Primary Biliary Cirrhosis and Granulomatous Pulmonary Infiltrates: Causal Association or Casual Association?

Abstract

Purpose: Introduction: Primary biliary cirrhosis (PBC) is thought to be a systemic disease and is characterized by granulomatous inflammation of the septal and interlobular bile ducts. Extrahepatic granuloma as an extrahepatic manifestation of PBC has rarely been reported. We report a case of PBC presented with granulomatous pulmonary infiltrates. Case Report: A 44-yearold woman, who underwent a medical checkup every year, demonstrated an abnormal shadow on chest X-ray. CT scan showed abnormal interstitial shadow of the lung in this patient. Examination of broncho-alveolar lavage fluid (BALF) and the specimen from transbronchial lung biopsy (TBLB) showed cryptogenic interstitial pneumonia with marked granulomatous lesions. Two months later, the patient showed liver function test disorder. The laboratory data disclosed the following values (normal reference ranges are given in parentheses): total protein, 8.3 g/dl (6.5-8.2 g/dL); albumin, 4.0 g/dL (3.8-5.4 g/dL); total bilirubin, 0.6 mg/dL (0.2-1.0 mg/dL); aspirate aminotransferase (AST), 61 IU/L (<40 IU/L); alanine aminotransferase (ALT), 85 IU/L (<40 IU/L); alkaline phosphatase, 1,158 IU/L (100-340 IU/L); and gamma-glutamyl transpeptidase, 365 IU/L (<30 IU/L). The patient tested negative for anti-mitochondrial antibody by indirect immunofluorescence assay (IF) but tested positive by enzyme-linked immunosorbent assay (ELISA). Histopathological examination of the specimen from liver biopsy demonstrated epithelioid cells in the peripheral portal area and disappearance of the bile duct in the portal area. These findings indicated a diagnosis of PBC. Liver function test of the patient returned to almost the normal level following oral administration of ursodeoxycholic acid. Discussion: Granuloma is commonly found in the liver of patients with PBC, which consists of epithelioid cells without necrosis and is similar to the sarcoid type. Very occasionally extrahepatic granuloma has been found. A case of PBC presenting with granulomatous skin lesions has been reported. An overlap of pulmonary sarcoid and PBC has long been recognized as well. Interstitial pneumonia is rarely accompanied by PBC and is not considered related to PBC itself but to the presence of an associated connective tissue disease such as Sjogren's syndrome. In the case presented here, neither the clinical symptoms nor a variety of blood examinations detected any associated connective tissue diseases. Therefore, we thought it most appropriate to consider that granulomatous pulmonary infiltration in this case may have been an extrahepatic manifestation of PBC. Further research and accumulation of cases are required to fully clarify this association.