SSc - PID Luc Mouthon luc.mouthon@cch.aphp.fr Pôle de Médecine Interne, Centre de référence pour les vascularites nécrosantes et la sclérodermie systémique, hôpital Cochin, Assistance publique-hôpitaux de Paris, Paris Université Paris Descartes, Inserm U1016, Institut Cochin, Paris Uth rs DHU
Conflits d intérêt Consultant: Actelion, CSL Behring, LFB Biotechnologies, Lilly, Pfizer, Octapharma Financial support to ARMIIC Invertigateur: Actelion, CSL Behring, Pfizer Soutien financier (ARMIIC): Actelion, CSL Behring, GSK, LFB Biotechnologies, Pfizer Conférence invitée: SOBI, Roche, Actelion, CSL Behring, Octapharma, GSK, LFB Biotechnologies, Pfizer, Lilly, UCB pharma et Abbvie Depuis janvier 2014: Président du groupe d experts de l AP-HP, juste prescription
Atteintes pulmonaires au cours des maladies systémiques La maladie systémique Immunodépression secondaire au traitement de la maladie systémique Pneumopathie médicamenteuse Autre Pathologie thrombo-embolique Pneumothorax Pneumopathies infectieuses Néoplasie.
Classification des PID (1) PID TDM Anatomopathologie Evolution, pronostic UIP RM, DDB par traction Remodelage dense, hétérogène ; foyers fibroblastiques ; distribution sous pleurale et para-septale Aggravation progressive Peu sensible aux traitements PINS VD, opacités en bandes, opacités réticulées Infiltration interstitielle lymphocytaire dominante, fibrose collagène modérée, lésions uniformes Evolution le plus souvent lente. Sensible aux traitements Katzenstein AL, Myers JL. AJRCCM 1998
Classification des PID (2) PID TDM Anatomopathologie Evolution, pronostic DAD Condensations alvéolaires diffuses, VD Dommage alvéolaire diffus hase aiguë exsudative, puis phase d organisation Mauvais pronostic COP Condensations alvéolaires multifocales, parfois migratrices Bourgeons conjonctifs intra-alvéolaires caractéristiques Corticosensibilité Restitution integrum ad Katzenstein AL, Myers JL. AJRCCM 1998
Classification des PID (3) PID TDM Anatomopathologie Evolution, pronostic PIL VD infiltration diffuse de l interstitium pulmonaire : lymphocytes matures et plasmocytes. Remaniements architecturaux rares ou discrets Fonction l étiologie de PHS VD, micronodules mal limités Phase aiguë : Infiltration interstitielle lymphocytaire, plasmocytaire, Phase chronique : fibrose non spécifique Evolution favorable si diagnostic précoce et éviction de l allergène Katzenstein AL, Myers JL. AJRCCM 1998
Courtesy M Brauner UIP PINS BOOP PHS
PID idiopathiques et des connectivites Idiopathiques UIP +++ NSIP ++ Connectivites + PR +++ Sclérodermie PM/DM DIP + 0 RB-ILD + 0 LIP + + Sjogren COP ++ + DAD ++ + Mouthon L et al, Rev Mal Resp 2005
Pneumopathies infiltratives diffuses observées au cours des collagénoses Collagénose Fréquent Rare LED DAD, PINS, UIP, COP PR UIP ScS PINS UIP, DAD, COP PM/DM PINS PHS, COD, UIP, DAD Syndrome de Sjögren PINS LIP, UIP, COP Connectivites mixtes PINS UIP, PIL Mouthon L et al, Rev Mal Resp 2005
SYSTEMIC SCLEROSIS : EVOLUTION Diffuse ILD + PAH Myositis Lung Bowell PAH Kidney Bowell Raynaud s syndrome ILD Limited cutaneous 0 2 4 6 8 10 Years Skin score Visceral involvement
Manifestations pulmonaires au cours de la sclérodermie systémique Pneumopathies infiltratives diffuses Hypertension artérielle pulmonaire Pneumopathie d inhalation Pleurésie Pneumothorax spontané Pneumopathie médicamenteuse Pneumoconiose Cancer pulmonaire
Atteinte pulmonaire au cours de la sclérodermie: manifestations cliniques Signes cliniques souvent modestes. Symptômes Toux sèche Dyspnée Signes cliniques Diminution de l expansion thoracique Crépitants des bases pulmonaires Signes droits (HTAP) Pas d hippocratisme digital
Interstitial Lung Disease in Systemic Sclerosis A Simple Staging System Goh NSL, AJRCCM 2008
Examens complémentaires Le mauvais pronostic de la PID au cours de la ScS impose son dépistage systématique. Pas de recommandations consensuelles sur les examens de dépistage et la fréquence à laquelle les renouveler. Le bilan doit comporter: tomodensitométrie thoracique haute résolution (TDMHR) épreuves fonctionnelles respiratoires (EFR) avec mesure du coefficient de transfert du monoxyde de carbone (DLCO) test de marche de 6 min avec mesure de la saturation en oxygène et l estimation de la dyspnée à l aide de l indice de Borg.
Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome Bouros et al. Am J Respir Crit Care Med 2002. 165: 1581-6 Surgical biopsies of 80 patients with systemic sclerosis seen over a 12-year period. 62 (77,5%) nonspecific interstitial pneumonia; 6 usual interstitial pneumonia; 6 unclassifiable end-stage fibrosis; 4 respiratory bronchiolitis-associated interstitial lung disease; 1 organizing pneumonia.
UIP NSIP
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18/01/12
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CT features of lung disease in patients with SSc Desai S.R. Radiology 2004; 232: 560-567
Combined Pulmonary Fibrosis and Emphysema Syndrome in Connective Tissue Disease Cottin et al Arthritis Rheum 2010
SSc-ILD Prognosis (II) Main parameters of prognostic value in SSc-ILD: Severe ILD at diagnosis Clinical symptoms: dyspnea, crackles PFTs (DLCO and/of FVC<70%) HRCT (extended lesions with a dominant ground glass pattern) Rapidly worsening ILD defined by a loss of 10% FVC or 15% DLCO during the last 12 months. BAL data do not influence any more therapeutic decision
SSC: Intensive care unit Patients characteristics 42 patients with SSc were admitted to ICU at Cochin. No additional patient was diagnosed with SSc in the ICU. Most patients (63%) presented with diffuse cutaneous forms. The most frequent chronic organ involvements were the digestive tract, most especially esophageal disorders, and interstitial lung disease. 74% of patients had underlying pulmonary fibrosis responsible for altered CO diffusion and elevated PAP. 5 patients had chronic renal failure with MDRD-estimated creatinine clearance < 50 ml/min. Only one patient was under chronic hemodialysis. 23 (65%) and 9 (26%) patients were treated with long-term corticosteroids and/or other immunosuppressive drugs, respectively. Pene et al. J Rheumatol 2015 in press
Acute complications and organ failures Main cause of admission: acute respiratory failure (69% of patients). Pulmonary infection was diagnosed in 11 patients. Overall, 9 patients were intubated and mechanically ventilated, and 7 of them exhibited multiple organ failure requiring vasopressive support and renal replacement therapy. Non-invasive ventilation was attempted in 13 patients: successful in eight five patients secondarily required endotracheal intubation. Invasive mechanical ventilation required in 13 patients (often resulted in multiple organ failure). 10 and 7 mechanically ventilated patients exhibited: acute circulatory failure requiring vasopressors in 10 acute renal failure requiring RRT in 7 Pene et al. J Rheumatol 2015 in press
Treatment of SSc-ILD PPI Cyclophosphamide Low dose corticosteroids (10 mg/j) Oxygen Lung transplantation Rehabilitation
Hôpital Cochin Paris www.vascularites.org Luc.mouthon@cch.aphp.fr Referral Center for Rare Systemic and Autoimmune Diseases