Presentation on theme: "Allergic Bronchopulmonary Aspergillosis (ABPA)"— Presentation transcript:
1Allergic Bronchopulmonary Aspergillosis (ABPA) CF cases are slightly different (eg, criteria for dx, lab values)
2ABPA – Definition and Epidemiology Hypersensitivity reaction d/t colonization of bronchi by Aspergillus bronchial obstruction, inflammation, mucous plugging bronchiectasis, fibrosis, resp failureOccurs primarily in pts w/ asthma (prevalence = 1-2%) or CF (prevalence = 1-15%)Most cases present in the 3rd to 4th decadeNo gender predilectionSome pts have (+) family history of ABPA
3Pathophyisology Incompletely understood Genetic predisposition + inhalation of Aspergillus fumigatus spores (that later germinate into hyphae and release antigens) 1) Airway barrier compromise (in part by dec’d mucociliary clearance, and action of proteolytic and mycotoxins)2) Activation of innate lung immunity Influx of inflammatory cells3) Presentation of antigens to T cells Activation of Th2 cells and inc’d production of Th2 cytokines (Il-4, -5, and -13) Inc’d total and A fumigatus-specific IgE, mast cell degranulation, and eosinophilic response.4) Also Type III (IgG and IgA) hypersensitivity reactions“No apparent relation b/w intensity of exposure to airborne Aspergillus spores and rates of sensitization to the fungus as measured by skin testing”.
4PathologyVaries b/w different patients and w/in different lung ares w/in a ptTypical HistologyMucus, fibrin, Curschmann spirals, Charcot-Leyden crystals, inflammatory cells (primarily eosinophils).Hyphae can often be seen in the bronchiectatic cavitiesOther Possible FindingsFungal growth in lung parenchymaNon-caseating granulomas w/ eosinophils and multi-nucleated giant cells centered on airwaysInvasive aspergillosis (rare)
5Clinical Presentation Common SxsLow-grade feverWheezingBronchial hyperactivityHemoptysisProductive cough (often w/ expectoration of brownish black sputum)Occasionally aSx’c and dx’d on routine screening (eg, 2/2 aSx’c consolidation).
6Physical Exam Can be normal Other possible findings include: Polyphonic wheezingClubbing (16%)Coarse crackles (15%)Sxs of pulmonary HTN and/or respiratory failure
7Dx'c Criteria Major Criteria: (? 6 of 8 needed for dx) 2 Types 1) H/o asthma2) Immediate skin test reactivity to Aspergillus antigens3) Precipitating serum Abs to A. fumigatus4) Serum total IgE > 1000 ng/mL (can be lower if on steroids)5) Peripheral eosinophilia > /mm(3)6) Infiltrates on CXR or HRCT7) Central bronchiectasis on chest CT8) Elev’d specific serum IgE and IgG to A. fumigatusOther Common Findings -- Expectoration of mucous plugs. Aspergillus in sputum, late skin reactivity to Aspergillus Ag2 TypesABPA-CB (central bronchiectasis) -- 1, 2, 4, 7, 8ABPA-S (seropositive) -- 1, 2, 3, 4 but NO accompanying central bronchiectasisNo one dx’c test. Criteria are controversial and continue to be modified d/t the lack of evidence on the # of criteria neededSkin test -- Uses A fumigatus antigen. Test is read q 15 min x 1 hr and again at 6-8 hours. InterpretationType I ( 1 of the characteristic findings of ABPA) - (+) wheal and erythema after 1 min that reaches maximum intensity after min, and resolves w/in 1-2 hours. Indicates presence of A fumigatus specific IgE AbsType III (immune complex hypersensitivity) - Any amount of subcut edema after 6 hours.Often do skin test first. If this is (-) as is intradermal reactivity to Aspergillus, ABPA is essentially excluded.If skin prick is (+), check total serum IgE and precipitans to Aspergillus. If IgE < 1000 or if precipitans are (-), Aspergillus is excluded.
8Radiographic Features - CXR Parenchymal infiltrates (generally of upper lobes)Atelectasis d/t mucous pluggingFindings c/w bronchiectasis“Tram line” shadows d/t thickened non-dilated bronchial walls“Parallel lines” d/t ectactic bronchiRing shadows d/t mucous filled bronchi or small abscesses“Toothpaste shadows” d/t mucous plugging in 2nd to 4th order bronchi“Gloved finger shadows” (branched tubular radiodensities, 2-3 cm long, 5-8 cm wide, extending from the hilum) d/t intrabronchial exudates w/ bronchial wall thickening
12Top R - Bilateral central bronchiectasis w/ centrilobular nodules & tree-in-bud opacities in L lung. Top L - Bilateral central bronchiectasis w/ many mucus-filled bronchi.Bottom L & R - High- attenuation mucoid impaction.
13PFTs Not really used in dx’g ABPA but findings can show Airflow obstructionMixed obstructive and restrictive pattern if bronchiectasis or fibrosisAir trappingDec’d FEV1 and RV(+) Bronchodilator response in < 50%
14Stages of ABPA (not necessarily progressive) Stage I = Acute flareInfiltrates, markedly elev’d IgEStage II = RemissonNo infiltrates, off steroids > 6 mos, elev’d or NL IgEStage III = Recurrent exacerbationsStage IV = Glucocorticoid-dependent asthmaInfiltrates present intermittently or not at all, elev’d or NL IgEStage V = Fibrotic (end stage) lung dzFibrotic, bullous, cavitary lung lesions, IgE may be normal
15Tx - Goals1) Early control of immunologic activity / inflammation to try to prevent progression to bronchiectasis and fibrosis2) Monitoring for response and early detection of relapses3) ?? Dec fungal burden in airways
16Tx - SteroidsDoses vary depending on stage and prescriber preference. Higher dosages for longer durations may be more effective for tx’g flares.Stages 1 & 3 – Prednisone mg/kg Qday x 14 days, then QOD x 6-8 wks, then taper by 5-10 mg q 2 weeks until d/c’dShould see resolution of infiltrates and 35-50% dec in serum total IgE (measured q1-2 months during acute treatment)Stage 2 – Steroids not needed. Monitor IgE q6 months x 1 year then q 1-2 years. Doubling of baseline IgE indicates relapse (stage 3)Stage 4 – Steroid dependent. Aim for lowest possible doseStage 5 – Steroids not helpfulSteroid “prophylaxis” – Ca, Vit D, bisphosphonateNeed systemic form (inhaled form may help w/ underlying asthma but has no efficacy in ABPA)
17Tx - ItraconazoleDec’s antigenic stimulus for bronchial inflammation, possibly by dec;g specific Aspergillus IgGDec’d metabolism of steroids, so may be able to use lower dosages16 week course + steroids significant increased likelihood of clinical response (46 vs 19%)200 TID x 3 days, then 200 BID x 16 wks, +/- Qday x 16 wksMonthly LFTs