Comparison of Radiological and Histological Findings of Lung Parenchyma in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides mainly affecting small vessels from capillaries to intraparenchymal arteries. AAV consists of three variants including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).1 AAV can affect various organs, including the kidneys, lungs, and peripheral nerves. Among these, lung (chest) manifestations are described as wheeze, nodules or cavities, pleurisy, infiltrate, endobronchial involvement, alveolar haemorrhage, and respiratory failure.2, 3 In patients with AAV, the rate of lung involvement ranges from 20% to 80% according to AAV variants: 60–80% for MPA, 20–60% for GPA, 34–56% for ANCA-positive EGPA and 60–76% for ANCA-negative EGPA.4 The major pulmonary symptoms related to AAV are progressive dyspnoea (50–73%) and cough (21–60%), and are accompanied by constitutional and extra-pulmonary symptoms at a rate of approximately 80%.5 In addition, previous studies have indicated that lung involvement has an unfavourable impact on long-term prognosis and relapse rate in AAV patients.6, 7, 8

Chest computed tomography (CT) patterns of lung parenchymal lesions related to AAV include ground glass opacities, reticular shadowing, interlobular septal thickening, consolidation and honeycomb appearance. Of these findings, the most common chest CT pattern is unusual interstitial pneumonia (UIP), followed by non-specific interstitial pneumonia (NSIP).5, 6 The histological features on surgical lung biopsy depend on the subtype of AAV. The typical pathologic findings in GPA are necrotizing granuloma vasculitis involving adventitia, media of small vessels; lung biopsies from EGPA patients display eosinophilic vasculitis or eosinophilic granuloma; and the histological findings in MPA are typically pulmonary haemorrhage, hemosiderin-laden macrophages in the alveolar space and neutrophilic capillaritis.7

When lung parenchymal lesions are suspected on chest X-ray (CXR) or chest CT, a surgical lung biopsy is a standard test to confirm lung involvement of AAV. However, lung biopsy is an invasive and risky procedure, such that it cannot be recommended in all patients suspected of lung involvement of AAV. Thus, in clinical settings, biopsies targeting other organs such as the kidneys, nerves and maxillary sinus are performed before lung biopsy to diagnose AAV. For these reasons, previous studies have been unable to clearly answer questions on whether histological features of lung involvement are AAV variant-specific and how different the rates of consistency between radiological and histological features are among MPA, GPA and EGPA. Furthermore, to the best of our knowledge, there has been no report on the consistency between radiological and histological features in AAV patients in Korea. Hence, in this study, we investigated the chest CT patterns of 74 AAV patients and analysed both histological features of lung involvement and the rate of consistency between radiological and histological features among MPA, GPA, and EGPA in 28 AAV patients who underwent lung biopsy within 4 weeks before and after diagnosis of AAV.

In this study, we investigated chest CT patterns in 74 AAV patients and analysed both the histological features of lung involvement and the consistency between radiological and histological results in 28 AAV patients who underwent lung biopsy according to AAV variants. Of 145 patients who had results of CXR at diagnosis of AAV, 74 patients (51.0%) underwent chest CT. The most frequent extra-pulmonary manifestation of them was renal manifestation, followed by general manifestation. Similarly, previous reports revealed that patients with AAV exhibited kidney-related symptoms in up to 100% and constitutional symptoms in approximately 80%.5

In this study, we founded that lung histological features differ among AAV variants. In MPA patients, the major histological features were necrotizing vasculitis and hemosiderin-laden macrophages in MPO-ANCA positive patients, and none exhibited necrotising granuloma or eosinophilic infiltration in lung tissues. Meanwhile, in GPA patients, the major histological features were necrotizing vasculitis and necrotizing granuloma, and the major histological feature of EGPA patients was only necrotizing vasculitis.

The consistency rates between radiological and lung histological findings were based on AAV variants. The consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%). Two patients suspected of vasculitis on chest CT had no evidence of AAV on lung histology but they were finally classified as MPA by renal histological findings. Interestingly, 1 patient suspected of other ILD and 1 patients suspected of pneumonia exhibited histological features of MPA. Meanwhile, 1 of 2 EGPA patients with histological features compatible with AAV was suspected of pneumonia, rather than AAV on chest CT. Therefore, in MPA and EGPA patients, when lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for proper classification of AAV, due to discordance between radiological and histological findings.

While radiological features on chest CT could suggest GPA, physicians should not put blind belief in chest CT patterns showing cavitary lung parenchymal lesions before the final classification of AAV. It could be reasonably speculated that lung cavitary parenchymal lesions are important predictive clues for GPA. However, one patient with MPA who exhibited cavitary parenchymal lesions in chest CT was finally confirmed to have a fungal infection on lung biopsy. In this case, MPA was confirmed by MPO-ANCA positivity and renal biopsy. Furthermore, the aspergillosis antigen was detected in the serum of this patient and typical Aspergillus hyphae was observed on lung histology.12, 13 The halo sign in chest CT images has been used to discern the aetiologies of pulmonary cavitary nodules; however, this can be observed in various diseases beyond GPA, including invasive aspergilloma.14 Herein, three of 9 GPA patients who exhibited cavitary lesions in chest CT underwent lung biopsy to exclude other lung pathologic conditions including fungal infection despite the presence of histology of nasal cavity compatible with GPA in our study.15

One MPA patient and one EGPA patient had overlapping syndromes with AAV and Sjogren syndrome. Both patients had anti-SSA/Ro antibody and decreased lacrimal and salivary gland function. In these patients, chest CT mostly suggested UIP, and lung biopsies revealed patchy interstitial fibrosis with honeycomb change, which was consistent with a UIP pattern, with many lymphoid follicles.16, 17 When AAV was accompanied by autoimmune connective tissue disease, at least confined to this study, lung histology did not seem helpful to confirm vasculitis. Also, lung biopsy alone could not confirm AAV when chest CT showed diffuse ground glass opacity lesions suggestive of ILD, pulmonary haemorrhage, and atypical pneumonia in patients with AVV. Meanwhile, the diagnosis of MPA was usually made through kidney biopsy, and that of EGPA was done through nerve biopsy. However, physicians should consider a lung biopsy, because other aetiologies, such as fungal infection, tuberculosis and lung cancer, must be excluded before treatment for AAV.

The administration of glucocorticoid before lung biopsy may have an influence on histological features of lung parenchyma and may confuse the precise classification of AAV. Therefore, we reviewed the medical records of 28 AAV patients who underwent lung biopsy and counted the number of patients who received glucocorticoids before lung biopsy. Glucocorticoids were administered to five MPA patients before lung biopsy. Two of the five MPA patients had previously received glucocorticoids due to DAH. Four of the five patients exhibited histological features compatible with MPA, while one patient did not. Thus, we assume that the administration of glucocorticoid might hide the histological features of AAV in MPA patients who exhibit ground-glass opacity on chest CT, despite the small number of patients and the retrospective study design.

Our study has merit in that we, for the first time, described both histological and radiological features in the same AAV patients, compared them and assessed the consistency between them in all variants of AAV. However, our study also has several limitations: First, we retrospectively reviewed medical records of AAV patients, which prohibited us from interpreting radiological features with more information, particularly clinical symptoms and signs at diagnosis. Second, only 28 of 74 patients who exhibited abnormal lung parenchymal findings on chest imaging studies underwent lung biopsy because of various clinical reasons. Accordingly, we believe that additional cases of lung biopsy could have further clarified the link between radiological and histological information in AAV patients.

In conclusion, the consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%). Therefore, in MPA and EGPA patients, when lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for the proper classification of AAV, due to discordance between radiological and histological findings.