What is the role of Transbronchial Lung Biopsy (TBLB) in diagnosing Eosinophilic Granulomatosis with Polyangiitis (EGPA) and what are the associated risks and benefits in a patient with suspected vasculitis?

Role of Transbronchial Lung Biopsy (TBLB) in Suspected EGPA

Transbronchial lung biopsy is recommended when feasible in suspected EGPA but is not essential for diagnosis, as the diagnosis can be made based on highly suggestive clinical features, laboratory findings, and ANCA status without histopathological confirmation. 1

Diagnostic Role and Utility

When TBLB Should Be Considered

• Biopsy of affected organs is encouraged when feasible because tissue examination can contribute to diagnostic evaluation, exclude differential diagnoses, and reflect the degree of disease activity/chronicity 1

• TBLB can reveal characteristic histopathological findings including extravascular eosinophilic-predominant inflammation, eosinophilic vasculitis, granulomatous changes, and eosinophilic pneumonia 2

• Lung tissue biopsies can reveal typical EGPA lesions, though they are seldom performed in routine clinical practice 1

Diagnostic Limitations

• TBLB has significantly lower sensitivity compared to other biopsy sites, with only approximately 12% of transbronchial biopsies showing positive findings for vasculitis 3

• Diagnostic biopsy is often lacking in EGPA patients, and the diagnosis frequently relies on clinical features rather than histopathology 1

• Sino-nasal mucosal/polyp biopsies are often non-diagnostic despite structured histopathological evaluations, making them less useful than lung tissue 1

Benefits of TBLB

Diagnostic Confirmation

• Can provide definitive tissue diagnosis when it demonstrates the characteristic triad of extravascular granuloma, eosinophilic vasculitis, and eosinophilic infiltration 2

• Particularly valuable in ANCA-negative cases where serological confirmation is absent and tissue diagnosis becomes more important 2

• Helps exclude important differential diagnoses including other eosinophilic disorders (hypereosinophilic syndromes, allergic bronchopulmonary aspergillosis), other vasculitides, and malignancies 1

Clinical Decision-Making

• Can detect disease progression or relapse when clinical features are ambiguous, as demonstrated in cases where TBLB revealed recurrent disease 2

• May guide treatment intensity by confirming active vasculitis versus other pulmonary complications 1

Risks of TBLB

Procedural Complications

• Bleeding risk is a significant concern in patients with vasculitis who may have thrombocytopenia from disease or treatment, and who have friable, inflamed vascular tissue 3

• Pneumothorax risk is inherent to any transbronchial biopsy procedure, though specific rates in EGPA patients are not well-documented in the provided evidence

• Lower diagnostic yield compared to invasiveness makes the risk-benefit ratio less favorable than for other biopsy sites 3

Clinical Context Considerations

• May delay treatment initiation in patients with severe manifestations who require urgent immunosuppression 4

• Not always feasible depending on the location and extent of pulmonary involvement, patient stability, and coagulation status 1

Alternative and Preferred Biopsy Sites

Higher-Yield Options

• Kidney biopsy typically shows crescentic necrotizing glomerulonephritis with eosinophilic infiltrates and provides higher diagnostic yield when renal involvement is present 1

• Skin biopsy from palpable purpura invariably reveals necrotizing vasculitis and can be accompanied by extravascular granulomas with excellent diagnostic accuracy 1

• Open lung biopsy provides higher diagnostic yield with relatively low complication risk, though it is more invasive than TBLB 3

Optimizing Biopsy Strategy

• Careful endoscopically directed biopsy after cleaning and decongesting the area may improve yield 3

• Target abnormal tissue identified on imaging such as pulmonary infiltrates, nodules, or masses to maximize diagnostic success 3

• Consider multiple biopsy sites when initial attempts are non-diagnostic, prioritizing the most accessible affected organs 3

Practical Algorithm for TBLB Decision-Making

Proceed with TBLB When:

• Diagnosis remains uncertain after comprehensive clinical evaluation, laboratory testing (including ANCA), and imaging 1

• Patient is ANCA-negative and lacks other definitive diagnostic features, making tissue confirmation more valuable 2

• Pulmonary infiltrates are present on imaging without other easily accessible biopsy sites 1

• Patient is stable enough to tolerate the procedure without delaying urgent treatment 4

Avoid or Defer TBLB When:

• Clinical diagnosis is highly confident based on characteristic features (asthma, eosinophilia, neuropathy, ANCA positivity) meeting classification criteria 1

• More accessible biopsy sites are available such as skin with palpable purpura or kidney with glomerulonephritis 1

• Severe disease requires immediate treatment that cannot be delayed for biopsy results 4

• Significant bleeding risk exists from thrombocytopenia or coagulopathy 3

Key Clinical Pitfalls

• Do not delay treatment waiting for biopsy confirmation in patients with severe manifestations such as cardiac involvement, rapidly progressive glomerulonephritis, or extensive neuropathy 1, 5

• Do not rely solely on biopsy results as negative TBLB does not exclude EGPA given its low sensitivity 3

• Do not confuse classification criteria with diagnostic criteria - the 1990 ACR and 2022 ACR-EULAR criteria were not developed for diagnosis and should not be rigidly applied as such 1

• Remember that glucocorticoid therapy is often initiated before definitive diagnosis in clinical practice, which may alter biopsy findings if performed later 4