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
?
9.68.4
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