New insights into pulmonary manifestations of ANCA (Anti-neutrophil cytoplasmic antibodies) positivity

Medical News: Understanding the Role of ANCA in Lung Diseases
Anti-neutrophil cytoplasmic antibodies (ANCA) are widely recognized for their association with vasculitis, a group of conditions that cause inflammation in small blood vessels. However, recent studies indicate that ANCA positivity can also be seen in various lung diseases, complicating diagnosis and treatment. In this new case series conducted by researchers from the Fattouma Bourguiba University Hospital of Monastir, Tunisia, a group of patients presented with lung problems related to ANCA positivity but were ultimately diagnosed with different conditions.


New insights into pulmonary manifestations of ANCA (Anti-neutrophil cytoplasmic
antibodies) positivity

This Medical News report provides a comprehensive overview of the findings and emphasizes the importance of multidisciplinary approaches in diagnosing lung diseases associated with ANCA positivity.
 
Study Overview
The study aimed to explore how ANCA positivity can present in various pulmonary conditions, aside from its more common association with vasculitis. The research team, consisting of experts from the departments of pneumology, radiology, immunology, and internal medicine, recruited four patients over two years (2020-2022). These patients, aged between 41 and 67 years, presented with a range of pulmonary manifestations and tested positive for ANCA.
 
ANCA screening was done through indirect immunofluorescence techniques, and further typing was carried out using line-blot techniques. In this study, ANCA was found to be both perinuclear (pANCA) and cytoplasmic (cANCA) depending on the case. The patients were ultimately diagnosed with various conditions, including pulmonary tuberculosis, systemic lupus erythematosus (SLE), bronchiolitis obliterans organizing pneumonia (BOOP), and pulmonary aspergillosis.
 
Case Studies: A Diverse Spectrum of Diagnoses
-Pulmonary Tuberculosis and ANCA Positivity
The first case involved a 67-year-old woman who had a history of diabetes and hypertension, as well as a previous COVID-19 infection. She presented with symptoms such as hemoptysis (coughing up blood), dyspnea, and skin nodules. A chest CT scan revealed lesions indicative of encysted bronchi dilatation, pulmonary nodules, and cavitations. Her ANCA tests were positive for pANCA, specifically anti-myeloperoxidase (MPO). Despite the initial confusion, a biopsy revealed the presence of caseating granulomas, leading to the diagnosis of pulmonary tuberculosis based on World Health Organization (WHO) criteria. Anti-tuberculosis treatment was initiated, but the patient was lost to follow-up.
 
-Systemic Lupus Erythematosus with Pulmonary Complications
In the second case, a 46-year-old woman presented with dyspnea, cervical pain, and swelling in her lower limbs. She tested positive for cANCA, though further typing was negative. Imaging studies revealed pericarditis and pleural effusion. A pleural biopsy showed non-specific inflammation, and she was eventually diagnosed with systemic lupus erythematosus (SLE) based on the Systemic Lupus International Collaborating Clinics (SLICC) criteria. The patient responded well to treatment with hydroxychloroquine, corticosteroids, and azathioprine. Her respiratory symptoms improved significantly after a few months of therapy.
 
-Bronchiolitis Obliterans Organizing Pneumonia (BOOP) Mimicking Vasculitis
A 63-year-old woman with a history of diabetes, hypertension, and chronic myeloid leukemia developed unexplained pulmonary nodules. Her ANCA tests showed positive pANCA with anti-MPO. Further radiological investigations showed angiocentric excavated nodules, and a nasal biopsy revealed slight chronic inflammation. Based on her symptoms and imaging, she was diagnosed with BOOP, a rare lung condition that mimics vasculitis. She was treated with glucocorticoids, and her condition improved over time.
 
-Pulmonary Aspergillosis with ANCA-Associated Vasculitis
The final case involved a 41-year-old man who had previously been treated for pulmonary tuberculosis. He presented with mild hemoptysis and was diagnosed with pulmonary aspergillosis after positive aspergillus serology and imaging showed cavitary lesions. Immunological analysis revealed positive cANCA, specifically targeting anti-leukocyte proteinase 3 (PR3). His condition was classified as ANCA-associated vasculitis triggered by aspergillus infection, a rare but serious complication. After treatment with antifungals and immunosuppressive therapy, the patient’s condition improved.
 
Challenges in Diagnosis
The case study series emphasize that the presence of ANCA does not always point to ANCA-associated vasculitis (AAV). Distinguishing between AAV and other conditions like infections, autoimmune diseases, or pulmonary conditions can be difficult, especially since treatment strategies for these conditions differ dramatically.
 
For example, tuberculosis, as seen in the first case, can present with ANCA positivity, which could be confused with AAV. However, initiating immunosuppressive treatment for AAV without ruling out tuberculosis could be dangerous. Similarly, ANCA positivity in pulmonary aspergillosis, as seen in the fourth case, can lead to a delayed diagnosis of the underlying infection.

In all cases, a multidisciplinary approach involving radiological imaging, histological analysis, and immunological testing was crucial for reaching a definitive diagnosis. The study underscores the importance of considering various potential diagnoses when ANCA is detected in patients with respiratory symptoms.
 
ANCA positivity can be associated with conditions other than vasculitis, such as pulmonary tuberculosis, SLE, BOOP, and pulmonary aspergillosis.
 
Accurate diagnosis requires a combination of imaging, histological analysis, and detailed immunological testing.
 
Treatment should be carefully considered, as misdiagnosis can lead to inappropriate therapy, which may worsen the patient's condition.

The broad spectrum of pulmonary diseases associated with ANCA positivity highlights the need for a tailored, multidisciplinary approach to patient care.
 
Conclusions
The findings from this case series suggest that the presence of ANCA in patients with respiratory symptoms should prompt clinicians to consider a wide range of potential diagnoses beyond ANCA-associated vasculitis. While ANCA remains a valuable biomarker for identifying vasculitis, it is clear that its presence can be misleading in cases of infections, autoimmune diseases, and other lung conditions.
 
It is essential for healthcare providers to adopt a cautious and comprehensive approach when interpreting ANCA results. Diagnostic uncertainty can be minimized by combining different investigative tools, including radiology, immunology, and pathology, to guide therapeutic decisions. In cases of doubt, collaboration between specialists from various medical disciplines is key to ensuring accurate diagnosis and optimal treatment.
 
The study findings were published in the peer-reviewed journal: Respiratory Medicine Case Reports.
https://www.sciencedirect.com/science/article/pii/S2213007124001369
 
For the latest on infections involving Anti-neutrophil cytoplasmic antibodies (ANCA), keep on logging to Thailand Medical News.
 
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