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. Donnelly JP, Chen SC, Kau man CA, S einbach WJ, Baddley JW,
Ve weij PE, e al. Re ision and upda e o he consensus defini-
ions o in asi e ungal disease om he Eu opean O ganiza ion
o Resea ch and T ea men o Cance and he Mycoses S udy
G oup Educa ion and Resea ch Conso ium. Clin In ec Dis. 2020
Sep 12;71(6):136776.
2. Blo SI, Taccone FS, Van den Abeele AM, Bulpa P, Mee sseman W,
B usselae s N, e al. A clinical algo i hm o diagnose in asi e pul-
mona y aspe gillosis in c i ically ill pa ien s. Am J Respi C i
Ca e Med. 2012 Jul 1;186(1):5664.
3. Gago S, Denning DW, Bowye P. Pa hophysiological aspec s o
Aspe gillus coloniza ion in disease. Med Mycol. 2019 Ap 1;57
(Supplemen _2):S21927.
4. Ganassini A, Cazzado i A. In asi e pulmona y aspe gillosis com-
plica ing alle gic b onchopulmona y aspe gillosis. Respi Med.
1995;89(2):1435.
5. Ha ada M, Imokawa S, Miwa S, e al. 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.