Pulmonary Disease in Vasculitis Ashley Henderson, MD Associate Professor UNC Pulmonary/Critical Care

Vasculitides that frequently affect the lung (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

Exam 95% on 5L O2 Diffuse bilateral lung crackles Skin with non‐blanching erythematous  papular lesions on LE, abdomen, flank,  some UE

Labs 1 month ago

presentation

Creatinine

1.55

2.1

Hgb



9.68.4

PT/PTT

12/24.5

U/A

2+ prot, 3+ blood,  81 RBCs

ESR

41

ANCA

PR3‐ANCA+

Patient’s Chest Xray

Normal Chest Xray

Patient’s Chest CT

What Causes Hemoptysis? • 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

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 presentation s/p cyclophosphamide and prednisone Cr 0.71 (up from 0.5) Urine dip 2+ blood Microscopic exam with 5‐10 RBCs/hpf 15% dysmorphic PFTs still obstructed

How Small Vessel Vasculitis Presents Radiologically

Masses and  Consolidation

Alveolar Infiltrates

Nodules (all sizes)

Pleural effusions Am J Roentgenol 192: 676‐682, 2009

Cavitary Lesions

How Small Vessel Vasculitis Presents Radiologically

Cavitary lesions Tracheal thickening

Radiographic Presentation Small Vessel Vasculitides GPA Masses and Nodules

EGPA

MPA

90%

Pulmonary Fibrosis

up to 36%

Consolidation

20‐50%

90%

DAH/Diffuse GGOs

10%

3‐8%

Bronchiectasis

10‐20%

Airway thickening with  narrowing

15%

Pleural Effusions

10‐36%

?due to asthma 10‐50%

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

Bronchoscopy as a  diagnostic tool

www.bronchoscopy.com

Mercydesmoines.org

tcmdiscovery.com

cbsnews.com

Bronchoscopy Risks Inmagine.com

www.certain.com

Normal Airway Looking at the Main Carina

Bronchoscopy with hemorrhage

Diffuse Alveolar Hemorrhage

GPA Airway

Differential diagnosis of pulmonary‐renal syndrome Disease 

Vasculitis

Granulomata

ANCA status

• •

Granulomatosis with polyangiitis Present Microscopic polyangiitis Present

Present Absent

PR3‐ANCA MPO‐ANCA

• •

Churg‐Strauss syndrome (EGPA) Present Goodpasture’s disease Present

Present Absent

MPO‐ANCA (50%) 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. subacute bacterial  endocarditis)

Absent

Negative 

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

Respiratory Morbidity and Mortality in Vasculitis?

Outcomes with GPA 1992 (USA)— 17% with moderate to severe progressive pulmonary insufficiency 20% mortality rate 3% renal 3% pulmonary 1% renal + pulmonary 3% infection 2.5% malignancy

2006 (Sweden)— 13% mortality rate at 5 years only 14% of those related to active vasculitis 41% on HD at time of death Lung disease not confirmed as an increased risk factor, except DAH

*up to 85% develop lung disease

Hoffman et al, Annals of IM, 1992; 116: 488‐498 Eriksson et all, JIM 265; 496‐506 Hogan et al, J am Soc Nephol 1996; 7:23‐32

Outcomes with EGPA 2/3 with lung involvement Mortality 3% at 5 years  (8% at 8 years)

Outcomes with MPA 29‐36% with DAH 7‐36% with pulmonary fibrosis Mortality with fibrosis is 40‐50% at 5 years, median survival time  80 months

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

Outcomes in DAH with AAV

Survival at 1 yr Laugue

82

Gallagher

50

Hruskova

Survival at 2 yr

Survival at 5 yr 68

36 58.5 (*49mo)

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

1 Laugue Medicine 79: 222 2000 2 Hruskova, Scand J Rheum 2013 3 Klemmer AJKD 42: 1149

Outcomes of Pulmonary Vasculitis  Admitted to ICU

Outcomes of Pulmonary Vasculitis Admitted to ICU

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

HOLGUIN, FERNANDO; MD, MPH; RAMADAN, BASSEL;  GAL, ANTHONY; ROMAN, JESSE American Journal of the Medical Sciences. 336(4):321‐ 326, October 2008.

2

Length of hospital stay

Outcomes of Pulmonary Vasculitis Admitted to ICU

HOLGUIN, FERNANDO; MD, MPH; RAMADAN, BASSEL;  GAL, ANTHONY; ROMAN, JESSE American Journal of the Medical Sciences. 336(4):321‐ 326, October 2008.

2

Using Objective Measures of Lung Disease: Spirometry

Pulmonary Function Tests: Spirometry 2 Months post‐dx

Ref FVC FEV1 FEV1/FVC FEF25-75% IsoFEF25-75 FEF50% PEF FET100%

Liters Liters % L/sec L/sec L/sec L/sec Sec

5.93 4.90 84 5.07 5.07 10.60

Pre Meas 6.18 2.01 33 0.66 0.66 0.72 3.90 12.88

Pre % Ref 104 41 13 13 37

Post Meas 5.96 1.98 33 0.73 0.78 0.80 4.33 12.62

Post % Ref 100 40 14 15 41

Post % Chg -4 -1 11 18 11 11 -2

Flow‐Volume Loops

Pulmonary Function Tests: Spirometry with Flow Volume Loops

Pulmonary Function Tests Diffusing Capacity

Pulmonary Fibrosis in Microscopic Polyangiitis

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

Pulmonary Function Tests in GPA

41% with reduced FVC 55% with reduced FEV1 (“majority” not due to volume loss alone) 36% had reduced TLC 32% had increased RV/TLC 36% had decreased DLCO Rosenberg et al, AJM, 1980, 69: 387

Rosenberg et al, AJM, 1980, 69: 387

Spirometry in UNC Cohort of Patients with Pulmonary Disease

PFT pattern

Total

Mild

Moderate

Severe

Very Severe

Obstruction (GOLD criteria)

12

1

5

5

1

Restriction

8

2

5

1

NA

8 Subjects with normal spirometry

Spirometry in UNC Cohort of Patients with Pulmonary Disease

N

FVC (%)

FEV1 (L)

FEV1 (%)

FEV1/FVC (%)

DLCO

Cavities / 17 3.2 nodules

75.6

2.2

66.8

68.8

64.0

No cavities / nodules

75.0

2.1

69.9

73.7

60.3

11

FVC (L)

3.0

Spirometric Response to Therapy 2 Months post‐dx Ref FVC FEV1 FEV1/FVC FEF25-75% IsoFEF25-75 FEF50% PEF FET100%

Liters Liters % L/sec L/sec L/sec L/sec Sec

5.93 4.90 84 5.07 5.07 10.60

Pre Meas 6.18 2.01 33 0.66 0.66 0.72 3.90 12.88

Pre % Ref 104 41

Pre Meas 7.29 4.10 56 2.01 2.01 2.50 8.27 12.70

Pre % Ref 123 84

13 13 37

Post Meas 5.96 1.98 33 0.73 0.78 0.80 4.33 12.62

Post % Ref 100 40 14 15 41

Post % Chg -4 -1 11 18 11 11 -2

3 years post‐dx Ref FVC FEV1 FEV1/FVC FEF25-75% IsoFEF25-75 FEF50% PEF FET100%

Liters Liters % L/sec L/sec L/sec L/sec Sec

5.91 4.86 83 4.97 4.97 10.65

40 40 78

Post Meas

Post % Ref

Post % Chg

Therapy Results

Before treatment

After treatment

In Conclusion • 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