol 192: 676‐682, 2009

How Small Vessel Vasculitis Presents Radiologically

Cavitary lesions

Tracheal thickening

RadiographicPresentationSmallVesselVasculitides

GPA EGPA MPAMasses and Nodules 90%Pulmonary Fibrosis up to 36%Consolidation 20‐50% 90%DAH/Diffuse GGOs 10% 3‐8% 10‐36%Bronchiectasis 10‐20%Airway thickening with narrowing

15% ?due to asthma

Pleural Effusions 10‐50%

Adapted from Semin US CT MRI 33: 567‐579Vaglio, Allergy 68: 2013: 26

Bronchoscopy as a diagnostic tool

www.bronchoscopy.com

Mercydesmoines.org

BronchoscopyRisks

www.certain.com

cbsnews.com

tcmdiscovery.com

Inmagine.com

NormalAirwayLookingattheMainCarina

Bronchoscopywithhemorrhage

DiffuseAlveolarHemorrhage

GPAAirway

Differentialdiagnosisofpulmonary‐renalsyndrome

Disease  Vasculitis Granulomata ANCA status

• Granulomatosis with polyangiitis Present Present PR3‐ANCA• Microscopic polyangiitis Present Absent MPO‐ANCA

• Churg‐Strauss syndrome (EGPA) Present Present MPO‐ANCA (50%)• Goodpasture’s disease Present Absent Seldom positive

(10‐38%)

• Systemic lupus erythematosus Present Absent Seldom positive

• Henoch‐Schonlein purpura Present Absent Negative

• Behcet’s disease Present Absent Negative

• Infection Rarely present (e.g. Absent Negative subacute bacterial endocarditis)

Harper et al, Medicine: 38 (2), Feb 2010, 84‐92

RespiratoryMorbidityandMortalityinVasculitis?

OutcomeswithGPA

1992 (USA)—17% with moderate to severe progressive pulmonary insufficiency20% mortality rate

3% renal3% pulmonary1% renal + pulmonary3% infection2.5% malignancy

2006 (Sweden)—13% mortality rate at 5 years

only 14% of those related to active vasculitis41% on HD at time of deathLung disease not confirmed as an increased risk factor, except DAH

Hoffman et al, Annals of IM, 1992; 116: 488‐498Eriksson et all, JIM 265; 496‐506Hogan et al, J am Soc Nephol 1996; 7:23‐32*up to 85% develop lung disease

OutcomeswithEGPA2/3 with lung involvementMortality 3% at 5 years  (8% at 8 years)

OutcomeswithMPA29‐36% with DAH7‐36% with pulmonary fibrosisMortality with fibrosis is 40‐50% at 5 years, median survival time 80 months

Cohen et al, Arthritis Rheum 2007; 57: 686‐693Homma, Clin Exp Nephrol, 2013 17: 667‐671

OutcomesinDAHwithAAV

Survival at 1 yr Survival at 2 yr Survival at 5 yr

Laugue 82 68

Gallagher 50 36

Hruskova 58.5 (*49mo)

DAH + renal impairment predicts late mortality 1DAH higher in PR3‐ANCA 2Recurrence is 10‐31% 1,3

1 Laugue Medicine 79: 222 20002 Hruskova, Scand J Rheum 20133 Klemmer AJKD 42: 1149

Outcomes of Pulmonary Vasculitis Admitted to ICU

2

OutcomesofPulmonaryVasculitisAdmittedtoICU

HOLGUIN, FERNANDO; MD, MPH; RAMADAN, BASSEL; GAL, ANTHONY; ROMAN, JESSE

American Journal of the Medical Sciences. 336(4):321‐326, October 2008.

Table 2.  Initial Clinical Findings of Patients with ANCA‐Related Lung Disease

Length of hospital stay

2

OutcomesofPulmonaryVasculitisAdmittedtoICU

HOLGUIN, FERNANDO; MD, MPH; RAMADAN, BASSEL; GAL, ANTHONY; ROMAN, JESSE

American Journal of the Medical Sciences. 336(4):321‐326, October 2008.

UsingObjectiveMeasuresofLungDisease:Spirometry

Ref Pre Pre Post Post PostMeas % Ref Meas % Ref % Chg

FVC Liters 5.93 6.18 104 5.96 100 -4FEV1 Liters 4.90 2.01 41 1.98 40 -1FEV1/FVC % 84 33 33 FEF25-75% L/sec 5.07 0.66 13 0.73 14 11IsoFEF25-75 L/sec 5.07 0.66 13 0.78 15 18FEF50% L/sec 0.72 0.80 11PEF L/sec 10.60 3.90 37 4.33 41 11FET100% Sec 12.88 12.62 -2

PulmonaryFunctionTests:Spirometry

2 Months post‐dx

Flow‐VolumeLoops

PulmonaryFunctionTests:SpirometrywithFlowVolumeLoops

PulmonaryFunctionTestsDiffusingCapacity

Tzelepis, et al,  ERJ 2010; 36: 116‐121

PulmonaryFibrosisinMicroscopicPolyangiitis

PulmonaryFunctionTestsinGPA

Rosenberg et al, AJM, 1980, 69: 387

41% with reduced FVC55% with reduced FEV1 (“majority” not due to volume loss alone)36% had reduced TLC32% had increased RV/TLC36% had decreased DLCO

Rosenberg et al, AJM, 1980, 69: 387

PFT pattern Total Mild Moderate Severe Very Severe

Obstruction(GOLD criteria)

12 1 5 5 1

Restriction 8 2 5 1 NA

SpirometryinUNCCohortofPatientswithPulmonaryDisease

8 Subjects with normal spirometry

N FVC (L) FVC (%) FEV1 (L) FEV1 (%) FEV1/FVC (%) DLCO

Cavities / nodules

17 3.2 75.6 2.2 66.8 68.8 64.0

No cavities / nodules

11 3.0 75.0 2.1 69.9 73.7 60.3

SpirometryinUNCCohortofPatientswithPulmonaryDisease

Ref Pre Pre Post Post PostMeas % Ref Meas % Ref % Chg

FVC Liters 5.93 6.18 104 5.96 100 -4FEV1 Liters 4.90 2.01 41 1.98 40 -1FEV1/FVC % 84 33 33 FEF25-75% L/sec 5.07 0.66 13 0.73 14 11IsoFEF25-75 L/sec 5.07 0.66 13 0.78 15 18FEF50% L/sec 0.72 0.80 11PEF L/sec 10.60 3.90 37 4.33 41 11FET100% Sec 12.88 12.62 -2

Ref Pre Pre Post Post PostMeas % Ref Meas % Ref % Chg

FVC Liters 5.91 7.29 123 FEV1 Liters 4.86 4.10 84 FEV1/FVC % 83 56 FEF25-75% L/sec 4.97 2.01 40 IsoFEF25-75 L/sec 4.97 2.01 40 FEF50% L/sec 2.50 PEF L/sec 10.65 8.27 78 FET100% Sec 12.70

Spirometric Response to Therapy2 Months post‐dx

3 years post‐dx

TherapyResults

Before treatment After treatment

InConclusion

• Pulmonary vasculitis is common in AAV• Pulmonary disease can be obstructed or restricted; might be associated with type of ANCA

• Overall prognosis better with current treatments• Worse with DAH• ?worse with MPA fibrosis

• Significant amount of unknowns