Long-Standing Asymptomatic Primary Sclerosing Cholangitis Report of Three Cases R.W.G. CHAPMAN, BSC, MRCP, A.K. BURROUGHS, MRCP, N.M. BASS, PHD, MRCP, and SHEILA SHERLOCK, DBE, MD, FRCP Three patients, two males and one female, with asymptomatic primary sclerosing cholangitis (PSC) are described. The diagnosis was made in each case by endoscopic retrograde cholangiography after investigation of persistent elevation of the serum alkaline phosphatase, All three have remained completely well without any medical or surgical treatment for 3, 7, and 15 years, respectively, despite extensive involvement of the biliary tree. Follow-up liver biopsies in two have shown no histological evidence of progression to secondary biliary cirrhosis. PSC may occur more frequently and may follow a less severe clinical Course than previously recognized. Primary sclerosing cholangitis (PSC) is an uncom- mon disease of unknown etiology. It is character- ized by an intense inflammatory fibrosis usually affecting both the intra- and extrahepatic biliary tree (1). PSC is characterized clinically by a progressive cholestatic jaundice associated with fever, weight loss, pruritus, and abdominal pain, leading to liver failure and death (2). We describe three patients with 'asymptomatic' P.S.C. despite long-standing and extensive involve- ment of the biliary system, who presented over a seven year period. The diagnosis of P.S.C. in each patient was established after investigation of a persistently raised serum alkaline phosphatase. Manuscript received May 19, 1980; revised manuscript re- ceived December 1, 1980; accepted December 4, 1980. From the Department of Medicine, Royal Free Hospital, London, NW3 2QG, England. R.W.G. Chapman is Watson Smith Research Fellow of the Royal College of Physicians of London. Address for reprint requests: Dr. R.W.G. Chapman, Academ- ic Department of Medicine, Royal Free Hospital, Pond Street, Hampstead, London, NW3 2QG, England. MATERIALS AND METHODS Patient 1. A 34-year-old Caucasian woman developed low back pain in 1973. She was found to be HLA B27- positive and diagnosed as having ankylosing spondylitis. Later that year she developed diarrhea without rectal bleeding, Appearances on sigmoidoscopy, rectal biopsy, and colonoscopy were that of ulcerative colitis. Physical examination was otherwise normal. A persistently raised alkaline phosphatase of 44 KAU/dl (normal range 3-13) was noted on routine liver tests which were otherwise normal. Liver histology showed portal fibrosis with an inflammatory infiltrate and ductular proliferation consis- tent with a biliary lesion. An endoscopic retrograde cholangiogram (ERC)showed beading and stricturing of the bile ducts throughout the biliary tree, the changes characteristic of PSC (4) (Figure 1). Since that time, apart from two mild exacerbations of ulcerative colitis, she has remained well on salazopyrine, 1 g twice daily. She was readmitted in 1980 for reassessment. Physical examination was normal. Investigations showed that the serum alkaline phosphatase had fallen to 22 KAU/dl and that her liver tests were otherwise normal. Autoantibo- dies were again negative; however, the serum IgM had increased to 5.0 g/liter (normal range 0.7-2.8 g/liter). Liver histology was unchanged. Repeat ER C was techni- cally unsuccessful. Patient 2. A 45-year-old male Asian banker was found to have a raised serum alkaline phosphatase of 20 KAU/dl 778 Digestive Diseases and Sciences, Vol. 26, No. 9 (September 1981) 0163-2116/81/I)900-0778503.00/1 9 1981DigestiveDisease Systems, Inc.