Post on 12-Oct-2020
Ma#hieuGROHMédecineInterne,HôpitalFoch
CEREO-CentredeRéférencedesSyndromesHyperéosinophiliques
Eosinophileseta-eintesrespiratoires
1. Généralités• Physiopathologie• Défini<ons• Epidémiologie
2. Quoiévoquerdevantunea#eintebronchique?
3. Quoiévoquerdevantunea#einteparenchymateuse?
Plan
1. Généralités• Physiopathologie• Défini<ons• Epidémiologie
2. Quoiévoquerdevantunea#eintebronchique?
3. Quoiévoquerdevantunea#einteparenchymateuse?
Plan
Rosenberg,NatRevImmunol2013
EffetstoxiquesduPNE
• Sécré%ondescytokinesdérivéesdescellulesépithéliales,IL-33,IL-25etTSLP,parlescellulesépithélialespulmonairesenréponseàdifférentess%muli(champignons,virus)
• Ac%va%ondesILC2danslespoumons,promouvantlasécré%ond’IL-4,IL-5etIL-13
• IL-5produiteparlesILC2conduisantaurecrutementdeséosinophiles
• Chezl’homme,augmenta%ondesILC2danslesangetleLBAdespa%entsasthma%ques,enpar%culierchezlespa%entsavecasthmeéosinophiliquesévèreCTdépendant
ILC2etmaladiesàPNE
Ebbo,NatRevImmunol2017
Ogbogu,JAllergyClinImmunol2009
N=188pa4ents.Sex-Ra4o1♀/1♂
A#eintesrespiratoiresaucoursdesSHE
57% 52%
45%
34%
16% 16%
N=44pa%ents
Sex-Ratio 43♂ / 1♀
SONT EVOCATEURS • Erosions muqueuses • Toux rebelle, asthme, infiltrats • Atteinte cardiaque • B12 et tryptase élevées • Cortico-résistance • Sensibilité ++ à l’Imatinib
LCEF/P+eta#einterespiratoire
Legrand,Medicine2013
13F/8H42ans[5-75]
SONTEVOCATEURS
• Angioedèmes• Eczéma• IgEtotalesélevées• Cor4cosensibilité
SHEL3-4+eta#einterespiratoire
Lefèvre,Medicine2014
Opacitéspulmonaires(OUaYeintebronchique)àl’imagerie(TDM)
+• uneéosinophiliepériphérique=cut-off>1G/L(ou0,5?)
OU• unehyper-éosinophilieauLBA>25%(aigue)ou40%(chronique)
OU• unehyper-éosinophilie4ssulairesurunebiopsiepulmonaire
C’estquoienpra<que??
Co^n,ClinChestMed2016
EosinophiliebronchiqueetTVO
APBAAsthmebronchiteetbronchioliteàéosinophileWidalGEPA(Churg-Strauss) Eosinophiliealvéolaire
ParasitesetInfec%onsMédicaments-ToxiquesPneumopathieaigue/chroniqueàPNEGEPA(syndromedeChurg-Strauss)
EosinophilieORLRhinosinusiteavecHERSavecpolyposeNSetEOWidalGEPA
Commentraisonner?
1. Généralités• Physiopathologie• Défini<ons• Epidémiologie
2. Quoiévoquerdevantunea#eintebronchique?
3. Quoiévoquerdevantunea#einteparenchymateuse?
Plan
GEPAet/ouSHE:Passisimple!
1. Masi,AR19902. Wechsler,NEJM20173. Comarmond,AR2013
4. Josselin-Mahr,Rheumatology20145. Emmi,Rheumatology2015
6. Puéchal,AR2017
• Critèresu4liséspourlediagnos4c/inclusiondansdesessaisthérapeu4quessont«souples»…1,2
• PreuvehistologiquedevasculariteaucoursdeGEPA….<50%despa4ents!3
• Certainspa4entsauphénotypedeGEPA...sontF/P+4,5!
• «Echec»desISconven4onnels6…vsefficacitédesan4-IL52
GEPA…ouHASM?…ouSHE?
Co^n,AutoimmunRev2016Lefèvre,AutoimmunRev2016
GEPAvs.SHE?
Leurs,JACIPract2018
IntérêtdelaCRP++++
AspergilloseBroncho-PulmonaireAllergique(ABPA)
Agarwal,ClinExpAllergy2013
However, there was inconsistency in results obtainedfrom different centres [136]. Thus, the expert group feltthat although the current data suggest a promising roleof recombinant antigens in diagnosis of AS and proba-bly ABPA [141–143], there is need for larger studiesfrom different centres to give a final recommendationon the diagnostic value of these allergens.
Diagnosis and diagnostic criteria
The diagnosis of ABPA is currently made on a combina-tion of clinical, radiological and immunological findingsusing the Patterson criteria [3, 6]. The expert group feltthat these criteria need revision as they offer equalimportance to all parameters while some components ofthe criteria are more important than others. For exam-ple, the specificity of Aspergillus IgG for ABPA asopposed to other forms of aspergillosis remainsunknown. Moreover, there is neither any consensus onthe number of major or minor criteria required to makethe diagnosis, nor receiver operator curve (ROC) analysisof the optimum cut-off values for IgE levels and eosino-phil count. From a clinical perspective, it would be help-ful to have simpler criteria, if possible. New diagnosticcriteria were formulated with an aim to improve thediagnosis and care of patients with ABPA and limit theweaknesses of the previous criteria (Table 4). The refine-ment in inclusion/exclusion criteria will also benefitclinical research particularly studies planning to evalu-ate aetiology and/or new therapies. The new criteria willneed validation and further refinement. Bronchiectasiswas removed from the diagnostic criteria as ABPA maypresent without CB. The minor criteria of Patterson et al.although sometimes present should not be required fordiagnosis, and hence have also been removed. Theexpert group agreed that a cut-off value of 1000 IU/mLcan help in differentiating SAFS from ABPA-S butwould require validation. In clinical practice, many
patients will fall short of diagnostic criteria for ABPA.These patients may be labelled as ‘ABPA- at risk’ andrequire close monitoring and follow-up.
While investigating a patient with asthma for ABPA,it is recommended to perform an Aspergillus skin testand/or A. fumigatus specific IgE levels, with the latterbeing more sensitive [88]. If either is positive, the totalserum IgE levels should be measured. If the value is> 1000 IU/mL, other tests for ABPA including a CT ofthe chest, IgG specific to A. fumigatus or serum precipi-tins to A. fumigatus and total eosinophil count shouldthen be performed to fully characterize the disease(Fig. 6). Allergic bronchopulmonary mycosis can bediagnosed in the same way, with sensitization toanother fungus being predominant [15].
Natural history
The natural history of ABPA remains unclear becauseof its variable course in different patients [6, 7, 144–147]. However if untreated, the inexorable inflamma-tory process can result in bronchiectasis and pulmonaryfibrosis, and ultimately respiratory failure and cor pul-monale [83]. Allergic bronchopulmonary aspergillosisgenerally does not remit but it can remain quiescent forlong periods. Given its relapsing nature, with develop-ment of serious complications, it is important toprovide a clinical framework for staging the disease.
Clinical staging of allergic bronchopulmonaryaspergillosis
Although ABPA has been classified into five stages [5];there is considerable ambiguity in description of these
Table 3. Recombinant Aspergillus fumigatus antigens evaluated in
allergic bronchopulmonary aspergillosis (ABPA) complicating asthma
Antigen
Sensitivity, n/N (%) Specificity, n/N (%)
ABPA
Aspergillus
sensitization
Asthma or
controls References
rAsp f1 84/105 (80) 30/60 (50) 0/13 (100) [137, 139, 261]
rAsp f2 24/25 (96) Not done 0/20 (100) [262]
rAsp f3 66/71 (93) 26/48 (54) 0/24 (100) [137, 263]
rAsp f4 58/72 (81) 0/52 (0) 0/25 (100) [137, 264]
rAsp f6 38/72 (53) 0/52 (0) 0/25 (100) [137, 264]
rAsp f34 60/64 (94) 11/24 (46) 0/7 (100) [265]
rAsp f1
or f3
58/60 (97) 30/40 (75) 0/20 (100) [137]
rAsp f4
or f6
65/72 (90) 0/52 (0) 0/25 (100) [137, 264]
Table 4. Newly proposed diagnostic criteria for allergic bronchopul-
monary aspergillosis
Predisposing conditions
Bronchial asthma, cystic fibrosis
Obligatory criteria (both should be present)
Type I Aspergillus skin test positive (immediate cutaneous
hypersensitivity to Aspergillus antigen) or elevated IgE levels
against Aspergillus fumigatus
Elevated total IgE levels (> 1000 IU/mL)*
Other criteria (at least two of three)
Presence of precipitating or IgG antibodies against A. fumigatus in
serum
Radiographic pulmonary opacities consistent with ABPA†
Total eosinophil count > 500 cells/lL in steroid na€ıve patients (may
be historical)
*If the patient meets all other criteria, an IgE value < 1000 IU/mL
may be acceptable.†The chest radiographic features consistent with ABPA may be tran-
sient (i.e. consolidation, nodules, tram-track opacities, toothpaste/fin-
ger-in-glove opacities, fleeting opacities) or permanent (i.e. parallel
line and ring shadows, bronchiectasis and pleuropulmonary fibrosis).
© 2013 John Wiley & Sons Ltd, Clinical & Experimental Allergy, 43 : 850–873
858 R. Agarwal et al
Condi4onssinequanon:- IgEtotale>1000UI*- ETIgEan%-aspergillaire
augmenté(>0.35)ouPrick-test>0
- ETaumoins2des3critèressuivants
§ Sérologieaspergillaire>0§ Imageriecompa%ble§ PNE>500
BronchioliteoblitéranteàPNE
Cordier,EurRespJ2013
1. Généralités• Physiopathologie• Défini<ons• Epidémiologie
2. Quoiévoquerdevantunea#eintebronchique?
3. Quoiévoquerdevantunea#einteparenchymateuse?
Plan
ASYMPTO
DRESS
MAIS AUSSI, en cours d’hospitalisation - An4bio4ques
- HBPM
- AVK- PDCiodés
M DUREE10jà6MOIS++++
Sedonnerdutemps
PNEethypersensibilitémédicamenteuse
Ascaridiose
Toxocarose
Hyda4dosepulmonaire
Filariose
Cryptococcose
Histoplasmose
Coccidiodomycose
Aspergillose
Paragonimose
Eosinophiliesparasitaires
Valent, J Allergy Clin Immunol 2012
Maladiegastrointes%nalesàEosinophiles(colite,gastro-entérite,oesophagite)
Cholangiteàéosinophiles
Pancréa%teàéosinophiles
Asciteàéosinophiles
Asthmeéosinophilique
Bronchiteetbronchioliteàéosinophiles
Pneumopathieaigueetchroniquesàéosinophiles
Néphriteinters%%elleàéosinophiles
Cys%teàéosinophiles
Mas%teàéosinophiles
Myocarditeàéosinophiles
Myositeàéosinophiles
Endométriteàéosinophiles
Synovitesàéosinophiles
Fasciiteàéosinophiles
MaladiesàPNEspécifiquesd’organe
Pneumopathieaigue/chroniquesàPNE
Co^n,ClinChestMed2016
CordierSeminRespirCritCareMed2006
Pneumopathieaigue/chroniquesàPNE
ü Toujourspra4querunLBA,carû LeLBApeutêtrenonéosinophiliquemalgrélaprésenced’une
éosinophiliesanguineû Ilexistedeséosinophiliespulmonairessanséosinophiliesanguineû L’éosinophiliepériphériquenereprésentepas«laréalitépulmonaire
»carelleestsouventtrèsinferieureàl’éosinophilie%ssulaire.
ü Unpoumonn’est«éosinophile»quesil’éosinophileestlapopula4onmajoritairesurleLBA(horsmacrophage)û Sinon=formulepanachée:POC,pathologierespiratoirechezun
asthma%que….
ü Toujoursfaireun«bilansystémiquedeSHE»(origineetreten4ssementextra-respiratoiredel’éosinophilie)
ü Unea-eintebronchique…n’estpasforcémentuneGEPA
ü Penseràl’EP
Conclusion
Remerciements
CEREO • Annecy: Dr Morati-Hafsaoui, Dr Alice
Berezne • Bordeaux: Pr Viallard • Foch-Surenes: Dr JE Kahn, Dr M Groh,
Dr F Ackermann • Lille: Dr G Lefevre, Dr N Etienne, Pr
Staumont Salle, Dr Terriou, Pr Launay, Pr Hatron, Pr Hashulla, Morschhauser,
• Marseille: Pr Schleinitz, Dr Ebbo • Nantes: Pr Hamidou, Dr A Neel • Strasbourg: Pr Martin • Lyon: Pr Salles, Dr Khouatra, Pr Ninet, Pr Seve,
Pr Cordier • Paris: Pr Baruchel, Pr Rousselot, Pr Michel, Pr
Fain, Dr Barete, Pr Sene, Pr Haroche, Pr Costedoat-Chalumeau
Immunologie – Pr M Labalette J. Trauet, V. Lekeux, V. Bétrancourt, V. Dutriez
Anatomo-pathologie – Pr Copin
Hématologie – Pr Preudhomme Collaboration: Dr C. Roumier Clonalité T / PCR: Dr N. Grardel Séquençage: S. Geffroy, Dr S. Poulain
Cytogénétique Dr C. Roche-Lestienne
Plate-forme de génomique fonctionnelle U837
M Cheok, P Peyrrouze
avis.cereo@gmail.com jean-emmanuel.kahn@aphp.fr guillaume.lefevre@chru-lille.fr m.groh@hopital-foch.com