Genitourin Med 1997;73:271-273

Pancreatic abnormalities and AIDS relatedsclerosing cholangitis

Julian P Teare, Carnel A Daly, Catherine Rodgers, Simon P G Padley, Richard J Coker,Janice Main, John RW Harris, David Scullion, Gary P Bray, John A Summerfield

Objectives: Biliary tract abnormalities are well recognised in AIDS, most frequently related toopportunistic infection with Cryptosporidium, Microsporidium, and cytomegalovirus. We noted ahigh frequency of pancreatic abnormalities associated with biliary tract disease. To define thesefurther we reviewed the clinical and radiological features in these patients.Methods: Notes and radiographs were available from two centres for 83 HIV positive patientswho had undergone endoscopic retrograde cholangiopancreatography for the investigation ofcholestatic liver function tests or abdominal pain.Results: 56 patients had AIDS related sclerosing cholangitis (ARSC); 86% of these patients hadepigastric or right upper quadrant pain and 52% had hepatomegaly. Of the patients with ARSC,10 had papillary stenosis alone, 11 had intra- and extrahepatic sclerosing cholangitis alone, and 35had a combination of the two. Ampullary biopsies performed in 24 patients confirmed an oppor-tunistic infection in 16. In 15 patients, intraluminal polyps were noted on the cholangiogram.Pancreatograms were available in 34 of the 45 patients with papillary stenosis, in which 29(81%) had associated pancreatic duct dilatation, often with associated features of chronic pan-creatitis. In the remaining 27 patients, final diagnoses included drug induced liver disease, acal-culous cholecystitis, gall bladder empyema, chronic B virus hepatitis, and alcoholic liver disease.Conclusion: Pancreatic abnormalities are commonly seen with ARSC and may be responsible forsome of the pain not relieved by biliary sphincterotomy. The most frequent radiographic biliaryabnormality is papillary stenosis combined with ductal sclerosis.(Genitourin Med 1997;73:271-273)

Keywords: AIDS; cholangitis, sclerosing; pancreas, abnormalities

Department ofGastroenterology, StMary's Hospital,Paddington, LondonJ P TeareJ A SummerfieldDepartment of Genito-urinary Medicine, StMary's Hospital,Paddington, LondonC RodgersRJ CokerJ MainJ RW HarrisDepartment ofRadiology, St Mary'sHospital, Paddington,LondonD ScullionDepartment ofRadiology, Chelseaand WestminsterHospital, FulhamRoad, LondonC A DalyS P G PadleyDepartment ofGastroenterology,Chelsea andWestminster Hospital,Fulham Road, LondonG P BrayCorrespondence to:Dr J P Teare, EndoscopyUnit, Clarence Wing, StMary's Hospital, PraedStreet, London W2 lNY.Accepted for publication3 March 1997

IntroductionInvestigation of HIV infected patients withright upper quadrant pain and obstructive liverfunction tests led to the recognition of a syn-drome termed AIDS related sclerosing cholan-gitis (ARSC).'2 Cello' classified biliary tractabnormalities in a series of 26 patients withAIDS into four distinct radiographic patterns:

(1) papillary stenosis alone, with a commonbile duct greater than 8 mm in diameter anddistal 2-4 mm tapering of the common bileduct,

(2) intrahepatic sclerosing cholangitis alone,(3) sclerosing cholangitis in association with

papillary stenosis,(4) long extrahepatic bile duct strictures

with or without intrahepatic sclerosing cholan-gitis.

The most common pattern was sclerosingcholangitis in association with papillary steno-sis.' The majority of these biliary abnormali-ties are associated with cytomegalovirus(CMV) and Cryptosporidium sp infection.' All26 patients in this early series' were noted tohave normal pancreatograms. Furthermorepancreatic abnormalities were not reported ina recent larger series of 45 patients.4

Pancreatic disease in human immunodefi-ciency virus (HIV) infection can be the resultof opportunistic infection, neoplasia, drug tox-icity or causes unrelated to AIDS such as alco-hol abuse or gallstones.5 The spectrum ofdisease ranges from asymptomatic necropsyfindings6 to acute lethal pancreatitis.7

Opportunistic infection is most commonlycaused by CMV,7 with 13% of unselectednecropsies having evidence of CMV pancre-atic involvement. CMV may cause minimalpancreatic inflammation,8 or acute pancreati-tis.9 In only one case has pancreatic infectionbeen noted to be associated with hepatobiliaryinvolvement and ARSC.8We noted the presence of pancreatic abnor-

malities at endoscopic retrograde cholan-giopancreatography (ERCP) performed forthe investigation of cholestatic liver functiontests and right upper quadrant pain and there-fore performed a retrospective analysis of 83patients to document the prevalence of suchchanges.

Patients and methodsThe study was based at two specialist referralcentres providing care for HIV positivepatients. The case records, laboratory results,radiological findings, and computerisedrecords of patients presenting with obstructiveliver function tests or abdominal pain whounderwent ERCP between 1989 and July1995 were analysed retrospectively. The radio-graphs were then reported blindly.

ResultsERCP was performed in a total of 83 patientswith obstructive liver function tests, of which56 were shown to have ARSC. Of the patients

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Teare, Daly, Rodgers, Padley, Coker, Main, et al

Figure 1 PapiUlarystenosis with dilated intra-and extrahepatic bilarytree and mild intrahepaticduct irregularity (type IIIARSC). Dilated irregularmain pancreatic duct withectatic side branches.

with ARSC, 48 (86%) experienced epigastricor right upper quadrant pain, 37 (66%) haddiarrhoea, 30 (53%) had weight loss of > 4 kg,and 13 (24%) had fever. Hepatomegaly, oftentender, was seen in 29 (52%). Three patientswere asymptomatic.

RADIOLOGICAL FINDINGSTen patients had papillary stenosis alone (typeI), 11 patients had intra- and extrahepaticsclerosing cholangitis alone (type II), and 35had a combination of the two (type III). Nopatient had the fourth type'0 with a long extra-hepatic biliary stricture. In the 45 patients witha dilated common bile duct (types I and III),the main pancreatic duct was opacified in 34patients and found to be dilated in 29. Thenormal diameter was taken to be 4 mm in thehead, 3 mm in the body, and 2 mm in the tail.In 18 the duct was enlarged greater than 6 mmin diameter associated with irregularities of themain duct and side branches similar to thechanges seen in idiopathic or alcohol induced

Figure 2 Papillarystenosis with dilated intra-and extrahepatic bilarytree and mild intrahepaticduct irregularity (type IIIARSC). Dilated irregularmain pancreatic duct withpaucity of side branches.

- -. . .~~~~~~~~~~~~~~~~4.

Figure 3 Papillary stenosis with dilated extrahepaticbilary tree and moderate intrahepatic duct irregularity(type IIIARSC). Polypoidfilling defects noted within theduct lumen.

chronic pancreatitis (figs 1 and 2). There wereno clinical characteristics specific for thisgroup. One of the patients with type I and 11 ofthe patients with type III ARSC had polypoidfilling defects within the biliary tree (fig 3).

Ampullary or biliary biopsy was successfulin obtaining a microbiological diagnosis in 16of 24 patients where performed: CMV in six,Cryptosporidium in six, CMV and Crypto-sporidium in one, and one each demonstratedMicrosporidium, Mycobacterium avium intracel-lulare, or fungi. One patient had ampullarynon-Hodgkin's lymphoma."l In this patientthe cholangiographic findings regressed ontreatment of the lymphoma.Mean survival for patients with ARSC was

6-8 months (range 2 days to 24 months).

BIOCHEMICAL FINDINGSThere were no significant differences in bio-chemical indices between any of the patientsubgroups (table).

In the 27 patients who did not have ARSCon cholangiography, it can be seen that thebiochemical values differed little. Clinicalsymptoms and signs were also similar withabdominal pain present in 23 (85%), diar-rhoea in 10 (38%), weight loss in 12 (45%),hepatomegaly in 17 (63%), and fever in seven(28%). Final diagnoses in this group includedhepatic non-Hodgkin's lymphoma (two),cholecystitis (one), acalculous cholecystitis(two), gall bladder empyema (one), ampullaryKaposi's sarcoma (one), drug induced liverdisease (two), chronic hepatitis B virusinduced liver disease (three), choledocholithi-asis (one), CMV colitis (one), and alcoholicliver disease. The final diagnosis or reason forthe ERCP was unclear in the remainder.

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Pancreatic abnornalities andAIDS related sclerosing cholangitis

Biochemicalfindings in patients subgroups

Type I Type II Type III Non-ARSC

n 10 11 35 27ALT 38 (201) 77 (112) 50 (102) 49 (133)

24-1640 35-298 12-546 10-900AST 39 (344) 83 (102) 47 (73) 37 (88)

25-1560 22-206 14-535 10-520Alk P 478 (706) 584 (1017) 565 (909) 376 (681)

77-1590 247-3953 128-3730 46-2449Bilirubin 6-5 (19) 9 (22) 9-5 (30) 14 (40)

5-82 4-104 3-373 4-181CD4 count 16 (75) 21 (27) 16 (72) 20 (61)

5-300 5-64 1-867 2-450

Figures represent the median with means bracketed and the range.ALT = alanine transaminase U/1 (NR < 40); AST = asparate transaminase U/1 (NR < 40); Alk P= alkaline phosphatase U/1 (30-130); Bilirubin = total bilirubin gmol/l (NR < 17); CD4 count -median T helper cell count (NR > 500 x 106/1).

DiscussionThis series represents the largest reported ofARSC. It also appears to be the first time thatthe association of pancreatic abnormalitieswith ARSC has been described.

In keeping with previous series,' the mostcommon form of ARSC was type III-papil-lary stenosis in association with sclerosingcholangitis. In an earlier series the presence ofintraluminal polypoidal filling defects wasnoted12 and we noted these in almost a third ofcases, particularly in association with type IIIARSC. Since the polyps are seen with diffuse,severe biliary inflammation their aetiology maybe similar to pseudopolyps found in ulcerativecolitis.

Opportunistic infections that mostcommonly cause ARSC include CMV, Crypto-sporidium Sp,3 and less commonly Myco-bacterium avium intracellulare'0 and Micro-sporidium."3 In addition to these organisms,pancreatic disease in HIV infected patientsmay also be caused by Cryptococcus neoformans,Pneumocystis carinii, Toxoplasma gondii, andMycobacterium tuberculosis. CMV and Crypto-sporidium are responsible for 45% of infectivecauses of pancreatitis.5 As many patients withARSC have intestinal infection with cyto-megalovirus or Cryptosporidium at the time ofdiagnosis,"4 it can be postulated that ARSC isa result of either ascending biliary infection forthe protozoal infections, or systemic blood-borne infection for CMV and other oppor-tunistic infections. This may explain the

common association between ARSC and pan-creatic abnormalities, with the organisms ableto colonise both the pancreas and biliary tree.In the same way that infection causes stenosisof the biliary sphincter, we postulate that asimilar process affects the pancreatic sphinctercausing the ductal dilatation. The pancreaticabnormalities that we have detected may giverise to some of the abdominal pain that is afeature of ASRC and explain why biliarysphincterotomy is not always useful in reliev-ing the pain.4The results of our study support the impor-

tant diagnostic role of ERCP in patients sus-pected of having ARSC and support the use ofampullary biopsy for microbiological diagnosisof infective causes. In addition the frequentfinding of pancreatic abnormalities suggests anadditional mechanism for the pain of the con-dition.

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11 Teare JP, Price R, Foster GR, McBride M, Main J.Reversible AIDS-related sclerosing cholangitis due tolymphoma. J Hepatol 1995;23:209-1 1.

12 Collins CD, Forbes A, Harcourt-Webster JN, Francis ND,Gleeson JA, Gazzard BG. Radiological and pathologicalfeatures ofAIDS-related polypoid cholangitis. Clin Radiol1993;48:307-10.

13 Beaugerie L, Teilhac MF, Deluol AM, Fritsch J, GirardPM, Rosenbaum, et al. Cholangiopathy associated withMicrosporidia infection of the common bile duct mucosain a patient with HIV infection. Ann Intern Med 1992;117:401-2.

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