A 74-year-old woman presented in September 2014 with a 2-week history of dry cough followed by progressive dyspnea and a fever. She was diagnosed with bacterial pneumonia 10 days later, for which she had received treatment with levofloxacin (500 mg/day orally) for 2 weeks, and was referred to our hospital with complaints of worsened dyspnea. She was a never-smoker and had not been exposed to known toxins. On an examination, she was alert and did not seem to be overtly sick. Her body temperature was 38.2C. Pulse oximetry showed an oxygen saturation of 94% on ambient air. Fine crackles were heard in the bilateral lung fields without wheezing. Physical examination findings were negative for signs of connective tissue disease such as heliotrope rash or Gottron's sign.
Chest X-ray films showed right-sided predominant bilateral progressive pulmonary infiltrates (Fig. 1). High-resolution computed tomography (HRCT) of the chest revealed bilateral and progressive multiple areas of subpleural and peribronchial patchy consolidation with ground glass opacities (Fig. 2).
An arterial blood gas analysis on room air revealed marked hypoxemia [partial pressure of oxygen (PaO2) 56.8 mmHg]. Blood and serologic examinations revealed leukocytosis (15.1x104 cells/muL) and mild eosinophilia (510 eosinophils/muL); markedly increased values of C-reactive protein (CRP) (23.34 mg/dL), erythrocyte sedimentation rate (ESR; 115 mm/60 minutes), and ferritin (1,725 ng/mL; normal female range: 3.6-11.4); and mildly-to-moderately increased values of surfactant protein-D (SP-D) (141.9 ng/mL; normal <110) and surfactant protein-A (SP-A) (92.3 ng/mL; normal <43.8). There was no notable increase in the value of Krebs von den Lungen-6 (KL-6) (Table and Fig. 3).
On the fourth hospital day when the patient was transferred to the respiratory care unit, we managed to perform bronchoscopy under a clinical suspicion of organizing pneumonia. Bronchoalveolar lavage fluid (BALF) from the right B5a showed a cell count of 1.14x105 cells/mL, and a cellular analysis of the BALF revealed increased neutrophils (23.8%) and lymphocytes (5.2%), with a CD4+/CD8+ ratio of 3.2. No pathogens were cultured. A TBLB obtained two samples from the right upper lobe (rtB2b) and right lower lobe (rtB8b and rtB9b), and the TBLB specimens revealed histologic features of FOP (Fig. 4). One specimen from the right upper lobe showed hyalinisation and fibrosis of the central core of the Masson body, and another sample also from the right upper lobe showed granulation tissues in many terminal air spaces, mainly of the alveolar ducts, with adhesion of the alveolar duct walls due to intervening granulation tissues (obliterative alveolar duct fibrosis) and foamy cells in the alveolar spaces (Fig. 4e-h). The sample from the right lower lobe showed granulation tissues mainly in the alveolar ducts without adhesions of the alveolar duct walls. Another sample from the right lower lobe showed fibrination in the alveolar ducts and infiltration of a few neutrophils in the fibrin. The fibrination did not show organisation. We considered the possibility of an artificial effect from the transbronchial biopsy (not shown). None of the four lung specimens showed any malignant cells, granulomas, or significant infiltration of eosinophils or neutrophils (Fig. 4).
Empirical broad-spectrum antibiotics were initially administered. However, during the subsequent four days, the patient's condition continued to deteriorate, with worsening of chest radiograph findings (Fig. 1, 2) and hypoxemia. She developed dyspnea on the seventh hospital day. On the eighth hospital day, mechanical ventilation and intravenous methylprednisolone treatment (1,000 mg per day for three consecutive days) was started (Fig. 3). On the seventh hospital day, a histopathologic diagnosis of FOP was rendered by the lung pathologist of this article (Fig. 4). The patient received 750 mg/day cyclophosphamide (CY) intravenously in addition to corticosteroid therapy. Initially, despite these regimens, her chest radiograph findings and hypoxemia did not stop deteriorating, Therefore, 100 mg (2.0 mg/kg) cyclosporin A (CsA) was added. The chest radiograph findings and hypoxemia gradually improved, and she was successfully extubated on hospital day 22. The peribronchovascular consolidation revealed by chest radiography resolved steadily. She was discharged on hospital day 73 when prednisolone was tapered to 20 mg/day (Fig. 3). Her symptoms and the HRCT findings of the lungs improved during the follow-up 150 days later. She was fine 500 days later and did not develop any symptoms or signs of connective tissue disease (Fig. 3).