A 73-year-old woman with hypertension and dyslipidemia had persistent cough for 5 years and dyspnea on exertion for 3 years. Two years earlier, chest radiography conducted during a medical checkup revealed abnormal shadows, and she visited a hospital. She was taking angiotensin II receptor blockers and statins, but no other medications such as herbal medicines or health supplements. She had no history of smoking and had been engaged in plaster grinding for 5 years. She lived in a 26-year-old wooden structure with molds in the bathroom. Her respiratory status was not imminent: respiratory rate, 16 breaths/min; and oxygen saturation, 95% in room air. Chest auscultation revealed fine crackles on her back. Chest radiography revealed decreased permeability with a bilateral predominance in the lower lung fields. Chest computed tomography (CT) revealed ground-glass opacity (GGO), traction bronchiectasis, interlobular wall thickening, and bilaterally diffused reticular shadows predominantly in the lower lobes, without centrilobular nodules (Fig. 1). The CT findings in this case were categorized as an alternative diagnosis in the clinical practice guideline for idiopathic pulmonary fibrosis and were compatible with the fibrotic HP pattern in the clinical practice guideline for hypersensitivity pneumonitis.
The laboratory findings were as follows: white blood cell count, 8750/muL; hemoglobin, 13.9 g/dL; platelet count, 23.9 x 104/muL; lactate dehydrogenase, 330 U/L; C-reactive protein, 0.07 mg/dL; and Krebs von den Lungen 6 (KL-6) level, 8758 U/mL. The test for anti-Trichosporon asahii antibodies gave positive results. The respiratory function tests results were as follows: forced vital capacity (FVC), 2.1L; %FVC, 89.7%; and, % diffusion capacity for carbon monoxide (DLco), 68.4%. The patient underwent bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). The color of the BAL fluid (BALF) was normal and the cellular pattern comprised 54.4% lymphocytes, 40.3% macrophages, and 5% neutrophils. The CD4/8 ratio was 6.9. TBLB revealed lymphocytic infiltration, mild thickening due to fibrosis, and hyperplasia of type II pneumocytes in the alveolar wall (Fig. 2). No obvious granulomatous lesions or airway-centered fibrosis was observed.
The moderate-confidence diagnosis of HP was based on CT findings, BALF findings, positive results for anti-Trichosporon asahii antibodies, and histopathology in the clinical practice guideline of hypersensitivity pneumonitis. The patient was asked to clean her home; however, 9 months later, a respiratory function test showed a decreased FVC at 1.87 L and her chest CT showed worsening GGO despite a slight decline in the level to 7594 U/mL. The patient was diagnosed with HP exacerbation and treatment was started with oral prednisolone (PSL) at 0.5mg/kg/day (25mg/day). Two months later, when FVC improved to 2.18 L and KL-6 dropped to 5317 U/mL, FVC did not change considerably, but the KL-6 level increased again to 9141 U/mL. Considering it to be an exacerbation of HP that could be controlled by PSL, cyclosporine was additionally administered, and the PSL dosage was gradually decreased. Three months later, dyspnea on exertion worsened, the chest CT showed GGO spreading throughout the lung field with marked thickening of the interlobular septum, resulting in a so-called crazy-paving appearance (Fig. 3), and the KL-6 level increased to 26,974 U/mL (Fig. 4).
BAL was performed again, cloudy white BALF was collected, and the cellular pattern comprised 8.0% lymphocytes, 50.0% macrophages, and 42.0% neutrophils. The CD4/8 ratio was 0.5. TBLB showed an alveolar space was filled with acidophilic, unstructured material on hematoxylin and eosin staining (Fig. 5A), which tested positive for granules on Periodic acid-Schiff stain (Fig. 5B) and also on Surfactant apoprotein A staining (Fig. 5C).
AS the test for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies returned positive results at 35.5 U/mL (cut-off value, 1.0 mug/mL), autoimmune PAP was diagnosed. The patient was transferred to our hospital for whole-lung lavage. However, as we had no experience with this technique and it was difficult for her to visit a distant hospital during the COVID-19 pandemic, she underwent segmental BAL under high-flow nasal cannula oxygen therapy repeatedly. Subsequently, her respiratory status and chest CT findings showed slight improvements. Subsequently, when the steroids and cyclosporine dosages were reduced and discontinued, the fibrotic changes were exacerbated. She was treated with nintedanib for progressive fibrosing interstitial lung disease, which was thought to be an exacerbation of fibrotic HP.
Computed tomography image showing ground-glass opacity, traction bronchiectasis, interlobular wall thickening, and bilateral and diffuse reticular shadows compatible with fibrotic HP.