A 77-year-old man with a smoking history (96 pack-years) was diagnosed with T4aN1M1 liver and peritoneal metastasis, stage IVB advanced gastric cancer (Japanese Classification of Gastric Carcinoma, 15th Edition). He had no recent history of exposure to dust. He was prescribed acetaminophen and acetaminophen, started 3 months before admission, and the newest oral drug was an antipyretic and analgesic drug for fever, postoperative pain, and chemotherapy-related lower limb pain. The patient characteristics are shown in Table 1. He was treated with capecitabine, oxaliplatin, and trastuzumab as first-line chemotherapy. After four cycles, prolonged nausea and fatigue developed. Abdominal CT revealed progression of gastric cancer and gastric dilation with gastric outlet obstruction. He underwent laparoscopic gastrojejunostomy and was discharged 2 weeks after surgery.
Nano albumin-bound (nab)-paclitaxel and ramucirumab were induced as second-line chemotherapy. On day 8 of the first cycle, nab-paclitaxel administration was interrupted because of neutropenia. On day 18, he had a high-grade fever (38  C) and malaise and was started on levofloxacin. On day 22, the high-grade fever persisted, and chest CT showed an abnormal shadow in the lung fields. He was then referred to our hospital.
On admission, the findings of his physical examination were unremarkable. A peripheral blood test showed elevated levels of C-reactive protein (CRP) (8.44 mg/dL). Krebs von den Lungen (KL)-6 (342 U/mL) and beta-D glucan (14.4 pg/mL) were within the normal limits (Table 2). Arterial blood analysis showed that the arterial partial pressure of oxygen (PaO2) was 86.4 Torr in ambient air. Chest CT showed bilateral diffuse GGO and ill-defined centrilobular nodules (Fig. 1A and B), suggesting a non-fibrotic typical HP pattern. Bronchoscopy for bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. BAL fluid analysis showed a total cell count of 1.07 x 106 and an increase in lymphocytes (43.8%) with a CD 4/8 ratio of 4.2% and eosinophils (16.6%). Culture of BAL fluid yielded negative results for bacteria, fungi, mycobacteria, and pneumocystis spp. There was no evidence of suspected infectious diseases. TBLB showed fibro-cellular alveolitis and accumulation of histiocytes without granulomas (Fig. 2). He was negative for the anti-Trichosporon asahii (T. asahii) antibody and parakeet IgG (2.21 mg A/L), parrot IgG (3.93 mg A/L), and pigeon IgG (4.53 mg A/L) were within normal limits. Serum IgG against bird antigens was measured with ImmunoCAP  system (Thermo Fisher Scientific, Uppsala, Sweden).
He was diagnosed as DRP with radiographic HP pattern, probably due to nab-paclitaxel, after excluding other possible ILD caused by infection (pneumocystis spp. or mycobacterium spp.), connective tissue disease, and hypersensitivity pneumonitis (summer type or bird fancier's lung). His DRP was categorized as grade 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Chemotherapy was discontinued, and his condition was carefully monitored. He had no respiratory symptoms and oxygen desaturation during the 6-min walk test; however, high fever did not improve. On day 33 of the admission, steroid pulse therapy with methylprednisolone (500 mg/day) was started for 3 days. His fever and abnormal shadow improved, without maintenance of steroid therapy (Fig. 1C). He was discharged 8 days after initiation of steroid therapy. Acetaminophen was discontinued after symptom relief. One month after discharge, nivolumab as the third-line therapy was started, and he was diagnosed with nivolumab-related renal failure at the previous hospital. He subsequently underwent temporary hemodialysis and was treated with prednisolone 50 mg per day. Thereafter, his chest CT showed complete resolution of the shadow (Fig. 1D). For a diagnosis of DRP, scores according to the Naranjo Scale were five points (probable confidence). If we judge as exposure to nab-paclitaxel, his ILD could be diagnosed as HP with high confidence (80-89% confidence), according to the ATS/JRS/ALAT HP guideline.