CTD-related Lung Disease
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1 13 th Cambridge Chest Meeting King s College, Cambridge April 2015 Imaging of CTD-related Lung Disease Dr Sujal R Desai King s College Hospital, London
2 Disclosure Statement No Disclosures / Conflicts of Interest
3 Background Lung disease in CTDs cause morbidity & mortality Patterns of ILD (but not prevalence) mirrors those seen in the IIPs Lung injury in CTDs not restricted to ILDs - Airways disease (follicular bronchiolitis, OB ) - Iatrogenic / Opportunistic infections
4 Initial Considerations RhA, SLE, SYSTEMIC SCLEROSIS, PM/DM, SJÖGREN S SYNDROME, MCTD UIP, NSIP, LIP, Diffuse Alveolar Damage, Organising Pneumonia, Constrictive OB, Follicular Bronchiolitis, Pulmonary Hypertension One associated with many (at the same time) and many associated with one Non-specific clinical features Cough / Dyspnoea Pulmonary Function Tests Blunt reflection of variable disease process(es) is different lung units Difficult to perform for some Wide range of normality
5 Patterns of CTD-related Lung Involvement RhA (UIP) RhA (bronchiectasis) RhA (nodules) PMDM (OP) SSc (NSIP) SLE (Pulm haemorrhage)
6 Areas to Consider Radiological/pathological patterns - Classification/prevalence of CTD-ILDs - Mixed CT / pathological patterns - ILD / IIPs without overt CTD The problem of limited (subclinical) disease - What does it mean? - Staging severity & predicting progressive disease Prognostication - CTD-UIP / CTD-non-UIP versus IIP - Survival related to disease patterns - Importance of specific CT patterns (e.g. honeycombing, TBx)
7 Patterns of CTD-Related Interstitial Lung Disease
8 Lung Disease in CTDs Classification of ILD MAJOR Idiopathic Pulmonary Fibrosis (IPF) / UIP Idiopathic Non-Specific Interstitial pneumonia (NSIP) Respiratory Bronchiolitis-Interstitial Lung Disease Desquamative Interstitial Pneumonia Cryptogenic Organising Pneumonia Acute Interstitial Pneumonia RARE Idiopathic Lymphoid Interstitial Pneumonia Idiopathic Pleuroparenchymal Fibroelastosis UNCLASSIFIABLE Travis WD et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias Am J Respir Crit Care Med 2013;188:
9 Lung Disease in CTDs Variable Prevalence: NSIP NON-SPECIFIC INTERSTITIAL PNEUMONIA Systemic sclerosis PM / DM Sjögrens syndrome SLE Rheumatoid arthritis
10 % Ground-glass opacification Non-Specific Interstitial Pneumonia ILD in Systemic Sclerosis 100 * SSc versus UIP; p< * 0 SSc NSIP UIP Desai SR et al. CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and non-specific interstitial pneumonia Radiology 2004;232:
11 Lung Disease in CTDs Variable Prevalence: UIP USUAL INTERSTITIAL PNEUMONIA Rheumatoid Arthritis Systemic Sclerosis SLE Sjögren s syndrome
12 Lung Disease in CTDs Variable Prevalence: Others ORGANISING PNEUMONIA PM/DM Rheumatoid arthritis Systemic sclerosis SLE Sjögren s syndrome LYMPHOID INTERSTITIAL PNEUMONIA Sjögren s syndrome Rheumatoid arthritis Systemic sclerosis SLE
13
14 Usual Interstitial Pneumonia Mixed Patterns in Rheumatoid Arthritis Tanaka N et al. Rheumatoid arthritis-related lung diseases: associated with collagen vascular diseases: CT findings. Radiology 2004;232:81-91
15 Usual Interstitial Pneumonia Mixed Patterns in Rheumatoid Arthritis Tsuchiya Y et al. Lung disease associated with rheumatoid arthritis and their relationship to outcome. Eur Respir J 2011;37:
16
17 Lung Disease in CTDs ILD sine CTD 75 patients with IIP 28 with UCTD 47 controls not fulfilling UCTD criteria IPF=41; NSIP=2; DIP=1; no biopsy/inclusive=3
18 24/28 two symptoms 19/28 three symptoms Athralgia/joint swelling (64%) Raynaud s (61%) Both (43%) Kinder BW et al. Idiopathic non-specific interstitial pneumonia: lung manifestations of undifferentiated connective tissue disease? Am J Respir Crit Care Med 2007;176:
19 Lung Disease in CTDs ILD sine CTD Kinder BW et al. Idiopathic non-specific interstitial pneumonia: lung manifestations of undifferentiated connective tissue disease? Am J Respir Crit Care Med 2007;176:
20 Lung Disease in CTDs ILD sine CTD UCTD criteria 15/17 (88%) most patients previously classified as having idiopathic NSIP have clinical, serologic, radiographic, Biopsy-proven NSIP and n=17 pathologic characteristics that meet criteria for UCTD No UCTD criteria 2/17 (12%) Kinder BW et al. Idiopathic non-specific interstitial pneumonia: lung manifestations of undifferentiated connective tissue disease? Am J Respir Crit Care Med 2007;176:
21 Lung Disease in CTDs ILD sine CTD IIP (n=101) IPF/UIP (n=56) NSIP (n=45) Corte TJ et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia Eur Respir J 2012;39:
22 Lung Disease in CTDs ILD sine CTD SYMPTOMS Raynaud s phenomenon Arthralgia / joint swelling Morning joint stiffness Sicca features Proximal muscle weakness SEROLOGY ANA RhF ENA Anti-Scl70 Anti RNP Anticentromere SS-A SS-B Jo-1 Corte TJ et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia Eur Respir J 2012;39: Mosca M et al. Undifferentiated connective tissue diseases: a review of the literature and a proposal for preliminary classification criteria Clin Exp Rheumatol 1999;17:15-20
23 Lung Disease in CTDs ILD sine CTD Mosca definition UCTD in 21% Kinder definition UCTD in 52% NSIP IPF NSIP IPF UCTD 31% 13% 71% 36% Corte TJ et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia Eur Respir J 2012;39: Mosca et al. Undifferentiated connective tissue diseases: a review of the literature and a proposal for preliminary classification criteria Clin Exp Rheumatol 1999;17:15-20
24 Lung Disease in CTDs ILD sine CTD Mosca definition UCTD in 21% Kinder definition UCTD in 52% NSIP IPF NSIP IPF UCTD 31% 13% 71% 36% Corte TJ et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia Eur Respir J 2012;39: Mosca et al. Undifferentiated connective tissue diseases: a review of the literature and a proposal for preliminary classification criteria Clin Exp Rheumatol 1999;17:15-20
25 Lung Disease in CTDs ILD sine CTD Mosca definition UCTD in 21% Kinder definition UCTD in 52% NSIP IPF NSIP IPF UCTD 31% 13% 71% 36% Corte TJ et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia Eur Respir J 2012;39: Mosca et al. Undifferentiated connective tissue diseases: a review of the literature and a proposal for preliminary classification criteria Clin Exp Rheumatol 1999;17:15-20
26 Lung Disease in CTDs ILD sine CTD Changing / Evolving Terminology Lung-dominant CTD Autoimmune-featured ILD Interstitial pneumonia with autoimmune features (IPAF)
27 Lung Disease in CTDs ILD sine CTD - Terminology IIP IIP + AI features (IPAF) IIP CTD Defined CTD + ILD
28 Detection & Limited Interstitial Lung Disease
29 Is Lung Disease Present?
30 Lung Disease Present So What?! Desai SR et al. CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and non-specific interstitial pneumonia Radiology 2004;232:
31 Lung Disease in CTDs Staging Disease & Predicting Progression 43% 10 ys 67% 10 ys Goh NSL et al. Interstitial lung disease in systemic sclerosis a simple staging system Am J Respir Crit Care Medicine 2008;177:
32 Lung Disease in CTDs Staging Disease & Predicting Progression <20% >20% Goh NSL et al. Interstitial lung disease in systemic sclerosis a simple staging system Am J Respir Crit Care Medicine 2008;177:
33 Lung Disease in CTDs Staging Disease & Predicting Progression Moore OA et al. Extent of disease on high-resolution computed tomography is a predictor of decline and mortality in systemic sclerosis-related interstitial lung disease Rheumatology 2013;52:
34 Lung Disease in CTDs Subclinical (Limited) Disease in RhA Asymptomatic RhA patients (n=64) ILD on HRCT in 21/64 (33%) 15/21 [71%]) former smokers Progression 12/21 (57%) o Clinical factors o Baseline HRCT scores o Baseline PFTs o Methotrexate o Interferon o TGF- Gochuico BR et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis Arch Intern Med 2008;168:
35 Prognostication
36 Idiopathic Interstitial Pneumonias Prognostic Significance of Histopathological Pattern Bjoraker JA et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199 Daniil ZD et al. A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis Am J Respir Crit Care Med 1999;160:899 Nicholson AG et al. The prognostic significance of the histologic pattern of interstitial pneumonia in patients with the clinical entity of cryptogenic fibrosing alveolitis Am J Respir Crit Care Med 2000;162;2213 Travis WD et al. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns. Survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia Am J Surg Pathol 2000;24:19
37 Prognosis in CTD-related ILD Influence of Histopathological Pattern: SSc ~7.5 yrs Bouros D et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 2002;165:1581
38 Prognosis in CTD-related ILD Influence of Histopathological Pattern: SSc Fischer A et al. Clinically significant interstitial lung disease in limited scleroderma: histopathology, clinical features, and survival. Chest 2008;
39 Prognosis in CTD-related ILD Influence of Histopathological Pattern: CTDs versus IPF CTD-UIP IPF/UIP Flaherty KR et al. Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease. Am J Respir Crit Care Medicine 2003;167:
40 Prognosis in CTD-related ILD Prognostic Impact of CT Pattern: RhA Kim EJ et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease Eur Respir J 2010;35:
41 ILD in Rheumatoid Arthritis Prognostic Impact of CT Pattern: RhA Likely NSIP IPF RA-UIP Kim EJ et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease Eur Respir J 2010;35:
42 Fibrotic ILD in CTDs Prognostic Impact of CT Pattern: CTD All-Comers Walsh SLF et al. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants Thorax 2014;69:
43 Extent Honeycombing Ancillary features (Emphysema, nodules, etc ) Traction bronchiectasis Ground-glass opacification
44 Fibrotic ILD in CTDs Importance of Pattern Walsh SLF et al. Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants Thorax 2014;69:
45 Prognostic Factors in CTD-ILD Radiological / Histopathological Disease extent Limited versus Extensive Overall pattern UIP versus NSIP / other Honeycombing Traction bronchiectasis
46 Lung Disease in CTDs Different (& mixed) patterns of lung disease contribute to morbidity /mortality in CTDs - UIP (RhA) and NSIP (other CTDs) are common - ILD without defined CTD (?IPAF) now recognised Early / limited disease not uncommon - Identification of progressive disease - Screening? Variable outcome dependent on histopathological / CT appearance - UIP>NSIP/others - Independent impact of individual CT features
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