Diffuse alveolar haemorrhage with suspected idiopathic pulmonary hemosiderosis and decrease in lung diffusing capacity and chronic respiratory failure

BACKGROUND

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown aetiology that causes recurrent episodes of diffuse alveolar haemorrhage (DAH). IPH is extremely rare, and its incidence in children is estimated to be 0.24–1.23 per 1 000 000.1 2 Recently, a previous study has reported IPH in adults aged ≥30 years.3 However, there are not many reports on adult-onset IPH. Many cases of adult-onset IPH have a chronic history; however, there are few reports on acute exacerbation in long-term chronic respiratory dysfunction.4

A previous study has confirmed respiratory dysfunction in IPH, such as restrictive ventilatory and pulmonary diffusing capacity impairments.5 To the best of our knowledge, there is no report on adult-onset IPH with only pulmonary diffusing capacity impairment. Here, we report the case of a patient suspected of having an adult-onset IPH in his 50s who presented with recurring hemoptysis, a decrease in pulmonary diffusing capacity and chronic respiratory failure, and was treated with glucocorticoids and azathioprine. We examined the patient’s disease course before and after treatment, along with respiratory function. Our case report anonymised the patient to protect his privacy and obtained written informed consent.

A male patient in his 50s presented with recurring hemoptysis of unknown aetiology and chronic respiratory failure for 6 years before he was hospitalised. Until the onset of hemoptysis 6 years prior, the patient smoked 30 cigarettes a day for 30 years. Before hospitalisation, a CT of the chest was performed; however, no pulmonary opacity other than emphysematous changes was observed. Pulmonary function tests performed before hospitalisation, when there were no symptoms of hemoptysis, showed a forced expiratory volume in 1 s (FEV₁) of 2.37 L, forced vital capacity (FVC) of 3.07 L, total lung capacity (TLC) of 4.67 L, residual volume (RV) of 1.55 L, FEV₁/FVC ratio of 77.2%, percentage-predicted FVC (FVC_%pred) of 81.2% and percentage-predicted TLC (TLC_%pred) of 82.5% (table 1). Obstructive and restrictive ventilatory impairment was not confirmed; therefore, chronic obstructive pulmonary disease (COPD) was not considered. However, the percentage-predicted diffusing capacity of the lungs for carbon monoxide (DLCO_%pred) was 27.1% and the DLCO/alveolar volume (VA) ratio was 2.32 mL/min/mm Hg/L, confirming notable pulmonary diffusing capacity impairment (table 1). Home oxygen therapy (oxygen via the nasal cannula at 2.5 L/min) was administered to treat the patient’s chronic respiratory failure of unknown aetiology; however, dyspnoea and hemoptysis exacerbated, and he was transported for emergency hospitalisation.

On admission, the patient’s consciousness level was normal. His body height was 173 cm, weight 93 kg, body temperature 38.5°C, pulse 133 beats/min, respiratory rate 32 breaths/min, blood pressure 158/87 mm Hg and oxygen saturation 64% on room air. Coarse crackles were audible in the chest, and anaemia was confirmed in the palpebral conjunctiva. There were no abnormal findings in any other physical examinations. Other than dyspnoea and hemoptysis, there was no significant symptom, such as arthralgia, peripheral neuropathy, rash, muscle pain, chest pain or abdominal pain. Laboratory findings revealed an inflammatory response and iron-deficiency anaemia (table 2). Chest X-ray revealed patchy opacity from the middle lung field to the lower lung field (figure 1). Contrast-enhanced CT of the chest did not reveal abnormality in chest blood vessels; however, diffuse pulmonary infiltrates were disseminated across the whole lung field, in addition to the existing emphysematous changes (figure 2). Bronchoalveolar lavage (BAL) was performed by wedging a bronchofiberscope into the right middle lobe (B4), and three serial aliquots of 50 mL of physiological saline were instilled and withdrawn. BAL fluid (BALF) was bloody, and Berlin blue stain revealed a large number of hemosiderin-laden macrophages (figure 3).

Non-invasive positive pressure ventilation (NPPV) was performed, and treatment with pulse steroid (intravenous methylprednisolone in a pulse dose, 1000 mg/day for 3 days) was started. On day 4 of hospitalisation, treatment was changed to intravenous administration of 80 mg of methylprednisolone per day (1 mg/kg/day) for 9 days. On day 10 of hospitalisation, NPPV was removed. Subsequently, the patient’s hemoptysis improved. On day 13 of hospitalisation, treatment was changed to oral administration of 50 mg of prednisolone per day, with a gradual decrease. On day 20 of hospitalisation, the patient’s respiratory failure improved, and he was discharged.

Differential diagnosis

The patient was diagnosed with DAH, and a differential diagnosis was made for diseases that cause DAH. There was no physical finding of collagen diseases or vasculitis, such as arthralgia, peripheral neuropathy, rash, muscle pain or abdominal pain. Laboratory findings did not reveal significant detection of haematuria, proteinuria, renal dysfunction or autoantibodies (table 2). Based on physical and laboratory findings, antineutrophil cytoplasmic antibody associated vasculitis, immunoglobulin A vasculitis, Goodpasture syndrome (anti-glomerular basement membrane disease) and collagen diseases were negative. Bleeding time, prothrombin time, activated partial thromboplastin time and platelet counts were normal. No organ other than the lung had any bleeding; thus, blood disease-associated bleeding was also negative. Contrast-enhanced CT of the chest did not reveal pulmonary infarction or pulmonary embolism. Cardiac ultrasound excluded heart diseases such as mitral valve stenosis. Cardiac catheterisation did not present any finding indicative of pulmonary hypertension and heart failure. The mean pulmonary artery pressure was 19 mm Hg, whereas the mean pulmonary capillary wedge pressure was 13 mm Hg. There was no history of bone marrow transplantation, lung transplantation, radiation therapy or medication that could cause DAH. Infections such as leptospirosis and infective endocarditis, which could cause DAH, were excluded from the medical history of conditions that were recurring in the past 6 years. Bacteria and fungi were not detected in blood culture. Only indigenous bacteria were isolated in the BALF culture. Given that the patient’s symptom improved without the administration of anti-infective drugs, infection was excluded. IPH is diagnosed when three main symptoms (anaemia, hemoptysis and diffuse pulmonary infiltrates) are found and when other diseases that can cause DAH are excluded. Our patient experienced hemoptysis with iron-deficiency anaemia and diffuse pulmonary infiltrates intermittently in the past 6 years and was hospitalised. As all diseases that cause DAH other than IPH were negative, the patient was suspected of IPH.

Outcome and follow-up

After being discharged, the patient’s hemoptysis and dyspnoea recurred when the oral administration of prednisolone was gradually reduced to 12 mg/day. Adding oral administration of azathioprine at 100 mg/day improved symptoms. Ultimately, the prednisolone dose could be reduced to 8 mg/day. Although diffuse pulmonary infiltrates improved, the emphysematous change and dyspnoea on exertion remained (figure 4). One year after hospitalisation and continuous administration of 8 mg/day of prednisolone and 100 mg/day of azathioprine, pulmonary function tests were performed when the patient was not experiencing hemoptysis. Results showed that FEV₁ was 2.67 L, FVC 3.48 L, TLC 5.38 L, RV 2.03 L, FEV₁/FVC ratio 76.7%, FVC_%pred 94.3%, TLC_%pred 95.9%, DLCO_%pred 30.0% and DLCO/VA 1.76 mL/min/mm Hg/L (table 1). Although FVC_%pred and TLC_%pred significantly improved, improvements in FEV₁ and DLCO_%pred were limited, and pulmonary diffusing capacity impairment persisted. However, the patient no longer required oxygen during rest, and his inflammatory response and anaemia improved. At the time of conducting this study, more than 1.5 years after hospitalisation, oral administration of 8 mg/day of prednisolone and 100 mg/day of azathioprine was continued. The pulmonary function test results were FEV₁ of 2.67 L, FVC 3.70 L, TLC 5.71 L, RV 1.93 L, FEV₁/FVC ratio 72.2%, FVC_%pred 101.6%, TLC_%pred 102.9%, DLCO_%pred 30.7% and DLCO/VA 1.80 mL/min/mm Hg/L (table 1). Although pulmonary diffusing capacity did not improve, the patient continued outpatient treatment without hemoptysis or recurrence of respiratory failure.