A 71-year-old woman was admitted to our hospital with a history of epigastric pain for 2 days. She was diagnosed with pancreatic ductal adenocarcinoma at the uncinate process, and had undergone endoscopic retrograde cholangiopancreatography with biliary stent placement 1 month prior due to a distal common bile duct (CBD) obstruction. Oral capecitabine was subsequently initiated 2 weeks before presentation.
On admission, an ascending cholangitis with CBD stent malposition was suspected. The patient was initially treated with intravenous ceftriaxone (2 g, daily).
Oesophagogastroduodenoscopy (EGD) was subsequently performed with a light intravenous sedation. A distal biliary stent migration was observed but remained in place. The stent was not retrieved, and the procedure was completed uneventfully.
The day after EGD, the patient developed a dry cough and low-grade fever. Chest radiography (CXR) demonstrated a new development of multifocal patchy and nodular consolidations, and ground-glass opacities in the left lung with a lower lung zone predominance (Fig. 1A-B). The antibiotic was subsequently changed to piperacillin/tazobactam. However, her symptoms rapidly deteriorated, and a progressive bilateral lung infiltration was demonstrated on CXR (Fig. 1C) after 1 week.
Physical examination revealed a body temperature of 36.8  C, blood pressure of 160/80 mmHg, heart rate of 88 beats/min, respiratory rate of 24 breaths/min, and oxygen saturation of 90% while breathing room air. Pulmonary examination revealed fine inspiratory crackles bilaterally, predominantly in the lower left lung zone. Abdominal examination revealed mild epigastric tenderness. No abnormal cutaneous lesions or musculoskeletal abnormalities were noted.
The complete blood count showed leucocytosis (18,000 cells/mm3) with 78% neutrophils, 13% lymphocytes, 8% monocytes, normal platelets, and haemoglobin. Liver function test results were total bilirubin 2.3 mg/dL, direct bilirubin 2 mg/dL, and ALP 234 U/L. The other serum biochemistry test findings were all within the normal ranges.
All blood and sputum cultures were negative. The level of C-reactive protein was 148.98 mg/L and that of procalcitonin was 0.17 ng/mL. Computed tomography (CT) of the chest showed multifocal peribronchovascular consolidations and patchy ground-glass opacities with superimposed interlobular septal thickening and intralobular lines (Fig. 2A and B).
A flexible bronchoscopy (FB) was performed. A whitish turbid bronchoalveolar lavage fluid (BALF) was retrieved with no characteristics of a bile-like fluid. The BALF showed a white blood cell count of 488 cells/mm3 with 61% neutrophils and 39% monocytes. Bacterial, fungal and acid-fast bacilli staining and cultures of BALF were negative. The polymerase chain reaction tests to detect Mycobacterium tuberculosis and respiratory 33 pathogens were also negative. The BALF cytology and cell block were positive for malignant cells, consistent with metastatic adenocarcinoma and did not demonstrate bilirubin crystallisation (Fig. 2C). Histopathological examination of a transbronchial biopsy demonstrated organizing diffuse alveolar damage (DAD) (Fig. 2D) with no evidence of food particles or bile pigment.
Based on the rapidly deteriorating clinical course, chest CT findings, histopathology of DAD, and the exclusion of potential infections and chemotherapy-induced interstitial lung disease (capecitabine), acute interstitial pneumonitis (AIP) was diagnosed. Given the history of pancreatic adenocarcinoma, a connective tissue disease-related interstitial lung disease secondary to malignancy was suspected, despite the absence of cutaneous and musculoskeletal manifestations leading to the diagnosis. Further investigation of autoantibodies was conducted, which was negative for anti-nuclear antibody (ANA), whereas anti-NXP2 antibody was positive in the myositis profile-4 EUROLINE immunoblot assay (EUROIMMUN AG, Germany). Serum creatine kinase and aldolase were tested and the results were 12 U/L and 5 U/L, respectively. Thus, a diagnosis of rapidly progressive interstitial lung disease (ILD) associated with anti-NXP2 antibodies was confirmed.
The patient developed acute respiratory failure and sudden cardiac arrest 1 hr after FB. Cardiopulmonary resuscitation was performed, and the return of spontaneous circulation was achieved in 10 min. The left side pneumothorax was demonstrated on CXR, and left intercostal drainage was inserted. After the diagnosis was made, dexamethasone (15 mg/day) was administered intravenously. Continuous improvement of the lesion was observed on the follow-up CXR (Fig. 1D). However, owing to anoxic encephalopathy, the patient did not regain consciousness. After explaining the underlying advanced cancer and irreversible brain damage to her relatives, a decision was made to discontinue ventilatory support and all active treatments and palliate her. The patient died 1 week later.