Acute fibrinous organising pneumonia presenting as a cavitary lung lesion and treatment response to azithromycin

Abstract

Acute fibrinous organising pneumonia is distinct from the classic diffuse alveolar damage, organising pneumonia and eosinophilic pneumonia. A 52-year-old woman presented with fever, productive cough, night sweats and left-sided pleuritic chest pain for a week. Physical examination was significant only for decreased breath sounds in the left infraclavicular area laterally. Imaging studies revealed a peripheral thick-walled left upper lobe cavitary lesion, left lower lobe consolidation and an enlarged subcarinal lymph node. She was treated with doxycycline for 10 days without improvement. Pertinent laboratory tests, microbiologic workup and fibre-optic bronchoscopy were non-diagnostic and a CT-guided left upper lobe lung biopsy revealed acute fibrinous organising pneumonia. She was treated with azithromycin with complete resolution of symptoms. To our knowledge, this is the first reported case of acute fibrinous organising pneumonia presenting as a cavitary lung lesion and the first with treatment response to azithromycin.

Background

Acute fibrinous organising pneumonia is a histopathological pattern of acute lung injury, distinct from the classic diffuse alveolar damage, organising pneumonia and eosinophilic pneumonia. We report a unique case of acute fibrinous organising pneumonia presenting as a cavitary lung lesion with negative infectious workup, who responded to azithromycin. To our knowledge, there are two novel aspects of our case: this is the first reported case of acute fibrinous organising pneumonia presenting as a cavitary lung lesion and the first with treatment response to azithromycin. Corticosteroids and immunosuppressant medications have traditionally been used to treat acute fibrinous organising pneumonia.

Case presentation

A 52-year-old woman presented to the emergency room with fever (100–101 Fahrenheit), cough productive of purulent sputum, mild streaking of blood in the sputum, night sweats and left-sided pleuritic chest pain for a week. She denied recent travel, exposure to chemicals and exposure to a patient with tuberculosis. She reported a negative purified protein derivative test about 8 months ago. Her medical history was significant for sarcoidosis diagnosed with a subcutaneous nodule biopsy and treated with prednisone for 6 months (in complete remission for 5 years), hypertension, hyperlipidaemia, tobacco abuse (1 pack-year) and diabetes mellitus. Past occupation included janitorial work. Physical examination was significant only for decreased breath sounds in the left infraclavicular area laterally and multiple lipomas on the abdomen. Chest radiograph revealed a cavitary nodular opacity in left upper lobe measuring about 4 cm (figures 1 and 2). She was treated with doxycycline for 10 days without improvement and referred to a pulmonary clinic.

Figure 1.

Chest radiograph posteroanterior view at presentation showing the left upper lobe cavitary opacity.

Figure 2.

Chest radiograph lateral view at presentation showing the left upper lobe cavitary opacity.

Investigations

Pertinent laboratory tests revealed white cell count 9.1×10⁹/L (neutrophils 58%, lymphocytes 35%, monocytes 5%, basophils 1% and eosinophils1%), haemoglobin 140 g/L and platelets 266×10⁹/L. A CT of the chest was remarkable for a peripheral thick-walled left upper lobe cavitary lesion 5.2×3.3×2.8 cm (figures 3 and 4), left lower lobe consolidation 3.0×0.8 cm and an enlarged 1 cm subcarinal lymph node. Sputum gram stain and culture, acid-fast bacillus smear and culture (×3) and T-spot test came back negative. Electrolytes, ACE, lactate dehydrogenase, renal and liver tests were all normal, except mildly elevated alkaline phosphatase (151 IU/L). Complete antinuclear antibody profile, antineutrophilic cytoplasmic antibody, HIV, fungitell, aspergillus-galactomannan and fungal serologies including Histoplasma, Coccidioides, Blastomyces and Aspergillus were all unremarkable. Endobronchial ultrasound with transbronchial needle aspiration of a 1 cm sized subcarinal lymph node revealed benign reactive lymphoid tissue with rare granulomata. Fibre-optic bronchoscopy with bronchoalveolar lavage revealed normal tracheobronchial anatomy. Bronchoalveolar lavage from left upper lobe had 87% macrophages, 12% lymphocytes and 1% neutrophils. All cultures including bacterial, mycobacterial and fungal were negative. Cytology did not show any malignant cells and transbronchial biopsies revealed lung tissue with focal anthracosis, mild chronic inflammation and focal fibrin deposition without neoplasia. A CT-guided left upper lobe lung biopsy revealed acute fibrinous organising pneumonia characterised by patchy fibrin exudates, intra-alveolar macrophages and focal loose non-caseating granulomas with a prominent cuff of lymphocytes (figure 5). No acid-fast or fungal organisms were identified on the sections. Subsequent cultures were negative as well.

Figure 3.

CT chest transverse images at presentation showing the left upper lobe cavitary lesion.

Figure 5.

CT-guided lung biopsy from left upper lobe cavitary lesion. (A, B) Intra-alveolar fibrinous exudate along with intra-alveolar macrophages (H&E ×100). (C, D) Interstitial loose granulomas composed of aggregates of histiocytes with a peripheral cuff of lymphocytes (H&E ×100, ×200).

Figure 4.

CT chest coronal images at presentation showing the left upper lobe cavitary lesion.

Treatment

The patient continued to have low-grade fever (99–100 Fahrenheit), night sweats, cough with small amount of phlegm expectoration and left-sided pleuritic chest pain. She was not a suitable candidate for corticosteroids due to uncontrolled diabetes, blood glucose in 300–400 mg/dL range despite insulin therapy. Azithromycin 250 mg three times a week was started after discussing all possible treatment options with the patient. She tolerated the medication without any adverse effects. The dose was increased to 500 mg three times a week after 2 weeks interval. She had complete resolution of the symptoms and significant improvement in the radiological abnormalities after 6 weeks of azithromycin therapy (figures 6 and 7).

Figure 6.

CT chest transverse images after 6 weeks of azithromycin therapy showing significant improvement in the left upper lobe cavitary lesion.

Figure 7.

CT chest coronal images after 6 weeks of azithromycin therapy showing significant improvement in left upper lobe cavitary lesion.

Outcome and follow-up

The patient reported complete resolution of her symptoms on the last visit in the pulmonary clinic after 6 weeks of azithromycin therapy. Currently, she is taking azithromycin 500 mg three times a week and scheduled to follow-up in the pulmonary clinic in 8 weeks.

Discussion

Acute fibrinous organising pneumonia is rare interstitial pneumonia,¹characterised by the predominant histological pattern of intra-alveolar fibrin deposition in the form of fibrin balls and organising pneumonia, in a patchy distribution.² This pattern of acute lung injury was first described by Beasley et al ² in 2002. The pattern is distinct from the classic hyaline membranes associated with the diffuse alveolar damage and intra-alveolar buds of granulation tissue seen in the classic organising pneumonia.^{2 3}

Presenting symptoms include fever, cough, shortness of breath, chest pain, haemoptysis and constitutional symptoms including malaise and arthralgias.^{2 4 5} Acute fibrinous organising pneumonia can be idiopathic or associated with collagen vascular diseases, infections, drugs, malignancies, haematological disorders, transplantation, chemical and occupational exposures.^{2 5} Our patient presented with fever, cough, haemoptysis, pleuritic chest pain and night sweats. We speculate that our patient had acute fibrinous organising pneumonia secondary to an infection, although microbiologic workup could not reveal any specific infectious aetiology. Paraskeva et al ⁶ reported acute fibrinous organising pneumonia as an important cause of chronic allograft dysfunction after bronchiolitis obliterans and a significantly worse survival as compared with bronchiolitis obliterans. The most common high-resolution CT findings associated with acute fibrinous organising pneumonia are lobar consolidation, ground-glass opacity and patchy consolidation in a bilateral basal distribution.^{4 5} Other CT findings include peribronchovascular opacities, band-like consolidation, pleural effusion, solitary nodule and reverse halo sign.^{4 5} Jabbour et al ⁷ reported a case of acute fibrinous organising pneumonia with an unusual finding of upper lobe infiltrate. Cavitation is rare in organising pneumonia and to our knowledge it has never been reported in acute fibrinous organising pneumonia. Our patient had left upper lobe infiltrate with cavitation, in contrast to most cases presenting as bilateral basilar infiltrates.2 4 5 7 Such presentation brings up mycobacterial and fungal disease among the top differential diagnoses, which were ruled out in our patient. Patients with acute fibrinous organising pneumonia may either have an acute severe disease with rapid progression to respiratory failure requiring mechanical ventilation or a subacute less severe disease with good recovery.^{2 8} Our patient had a subacute course and continues to recover.

Corticosteroids are the most commonly used treatment modality.2 4 5 8–10 Zhou et al ¹¹ reported a response of acute fibrinous organising pneumonia treated with corticosteroids and low-dose indomethacin. Various immunosuppressive medications including cyclophosphamide, mycophenolate, cyclosporine and azathioprine have been used alone or in combination with corticosteroids.^{5 12} Steroid use can be limited by chronic diseases like diabetes mellitus and hypertension due to significant adverse effects related to the therapy such as in our patient. Macrolides (clarithromycin and azithromycin) have been reported to be effective in the treatment of organising pneumonia and associated with fewer side effects and relapses, particularly in patients with normal pulmonary function.¹³ Inflammatory cytokines produced by alveolar macrophages including interleukin (IL)-6, IL-8 and transforming growth factor-β1 play an important role in the pathogenesis of organising pneumonia.¹⁴ Macrolides inhibit cytokine production by the alveolar macrophages decreasing their concentration in the serum and bronchoalveolar lavage in patients with organising pneumonia.^14–16 The anti-inflammatory effects of macrolides are the basis of their effectiveness in the treatment of organising pneumonia^14–16 and other diseases including chronic obstructive pulmonary disease, cystic fibrosis and panbronchiolitis. Macrolides have been successfully used to treat cryptogenic and secondary organising pneumonia either alone or in combination with corticosteroids.^17–19 We speculate that our patient had a good response to azithromycin due to the anti-inflammatory properties of the macrolides.

In conclusion, acute fibrinous organising pneumonia is rare interstitial pneumonia with variable clinical presentation and we add cavitation to the literature on it. In rare diseases such as acute fibrinous organising pneumonia, case reports such as ours reporting on the novel response to azithromycin would be valuable to clinicians.

Learning points.

• Acute fibrinous organising pneumonia is rare interstitial pneumonia, characterised by the predominant histological pattern of intra-alveolar fibrin deposition in the form of fibrin balls and organising pneumonia, in a patchy distribution.

• Acute fibrinous organising pneumonia can be idiopathic or associated with collagen vascular diseases, infections, drugs, malignancies, haematological disorders and transplantation, chemical and occupational exposures.

• Acute fibrinous organising pneumonia commonly appears radiologically as lobar consolidation, ground-glass opacity and patchy consolidation in a bilateral basal distribution. Our case adds a novel feature of left upper lobe distribution and cavitation to the literature.

• Acute fibrinous organising pneumonia may either cause an acute severe disease with rapid progression to respiratory failure or a subacute disease with good recovery.

• Corticosteroids and various immunosuppressive medications including cyclophosphamide, mycophenolate, cyclosporine and azathioprine have been used alone or in combination to treat the disease. Response to azithromycin is a novel aspect of our case and would be valuable to clinicians.