Aspergillus Updates week 51

1. Immunodeficiency, rare syndromes & aspergillosis risk

Standing Still: A Case of Stiff Person Syndrome and Common Variable Immunodeficiency

Khazar et al., Cureus, 2025

Summary

• Describes a rare coexistence of Stiff Person Syndrome (SPS) and Common Variable Immunodeficiency (CVID).

• Highlights autoimmune–immunodeficiency overlap and diagnostic complexity.

Why it matters

• CVID is a recognised risk factor for recurrent infections and chronic lung disease, including bronchiectasis and chronic pulmonary aspergillosis (CPA).

• Reinforces the need for multisystem thinking when patients present with neurological and respiratory symptoms.

Limitations

• Single case; no fungal infection reported.

• Indirect relevance to aspergillosis but important for risk stratification.

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Beyond Cystic Fibrosis: Recognising Shwachman–Diamond Syndrome in the Respiratory Clinic

Yang et al., Respirology Case Reports, 2025

Summary

• Emphasises misdiagnosis of Shwachman–Diamond syndrome (SDS) as cystic fibrosis.

• Includes discussion of allergic bronchopulmonary aspergillosis (ABPA) in the differential.

Why it matters

• Reinforces that non-CF genetic syndromes can present with:

  • Bronchiectasis

  • Recurrent infection

  • ABPA-like features

• Highly relevant to adult respiratory clinics and late diagnoses.

Clinical takeaway

• ABPA should prompt consideration of underlying immune or genetic disease, not just asthma or CF.

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2. Genetics & structural lung disease

Exome sequencing reanalysis identifies a novel CFAP54 variant in primary ciliary dyskinesia

Li et al., Frontiers in Medicine, 2025

Summary

• Identifies a new likely pathogenic CFAP54 variant.

• Expands the phenotypic spectrum of Primary Ciliary Dyskinesia (PCD).

Relevance to aspergillosis

• PCD → impaired mucociliary clearance → chronic infection, bronchiectasis, and secondary fungal disease.

• ABPA and CPA are increasingly recognised in non-CF bronchiectasis populations.

Strength

• Genotype–phenotype correlation strengthens diagnostic confidence.

Limitation

• Aspergillosis not a primary focus, but highly relevant to long-term respiratory outcomes.

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3. Haematology, malignancy & invasive aspergillosis

Mixed-Phenotype Acute Leukemia Transforming into AML-M4

Alhayek et al., Cureus, 2025

Summary

• Case of evolving leukemia complicated by pancytopenia, invasive pulmonary aspergillosis (IPA), and COVID-19.

Key points

• Illustrates real-world stacked risk:

  • Neutropenia

  • Chemotherapy

  • Viral infection

  • IPA

Clinical relevance

• Strong reminder that IPA often emerges during diagnostic or therapeutic transitions, not just during induction chemotherapy.

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Invasive fungal infections in haematologic diseases: evidence, challenges, and practice

Cho et al., Blood Research, 2025 – Review

Summary

• Comprehensive overview of invasive aspergillosis, candidiasis, and mucormycosis.

• Covers diagnostics, antifungal resistance, and treatment strategies.

Strengths

• Practical, guideline-aligned.

• Emphasises individualised risk assessment and early treatment.

Gap

• Limited discussion of long-term survivors and post-IPA chronic complications (e.g. CPA).

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4. Imaging & diagnostics

CT Pulmonary Angiography in invasive pulmonary aspergillosis

Tian, Future Microbiology, 2025

Summary

• Explores the role of CT pulmonary angiography (CTPA) in detecting angioinvasion.

Why it matters

• Vascular occlusion and infarction are hallmarks of IPA.

• CTPA may improve diagnostic confidence when standard CT is equivocal.

Limitations

• Case-based evidence.

• Needs integration into diagnostic algorithms.

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Sequential serum galactomannan as an outcome marker

Többen et al., Int J Infect Dis, 2025

Summary

• Registry-based exploratory analysis of serial galactomannan (GM).

Key finding

• Trends in GM may correlate with treatment response, not just diagnosis.

Clinical importance

• Supports GM as a monitoring biomarker, though interpretation remains complex.

Caution

• Not reliable in all patient groups (e.g. non-neutropenic, antifungal pre-exposure).

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5. Chronic pulmonary aspergillosis & structural disease

Molecular epidemiology of Aspergillus species in CPA (South India)

Spruijtenburg et al., Medical Mycology, 2025

Summary

• Describes species diversity and genetic variation in CPA patients.

Why it matters

• Highlights:

  • Geographic variation

  • Potential antifungal resistance implications

• Supports species-level identification in CPA.

Strength

• Strong laboratory–clinical interface.

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Advanced pulmonary sarcoidosis

Spagnolo et al., Seminars in Respiratory and Critical Care Medicine, 2025

Summary

• Reviews complications of advanced sarcoidosis, including:

  • Bronchiectasis

  • Pulmonary hypertension

  • Chronic pulmonary aspergillosis

Key point

• CPA should be actively considered, not viewed as rare, in fibrotic sarcoidosis.

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Rezafungin OPAT for chronic pulmonary aspergillosis

Law et al., JAC Antimicrobial Resistance, 2025

Summary

• First real-world case of rezafungin used via outpatient parenteral therapy for CPA.

• Includes a health-economic assessment.

Why this is important

• CPA treatment options are limited.

• Weekly dosing may:

  • Reduce hospital burden

  • Improve quality of life

Caution

• Single case; echinocandins are not standard CPA therapy.

• Best viewed as salvage or niche use.

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6. Tracheobronchial & atypical aspergillosis

Tracheobronchial Aspergillosis Mimicking Pseudotumour

Castillo Gamboa et al., Clinical Case Reports, 2025

Summary

• Rare presentation of tracheobronchial aspergillosis masquerading as malignancy.

Clinical lesson

• Endobronchial disease can be missed or mislabelled.

• Supports biopsy and fungal testing when appearances are atypical.

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7. Immunology, inflammation & host–pathogen interaction

PANoptosis in pathogen infection and systemic disease

Cai et al., Cell Biology and Toxicology, 2025 – Review

Summary

• Reviews PANoptosis (pyroptosis, apoptosis, necroptosis) in infections.

Relevance

• Aspergillus is discussed as a trigger of complex inflammatory cell death pathways.

• May help explain:

  • Severe tissue damage

  • Dysregulated inflammation in IPA

Translational value

• Still mechanistic; clinical applications remain distant.

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PD-1 / PD-L1 immune checkpoint in fungal infections

Zheng et al., Virulence, 2025 – Review

Summary

• Explores immune exhaustion in ABPA, CPA, and IPA.

Key insight

• Checkpoint pathways may:

  • Contribute to chronic infection persistence

  • Become future adjunctive immunotherapies

Important caution

• Immune checkpoint modulation carries significant risk in fungal disease.

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8. Antimicrobial stewardship & prophylaxis

Procalcitonin-guided antibiotics in RSV and influenza

Hessels et al., BMJ Open Respiratory Research, 2025

Finding

• Reduced antibiotic use without increased fungal infection risk.

Relevance

• Important reassurance that stewardship does not increase IPA risk in viral respiratory infections.

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Letermovir prophylaxis post-HSCT

Kimura et al., J Infect Chemother, 2025

Key result

• Letermovir did not increase invasive aspergillosis or candidemia risk.

Clinical reassurance

• Supports ongoing antiviral prophylaxis strategies in transplant patients.

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9. Experimental antifungals

Berberine suppresses Aspergillus fumigatus growth

Wang et al., ACS Infectious Diseases, 2025

Summary

• Demonstrates antifungal activity via:

  • Mitochondrial fragmentation

  • Reactive oxygen species

  • Hog1-MAPK activation

• Reduced fungal burden in a murine IPA model.

Important caution

• Pre-clinical only.

• Not a supplement recommendation for patients.

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Overall themes & take-home messages

Key trends this week

• Increasing recognition of rare immunodeficiency and genetic syndromes behind chronic lung disease.

• Better understanding of non-classical aspergillosis presentations.

• Strong interest in immune modulation, biomarkers, and novel therapies.

• Continued need for early diagnosis, especially in haematology and advanced lung disease.

For clinical practice

• Think beyond labels (asthma, CF, cancer).

• Revisit diagnoses when disease behaves atypically.

• CPA and ABPA remain under-recognised but increasingly documented across conditions.

If you’d like, I can:

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