ANCA positive systemic vasculitis in a known case of Idiopathic pulmonary fibrosis : case report

When a patient presents with pulmonary fibrosis, we perform tests to rule out connective tissue diseases and vasculitis. We report a patient who was diagnosed as Idiopathic pulmonary fibrosis (IPF), p-ANCA negative status who after two years presented with renal disease. On repeating, the p-ANCA came positive. We present this rare case of Idiopathic pulmonary fibrosis on anti fibrotic treatment who later developed p-ANCA positive systemic vasculitis. Key-words: Idiopathic pulmonary fibrosis, p-ANCA, systemic vasculitis Introduction: Anti neutrophilic cytoplasmic antibodies (ANCA) are directed against enzymes in the granules of polymorphonuclear leukocytes. ANCA positivity has been associated with vasculitides with the potential for pulmonary involvement. Cytoplasmic anti-neutrophilic cytoplasmic antibodies (c-ANCA) has high sensitivity and specificity for patients with granulomatosis with polyangiitis, whereas, perinuclear anti-neutrophilic cytoplasmic antibodies (p-ANCA) is characteristically associated with small vessel vasculitis (mainly-ChurgStrauss syndrome, pauci-immune glomerulonephritis and microscopic polyangiitis). ANCA is therefore an important serological biomarker for diagnosing and monitoring systemic vasculitis. The occurrence of pANCA in pulmonary fibrosis has been reported in a number of small studies [1,2], however, the appearance of p-ANCA in already established idiopathic pulmonary fibrosis (IPF), predating the manifestations of vasculitis has not been widely appreciated [2]. We report a case with radiographic evidence of established IPF where pANCA was negative at the time of diagnosis and became positive at presentation to us. Case History: A 69 year old Male presented with complains of abdominal pain since 3 days. Patient was a diagnosed case of Idiopathic pulmonary fibrosis since 2 years and was on perfinidone 1200mg/day. Figure 1,2 An ultrasound abdomen was performed which demonstrated grade II hyperechoic cortex in both kidneys but cortico medullary differentiation with smooth margins was maintained & the kidneys were normal in size shape and position. A simple cortical cyst of 2.5cm & 0.7 cm was seen in lower pole of left kidney. Spleen was mildly enlarged. Moderate prostatomegaly was seen. Rest of the organs visualised were normal in size and showed no obvious abnormailities. Serum creatinine was 3.0 mg/dl and BUN 37 mg/dl. Urine routine showed proteinuria of 5gm/day and microscopic hematuria. p-ANCA done was positive. Kidney biopsy was done which showed fibrinoid change in few glomeruli on light microscopy & moderate degree of tubular atrophy & interstitial fibrosis. Patient received 6 cycles of endoxan infusion therapy and then continued with azathioprine. Indian Journal of Basic and Applied Medical Research; December 2016: Vol.-6, Issue1, P. 378-381 378 www.ijbamr. com P ISSN: 2250-284X , E ISSN : 2250-2858 Figure 1 Figure 2 Figures 1 & 2 showing bilateral, peripheral extensive areas of honeycombing in lower lobes Discussion: The temporal relationship between p-ANCA positivity in already established pulmonary fibrosis and the development of vasculitis is poorly understood. Here, we report a case in which p-ANCA was negative at the time of diagnosis of pulmonary fibrosis and became positive during follow-up after 2 years thus predating the onset of fulminant vasculitis. There are no reported differences in the clinical or radio graphical characteristics of p-ANCA positive as compared to p-ANCA negative pulmonary fibrosis at the time of initial diagnosis [3]. However, in the presence of p-ANCA positivity, the clinical course of the disease may be affected, with increased morbidity and mortality observed [3,4]. The exact pathophysiological mechanism of the relationship between ANCA and pulmonary fibrosis remains undetermined. The predominant histological and radiological pattern for pulmonary fibrosis that has been reported in such cases is UIP [5]. Early histological studies did not detect marked differences in the degree of lung fibrosis among various types of vasculitis, suggesting that ANCA may cause a generalized type of tissue injury, possibly through the release of activated neutrophils. Increased MPO on activated neutrophils promote degranulation and oxidative bursts that could lead to alveolar epithelial damage, fibroblastic proliferation and ultimately the development of fibrosis [6]. Another conceivable mechanism is that at early stages of the disease, ANCA levels remain below the threshold of conventional laboratory measurements and once the levels rise and become detectable by laboratory methods, the disease manifest itself clinically, with features of vasculitis [7]. However the reason for this remains beyond cogitation and may be related to unidentified infectious or non-infectious antigens, autoimmunity, impaired regenerative responses,and the antagonistically pleiotropic action of genes involved in wound healing or development [8]. Our case suggests a possible rationale for serial p-ANCA measurements in patients with pulmonary fibrosis even in the absence of features suggestive of vasculitis. International IPF guidelines place high value on measuring autoimmune serology to distinguish IPF from pulmonary disease associated with connective tissue disease. However, the routine use of extended serological testing, in particular ANCA measurement has not been emphasized [9]. Furthermore, the required frequency of ANCA measurement in the absence of clinical features of vasculitis is unknown. Larger studies