Sir,
The antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides are multisystem disorders involving inflammation of the small blood vessels and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. GPA is characterized by necrotizing granulomatous inflammation involving ears, nose, upper and lower respiratory tracts, and necrotizing vasculitis affecting predominantly small-to-medium-sized vessels, often including necrotizing glomerulonephritis.[1,2] Common radiological presentations include nodules, cavitation within nodule, mass, ground glass density and pulmonary consolidation.[3,4] Here, we present a case of GPA presenting as exudative pleural effusion.
A 58-year female, never smoker, asthmatic for the last 30 years, presented with complaints of gradually progressive dyspnoea for 1 month associated with cough, fever and loss of appetite for 2 weeks. She had no history of haemoptysis, chest pain and connective tissue disease-related symptoms. She was diabetic, hypertensive and hypothyroid. She was pale and had bilateral pitting pedal oedema. Non-scarring alopecia and depigmentation patches were present over scalp. On auscultation, there was bilateral vesicular breath sound with decreased intensity in right infrascapular region, bilateral late inspiratory fine crackles and rhonchi. Examination of other systems was normal. Initial CXR showed non-homogenous opacity in right lower zone with right costophrenic and cardiophrenic angle blunting [Figure 1a]. Positive lab findings included Hb 6.6 g/dL, total leukocyte count 14.7k, platelet count 95k, erythrocyte sedimentation rate 30 mm/h, C reactive protein 91.6 mg/L and N-terminal pro-brain natriuretic peptide 366 pg/mL. Absolute eosinophil count was 360. ECG was normal. Peripheral smear revealed normocytic normochromic blood picture and diminished total iron-binding capacity. She was diagnosed as pneumonia with parapneumonic effusion and initiated on broad-spectrum intravenous antibiotics, nebulized bronchodilators, diuretics and four units of packed red blood cells (PRBC). Diagnostic thoracentesis revealed straw-coloured fluid, predominantly lymphocytic with glucose of 157 mg/dL, protein of 3.12 g/dL, Lactate Dehydrogenase (LDH) of 500 IU/L and adenosine deaminase (ADA) of 5.3 IU/L. No atypical cells were seen. Contrast-enhanced computed tomography of neck, thorax and abdomen revealed malignant appearing right lower lobe mass with mediastinal lymph nodes and minimal right pleural effusion with subsegmental collapse of right middle lobe and superior lingular segment [Figure 1b and c]. Fiberoptic bronchoscopy revealed normal bilateral bronchial tree. Bronchoalveolar lavage for bacterial, fungal, acid-fast bacilli smear, cartridge-based nucleic acid amplification test, and malignant cytology was negative. Transbronchial lung biopsy was negative for granuloma and malignancy. At this stage, the issues in the patient were refractory anaemia, malignancy was not ruled out, and general condition was not improving. So, a CT-guided transthoracic tru-cut biopsy was done. During the course of stay, pleural effusion kept on increasing so a thoracoscopic pleural biopsy was performed. Plaque-like deposits were seen over parietal pleura [Figure 2a]. The tru-cut biopsy from right lower lobe lung lesion showed alveolar spaces filled with old haemorrhage and oedema fluid. No mass lesion or dysplastic alveolar lining was noted. However, a few areas of the alveolar wall showed thin-walled blood vessels surrounded and infiltrated by a sheath of lymphomononuclear cells. Occasional tiny areas of hyaline membrane lining the alveolar walls were also noted. Overall histological features favoured a small vessel vasculitis [Figure 2b], most likely, GPA. Pleural biopsy was suggestive of multiple fibrocollagenous and fibromuscular tissue bits infiltrated by mixed inflammatory infiltrate. Features were suggestive of inflammatory lesion with secondary vasculitis. Serology done for PR3-ANCA was positive. p-ANCA, anti-nuclear antibody screening and ENA profile were negative. ENT evaluation revealed right nasal crusting with early synechiae changes. Urinary micro-albumin/creatinine ratio was raised to 436 mg/g (0–30). History of recurrent oral ulceration was present. Hence, a diagnosis of GPA was made. During induction phase, patient was initiated on rituximab (375 mg/m2) once weekly for a period of 4 weeks and steroids at a dose of 1 mg/kg. During maintenance phase, steroids were tapered and tab azathioprine was added. CXR showed marked improvement [Figure 2c]. Hb improved to 11.7 g/dL after 1 month of treatment.
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Figure 1: (a) CXR showing non-homogenous opacity in right lower zone. (b and c) Malignant appearing right lower lobe mass and minimal right pleural effusion with subsegmental collapse
Figure 2: (a) Plaque like deposits seen over parietal pleura. (b) HPE of lower lobe mass showing alveolar spaces filled with old haemorrhage and oedema fluid, alveolar wall showing thin-walled blood vessels surrounded and infiltrated by a sheath of lymphomononuclear cells suggestive of small vessel vasculitis. (c) CXR showing resolution of right lower zone opacities
Pleural effusion is a rare presentation of GPA. Only three case reports are available in literature.[5–7] Because of its varied radiological presentation, it is misdiagnosed as bacterial, viral, or fungal pneumonia, pulmonary tuberculosis, pulmonary oedema, acute respiratory distress syndrome, bronchioloalveolar carcinoma, or metastatic tumours.[8] Diagnosis is based on a combination of clinical manifestations, positive ANCA serology and histological evidence of necrotizing vasculitis, necrotizing glomerulonephritis or granulomatous inflammation from a relevant organ biopsy, such as skin, lung or kidney.[9] Our patient had a score of 10 (nasal crusting +3, positive c-ANCA +5, mass on lung imaging +2) according to the revised ACR/EULAR guidelines endorsed for the diagnosis of GPA.[10]
Patients with vasculitis present with nonspecific symptoms and are treated as infection or malignancy leading to delayed diagnosis. Biopsy of the lung mass/nodule or pleura should be done before initiating patient on any definitive treatment. GPA should be considered in differential diagnosis of undiagnosed pleural effusion.
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Conflicts of interest
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