Pulmonology

LETTER TO THE EDITOR Concomi an alle gic b onchopulmona y aspe gillosis and eosinophilic g anuloma osis wi h polyangii is a e Aspe gillus nige in ec ion Aspe gillus species can cause lung disease by di ec in ec- ion, such as in asi e pulmona y aspe gillosis (IPA), aspe gil- losis, e c.; o by hype sensi i i y eac ions o ungal p o eins, such as alle gic b onchopulmona y aspe gillosis (ABPA). 1 We he e desc ibe a pa ien ha simul aneously de eloped ABPA and eosinophilic g anuloma osis wi h polyangii is (EGPA) in he con ex o an Aspe gillus nige ai - way in ec ion and discuss he o e lapping c i e ia o hese condi ions. A 27-yea -old Indian male, esiden in Po ugal o he pas wo yea s, p esen ed mild in e mi en b onchial as hma. He de eloped p og essi e non-p oduc i e cough and dyspnoea o e he cou se o six weeks, and was admi - ed o he eme gency depa men o he sudden onse o in ense igh ches pain. Physical examina ion was un ema kable. Blood es s e ealed leucocy osis (13.1 £10 9 /L), wi h neu ophilia (10.7 £10 9 /L), eosinophilia (1.5 £10 9 /L) and ele a ed C- eac i e p o ein (CRP) 9.4mg/dL (no mal <0.5). Imaging showed a 6 cm-long igh hila mass, ex ending o he pleu a and enla ged hila lymph nodes. B onchoscopy obse ed bulky sec e ions obs uc ing he an e io segmen o he igh uppe lobe (RB3). Cul u es o b onchial aspi a e, la age and biopsies we e all posi i e o Aspe gillus nige . Eosinophils we e abundan on b onchial aspi a e, wi h Cha - co -Leyden c ys als, and in b onchial biopsies. The pa ien was hospi alized and o iconazole was ini i- a ed. Two weeks la e , o iconazole was changed o lipo- somal ampho e icin B due o d ug-induced hepa o oxici y. A e h ee weeks o an i ungal ea men , no clinical imp o emen was obse ed (inc easing e e , neu ophilia 13.84 £10^9/L, CRP 27.59mg/dL). Imaging showed a g ow- ing lung mass wi h suspec ed supe in ec ion (Fig. 1A-D). Empi ical pipe acillin- azobac am and ancomycin we e ini- ia ed. A e 10 days o an ibio ic he apy, neu ophilia and CRP had diminished (8.9 £10^9/L, 7.34mg/dL, espec- i ely). Howe e , anaemia de eloped (Hb 8.6g/dL, no mal 13.0-17.5) and clinical mani es a ions con inued o de e io- a e, wi h as henia, e e , dyspnoea and cough. In iew o he poo esponse o an i ungals and an ibio - ics, al e na i e diagnoses we e conside ed. Fu he in es i- ga ions showed ele a ed o al IgE (5175IU/mL, no mal <100), eosinophilia (0.71 £10 9 /L), nega i e p ocalci onin (while CRP again inc eased o 13.29mg/dL), posi i e p- an i- neu ophil cy oplasmic an ibodies (ANCA) and an i-myelo- pe oxidase (MPO) (8.5IU/ml, nega i e <3.5), while c-ANCA and an i-p o einase 3 (PR3) we e nega i e. Specific IgE (sIgE) and specific IgG (sIgG) o Aspe gillus umiga us we e s ongly posi i e (sIgE 9.16kU/L, no mal <0.35; sIgG 281.00mgA/l, no mal <83.00). Skin p ick es o Aspe gillus umiga us was posi i e (3mm). A his poin , he pa ien ulfilled diagnos ic c i e ia o bo h ABPA and EGPA (Table 1). Despi e he ini ial e idence o ungal coloniza ion/in ec ion and subsequen bac e ial supe in ec ion, i was conside ed ha T2 inflamma ion played he dominan ole in he disease. Me hylp ednisolone was s a ed a 1mg/kg/day, oge he wi h i aconazole. Nasal compu ed omog aphy (CT) scan du ing ea men wi h sys emic glucoco icoids showed mild maxilla y sinusi is. Clinical eco e y was apid and occu ed a e wo days o glucoco icoids, wi h esolu ion o e e and subsequen ly o as henia and cough. On day 10, CRP (0.49mg/dL), blood eosinophils (0.09 £10 9 /L) and haemoglobin (13.8g/dL) we e all no mal. The pa ien was discha ged asymp oma ic 20 days a e ini ia ing sys emic co icos e oids. I aconazole was main ained o 20 weeks and co icos e oids we e ape ed un il suspension. A he end o an i ungal ea - men , he ches X- ay was no mal (Fig. 1E) and he e was no elapse o he symp oms. Fou mon hs a e dis- cha ge, CT scan showed educed lung mass bu la ge a i- coid b onchiec asis in bo h lungs, pa icula ly in he igh uppe lobe (Fig. 1F-H). This is a a e case o simul aneous de elopmen o ABPA and EGPA in he con ex o Aspe gillus nige pulmona y in ec ion. The iden ifica ion o Aspe gillus in ai way samples complica ed ABPA/EGPA diagnosis. On hospi aliza ion, “p o en IPA”could no be confi med (no open lung biopsy was pe o med), bu he pa ien ulfilled he c i e ia o “pu a i e IPA” 2 (Table 1). No el c i e ia o in asi e ungal disease we e published by he EORTC/MSGERC consensus, 1 a e he desc ibed episode occu ed. Aspe gillus is known o con ibu e o he de elopmen o ABPA 3 and concomi an IPA and ABPA ha e been desc ibed. 4 h ps://doi.o g/10.1016/j.pulmoe.2021.12.004 2531-0437/Published by Else ie España, S.L.U. on behal o Sociedade Po uguesa de Pneumologia. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/). Pulmonology 28 (2022) 231234 www.jou nalpulmonology.o g In con as , he ole o Aspe gillus in he pa hophysiology o EGPA emains la gely specula i e. 5 The ela ionship be ween ABPA and EGPA is also incomple ely unde s ood. Se e al diagnos ic c i e ia a e common o bo h diseases and di e en ial diagnosis is ecommended. 6 Recen ly, epo s desc ibed he sequen ial occu ence o alle gic b onchopul- mona y mycosis (ABPM) and EGPA, o ice e sa. 7 How one es ablished disease may be p edisposed o he o he is unknown bu may include eosinophil ec ui men by Th2-d i en ABPM, o EGPA lung issue damage and sequelae p edisposing o ungal coloniza ion and subsequen hype sensi i i y. Concomi an ABPA and EGPA a p esen a ion seem o be a e han sequen ial de elopmen . In he case desc ibed he e, no pas in es iga ions we e a ailable. Howe e , he pa ien was la gely heal hy be o e his episode, and we conside ha ABPA and EGPA occu ed simul aneously. To he bes o ou knowledge, only h ee o he cases o simul a- neous ABPA/EGPA ha e been epo ed. 7 The possibili y ha EGPA and ABPA may co-exis in he same pa ien has impo an clinical implica ions. Besides di e en ial diagnosis a p esen a ion, long- e m ollow- up o one disease should explo e o “de no o”de elop- men o he o he disease. A fine unde s anding o he mechanisms in ol ed in ABPA, EGPA, o hei simul a- neous p esen a ion, will be equi ed o he choice o a ge ed he apies. Da a a ailabili y In o med consen was signed by he pa ien . Fig. 1 Compa ison o ches X- ay and CT a admission (A-D, a 6 cm-long igh hila mass is obse ed, ex ending o he pleu a and enla ged hila lymph nodes) and 4 mon hs a e disease esolu ion (E-H, la ge a icoid b onchiec asis in bo h lungs can be obse ed, pa icula ly in he igh uppe lobe.). 232 I. Alen Cou inho, M. Lopes, F. Lima e al. Table 1 Diagnos ic c i e ia o IPA, ABPA, EGPA. C i e ia ulfilled by he pa ien a e indica ed by “+”, while un ulfilled c i e ia a e ma ked “-“. NA, no assessed; NT, no es ed. Disease and diagnos ic c i e ia P esen in his case Pu a i e in asi e pulmona y aspe gillosis - all ou c i e ia mus be me (Blo SI, e al. Am J Respi C i Ca e Med. 2012 Jul 1;186(1):56-64. 1. Aspe gillus-posi i e lowe espi a o y ac specimen cul u e (= en y c i e ion) 2. Compa ible signs and symp oms (one o he ollowing) ○Fe e e ac o y o a leas 3 days o app op ia e an ibio ic he apy ○Rec udescen e e a e a pe iod o de e escence o a leas 48 h while s ill on an ibio ics and wi hou o he appa en cause ○Pleu i ic ches pain ○Pleu i ic ub ○Dyspnoea ○Haemop ysis ○Wo sening espi a o y insu ficiency in spi e o app op ia e an ibio ic he apy and en ila o y suppo 3. Abno mal medical imaging by po able ches X- ay o CT scan o he lungs 4. Ei he 4a o 4b 4a. Hos isk ac o s (one o he ollowing condi ions) Neu openia (absolu e neu ophil coun , <500/mm 3 ) p eceding o a he ime o ICU admission Unde lying haema ological o oncological malignancy ea ed wi h cy o oxic agen s Glucoco icoid ea men (p ednisone equi alen , .20 mg/d) Congeni al o acqui ed immunodeficiency 4b. Semiquan i a i e Aspe gillus-posi i e cul u e o BAL fluid (+ o ++), wi hou bac e ial g ow h oge he wi h a posi i e cy ological smea showing b anching hyphae Aspe gillus espi a o y ac coloniza ion + + - + NA + - + + + - + ABPA - ISHAM c i e ia (Aga wal R, e al. Clin Exp Alle gy. 2013 Aug;43(8):850-73.) P edisposing condi ions ○B onchial as hma ○Cys ic fib osis Obliga o y c i e ia (bo h should be p esen ) ○To al IgE>1000IU/ml* ○Posi i e Aspe gillus specific IgE o skin p ick es O he c i e ia (2 ou o 3) ○Raised A IgG o p ecipi ins ○Eosinophils>500 cells/uL ○Radiological ea u es consis en wi h ABPA + - + + + + + ABPA - Rosenbe g-Pa e son c i e ia (Rosenbe g M, e al. Ann In e n Med. 1977; 86:405-414) Majo c i e ia 1. As hma 2. P esence o ansien pulmona y infil a es (flee ing shadows) 3. Immedia e cu aneous eac i i y o A. umiga us 4. Ele a ed o al se um IgE 5. P ecipi a ing an ibodies agains A. umiga us 6. Pe iphe al blood eosinophilia 7. Ele a ed se um IgE and IgG o A. umiga us 8. Cen al/p oximal b onchiec asis wi h no mal ape ing o dis al b onchi Mino c i e ia 1. Expec o a ion o golden b ownish spu um plugs 2. Posi i e spu um cul u e o Aspe gillus species 3. La e (A hus- ype) skin eac i i y o A. umiga us + + + + + + + + - + NT EGPA (Masi AT, e al. A h i is Rheum. 1990 Aug;33(8):1094-100. & Jenne e JC, e al. A h i is Rheum. 1994 Feb;37(2):187-92).The p esence o ou o mo e c i e ia yields a sensi i i y o 85% and a speci- fici y o 99.7%.Fou o mo e c i e ia: ○As hma (wheezing, expi a o y honchi) ○Eosinophilia o mo e han 10% in pe iphe al blood* ○Pa anasal sinusi is ○Pulmona y infil a es (may be ansien ) ○His ological p oo o asculi is wi h ex a ascula eosinophils ○Mononeu i is mul iplex o polyneu opa hy + + + + + - 233 Pulmonology 28 (2022) 231234 Au ho s' con ibu ions IAC and FSR we e a ending physicians du ing hospi aliza ion and ollow-up, collec ed he da a and p epa ed he manu- sc ip . ML, FL, CV and ER we e a ending physicians o he pa ien du ing hospi aliza ion and collec ed pa ien ’s da a. JSC and TA con ibu ed o he diagnosis and he manusc ip . Conflic s o in e es The au ho s epo no conflic s o in e es s ega ding his manusc ip . FSR epo s speake and ad iso y ees om As aZeneca, No a is, Sanofi, GSK, Te a, Takeda, Ked ion and Lusomedicamen a, all ou side he submi ed wo k. Re e ences 1. 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Ch onic pulmona y aspe gil- losis may cause eosinophilic g anuloma osis wi h polyangii is ia alle gic b onchopulmona y aspe gillosis. Ox o d Med Case Repo s. 2019;2019(2):636. 6. G oh M, Pagnoux C, Baldini C, e al. Eosinophilic g anuloma osis wi h polyangii is (Chu g-S auss) (EGPA) Consensus Task Fo ce ecommenda ions o e alua ion and managemen . Eu J In e n Med. 2015;26(7):54553. 7. Ishigu o T, Takayanagi N, Takaku Y, Kagiyama N, Ku ashima K, Sugi a Y. Combined alle gic b onchopulmona y aspe gillosis and eosinophilic g anuloma osis wi h polyangii is: Th ee cases and a e iew o he li e a u e. In e n Med. 2016;55(7):7937. I. Alen Cou inho a, * ,1 , M. Lopes b,1 , F. Lima c , C. Ven u a b ,E. Rabad~ ao b , T. Al a o d , J.S. da Cunha b , F.S. Rega ei o a,e, a Alle gy and Clinical Immunology Uni , Cen o Hospi ala e Uni e si  a io de Coimb a, Coimb a, Po ugal b In ec ious Diseases Uni , Cen o Hospi ala e Uni e si  a io de Coimb a, Coimb a, Po ugal c In e nal Medicine Uni , Hospi al Di ino Espí i o San o de Pon a Delgada, Po ugal d Pulmonology Uni , Cen o Hospi ala e Uni e si  a io de Coimb a, Po ugal e Facul y o Medicine, Uni e si y o Coimb a, Po ugal ICBR - Coimb a Ins i u e o Clinical and Biomedical Resea ch, CIBB, Faculdade de Medicina, Uni e sidade de Coimb a, Po ugal 1 con ibu ed equally. * Co esponding au ho a : Se i¸co de Imunoale gologia, Cen o Hospi ala Uni e si  a io de Coimb a, P ace a P o esso Mo a Pin o, 3000-075 Coimb a, Po ugal. E-mail add esses: [email p o ec ed] (I. Alen Cou inho), [email p o ec ed] (M. Lopes), [email p o ec ed] (E. Rabad~ ao), [email p o ec ed] (J.S. da Cunha). Recei ed 3 Decembe 2021; Accep ed 22 Decembe 2021 A ailable online 28 Ma ch 2022 1 con ibu ed equally. 234 I. Alen Cou inho, M. Lopes, F. Lima e al.