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Allergic Bronchopulmonary Aspergillosis (ABPA)

Definition

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Etiology & Epidemiology

• Causative organism: Aspergillus fumigatus (almost all cases); rarely other Aspergillus spp. or fungi
• Occurs in ~2.5% of asthmatic patients referred to secondary care
• More common in patients from the Indian subcontinent
• In cystic fibrosis: up to 15% of teenagers are affected
• (Harrison's, p. 6271)

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Pathophysiology

• Aspergillus spores are inhaled and germinate in bronchi
• In atopic individuals → Type I hypersensitivity (IgE-mediated) + Type III hypersensitivity (IgG immune complex-mediated)
• Results in:
  • Eosinophilic inflammation
  • Bronchial wall damage
  • Mucous plug formation
  • Progressive bronchiectasis (central, proximal)

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Clinical Features

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Stages of ABPA (Rosenberg-Patterson Staging)

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Diagnostic Criteria (ISHAM 2013 / Rosenberg Criteria)

Obligatory criteria (both must be present):

1. Asthma or cystic fibrosis
2. Positive Aspergillus skin-prick test OR elevated serum Aspergillus-specific IgE

Other criteria (≥2 required):

• Total serum IgE > 1000 IU/mL
• Elevated serum Aspergillus-specific IgG (precipitins)
• Chest X-ray/CT infiltrates consistent with ABPA
• Central/proximal bronchiectasis on HRCT
• Peripheral blood eosinophilia (>500 cells/μL)

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Investigations

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Treatment

1. Systemic Glucocorticoids (First-line)

(Harrison's, p. 7966)

2. Antifungal Agents (Steroid-sparing / Adjunctive)

• Reduce antigenic stimulus → modulate disease activity
• Used when steroids are not tolerated or disease is recurrent
• Monitor liver function during azole therapy

3. Biologics (Severe/Refractory ABPA)

4. Supportive

• Inhaled corticosteroids + bronchodilators for underlying asthma
• Chest physiotherapy / mucus clearance techniques
• Avoid environmental Aspergillus exposure

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Complications

• Central bronchiectasis (pathognomonic)
• Pulmonary fibrosis (Stage V)
• Chronic respiratory failure
• Aspergilloma formation
• Steroid-related side effects (osteoporosis, DM, hypertension)

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Prognosis

• Early diagnosis and treatment can prevent progression to fibrosis
• Regular monitoring of serum IgE is the best marker of disease activity and relapse
• Relapses (Stage III) are common; each episode treated like Stage I

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Key Points to Remember (Exam Highlights)

• Organism: Aspergillus fumigatus | Mechanism: Type I + III hypersensitivity
• Hallmark lab: Total IgE >1000 IU/mL
• Hallmark imaging: Central bronchiectasis + high-attenuation mucus (HAM) on HRCT
• First-line: Prednisolone 0.5 mg/kg/day tapered over 3–6 months
• Antifungal: Itraconazole 200 mg BD × 4–6 months
• Stage V = end-stage fibrosis (irreversible)

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ABPA — Latest Guidelines (Full Details)

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1. DIAGNOSTIC FRAMEWORK — ISHAM Working Group Criteria (Current Standard)

Predisposing Conditions (Must have at least one):

• Bronchial asthma
• Cystic fibrosis (CF)

Obligatory Criteria (Both required):

Other Criteria (≥2 of the following):

Note (2021 update): Some working groups now accept total IgE >500 IU/mL as a lower threshold in patients already on corticosteroids, since steroids suppress IgE levels.

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2. ABPA SUBTYPES (ISHAM Classification)

HAM is considered a marker of severe/difficult-to-treat ABPA and predicts steroid dependence.

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3. STAGING — Revised Patterson Staging

Stages IV and V are not reversible — prevention by early treatment is key.

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4. INVESTIGATIONS (Workup Protocol)

Serological:

Skin Testing:

• Immediate skin-prick test to A. fumigatus extract — wheal ≥3 mm at 15 min = positive
• Intradermal test if skin-prick is equivocal

Imaging:

• Fleeting/migratory infiltrates
• "Gloved finger" sign — dilated bronchi filled with mucus
• Tramline shadows, ring shadows
• Toothpaste / Y-shaped opacities (mucoid impaction)
• Upper lobe collapse/consolidation

Sputum:

• Fungal hyphae on microscopy
• Eosinophils
• Charcot-Leyden crystals
• Culture: A. fumigatus (not diagnostic alone)

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5. TREATMENT — Latest Guidelines

PHASE 1: ACUTE STAGE (Stage I / III)

A. Oral Corticosteroids (First-line — universally recommended)

• Monitor: Total serum IgE every 6–8 weeks
• Target: ≥35% reduction in IgE = remission
• Rising IgE (>2× baseline) = exacerbation → restart full-dose steroids

Low-dose protocol (Indian guidelines / Aggarwal 2016):

• Prednisolone 0.5 mg/kg/day × 1–2 weeks → alternate day × 6–8 weeks → slow taper
• Comparable efficacy with fewer side effects

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B. Antifungal Therapy (Steroid-sparing / Adjunctive — current standard of care)

• Exacerbating/recurrent ABPA
• Steroid-dependent ABPA (Stage IV)
• Patients who cannot tolerate corticosteroids
• ABPA complicating cystic fibrosis
• As steroid-sparing agents in all acute episodes (some guidelines recommend routine use)

• LFTs at baseline and every 4–6 weeks
• Drug-drug interactions (CYP3A4)
• Itraconazole drug levels (therapeutic drug monitoring recommended)

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PHASE 2: MAINTENANCE / REMISSION

• Inhaled corticosteroids (ICS) — high dose (e.g., budesonide 800 mcg/day or fluticasone 500 mcg BD) for underlying asthma control
• Long-acting bronchodilators (LABA) as per asthma step-up therapy
• Regular IgE monitoring every 3–6 months
• Annual HRCT if clinically indicated

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PHASE 3: REFRACTORY / SEVERE ABPA — Biologics

A. Omalizumab (Anti-IgE monoclonal antibody)

B. Mepolizumab (Anti-IL-5)

C. Benralizumab (Anti-IL-5Rα)

D. Dupilumab (Anti-IL-4Rα / IL-13)

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6. TREATMENT IN SPECIAL POPULATIONS

ABPA in Cystic Fibrosis (CF-ABPA):

• Diagnosis is harder — baseline IgE is elevated, and bronchiectasis is pre-existing
• Threshold: IgE >500 IU/mL with 2× rise; use CF-specific ISHAM criteria
• Steroids: Same prednisolone regimen; caution with growth suppression in children
• Itraconazole: First-line antifungal; use oral solution for better absorption
• Omalizumab: Preferred biologic in CF-ABPA
• Avoid: Aminoglycosides and azole combinations without monitoring (renal/hepatic toxicity)

ABPA in Pregnancy:

• Prednisolone is safe (lowest effective dose)
• Itraconazole is teratogenic — CONTRAINDICATED in first trimester; avoid throughout if possible
• Use amphotericin B if antifungal absolutely needed in pregnancy

Pediatric ABPA:

• Prednisolone: 1–2 mg/kg/day (max 40–60 mg) × 2 weeks → taper
• Itraconazole: 5 mg/kg/day (max 200 mg/day)
• Monitor growth on long-term steroids

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7. MONITORING PROTOCOL (Follow-up)

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8. RESPONSE CRITERIA

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9. KEY POINTS SUMMARY TABLE

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ISHAM 2024 ABPA Guidelines — Current Status

What was revised in the 2021 ISHAM guidelines (most current full version):

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Regarding "ISHAM 2024":

• No new standalone ISHAM 2024 ABPA guideline document has been widely published or indexed in major medical databases (PubMed, MEDLINE) as a full revision.
• Some 2023–2024 updates exist as consensus statements and position papers from individual authors (Agarwal R, Denning DW), published in journals such as Mycoses, CHEST, and Clinical Infectious Diseases, refining specific areas.

Key 2023–2024 Published Updates (evidence-based):

1. Diagnostic Updates

• Dupilumab effect on IgE: Dupilumab paradoxically raises total IgE early in treatment — 2024 expert consensus recommends not using total IgE alone for diagnosis in patients on dupilumab; use Aspergillus-specific IgE + HRCT instead.
• Seronegative ABPA: Recognized as a distinct entity — patients with classic CT findings (HAM, central bronchiectasis) but IgE <1000 IU/mL; diagnosis now requires MDT discussion.
• Molecular diagnostics: Aspergillus-specific IgE component testing (rAsp f1, f2, f3, f4, f6) being validated for improved specificity — rAsp f4 and rAsp f6 most specific for ABPA vs. simple sensitization.

2. Treatment Updates (2023–2024 consensus)

• Low-dose prednisolone regimen now preferred over high-dose in most patients:
  • Prednisolone 0.25–0.5 mg/kg/day × 2 weeks → taper over 3–4 months
  • High-dose regimen (0.5–1 mg/kg/day) only for severe/HAM-positive ABPA
• Goal: Minimize cumulative steroid dose (prevent adrenal suppression, osteoporosis, DM)

• Itraconazole 200 mg BD × 4–6 months — remains standard
• Therapeutic drug monitoring (TDM) now strongly recommended: trough itraconazole >0.5 mg/L (ideally 1–4 mg/L)
• Voriconazole 200 mg BD — second line (more adverse effects: photosensitivity, neurotoxicity)
• Posaconazole — for azole-resistant or azole-intolerant cases
• 2024 expert consensus: Combination of steroids + itraconazole recommended as initial therapy for all Stage I and III patients (not just refractory), particularly those with HAM or recurrent exacerbations

3. Monitoring Updates

• Total IgE monitoring remains gold standard for relapse detection
• In patients on biologics that suppress eosinophils/IgE, use CT findings + clinical symptoms as primary monitoring tools
• HRCT should be repeated at 6 months after initial treatment to assess for new bronchiectasis or HAM resolution

4. ABPA in Cystic Fibrosis (CF) — 2024 Position

• CFTR modulators (Elexacaftor/Tezacaftor/Ivacaftor — ETI/Trikafta) have significantly reduced ABPA prevalence in CF patients in recent studies (2022–2024)
• Mechanism: Improved mucociliary clearance → less fungal colonization
• Monitoring: CF patients on CFTR modulators still require annual Aspergillus-IgE and IgE screening

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Summary: What Is New vs. 2013

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Important note: If you need the exact ISHAM 2024 full document, it should be accessed directly via:

• European Respiratory Journal or Mycoses journal (Agarwal R et al.)
• ISHAM website: www.isham.org
• PubMed search: "ABPA guidelines 2024 Agarwal"