ABPA case in 60 male patient, misdiagnosed by TB

1. Laporan Pagi Jumat
25 November 2016

2. RESUME :
• Laki-laki 60 tahun dirawat di Dahlia 3
• Keluhan utama : sesak dan batuk memberat 2 MSMRS
• Batuk dahak lama ± 1 tahun kambuh-kambuhan, dahak putih kekuningan (+),
batuk darah (-), sesak (-)
• 3 bulan yll mulai disertai sesak (+), mengi (+), demam hilang timbul (+), ⬇ BB
(+) ± 10 kg / 3 bulan ini
• 2 minggu batuk dan sesak memberat, semakin berdahak, darah (-), bau (-)
• Periksa di RSUD Purworejo dikatakan TB dan dimulai pengobatan OAT,
regimen pirazinamide dan etambutol oleh Sp.P
• Riwayat asma saat muda (-), RPK atopi (-), riw DM sejak 2003
• Pasien sering batuk dan bersin jika terpapar debu dan asap
• Riw perokok 5 tahun, berhenti sejak 1982

3. RESUME :
• KU sedang, CM
• IMT = 19
• TD 100/60, N 104, RR 26, T 37,5
• JVP tidak meningkat,
• Paru : simetris (+), retraksi (+), sonor (+), ronchi (+) di paru kanan,
wheezing (-)
• Cor dalam batas normal
• hepatomegali (-)
• Sianosis (-), clubbing finger (-), edem tungkai (-)

4. Pemeriksaan Penunjang
Darah rutin
Hb 11.5  10
AL 14.26  10,6
AT 310  241
AE 4.11  3,4
Hmt 33.8  30
S 37.4  44,9
L 13.9  12,7
M 7.2  4,6
E 40.3  35,4
B 1.2  0,7
MCV 82.2  86,7
MCH 28  28,8
Hati
GOT 13
GPT 18
Alb 3.5
Glukosa
GDS 234
Elektrolit
Na 137.4
K 2.71  3,7
Cl 96
Ginjal
BUN 7.8
Crea 1.04
AGD
pH 7.46
pCO2 64,8
pO2 91,7
HCO3 46,5
BE
SO2 95
AaDO2 474
fiO2 30
pO2/FiO2 303

5. Ro thorax 12/11/16 :mengarah gambaran bronchiectasis terinfeksi

6. EKG 11/11/16: STC, heart rate 110 kali/menit, normoaksis

7. APAKAH diagnosis banding anda.....??????
BRONCHIECTASIS E.C TUBERCULOSIS PARU ...... ?????

8. MSCT thorax 17/11/16 : infected bronchiectasis tipe kistik pulmo dextra

9. Bronkoskopi 23/11/16 : penyempitan cabang RUL (C3)

10. Ig E total > 1000 kUI/L (normal <100)
IgE spesifik aspergilosis (+) 5,24  high
Skin prick test  tidak valid dinilai
Gene expert sputum : MTB not detected

11. • Assessment :
• Bronchiectasis infected
• Hipereosinofilia syndrome ec ABPA
• DM2NO
• Tinea Cruris et corporis

12. Menunggu hasil
• Sitologi BAL
• Sitologi brushing
• Kultur aspergillus BAL
• Kultur BTA BAL
• Gene expert BAL

13. Terapi :
• Diet diabetes mellitus 1500 kalori
• O2 3 L /mnt
• Inj. Ceftazidime 2 gram/8 jam
• Inj. Levofloxacin 750 mg/24 jam
• Atrovent pulmicort = 2cc:2cc/ 8
jam
• asetilsistein 3x1 tab
• asparK 3x1
• Novorapid 4-4-4
• Fluconazole 150mg/minggu
selama 6 minggu
• Myconazole cream 2 dd ue
Plan :
• LACAK HASIL
• Chest fisioterapi
• spirometri

14. Allergic BronchoPulmonary Aspergillosis (ABPA)
the disease entity is still underrecognized
Laporan Pagi
Jumat 25 November
2016

15. Definition
 Pulmonari alergi karena hipersensitivitas terhadap
Aspergillus fumigatus 1
 Terjadi pada asthma atau cystic fibrosis2
 Menyebabkan bronchiectasis, pulmonary fibrosis, dan ⬇
fungsi paru
 Pertama ditemukan Hinson et al pada 1952 di UK
1.CHEST 2009; 135:805–826.
2. Middleton’s Allergy, Principle&Practice 7th edition.

16. Allergic Bronchopulmonary Aspergillosis: An Unusual Complication of
Bronchial Asthma
Pages with reference to book, From 329 To 331
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital, Karachi. ) M.
Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )

17. Kasus 1.
Pria 19 tahun, asma sejak kecil, datang karena demam, batuk, hemoptoe dan
infiltrat di paru. Di Tx OAT 9 bulan. 5 tahun kmudaian datang lagi dengan
keluhan sama
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital,
Karachi. ) M. Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )

18.  Sputum BTA (-)  klinis curiga TB  OAT lagi
 Juga mendapat bronchodilators, inhaled steroids
dan oral prednisolone.
 6 bulan berikutnya (dalam Tx OAT)  nyeri pleuritic
rekuren, demam, batuk, wheezing, hemoptoe  Ro
= infiltrat di paru kanan (Figure ib).
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital,
Karachi. ) M. Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )

19. S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital,
Karachi. ) M. Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )

20.  BTA sputum (-), eosinofilia 12%, Ig E > 1000,
antibodi aspergilus (-)
 Diagnosis = ABPA
 Tx = prednisolone 30 mg daily
 Rapid resolution
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital,
Karachi. ) M. Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )
Allergic Bronchopulmonary Aspergillosis: An Unusual Complication of
Bronchial Asthma
Pages with reference to book, From 329 To 331
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital, Karachi. ) M.
Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )

21. Allergic Bronchopulmonary Aspergillosis: An Unusual Complication of
Bronchial Asthma
Pages with reference to book, From 329 To 331
S. Fayyaz Hussain, Javaid A. Khan ( Department of Medicine, The Aga Khan University Hospital, Karachi. ) M.
Ata Khan ( Department of Medicine, The Aga Khan University Hospital. Karachi. )
Gambaran klinis ABPA (batuk, demam, hemoptoe dan
infiltrat paru) mirip dengan TB

22. CHEST. 2006;130(2):442-448. DOI:10.1378/CHEST.130.2.442
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS*:LESSONS FROM 126
PATIENTS ATTENDING A CHEST CLINIC IN NORTH INDIA.
RITESH AGARWAL, MD, DM, FCCP; DHEERAJ GUPTA, MD, DM, FCCP; ASHUTOSH N. AGGARWAL, MD, DM;
DIGAMBER BEHERA, MD, FCCP; SURINDER K. JINDAL, MD, FCCP
 Five hundred sixty-four patients were screened using an Aspergillus skin test; 223 patients (39.5%)
were found to be positive, and ABPA was diagnosed in 126 patients (27.2%). There were 34 patients
(27%) with ABPA-S, 42 patients with ABPA-CB, and 50 patients with ABPA-CB-ORF. Fifty-nine patients
(46.8%) had received antitubercular therapy in the past. The vast majority of patients had bronchiectasis
at presentation to our hospital. High-attenuation mucous impaction was noted in 21 patients (16.7%).
There was no significant difference between the stages of ABPA and the duration of illness, the severity
of asthma, and the serologic findings (ie, absolute eosinophil count, IgE levels [total] and IgE levels
[for Aspergillus fumigatus]).
 Conclusions: There is a high prevalence of ABPA in asthmatic patients presenting at our hospital. The
disease entity is still underrecognized in India; the vast majority of patients
have bronchiectasis at presentation, and almost half are initially
misdiagnosed as having pulmonary tuberculosis. There is a need to redefine the
definitions of ABPA and the optimal dose/duration of glucocorticoid therapy. This study reinforces the
need for the routine screening of asthmatic patients with an Aspergillus skin test.
59 pasien (48%) mendapat terapi OAT sebelumnya (misdiagnosis)

23. Respiratory Medicine CME
Volume 4, Issue 4, Pages 149-200 (2011)
Case Report
Allergic bronchopulmonary aspergillosis presenting with cough variant
asthma with spontaneous remission
Hirofumi Matsuoka, Towa Uzu, Midori Koyama, Yasuko Koma, Kensuke
Fukumitsu, Yoshitaka Kasai, Daiki Masuya, Harukazu Yoshimatsu, Yujiro Suzuki
Wanita 60 tahun, keluhan batuk kering tanpa sesak / wheezing.
CT scan = mucoid impaction

24. Fig. 1. Chest radiograph
showing bilateral infiltrates.
Fig. 2.
a: Chest CT image during
the acute phase shows an
image of mucoid
impactions in the right
middle lung lobe and the
left lingular bronchus.
b: Chest CT image during
the remission stage
shows bronchiectasis in
the lingula of the left
lung. The image of m...
Fig. 3. Bronchofiberscopy
findings. Mucoid impaction in
the right middle lung lobe
bronchus
Respiratory Medicine CME, Volume 4, Issue 4, 2011, 175–177
A 60-year-old woman presented with a dry cough without dyspnea or wheezing.

27.  17. D´Urzo,Mclvor A.R. Allergic bronchopulmonary aspergillosis in asthma.
Can Fam Physician. 2000 Apr; 46: 882–884.
 18. Shah A, Panchal N, Agarwal AK. Concomitant allergic bronchopulmonary
aspergillosis and allergic aspergillus sinusitis: a review of an uncommon
association. Clin Exp Allergy 2001;31:1896–1905. [CrossRef] [Medline]
 19. Agarwal R, Srinivas R, Jindal SK. Allergic bronchopulmonary aspergillosis
complicating chronic obstructive pulmonary disease. Mycoses 2007;51:83–85.
 20. Boz AB, Celmeli F, Arslan AG, Cilli A, Ogus C, Ozdemir T. A case of allergic
bronchopulmonary aspergillosis following active pulmonary
tuberculosis. Pediatr Pulmonol 2009;44:86–89. [CrossRef] [Medline]
 21. Judson MA. Allergic bronchopulmonary aspergillosis after infliximab therapy
for sarcoidosis: a potential mechanism related to T-helper cytokine
balance. Chest 2009;135:1358–1359. [CrossRef] [Medline]
 39. Agarwal R, Singh N, Gupta D. Pulmonary hypertension as a presenting
manifestation of allergic bronchopulmonary aspergillosis. Indian J Chest Dis Allied
Sci 2009;51:37–40. [Medline]
Uncommon associations of allergic bronchpulmonary aspergillosis

28. Epidemiologi
 1–2% pada asma kronik 1
 2–15% pada cystic fibrosis 2
 Meta-analysis, prevalensi ABPA pada asthma
12.9%3
1. Greenberger PA et al. J Allergy Clin Immunol 1988;82:164–
70.
2. Stevens D, et al. Clin Infect Dis 2003;37(suppl 3):S225–
64.

29. Studies Describing Prevalence of AH and/or ABPA in Patients with Bronchial Asthma Over
the Last Two Decades
CHEST 2009; 135:805–826
(43%
)
(18%
)
(23%
)
(22%)
(28%
)
(38%)
(30%)
(6%)
(25%)
(16%
)
(7%
)
(20%
)
(7%)

30. Relative risk of Aspergillus infection
Patients whose immune system is already weakened are most
susceptible.
.
Immune malfunction
Frequencyofaspergillosis
Immune hyper-reactivity
Frequencyofaspergillosis Acute invasive
aspergillosis
Aspergilloma
Allergic aspergillosis
Allergic sinusitis
Normal
immune
function

31. Pathophysiology of ABPA. From Aspergillus adherence and penetration of the bronchial
mucosa to the B and T cell response
Allergy 2005: 60: 1004–1013

32. Pathology
• Musin dengan
sebukan eosinofil
dan Charcot
leyden crystals
Clin Infect Dis 2008;47:540–1

33. Pathology
• silver stain : fungal
hyphae
morphologically
consistent with
Aspergillus species
Clin Infect Dis 2008;47:540–1

34. Agarwal, R.; et al., Clin. Exp. Allergy 2013, 43, 850–873.

35. Clinical staging of ABPA
CHEST 2009; 135:805–826

36. Treatment
Managemen
t of ABPA
Inhaled
corticosteroids
Systemic
glucocorticoid
therapy
Other
therapies
Oral
Antifungals

37. Management
 Systemic Glucocorticoid Therapy
◦ treatment of choice for ABPA
◦ Suppress immune hyperfunction & antiinflammatory
◦ Long term therapy not recommended
 Regimen 1 (relapse /steroid dependence 45%) / medium dose regiment
◦ Prednisolone, 0.5 mg/kg/d, for 1–2 wk, then on AD for 6–8 wk. Then taper
by 5–10 mg every 2 wk and discontinue
◦ Repeat total serum IgE and chest radiograph in 6 to 8 wk
 Regimen 2 (steroid dependence 13.5%) high dose regiment
◦ Prednisolone, 0.75 mg/kg/d, for 6 wk, 0.5 mg/kg for 6 wk, then tapered by
5 mg every 6 wk to continue for total duration of at least 6 to 12 mo.
◦ total IgE levels are repeated every 6 to 8 wk for 1 yr to determine baseline
IgE CHEST 2009; 135:805–826

39. Management
 Follow-up and monitoring
 Evaluasi gejala dan tanda klinis, rontgen, MSCT
torax, IgE total setelah 6 minggu
 Penurunan IgE 35% dari baseline = respon terapi
baik
 Doubling of baseline IgE : silent ABPA exacerbation
 Monitor efek samping (eg, HT, secondary DM)
 Prophylaxis osteoporosis: oral calcium and
bisphosphonates CHEST 2009; 135:805–826

40. Management
 Oral itraconazole
◦ Dose: 200 mg bid for 16 wk then once a day for 16 wk
◦ Indication: glucocorticoid-dependent ABPA
Follow-up and monitoring
◦ Monitor for adverse effects
◦ Monitor for drug–drug interactions
◦ Monitor clinical response based on clinical course,
radiography, and total IgE levels
CHEST 2009; 135:805–826

42. Dilema pada pasien ini:
 Stage V  apakah corticosteroid masih efektif
 Efek samping steroid  pasien DM, infeksi jamur
kulit
 TB paru harus diekslusi  lacak hasil Gene expert
BAL

43.  Stage V  apakah corticosteroid masih efektif
Tillie et al., 2005

44. TAKE HOME MESSAGES
 Gejala klinis ABPA mirip dengan TB sehingga sering
terjadi misdiagnosis
 Selalu pikirkan ABPA sebagai diagnosis banding
terutama pada pasien asma dengan gejala yang
menyerupai pneumonia atau TB dengan
hipereosinofilia
 Diagnostik dini menentukan keberhasilan terapi
APBA

45. THANK YOU....

46. Primary criteria:
 Asthma  ?
 Peripheral blood eosinophilia
 Positive skin test for aspergillus  NA
 Precipitating antibodies(IgG) in serum
 Serums Af spesific IgG and IgE
 IgE elevation (>1000mL)
 Pulmonary infiltrations
 Central bronchiectasis
Secondary criteria:
 Positive sputum culture for aspergillus  menunggu hasil
 History of brown mucus plug expectoration
 Positive type III(Arthus) reaction for aspergillosis
ABPA Diagnostic Criteria
Soubani AO.Chest 2002;121:1988-1999
Lazarus AA. Dis Mon 2008;54:547-564
Agarwal R. Chest 2009;135:805-826

47. Management
 Inhaled Corticosteroids
◦ DBPC multicenter (32 pts.) no superiority over placebo
◦ Use only for control of asthma once oral prednisolone
dose is reduced to 10 mg/d
 Other Therapies
◦ other antifungal agents (e.g. amphotericin B,
ketoconazole, clitromazole, nystatin and natamycin)
severe adverse effects and no significant beneficial
effects
◦ Omalizumab (case report)
CHEST 2009; 135:805–826

48. Treatment of Allergic Bronchopulmonary Aspergillosis
(ABPA) in CF With Anti-IgE Antibody (Omalizumab)
Adaobi Kanu. Pediatr Pulmonol. 2008; 43:1249–1251
Successful treatment of allergic bronchopulmonary
aspergillosis with recombinant anti-IgE antibody
Cornelis K van der Ent . Thorax 2007;62;276-277
Steroid-Sparing Effect of Omalizumab for Allergic
Bronchopulmonary Aspergillosis and Cystic Fibrosis
Jacquelyn M. Zirbes . Pediatr Pulmonol. 2008; 43:607–610
Omalizumab (ABPA)

49. Sumber infeksi
 Aspergillus ditemukan di:
 tanah, sampah organik
 Udara : spora  terhirup
 Air
 Rumah tangga (bantal, kasur)
 Sistem AC
 Kipas angin
 dll
