alberto m. marra, md - simi.it malattie respiratorie e le... · alberto m. marra, md -research...
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Alberto M. Marra, MD
-Research Fellow, Pulmonary Hypertension Center Thoraxclinic at Heidelberg University -Italian Young Internists Group (GIS),
Italian Society of Internal Medicine (SIMI) -Young Internists Subcommittee,
European Federation of Internal Medicine (EFIM)
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Lung-CTD: una relazione pericolosa
No-CTD 70%
CTD 30%
114 ILD pz
Coorte retrospettiva di 114 pazienti con ILD seguito presso la Johns Hopkins Interstitial Lung Disease Clinic Nel 15% dei pazienti la diagnosi di ILD ha costituito la prima manifestazione di una CTD misconosciuta
Mittoo S et al. , Resp Med 2009
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Presenza CTD silente
62%
38% UCTD*
Idiopathic
71%
29% NSIP
Others (UIP,OP,etc.)
Kinder BW et al., Am J Resp Crit Care Med 2007
*UCTD: Undifferenciated CTD almeno un sintomo di CTD e presenza di evidenza biologica di infiammazione sistemica (positività almeno 1 autoanticorpo e/o positività indici infiammazione aspecifica i.e. VES, PCR)
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CTD “occulta” 38 ILD patients underwent an minor salivary gland biopsy (MSGB) to confirm a diagnosis of Sjögren Syndrome
34%
Fischer A et al. Chest 2009
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Siamo medici o caporali?
Cottin V, Eur Resp J 2014
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Ruolo protettivo delle CTD?
Park JH et al., Am J Resp Crit Care Med 2007
269 with I-ILD and 93 with CTD-ILD
V. Navaratnam et al., Resp Med 2011
2209 cases of I-ILD and 324 with CTD-ILD
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84%
12%
2% 1% 1% Interstitial Lung Disease (ILD)
Pulmonary Arterial Hypertension (PAH)
Drugs related complications
Opportunistic Infections
Airway Disease
Capobianco J et al., Radiographs 2012
Fischer A et al. Lancet 2012
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Forme associate a CTD Forme idiopatiche
Pattern Frequente NSIP (UIP nell’Artrite Reumatoide)
UIP
Sesso Femminile Maschile
Età < 50 anni > 50 anni
Coinvolgimento Multicompartimentale (parenchima, vie aeree, pleura, vascolatura)
Segmentario
Linfoadenopatie mediastiniche
Frequenti Rare
Autoanticorpi Positivi: ANA ad alto titolo (> 1:320), ENA, autoanticorpi specifici, anti-Scl70, anti-Ro, anti-La, anti-dsDNA, anti-Smith, anti-RNP, anti-tRNA sintetasi)
Negativi
Manifestazioni sistemiche Pericarditi, Raynaud, Esofagee, Sclerodattilia, Miopatie, Teleangectasie, Ulcere, Sindrome sicca
Rare
Ada
pted
from
Cot
tin V
, Eur
Res
p J 2
014
M
ittoo
S e
t al.
, Res
Med
200
9
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INTERSTITIAL LUNG DISEASE QUADRI TIPICI
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Systemic Sclerosis
Interstitial Lung Disease (forma diffusa)
Pulmonary Arterial Hypertension (forma limitata)
2125 consecutive patients evaluated at the University of Pittsburgh between 1 January 1972 and 31 December 1996. Survival were determined in a 5-years term
Stehen VD et al., Ann Rheum Dis 2007
Pulmonary Hypertension due to Lung Disease
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Test funzionalità respiratoria • Tipico pattern restrittivo: FEV1 e FVC ridotti, FEV1/FVC normale
o lievemente aumentato
• Riduzione DLCO
Il declino della DLCO si associa ad
un drammatico peggioramento
della prognosi
Bouros D et al., Am J Respir Crit Care Med 2002
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Pattern HRCT
Tipico quadro NSIP caratterizzato da: • interessamento polmonare
spazialmente e temporalmente omogeneo
• Ground-glass opacity e anomalie reticolari
• Lievi bronchiectasie da trazione • malattia bilaterale con prevalenza
lobo inferiore e distribuzione periferica
• subpleural sparing
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BAL nella Sclerosi Sistemica
Rossi G et al. , Am J Clin Pathol 2008
…in patients with SSc, the globules were significantly related to BAL neutrophilia or eosinophilia and extensive ILD in high-resolution computed tomography (P < .0001).
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Algoritmo diagnostico/follow-up
Cappelli S et al., Eur Respir Rev 2015
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Algoritmo terapeutico
Cappelli S et al., Eur Respir Rev 2015
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LES in fabula
Coinvolgimento
Acuto
-50-60% pleuriti -Comunity Acquired Pneumonia -Atypical Pneumonia -Pulmonary Oedema -Acute lupus pneumonitis (2-10%)
Cronico
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Acute lupus pneumonitis
Pattern HRCT di Diffusa emorragia alveolare con quadro clinico contraddistinto da -emottisi -febbre -anemia con riduzione Hct -elevata mortalità (70-90) -BAL utile
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Interessamento polmonare cronico in corso di LES
• “Shrinking lung” syndrome: raro disordine caratterizzato da dolore toracico, dispnea, elevazione del diaframma e anormalità test funzionalità in assenza di patologia parenchimale o pleurica
• Interstiziopatia polmonare (sia quadri NSIP che UIP)
• Aumento prevalenza BPCO e di Combined pulmonary fibrosis and emphysema syndrome
• Aumento incidenza neoplasie polmonari e pleuriche
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Sindrome di Sjögren
27%
73%
Norwegian systemic CTD and vasculitis registry (NOSVAR)
Lung Involvment
Normal Lung
Palm O. et al, Rheumatology (Oxford) 2013
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Pattern HRCT nella Sjögren Lymphoid Interstitial Pneumonia (LIP)
Cisti perivascolari Cisti perivascolari
Anomalie reticolari
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Polimiosite/Dermatomiosite • Interessamento polmonare nel 40% dei casi
• Ab-ingestis, Debolezza muscolatura respiratoria
Quadri misti di overlap tra NSIP ed Organizing Pneumonia
Consolidamento unilaterale o bilaterale prevalentemente nei lobi inferiori. Spesso presente l’ “atoll sign” (area di maggiore consolidamento a forma di anello). Distribuzione periferica o peribronchiale con risparmio delle aree subpleuriche
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COMBINED PULMONARY FIBROSIS AND EMPHYSEMA SYNDROME (CPFE)
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Combined pulmonary fibrosis and emphysema syndrome (CPFE)
Entità clinica caratterizzata da • Enfisema centrolobulare o parasettale • Opacità infiltrative diffuse suggestive di
fibrosi predominante nei lobi inferiori
In presenza di quadro clinico caratterizzato da: • Dispnea severa • Alterazioni scambio gassoso a riposo e sotto
sforzo • Valori spirometrici sub-normali • Forte associazione con fumo di sigaretta
Cottin V et al., Arthritis & Rheumatism, 2011
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CPFE nelle malattie del connettivo
Cottin V et al., Arthritis & Rheumatism, 2011
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CPFE nelle malattie del connettivo
Cottin V et al., Arthritis & Rheumatism, 2011 Maggiore prevalenza NSIP (p:0.002) Maggiore presenza neutrofili nel BAL (p:0.046)
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IPERTENSIONE ARTERIOSA POLMONARE
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Sim
mon
eau
G. e
t al.
J Am
Col
l Car
diol
201
3
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Meccanismi molecolari
Schermurly R. et al., CHEST 2012
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Gruppo 1 vs Gruppo 3
Seeger et al., J Am Coll Cardiol 2013
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Gal
iè N
. et a
l., P
ulm
onar
y H
yper
tens
ion
Eur
opea
n gu
idel
ines
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Prevalenza PAH nelle CTD
0
5
10
15
20
25
Prevalenza (%) PAH
S-Sc
LES
AR
Mix-CTD
Sjögren
Mathai SC et al. Heart Fail Clin 2012
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Sopravvivenza
McLaughlin VV et al. , Chest 2004
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Gal
iè N
. et
al. ,
Eur
Hea
rt Jo
urna
l 201
0
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Challenges terapeutici
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Terapia immunosoppressiva
Sanchez O et al. 2006, Chest
Analisi retrospettiva 28 pazienti con PAH e CTD. -ottima risposta in pz con LES e Sjögren -assenza risposta in pz con Sclerosi Sistemica
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Take Home messages
• Il coinvolgimento respiratorio nelle malattie del tessuto connettivo è frequente, presenta diversi quadri e ha diverso impatto sull’outcome
• Le interstiziopatie polmonari possono essere la prima spia di una sottostante malattia reumatologica
• Nell’ambito delle CTD, è importante distingure le forme di ipertensione polmonare primitive e quelle secondarie a malattie del parenchima respiratorio
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Ringraziamenti
Task Force malattie respiratorie SIMI
Gruppo di lavoro malattie reumatologiche e del connettivo
-Dott. F. Luppi
-Dott.ssa S. Roversi
-Dott.ssa G. Montanari
-Dott. William Capeci
-Dott. Andrea Salzano
Società Italiana di Medicina Interna -Prof. G. R. Corazza -Prof. F. Perticone -Prof. L.M. Fabbri
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