INTRODUCTION

Acute fibrinous and organizing pneumonia (AFOP) was first described by Beasley in a pathologic study of 17 patients with acute/subacute lung injury in 2002[1]. It was defined as a rare type of the idiopathic interstitial pneumonia in 2013[2]. A few studies have reported the characteristics of AFOP in recent years, but the etiology is still not fully understood. AFOP may occur at any age, but usually presents in the elderly people. The clinical presentation of AFOP is nonspecific and often similar to common pneumonia, so it is easily misdiagnosed. The confirmation of AFOP diagnosis depends on pathological biopsy.

To date, the pathogenesis of AFOP remains unclear, and there is still no standard treatment. Steroid treatment was reported to be effective, but the information on dosage, duration and long-term side-effects is not available. We herein report a case of an 81-year-old female patient with AFOP, who was successfully treated with steroid monotherapy. We also report our observations of the dosage, duration and side-effects. This report can provide a new choice of AFOP treatment in geriatric patients.

Chief complaints

An 81-year-old retired female doctor was admitted to our hospital with dry cough, and breathlessness for 1 mo.

History of present illness

She had taken Azithromycin for 2 d, but there was no improvement.

History of past illness

She denied any history of disease.

Physical examination

On examination, her temperature was 36.5 °C, blood pressure was 108/72 mmHg, heart rate was 74 beats/min, oxygen saturation was 98% at room air, and respiratory rate was 19 breaths/min. Lung examination showed inspiratory crackles in the right lung base. The rest of her physical examinations were unremarkable.

Laboratory testing

Blood routine, liver function, renal function tests and serum sodium, potassium, creatinine, magnesium, calcium were all within normal limits. Blood tumor biomarker tests were negative. Serologic tests for antinuclear antibodies, rheumatoid factors and anti-neutrophil cytoplasmic antibodies were within normal limits. Tuberculin skin test, sputum stains for acid fast bacilli, and cultures of blood and sputum were all negative. Arterial blood gas analysis at room air revealed pH 7.4, PaO2 63 mmHg and PaCO2 35 mmHg. The pulmonary function test revealed moderate restrictive ventilatory impairment and a moderate decrease in diffusing capacity.

Imaging examination

Computed tomography (CT) scan of the chest on admission showed bilateral lesions, multiple patchy, consolidation and ground-glass opacities, associated with air bronchogram (Figure 1), especially in the right lung and the upper lobe of the left lung. The patient was treated with broad-spectrum antibiotics and anti-fungal therapy in the following 2 wk. But her symptoms of cough and chest tightness, and shortness of breath were not relieved. The repeat CT scan of the chest 2 wk later (Figure 2) showed that her condition was significantly advanced, which means a previous misdiagnosis. CT-guided percutaneous needle lung biopsy was then performed after informed consent was obtained from the patient.

Fan-Qing Meng, MD, Professor, Department of Pathology

The pathologic consultation revealed prominent fibrinous exudation within most the alveolar spaces (Figure 3). No necrosis or granulomas were observed, neither any evidence of diffuse alveolar damage, alveolitis or eosinophilic infiltration. No evidence of special infections was found. A diagnosis of AFOP was established.

FINAL DIAGNOSIS

AFOP.

TREATMENT

The patient was therefore started with intravenous methylprednisolone 40 mg/d for 1 wk. Considering the old age of the patient, and the considerable side effects of the drug, we then reduced the dosage to 12 mg twice daily taken orally for 1 wk. The patient discharged on a tapering schedule of methylprednisolone 20 mg/d for 10 d, then 16 mg/d for 10 d, 12 mg/d for 10 d, and 8 mg/d for 1 mo.

OUTCOME AND FOLLOW-UP

After 1 wk treatmengt of methylprednisolone 40 mg/d, her symptom of cough was improved. CT scan also showed significant improvement (Figure 4), and bilateral lesions resolved gradually. During the treatment with steroids, the main side-effects were hypertension and hyperglycaemia, which were resolved by antihypertensives and dietary and lifestyle modifications. No significant adverse side-effects were noticed. The repeat chest CT scan revealed almost normal findings after 3 wk (Figure 5).

DISCUSSION

In 2002, Beasley[1] described a new histological pattern of lung injury named AFOP, which is characterized by intra-alveolar fibrin balls and organizing pneumonia with a patchy distribution. Sporadic case reports have been published on this newly recognized clinicopathological entity that is still underdiagnosed. In 2013, it was finally defined as a rare type of the idiopathic interstitial pneumonia by the American Thoracic Society/European Respiratory Society[2]. AFOP is rarely reported worldwide. We searched the PubMed using the keywords “AFOP” or “acute fibrinous and organizing pneumonia”, and identified 74 relevant articles. The age of the patients was diverse from infant to elderly[3-5]. It is more common in males than in females[1]. Our patient was an 81-year-old female, who was the oldest one according to the literature.

Although the histopathological features are well described, the clinical manifestations, course, and treatment of AFOP are not characterized. Because the clinical manifestations are nonspecific, the pathogenesis of AFOP is not fully understood. It can be idiopathic or associated with a wide spectrum of clinical conditions, such as connective tissue diseases[4,6,7], bacterial infections or viral infections[3,8], specific etiologic agent like Chlamydophila pneumoniae[9], chronic renal insufficiency[10], drug reaction or drug-induced toxicity[11], hematologic disease[12,13], hematopoietic stem cell transplantation[14], and occupational or environmental exposures[1].

There is still no standard treatment for AFOP. Therapy with steroids alone or combined with immunosuppressants was attempted, but the dosage and duration of steroid treatment are still unclear. Usually 0.5-1 mg/kg daily of prednisone (or equivalent) are prescribed initially. A maximal dose of methylprednisolone was reported to be up to 1000 mg/d[4]. A pulse therapy of steroids was also administered in some fulminant patients[7,10,15,16]. Besides steroids, immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil, cyclosporine and azathioprine have been tried in AFOP patients complicated with connective tissue diseases[4,6,7,17]. In addition, Zhou et al[18] reported that low-dose indomethacin combined with methylprednisolone was a new choice of treatment. The role of anti-infective agents is not acknowledged, but in fact, most patients had been treated with sufficient anti-infective agents before a definite diagnosis could be established. We suggest that appropriate anti-infective agents should be given according to patient’s condition.

There is no consensus on treatment duration, and relapse may occur during the period when the dosage of steroids is reduced. Sauter et al[17] reported a long duration of steroid treatment of nearly 24 mo. The major side-effects of steroids include hypertension, hyperglycaemia, immune suppression, electrolyte imbalance, and femoral head necrosis, especially in geriatric patients. The dosage and duration of steroids should be individualized according to the patient’s condition, radiological evolution and the side-effects, and more studies on treatment of AFOP are required in order to reduce the complication and improve the survival rate and the patient’s life quality.

In the present case, steroid was prescribed as soon as the diagnosis was established. Considering the old age of the patient, and to avoid potential severe side effects of high-dose steroids, an initial dose of methylprednisolone 40 mg/d was used. Fortunately, her symptoms were soon controlled. And when the dose of methylprednisolone was decreased to 24 mg/d, the improvement continued in patient’s condition and radiological evolution, and the main side-effects included hypertension and hyperglycaemia, which were resolved by antihypertensives and dietary and lifestyle modifications.

AFOP is a rare lung disease with varying morbidity and mortality, and no definitive therapy is available. The successful use of steroids in this case indicates that the pulse therapy of steroids may not be necessary. This case report adds to the literature a new choice of treatment in terms of dosage of steroids for AFOP.

EXPERIENCES AND LESSONS

This case may serve as a reminder to respiratory physicians who encounter a suspected pulmonary infection case but unresponsive to optimum antibiotic therapy in their clinical practice. Although AFOP is a rare entity, it should be considered in the differential diagnosis of pulmonary infection unresponsive to optimum antibiotic therapy. On the other hand, AFOP might be under diagnosed and under reported especially in the developing countries due to the complicated means of obtaining a tissue diagnosis which are not routinely performed in the community and secondary hospitals. Our case is distinct. The patient was an 81-year-old woman and she had a good response to short-term steroid treatment. The last follow-up showed that no relapse occurred during tapering steroids. This case will contribute to a better understanding of the treatment of AFOP in geriatric patients, and provide a new choice of dosage and duration of it. Further more studies are needed to describe various clinical aspects of this rare disease.