Aspergillus & ABPA
Disease spectrum IPA Invasive pulmonary aspergillosis
ABPA
ABPA pathophysiology conidia of Aspergillus trapped in mucous and narrowed airways of asthmatics/cf germinate to form hyphae release of soluble/particulate antigens airway inflammation epithelial damage Antigen diffuses into interstitium inflammatory mediators released influx of inflammatory cells esp. E & Ag presented to Th2 cells IL-4, IL-5 & IL-13 cytokines synthesized and secreted IgE synthesis mast cell degranulation tissue injury bronchial obstruction, inflammation, mucous plugging bronchiectasis fibrosis respiratory failure
Diagnostic algorithm
Clinical Presentation Asymptomatic patient with or without pulmonary infiltrates OR Poorly controlled asthmatic patient (more common) Low-grade fever Wheezing Bronchial hyperactivity Haemoptysis Weight loss & malaise Productive cough (often w/ expectoration of brownish black sputum) Severe uncontrolled asthma with/out central bronchiectasis pulmonary fibrosis pulmonary hypertension Type 2 respiratory failure
Physical Exam Normal Other findings include: Polyphonic wheezing Clubbing (16%) Coarse crackles (15%) Sx of pulmonary HTN and/or respiratory failure
Differential Diagnosis of ABPA
Asthma vs. ABPA vs. AH
Immunological Findings Cutaneous hypersensitivity Intradermal test > Skin prick test Type 1 immediate +ve & Type 3 delayed +ve positive in virtually all ABPA 40% of asthmatics without ABPA also +ve
Immunological Findings Total IgE Cutoff >1000 IU/mL With Rx Reduction of often > 35% = REMISSION levels do NOT reach normal values repeated measurements needed to determine new baseline Doubling of baseline = relapse
Radiographic Features - CXR Parenchymal infiltrates (generally of upper lobes) Transient vs. fixed Atelectasis due to mucous plugging Findings consistent with bronchiectasis Tram line shadows d/t thickened non-dilated bronchial walls Parallel lines d/t ectactic bronchi Ring shadows d/t mucous filled bronchi or small abscesses Toothpaste shadows d/t mucous plugging in 2 nd to 4 th 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
Radiographic Findings - HRCT Widespread proximal cylindrical bronchiectasis (mostly of upper lobes) Bronchial wall thickening Mucous plugging Atelectasis Peripheral airspace consolidation Ground-glass attenuation Mosaic perfusion Air trapping
Diagnosis of ABPA
Diagnostic algorithm
Diagnosis 6/8 criteria If not confirmed i.e. less than full compliment of dx criteria FU with 6/52 IgE if increasing or >1000 IU/ml Rx ABPA-S (mild) vs. APBA-CB (moderate) vs. ABPA-CB-ORF Recurrent episodes of remissions and relapses
Staging of ABPA
Remission No established definition Reduction of often >35% Usually, by end of 6-9 months with a significant fall in IgE, patient said to be in remission i.e. Stage II (Remission) Complete remission if no exacerbation for next 03 months after stopping Rx FU with IgE every 6 months for 1 st year, then annually
Tx - Goals 1) Early control of immunologic activity / inflammation to try to prevent progression to bronchiectasis and fibrosis 2) Monitoring for response and early detection of relapses 3)?? Decrease fungal burden in airways
Tx - Steroids Doses vary depending on stage and prescriber preference. Higher dosages for longer durations may be more effective for tx g flares. Stages 1 & 3 Prednisone 0.5-1.0 mg/kg Qday x 14 days, then QOD x 6-8 wks, then taper by 5-10 mg q 2 weeks until d/c d Should 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 dose Stage 5 Steroids not helpful Steroid prophylaxis Ca, Vit D, bisphosphonate
Regime 2 Regime 1 Dose Calculated dose Duration 0.5 mg/kg/day mg/day 2/52 0.5 mg/kg/alternate days mg/alternate days 6-8/52 Reduce by 5mg Every 2/52 FU every 6/52 with CXR & IgE Total duration of treatment 6 12 months Dose Calculated dose Duration 0.75 mg/kg/day mg/day 6/52 0.5 mg/kg/day mg/day 6/52 Reduce by 5mg Every 6/52 FU every 6/52 with CXR & IgE Total duration of treatment 6 12 months
Total IgE levels Date Description Load IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml IU/ml
Tx - Itraconazole Decreases antigenic stimulus for bronchial inflammation, possibly by decreasing specific Aspergillus IgG Decreased metabolism of steroids, so may be able to use lower dosages 16 week course + steroids significant increased likelihood of clinical response (46 vs 19%) 200 TID x 3 days, then 200 BID x 16 wks, +/- once day x 16 wks LFTs: Twice weekly for 3 months Monthly
Miscellaneous
SAM The presence of concomitant allergic fungal sinusitis (AFS) and allergic bronchopulmonary mycosis in the same patient represents an expression of the same process of fungal hypersensitivity in the upper and lower airways. SAM syndrome: an acronym for sinobronchial allergic mycosis
Diagnostic Criteria chronic sinusitis involving multiple sinuses asthma total serum IgE levels are usually elevated as well immediate cutaneous reactivity to fungal allergens peripheral eosinophilia radiographic evidence of bronchiectasis. variety of chest radiographic abnormalities may occur: ranging from mass lesions to diffuse pulmonary infiltrates and even normal findings on chest radiographs.