Fibrotic Hypersensitivity Pneumonitis: A Diagnostic Challenge Leading to Lung Transplantation

Abstract

Background/Objectives: Hypersensitivity pneumonitis (HP), a subtype of interstitial lung disease (ILD), is often misdiagnosed as idiopathic pulmonary fibrosis (IPF), particularly when the causative antigen cannot be identified. Typically resulting from chronic exposure to inhaled organic particles smaller than 5 microns, HP presents a diagnostic challenge. This report outlines a case of fibrotic HP initially misclassified as asthma. No triggering antigen was identified despite extensive investigation. The disease progressed despite corticosteroid, immunosuppressive, and antifibrotic therapy, ultimately leading to an advanced fibrotic stage and requiring lung transplantation. This clinical course is rare and infrequently reported, particularly in cases requiring lung transplantation without an identifiable causative antigen. Such progression is uncommon and underreported, especially in patients initially misclassified as having asthma. Methods: Medical records of 24 patients diagnosed with HP were reviewed. Only one case demonstrated progression to fibrotic HP; this case was selected for detailed analysis. Results: Clinical and functional deterioration occurred despite standard therapy. Given the advanced stage of fibrosis and treatment resistance, lung transplantation was deemed the next appropriate therapeutic option. Conclusions: HP remains underdiagnosed due to difficulties in identifying the causative antigen and overlapping features with other ILDs. Early and accurate differentiation from IPF is essential, particularly in progressive fibrotic forms unresponsive to conventional therapies.

Keywords: antifibrotic therapy; fibrotic hypersensitivity pneumonitis; interstitial lung disease; lung fibrosis; lung transplantation.

Figure 1

Diagnostic criteria in HP [12,13,14,15,16,17].

Figure 2

HRCT scans from 2018, 2019, 2020, and 2024, showing serial radiologic progression of chronic HP. The images demonstrate a gradual increase in mosaic attenuation, reticulation, and fibrotic changes, culminating in the development of honeycombing consistent with advanced pulmonary fibrosis.

Figure 3

Surgical lung biopsy showing poorly formed, non-necrotizing granulomas with peribronchiolar distribution (arrow). H&E stain, 100× magnification.

Figure 4

Expiratory HRCT demonstrating areas of air trapping (arrows), indicative of small airway involvement consistent with chronic HP.