An 82-year old man with atrial flutter, coronary artery disease on clopidogrel, and high degree atrioventricular block with a permanent pacemaker was admitted to hospital with a diagnosis of pneumonia. His symptoms of cough and rusty sputum began seven days before admission. On the third day of hospitalization, he was transferred to the medical intensive care unit (MICU) for worsening hypoxic respiratory failure.
When the patient was transferred to the MICU, he was febrile to 39.2  C with a respiratory rate of 29 breaths per minute. On physical examination, a bilateral coarse breathing sound was heard. There was no rash, joint swelling, jugular venous distension, or pitting edema of the lower extremities. The laboratory test showed no leukocytosis with a near-normal platelet count and coagulation. Cardiac enzymes were within normal limits (Table 1). Bedside echocardiography showed normal ejection fraction without wall motion abnormality. The chest radiography showed non-homogeneous air space opacities (Fig. 1-a) and the initial blood gas analysis showed an arterial partial pressure of oxygen (PaO2) of 66.2 mmHg while the patient was receiving 6 L/min of oxygen via nasal cannula (P/F ratio: 146). The empiric antibiotics were switched from ceftriaxone to piperacillin-tazobactam and levofloxacin.
Due to the finding of the chest X-ray, fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed with the successive instillation and retrieval of 30 mL, 30 mL, and 40 mL of saline. The BAL fluid aliquots were progressively bloodier, suggesting DAH (Fig. 2). Therefore, the diagnosis of diffuse alveolar hemorrhage was made based on the symptom of rusty sputum, chest radiographic finding of non-homogeneous air space opacities, and progressive hemorrhage in the BAL sample. With this diagnosis, clopidogrel was stopped and methylprednisolone 1 mg/kg (total of 65mg) was started. For the treatment of severe hypoxia, 100% fraction of inspired oxygen (FiO2) was delivered through a high-flow nasal cannula with a flow of 40 L/min. The subsequent gas analysis showed PaO2 of 150.1 mm Hg.
Laboratory tests for vasculitis and connective tissue disease were added to investigate the etiology of the DAH. All the following results were negative: antineutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibodies, antinuclear antibodies, anticardiolipin antibodies, anti-beta-2-glycoprotein, complement levels, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies (Table 1). In addition, reverse transcription polymerase chain reaction (RT-PCR) and cultures were negative for the following pathogens; Mycoplasma pneumonia, Chlamydophila pneumonia, Legionella pneumophila, Pneumocystis jirovecii, Mycobacterium tuberculosis, influenza virus, parainfluenza virus, adenovirus, and cytomegalovirus.
On the second day of MICU admission, his hemoptysis and dyspnea improved. The FiO2 requirement decreased to 25%. The chest radiograph showed an improvement in diffuse ground-glass opacity (Fig. 1-b). However, the laboratory confirmed a positive result for RSV B in both BAL fluid and the nasopharyngeal swab. Additional history taking revealed that his granddaughter had an upper respiratory infection when she visited him a few weeks ago. Because all blood tests for vasculitis and connective tissue diseases were negative and RSV infection was confirmed, the steroid was discontinued after the first dose. This was because studies have shown worse outcomes with high-dose steroid use in viral pneumonia. Instead, intravenous ribavirin and human immunoglobulin were started from the second day of MICU stay.
However, over the four consecutive days without steroid, his hemoptysis symptom reappeared and the FiO2 requirement gradually increased to 65%. The lowest P/F ratio was found to be 131 during this period. The chest X-ray on day 5 of MICU stay showed worsening of the opacities (Fig. 1-c). Therefore, we decided to restart the steroid with a lower dose (methylprednisolone 0.5mg/kg) in addition to ribavirin and immunoglobulin. Surprisingly, a significant improvement was observed over the course of 48 hours. His FiO2 requirement decreased to 30% and the opacities on the chest radiograph resolved significantly (Fig. 1-d).
Since the patient did not present any symptoms and did not show signs of respiratory distress, he was transferred to the general ward on the eighth day of his stay in the MICU. He was continued on the same dose of steroid for the next six days. The patient was discharged home with an oral form of steroid and it was tapered off over the three weeks as an outpatient. Clopidogrel was restarted when the steroid was completely discontinued. There was no recurrence of cough or hemoptysis. The patient had monthly follow-up visits for six months, but no signs or symptoms of autoimmune diseases were observed. Follow-up labs were performed for vasculitis and connective tissue disease, but all results were negative.