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disease is highly suggestive of portal thrombosis or arterioportalfistula. We have observed the clinical picture described by Vogel etal in two patients with stable PBC not treated by UDCA-ie, asudden increase in oesophageal varices, ascites, gastrointestinalbleeding, and transient jaundice. These symptoms developedwithin 2 months of liver biopsy. Angiography, aimed at explainingthe sudden aggravation of portal hypertension, revealed an

arterioportal fistula in the biopsy track. Gastrointestinal bleedingnecessitated a portacaval shunt in one case; in the other,sclerotherapy of oseophageal varices and embolisation of the fistulawere done. A transient increase in serum bilirubin, transaminases,and alkaline phosphatase were observed, as in Vogel’s case, withoutany evidence of liver cancer or common bileduct stones. Thebiochemical worsening associated with the arterioportal fistulacould be explained by a decrease in the arterial blood flow to theliver and therefore to bileducts; vascularisation of bile ducts dependsonly on arterial perfusion. Did Vogel et al consider the possibility ofarterioportal fistula and was the effect of readministration of UDCAtested?

Hepatology Unit,Hôpital Saint-Antione,75012 Paris, France RAOUL POUPON

INSERM Unit 21,Villejuif RENÉE E. POUPON

*** This letter has been shown to Dr Vogel, and his colleagues,whose reply follows.-ED. L.

SIR,--Our case of deteriorating primary biliary cirrhosis wasclearly associated with treatment with UDCA and improved afterwithdrawal of the compound. The dosage was that used by Pouponet al. We agree that a post biopsy fistula could cause deterioration inchronic liver disease but this seems very unlikely in a patient whohad not had a liver biopsy done for 17 years. Furthermore,ultrasound investigation revealed patency of the portal vein,excluding one common cause of deterioration of portalhypertension in chronic liver disease. Permission for UDCA

rechallenged was refused by the patient because he was convincedthat deterioration in his disease had been caused by the drug. Ourpatient has subsequently been treated (at another clinic) withUDCA and once more deteriorated, with ascites and a rise in serumbilirubin to 8 mg/dl. 3 days after UDCA was withdrawn hisbilirubin was back at pretreatment levels.

Although we do not have much evidence on which to question thepotential benefits of UDCA in PBC we would emphasise that onlyfour patients with advanced PBC were treated by Poupon et al, nodose finding studies were published, and little evidence exists on themechanism of action in PBC.

Department of Internal Medicine,University of Innsbruck,A-6020 Innsbruck, Austria

WOLFGANG VOGELHERMANN KATHREINGERT JUDMAIERHERBERT BRAUNSTEINER

1. Poupon R, Chrètien Y, Poupon RE, Ballet F, Calmus Y, Damis F. Is ursodeoxycholicacid an effective treatment for pnmary biliary cirrhosis? Lancet 1987; i: 834-36.

VARIATION IN ANTIBODY ISOTYPE RESPONSES INCLINICALLY COVERT TOXOCARIASIS

SIR,-We read with interest Dr Caucanas and colleagues’ (May7, p 1049) response to our March 26 article on covert toxocariasis.We have been concerned about false-positive serodiagnoses oftoxocariasis due to cross-reactions between antibodies to blood

group A from hyperimmune blood donors (without toxocaraldisease) and the excretory-secretory (ES) antigens of the second-stage larvae used in the test.1.2 The parasite outer surfaces and theES antigen contain human-blood-group-like epitopes3 and humananti-A blood group antibodies recognise a 70 kD component in theES.2 We agree with Caucanas et al that a clinical syndrome of coverttoxocariasis exists.We have developed a specific IgE antibody assay which is run in

parallel with the conventional assay.’ Caucanas et al demonstrated

specific IgE in two-thirds of patients presenting with symptomssimilar to those we reported in covert toxocariasis. We have testedsera from both sources (Dublin and Toulouse). In sera from theToulouse area IgM, IgG, and IgE antibodies to ES were greatlyraised. In the sera from Dublin, IgM and IgG antibodies were alsovery high but only 38% had detectable IgE antibodies. In an in vitrolarval surface binding assay,’ sera from Toulouse bound the outersurfaces of metabolically arrested larvae whereas 78% of Dublinsera did not. The binding, by antibody, of the outer larval surfaces isa prerequisite for antibody-dependent cytotoxicity, the method bywhich larval entrapment and death is thought to occur. The abilityof serum antibodies in these two groups of patients to induce such aprotective mechanism seems to differ.

Adult covert toxocariasis from light infestation could be a chronicdisease state due to the inability of antibodies to mediate larvalkilling; however, our results suggest differing pathogenicmechanisms in the two populations. Although larval surface

binding by antibody in vitro is not synonymous with in vivo killing,it is indicative of a capacity to mount antibody-dependent cellularcytotoxic mechanisms directed towards larval entrapment anddeath. Thus, although the clinical manifestations of covert

toxocariasis are similar, the patients presenting with such symptomsdescribed by Caucanas et al may have acquired their light infectionin the recent past so that the pathogenesis in the two groups ofpatients are different. Certainly their IgE antibody profiles andlarval surface binding capacities differ. The Toulouse patients wereadult whereas most of the Dublin patients were children. Furtherepidemiological studies, such as age of presentation, eating habits,and pet ownership, and research into isotype, subclass, and epitopereactivity are now necessary.

Department of Bacteriology,Stobhill General Hospital,Glasgow G21 3UW

H. V. SMITHA. R. HINSONR. W. A. GIRDWOOD

National Children’s Hospital,Dublin 2, Ireland M. R. H. TAYLOR

1. Smith HV, Girdwood RWA, Kusel JR. Dangers of misinterpretation of toxocaralserodiagnostic tests. Br Med J 1984; 288: 1235.

2. Smith HV, Hinson AR, Girdwood RWA. Serodiagnosis of human toxocariasis. TransR Soc Trop Med Hyg 1987; 81: 516.

3. Smith HV, Kusel JR, Girdwood RWA. The production of human A and B bloodgrouplike substances by in vitro maintained second stage Toxocara canis larvae:their presence on the outer larval surfaces and in their excretions/secretions. ClinExp Immunol 1985; 54: 625-33.

4. Oliver ST, Cousland G, Smith HV, Girdwood RWA. Antibody isotype reactivity,isotype specific serodiagnosis, and IgE antibody specificity in humans infected withToxocara canis. Trans R Soc Trop Med Hyg 1986; 80: 985.

5. Taylor MRH, Keane CT, O’Connor P, Girdwood RWA, Smith HV. Clinical featuresof covert toxocariasis. Scand J Infect Dis 1987; 19: 693-96.

6. Smith HV, Kusel JR, Girdwood RWA. The effect of temperature and antimetaboliteson antibody binding to the outer surfaces of second stage Toxocara canis infectivelarvae. Mol Biochem Parasitol 1981; 4: 183-89.

LEGIONNAIRES’ DISEASE

SIR,-Dr Zumla and his colleagues (June 4, p 1275) say that therecognition of the outbreak of legionnaires’ disease in Glasgow in1984 was much delayed. In fact, as with the BBC outbreak, theproblem was acknowledged as soon as a cluster of cases wasrecognised. In the BBC outbreak, two cases presented to physicianswith prepared minds, who then recognised there was a cluster. InGlasgow seven cases being diagnosed by serology on one eveningand coming from the same postal district of the city also led to therecognition of an outbreak; an ad hoc committee was convened andan investigation was instituted forthwith. In addition to the

important questions "Where do you work?" and "Where have youbeen?" (ie, hospitals, hotels, ships, aircraft), an accurate map-identifiable address can be of critical value.2

Department of Laboratory Medicine,Ruchill Hospital,Glasgow G20 9NB R. J. FALLON

1. Ad Hoc Committee. Outbreak of legionellosis in a community. Lancet 1986; ii 380-832. Bhopal RS, Fallon RJ. Geographical epidemiology of legionnaires’ disease in Glasgow:

a preliminary report. Communicable Dis (Scotland) WR 1988; 22: 7-11