Allergic BronchoPulmonary Aspergillosis (ABPA) the disease entity is still underrecognized

Laporan Pagi Jumat25 November 2016

RESUME :Laki-laki 60 tahun dirawat di Dahlia 3Keluhan utama : sesak dan batuk memberat 2 MSMRSBatuk 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 ini2 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.PRiwayat asma saat muda (-), RPK atopi (-), riw DM sejak 2003Pasien sering batuk dan bersin jika terpapar debu dan asapRiw perokok 5 tahun, berhenti sejak 1982

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

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Pemeriksaan PenunjangDarah rutinHb11.5 10AL14.26 10,6AT310 241AE4.11 3,4Hmt33.8 30

S37.4 44,9L13.9 12,7M7.2 4,6E40.3 35,4B1.2 0,7MCV82.2 86,7MCH28 28,8HatiGOT13GPT18Alb3.5GlukosaGDS234ElektrolitNa137.4K2.71 3,7Cl96GinjalBUN7.8Crea1.04AGDpH7.46pCO264,8pO291,7HCO346,5BESO295AaDO2474fiO230pO2/FiO2 303

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

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

APAKAH diagnosis banding anda.....??????

BRONCHIECTASIS E.C TUBERCULOSIS PARU ...... ?????

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

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

Ig E total > 1000 kUI/L (normal 1000, antibodi aspergilus (-)

Diagnosis = ABPA Tx = prednisolone 30 mg dailyRapid resolutionS. 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 AsthmaPages with reference to book, From329To331S. 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 AsthmaPages with reference to book, From329To331S. 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

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, FCCPFive 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 [forAspergillus 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)

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

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, 175177A 60-year-old woman presented with a dry cough without dyspnea or wheezing.

kultur mukus = A. Niger (+) Ig E 5150 IU/mlIg E specific for Aspergillus (+)Tidak ada riw AsmaDiagnosis = allergic bronchopulmonary aspergillosis without asthma

17. DUrzo,Mclvor A.R. Allergic bronchopulmonary aspergillosis in asthma.Can Fam Physician. 2000 Apr; 46: 882884.

18.Shah A, Panchal N, Agarwal AK. Concomitant allergic bronchopulmonary aspergillosis and allergic aspergillus sinusitis: a review of an uncommon association.Clin Exp Allergy2001;31:18961905.[CrossRef][Medline]

19.Agarwal R, Srinivas R, Jindal SK. Allergic bronchopulmonary aspergillosis complicating chronic obstructive pulmonary disease.Mycoses2007;51:8385.

20.Boz AB, Celmeli F, Arslan AG, Cilli A, Ogus C, Ozdemir T. A case of allergic bronchopulmonary aspergillosis following active pulmonary tuberculosis.Pediatr Pulmonol2009;44:8689.[CrossRef][Medline]

21.Judson MA. Allergic bronchopulmonary aspergillosis after infliximab therapy for sarcoidosis: a potential mechanism related to T-helper cytokine balance.Chest2009;135:13581359.[CrossRef][Medline]

39.Agarwal R, Singh N, Gupta D. Pulmonary hypertension as a presenting manifestation of allergic bronchopulmonary aspergillosis.Indian J Chest Dis Allied Sci2009;51:3740.[Medline]

Uncommon associations of allergic bronchpulmonary aspergillosis

Epidemiologi 12% pada asma kronik 1215% pada cystic fibrosis 2Meta-analysis, prevalensi ABPA pada asthma 12.9%3

Greenberger PA et al. J Allergy Clin Immunol 1988;82:16470.Stevens D, et al. Clin Infect Dis 2003;37(suppl 3):S22564.Int J Tuberc Lung Dis 2009

Studies Describing Prevalence of AH and/or ABPA in Patients with Bronchial Asthma Over the Last Two Decades

CHEST 2009; 135:805826(43%)(18%)(23%)(22%)(28%)(38%)(30%)(6%)(25%)(16%)(7%)(20%)(7%)

Relative risk of Aspergillus infectionPatients whose immune system is already weakened are most susceptible. .

Immune malfunction

Frequency of aspergillosis

Immune hyper-reactivity

Frequency of aspergillosis

Acute invasiveaspergillosisAspergilloma

Allergic aspergillosisAllergic sinusitis

Normal immune function

Pathophysiology of ABPA. From Aspergillus adherence and penetration of the bronchial mucosa to the B and T cell responseAllergy 2005: 60: 10041013

Pathology

Musin dengan sebukan eosinofil dan Charcot leyden crystalsClin Infect Dis 2008;47:5401

Pathology

silver stain : fungal hyphae morphologically consistent with Aspergillus species Clin Infect Dis 2008;47:5401

Agarwal, R.; et al., Clin. Exp. Allergy 2013, 43, 850873.

Clinical staging of ABPA

CHEST 2009; 135:805826

TreatmentManagement of ABPA

Inhaled corticosteroidsSystemic glucocorticoid therapyOther therapies

Oral Antifungals

ManagementSystemic Glucocorticoid Therapytreatment of choice for ABPASuppress immune hyperfunction & antiinflammatoryLong term therapy not recommended

Regimen 1 (relapse /steroid dependence 45%) / medium dose regimentPrednisolone, 0.5 mg/kg/d, for 12 wk, then on AD for 68 wk. Then taper by 510 mg every 2 wk and discontinueRepeat total serum IgE and chest radiograph in 6 to 8 wk

Regimen 2 (steroid dependence 13.5%) high dose regimentPrednisolone, 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 IgECHEST 2009; 135:805826

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ManagementFollow-up and monitoringEvaluasi gejala dan tanda klinis, rontgen, MSCT torax, IgE total setelah 6 mingguPenurunan IgE 35% dari baseline = respon terapi baikDoubling of baseline IgE : silent ABPA exacerbationMonitor efek samping (eg, HT, secondary DM)Prophylaxis osteoporosis: oral calcium and bisphosphonatesCHEST 2009; 135:805826

ManagementOral itraconazoleDose: 200 mg bid for 16 wk then once a day for 16 wkIndication: glucocorticoid-dependent ABPA

Follow-up and monitoringMonitor for adverse effects Monitor for drugdrug interactionsMonitor clinical response based on clinical course, radiography, and total IgE levelsCHEST 2009; 135:805826

Dilema pada pasien ini: Stage V apakah corticosteroid masih efektifEfek samping steroid pasien DM, infeksi jamur kulitTB paru harus diekslusi lacak hasil Gene expert BAL

Stage V apakah corticosteroid masih efektif

Tillie et al., 2005

Take home messagesGejala 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

THANK YOU....

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 aspergillosisABPA Diagnostic CriteriaSoubani AO.Chest 2002;121:1988-1999Lazarus AA. Dis Mon 2008;54:547-564Agarwal R. Chest 2009;135:805-826

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ManagementInhaled CorticosteroidsDBPC multicenter (32 pts.) no superiority over placeboUse only for control of asthma once oral prednisolone dose is reduced to 10 mg/dOther Therapiesother antifungal agents (e.g. amphotericin B, ketoconazole, clitromazole, nystatin and natamycin) severe adverse effects and no significant beneficial effects Omalizumab (case report) CHEST 2009; 135:805826

Treatment of Allergic Bronchopulmonary Aspergillosis(ABPA) in CF With Anti-IgE Antibody (Omalizumab)Adaobi Kanu. Pediatr Pulmonol. 2008; 43:12491251Successful treatment of allergic bronchopulmonaryaspergillosis with recombinant anti-IgE antibodyCornelis K van der Ent . Thorax 2007;62;276-277Steroid-Sparing Effect of Omalizumab for AllergicBronchopulmonary Aspergillosis and Cystic FibrosisJacquelyn M. Zirbes . Pediatr Pulmonol. 2008; 43:607610Omalizumab (ABPA)

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Sumber infeksi

Aspergillus ditemukan di:

tanah, sampah organikUdara : spora terhirupAir Rumah tangga (bantal, kasur)Sistem ACKipas angindll