A 58-year-old women with UC who was on mesalazine (2400 mg per day) for 2 months was transferred to our hospital because of unresolved pneumonia. On the day of admission, she presented with wet cough, fever, and dyspnea on exertion for a week. She was a never-smoker and had no other medical illnesses. She had no allergic history to any medications.
Initial vital signs revealed a temperature of 38.3  C, respiratory rate of 24 breaths per minute, and O2 saturation of 91% on 4L/min oxygen via nasal cannula. Fine crackles were audible in the bilateral lung fields. There were no signs of clubbing, skin rash, or peripheral edema. Laboratory evaluation revealed white blood cell (WBC) count of 22,000/mm3 with 88% neutrophils, 8% lymphocytes, and 3% eosinophils, hemoglobin of 9.4 g/dl, and platelet count of 1,150,000/mm3. The serum levels of c-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), and surfactant protein-D (SP-D) were 15.26 mg/dl, 224 U/ml (<=500), and 130 ng/ml (<=110), respectively. Both procalcitonin (0.201 ng/ml) and beta-D-glucan (<2.9 pg/ml) were negative. Test results for antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibody were negative. Arterial blood gas analysis showed partial pressure of carbon dioxide (PaCO2) of 30.1 mmHg and partial pressure of oxygen (PaO2) of 70.8 mmHg with 4L/min oxygen via nasal cannula. A high-resolution CT of the chest showed bilateral and asymmetric air space consolidation and ground-glass opacity with a peribronchial and subpleural distribution (Fig. 1).
To exclude infectious etiology, we performed further bronchoscopic evaluation with bronchoalveolar lavage (BAL). Transbronchial lung biopsy (TBLB) was also performed to evaluate the histological pattern of radiological changes in the patient's lungs. Analysis of BAL fluid (BALF) showed a total cell count of 6.56 x 105/ml and WBC profile of 44% lymphocytes, 32.4% eosinophils, and 16% neutrophils. The CD4/CD8 ratio of BALF was 1.44. The BALF culture, cytology, viral isolation and Pneumocystis jirovecii polymerase chain reaction analysis were negative. Histopathological findings of TBLB showed patchy processes characterized primarily by organizing pneumonia involving alveolar ducts and alveoli with bronchiolar intraluminal polyps (Fig. 2). Sputum, blood, and urine cultures were negative. Extensive blood tests including paired complement fixation test and hemagglutination inhibition test for respiratory associated viruses (respiratory syncytial virus; adenovirus; seasonal influenza A and B; cytomegalovirus; parainfluenza virus 1-3) were all negative. Drug-induced lymphocyte stimulation test (DLST) for mesalazine was negative. Considering these findings and the clinical course, we suspected organizing pneumonia of UC or mesalazine-induced lung injury.
On the day of admission, mesalazine was discontinued and the patient was treated with corticosteroid therapy (intravenous methylprednisolone pulse therapy [1000 mg per day for 3 days] followed by low dose oral prednisolone). NPPV was immediately initiated to treat severe respiratory failure. Initial management of NPPV was positive end-expiratory pressure (PEEP) 5cmH2O with inspired fraction of oxygen (FiO2) of 0.60. According to the Berline definition of ARDS, she had mild ARDS: partial pressure of oxygen/FiO2 [PaO2/FiO2] with PEEP 5cmH2O was 206. Afterwards, oxygenation gradually improved and PaO2/FiO2 with PEEP 5 cmH2O was 355 on day 6. Follow up CT scan showed significant improvement (Fig. 3). NPPV was discontinued and from the patient no longer required oxygen therapy on day 11 (Fig. 4). Eventually, her respiratory status had fully recovered and she was discharged from the hospital on day 25. After resolution, her UC also subsided and no medication has been needed for 3 years. She has also been free from relapse of lung injury.
The diagnostic criteria of DLI are shown in Table 2. We diagnosed her with mesalazine-induced lung injury because she met criteria (1) to (4) starting from the past.
Chest radiograph and computed tomography (CT) on admission. . b): Chest CT shows bilateral and asymmetric air space consolidation and ground-glass opacity with a peribronchial and subpleural distribution.