Biomedical subjects

E Elias

Publications and source records attributed to E Elias.

At least 37 records · Page 2Linked to original sources

PubMed2000

Wilson's disease with superimposed autoimmune features: report of two cases and review.

We describe two females, 15 and 23 years old, respectively, who presented with classical features of Wilson's disease (WD) and several features of autoimmune hepatitis (AIH). The first patient was initially diagnosed as AIH and treated with prednisolone which caused clinical improvement, with an increase of serum albumin from 22 to 30 g/L, and a decrease of aspartate aminotransferase from 103 to 47 U/L. Subsequent diagnosis of WD and introduction of penicillamine gave excellent improvement and complete normalization of liver function tests. The second patient, at first also diagnosed as having AIH, was treated with steroids and azathioprine with initial improvement, but subsequent deterioration. The diagnosis of WD was made 2 years after initial diagnosis of AIH, as the patient reached end-stage liver disease and required a transplant. Therefore, d-penicillamine treatment was not attempted. We conclude that, in patients with AIH, a thorough screening for WD is necessary, particularly when the response to steroid therapy is poor. Conversely, in patients suffering from WD with superimposed features of AIH, a combination of steroids and penicillamine may be of benefit.

Adolescent↗

PubMed2000

Control by signaling modulators of the sorting of canalicular transporters in rat hepatocyte couplets: role of the cytoskeleton.

Hormonal control of the restoration of hepatocanalicular polarity in short-term cultured hepatocyte couplets was analyzed. One hour following isolation, couplets were unable to accumulate the fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF), and showed a nonpolarized distribution of F-actin and mrp2 over the cell body. A progressive, time-dependent restoration of couplet-polarized function and morphology was reached after 4 hours of culture. Both dibutyryl cyclic adenosine monophosphate (DBcAMP) and the Ca(2+)-elevating compound, thapsigargin, accelerated restoration of normal couplet morphology and function. The DBcAMP-mediated stimulus was inhibited by the Ca(2+) chelator, 1, 2-bis-(o-aminophenoxy)-ethene-N,N,N',N'-tetra-acetate tetra-(acetomethyl)ester (BAPTA/AM), but not by the protein kinase A (PKA) inhibitors, KT5720 or H89, suggesting that Ca(2+) elevation rather than PKA activation is involved. N-(6-aminohexyl-5-chloro-1-napththalenesulfonamide (W-7), a calmodulin inhibitor, and the protein kinase C (PKC) activator, phorbol dibutyrate, inhibited both the basal and the DBcAMP-stimulated recovery of functional polarity, whereas staurosporine and Gö 6976, 2 PKC inhibitors, accelerated the basal recovery of polarized function. Disruption of the microtubule cytoskeleton by colchicine induced only minor changes under basal, but not under DBcAMP-stimulated, conditions. The Golgi complex disruptor, brefeldin A, significantly delayed, and the microfilament-disrupting agent, cytochalasin D, fully blocked, both processes. However, DBcAMP stimulated trafficking of vesicles containing CLF to the pericanalicular region under the last condition. Our results indicate that restoration of couplet polarity following isolation occurs via a Ca(2+)-calmodulin-mediated mechanism, which depends on microfilament, but not on microtubule integrity. A second pathway is activated by DBcAMP activation via Ca(2+)-calmodulin formation, whose requirements with respect to cytoskeletal components are opposite. PKC has a negative regulatory role in both pathways.

Actins↗

PubMed2000

Delay in presentation of symptomatic referrals to a breast clinic: patient and system factors.

We attempted to identify factors associated with delay in presentation and assessment of women with breast symptoms who attended a London breast clinic. A total of 692 consecutive symptomatic referrals, aged 40-75 years, were studied. Patient delay, assessed prior to diagnosis, was defined as time elapsing between symptom discovery and first presentation to a medical provider. This was studied in relation to: reasons for delaying, beliefs and attitudes, socio-demographic and clinical variables, psychiatric morbidity and subsequent diagnosis. Thirty-five per cent of the cohort delayed presentation 4 weeks or more (median 13 days). The most common reason given was that they thought their symptom was not serious (odds ratio (OR) = 5.32, 95% confidence interval (CI) 3.6-8.0). Others thought their symptom would go away (OR = 3.73, 95% CI 2.2-6.4) or delayed because they were scared (OR = 4.61, 95% CI 2.1-10.0). Delay was associated with psychiatric morbidity but not age. Patients who turned out to have cancer tended to delay less (median 7 days) but not significantly. Median system delay--time between first medical consultation and first clinic visit--was 18 days. Patients who thought they had cancer and those so diagnosed were seen more promptly (median 14 days). Most factors, including socio-economic status and ethnicity were non-contributory. Beliefs about breast symptoms and their attribution are the most important factors determining when women present. Health education messages should aim to convince symptomatic women that their condition requires urgent evaluation, without engendering fear in them.

Adult↗

PubMed2000

Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy.

Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.

2-Aminopurine↗

PubMed2000

In vitro anti-HIV-1 virucidal activity of tyrosine-conjugated tri- and dihydroxy bile salt derivatives.

The cellular toxicity and anti-human immunodeficiency virus type 1 (HIV-1) virucidal activity of four synthesized tyrosine-conjugated bile salt derivatives with high surfactant activities, namely di-iodo-deoxycholyltyrosine (DIDCT), di-iodo-chenodeoxycholyltyrosine (DICDCT), di-iodo-cholylglycyltyrosine (DICGT) and deoxycholyltyrosine (DCT), were evaluated and compared with either sodium deoxycholate or nonoxynol-9. DIDCT, DICDCT and DCT but not DICGT showed virucidal activity against three different laboratory-adapted strains of HIV-1 (RF, IIIB and MN). All the bile salt derivatives tested excluding DICGT were virucidal at a concentration as low as 10 ng/mL. DCT had the highest anti-HIV-1 virucidal potency, suggesting that monopeptide 7alpha,12alpha dihydroxy bile salt derivatives have the most potent antiviral activity. Complexing of iodine to the bile salt derivative (as in DICGT) decreases virucidal potency.

Anti-HIV Agents↗

PubMed2000

Massive hepatic fibrosis in Gaucher's disease: clinico-pathological and radiological features.

Hepatomegaly is frequent in patients with type 1 Gaucher's disease and is associated with infiltration of the liver with pathological macrophages. Most patients suffer no significant clinical consequences, but a few develop portal hypertension which may progress to parenchymal liver failure. We describe four patients with Gaucher's disease who have developed portal hypertension. We have reviewed their clinical histories and all available histological and radiological material. All had severe Gaucher's disease with multi-organ involvement, and had undergone splenectomy in childhood. Histologically, this advanced liver disease was characterized by a picture of extreme and advanced confluent fibrosis occupying the central region of the liver. This massive fibrosis is associated with characteristic radiological appearances. The liver histology in these cases is highly unusual and virtually unknown in other conditions. Our studies indicate that without specific treatment the liver disease is progressive and rapidly fatal. However, institution of enzyme replacement therapy with imiglucerase may have beneficial effects even when the condition is far advanced.

Adolescent↗

PubMed2000

Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient.

BACKGROUND: In many transplant centres lamivudine is an important component of prophylaxis against, and treatment of, hepatitis B virus (HBV) graft infection. Drug resistant HBV species with specific polymerase mutations may emerge during lamivudine treatment. AIMS: To examine the clinical consequences of graft infection by lamivudine resistant virus. METHODS: The clinical course of four liver transplant patients who developed graft infection with lamivudine resistant virus was reviewed. The response of HBV infection to reduction of immunosuppression and to manipulation of antiviral therapy was assessed. For each patient, serum viral titre was measured and the viral polymerase gene was sequenced at multiple time points. RESULTS: High serum titres were observed following emergence of the lamivudine resistant species. Wild type HBV re-emerged as the dominant serum species after lamivudine withdrawal. All patients developed liver failure, and onset of liver dysfunction was observed when resistant virus was the dominant serum species. In three patients, liver recovery was observed when immunosuppression was stopped and when alternative antivirals were given. Wild type virus appeared to respond to ganciclovir, and to reintroduction of lamivudine. For one patient, introduction of famciclovir was associated with clinical, virological, and histological response. CONCLUSIONS: Failure of lamivudine prophylaxis may identify patients at special risk for the development of severe graft infection. Treatment of graft reinfection should include reduction of immunosuppression, and systematic exposure to alternative antivirals. Viral quantitation and genetic sequencing are essential components of therapeutic monitoring.

Adult↗

PubMed2000

Deficiency of natural anticoagulant proteins C, S, and antithrombin in portal vein thrombosis: a secondary phenomenon?

BACKGROUND: Hereditary deficiencies of natural anticoagulant proteins are implicated in the pathogenesis of portal vein thrombosis (PVT). Secondary deficiencies of these proteins have also been reported in PVT, making interpretation of concentrations difficult. AIMS: To characterise the coagulation profiles in adult patients with PVT and to investigate the possible mechanisms of natural anticoagulant protein deficiency. PATIENTS: Twenty nine adult patients with portal hypertension caused by PVT, and normal biochemical liver function tests. METHODS: Routine coagulation profiles and concentrations of proteins C, S, and antithrombin were measured; where indicated, corresponding concentrations in parents were also measured. Synchronous peripheral and hepatic or splenic vein concentrations were compared in seven patients undergoing interventional procedures, as were peripheral concentrations before and after shunt surgery in three patients. RESULTS: Deficiencies of one or more of the natural anticoagulant proteins occurred in 18 patients (62%), with six patients having combined deficiency of all three proteins. There were strong correlations between prothrombin and partial thromboplastin time ratios and concentrations of natural anticoagulant proteins. Family studies in nine cases of anticoagulant protein deficiency revealed possible hereditary deficiency in only three cases, and significantly lower concentrations of anticoagulant proteins in all PVT cases compared with parents. Levels of anticoagulant proteins tended to be lower in hepatic veins but higher in splenic veins compared with peripheral vein concentrations. Peripheral concentrations decreased after shunt surgery. CONCLUSIONS: Deficiency of natural anticoagulant proteins is common in PVT and is probably a secondary phenomenon in most cases, occurring as part of a global disturbance of coagulation variables. The mechanism for this remains unclear but may result from a combination of reduced hepatic blood flow and portosystemic shunting itself.

Adult↗

PubMed2000

Additive antiviral effects of lamivudine and alpha-interferon in chronic hepatitis B infection.

alpha-Interferon has limited efficacy against chronic hepatitis B virus (HBV) infection. Nucleoside analogues may confer greater benefits, however, it is likely that combination therapies will be required for effective control of this infection. We investigated the antiviral effect of lamivudine and interferon therapy in eight patients with high HBV-DNA levels. Six patients received lamivudine/interferon combination therapy followed, after a 6-month drug-free period, with lamivudine monotherapy. Mean HBV viral load (copies/ml) reduction was significantly greater after 4 months of combination therapy (4.3 x 10(3)) compared to an equivalent period of lamivudine monotherapy (2.9 x 10(2)) (P=0.03). Two patients were given 6 months of lamivudine/interferon combination therapy followed immediately by lamivudine monotherapy. Cessation of interferon in these patients led to a rapid 1-2 log10 increase in HBV viral load. These findings suggest that alpha-interferon has a direct antiviral effect on chronic HBV infection, which may be additive to, or synergistic with lamivudine.

Antiviral Agents↗

PubMed1999

Recurrence of autoimmune hepatitis after liver transplantation.

BACKGROUND: The literature data on the recurrence of autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLTX) is scanty. METHODS: We analyzed the frequency of recurrent AIH in 47 patients who had been transplanted for AIH and survived at least 1 year after surgery. The following criteria were applied to diagnose recurrence: (1) positive autoantibodies in the titer> or =1:40; (2) hypertransaminasemia; (3) histological features of chronic hepatitis; (4) need of reintroduction or significant increase of steroids; and (5) lack of serum markers of viral hepatitis. RESULTS: A total of 13 patients (1 male/12 females) developed recurrent AIH after an interval of 6-63 months after OLTX (mean 29 months). Mean AST level at recurrence was 542+/-129 U/L. Three patients from this group needed regrafting. Mismatch of DR3+ recipient and DR3- donor was not more common in the recurrent disease group (37%) compared to the nonrecurrence group (31%) (P=NS). CONCLUSIONS: Recurrence of AIH after OLTX was diagnosed in a high proportion of patients and some of them required regrafting. DR3+ patients are not particularly prone to develop recurrence.

Analysis of Variance↗

PubMed1999

Tauroursodeoxycholate and S-adenosyl-L-methionine exert an additive ameliorating effect on taurolithocholate-induced cholestasis: a study in isolated rat hepatocyte couplets.

The monohydroxy bile acid, taurolithocholate (TLC), causes cholestasis in vivo and in isolated perfused livers. It is also cholestatic in vitro and, in this study using isolated rat hepatocyte couplets, causes a reduction of the accumulation of (fluorescent) bile acid in the canalicular vacuoles (cVA) of this polarized cell preparation. The hepatoprotective bile acid, tauroursodeoxycholate (TUDCA), partially protects against the action of TLC when added at the same time. It also partially reverses the cholestatic effect if added after the cells have been exposed to TLC. A second hepatoprotective compound, S-adenosyl-L-methionine (SAMe) also not only partially protects against the action of TLC when added at the same time, but it too is able to partially reverse the cholestatic effect. Neither hepatoprotective agent is fully effective alone, but their effects are additive. In combination, a full restoration of cVA is observed in moderate cholestasis, but not in severe cholestasis. We discuss briefly some possible mechanisms involved in the additive mode of action of both hepatoprotective compounds. In summary, we show for the first time that SAMe and TUDCA can exert an additive effect in the amelioration of TLC-induced cholestasis in isolated rat hepatocyte couplets. This finding may be of possible clinical relevance.

Animals↗

PubMed1999

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation.

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Antiviral Agents↗

PubMed1999

Different pathways of canalicular secretion of sulfated and non-sulfated fluorescent bile acids: a study in isolated hepatocyte couplets and TR- rats.

BACKGROUND/AIMS: Fluorescent bile acids have proved useful for characterizing bile salt transport mechanisms. The aim of this study was to further validate the use of lysyl-fluorescein conjugated bile acid analogues as surrogate bile acids. METHODS: We analyzed biliary excretion kinetics of cholyl lysyl fluorescein (CLF), lithocholyl lysyl fluorescein (LLF) and sulfo-lithocholyl lysyl fluorescein (sLLF), both in the isolated rat hepatocyte couplet model and in TR- rats with a selective canalicular transport defect of non-bile acid organic anions. RESULTS: CLF and LLF, which like their natural nonsulfated bile acid congeners are expected to be handled by the canalicular bile salt export pump, were transferred into the bile canaliculus much faster than sLLF, a putative substrate for the canalicular multispecific organic anion transporter in both the in vivo and the in vitro models employed. The contention that different transport systems are involved in sulfated and non-sulfated lysyl fluorescein conjugated bile acids biliary excretion was supported further by studies using TR- rats, in which the cumulative biliary excretion of sLLF was reduced to 6% as compared with that of normal Wistar rats, in good agreement with values for its naturally-occurring radiolabeled parent compound sulfoglycolithocholate. In contrast, CLF and LLF were reduced to 66% and 52%, similar values to these for their congeners, [14C] glycocholate and [14C] lithocholate. CONCLUSION: The close similarity in behavior of lysyl fluorescein conjugated bile acids to that of their naturally-occurring parent compounds in these different models gives support for both sulfated and nonsulfated lysyl fluorescein conjugated bile acids as substitute molecules for studies of bile acid transport.

Animals↗

PubMed1999

Hepatitis C viral load, genotype and histological severity in patients with bleeding disorders.

We report the relationship between hepatitis C virus (HCV) titre, liver histology and HCV genotype in patients with bleeding disorders. One hundred and thirty-two RIBA-2-positive patients, including 56 who were also HIV positive, were identified at our centre. Fifty of these patients, including nine who were HIV infected, underwent percutaneous liver biopsy. Liver histology was assessed using a modified histological activity index (HAI). Qualitative serum HCV PCR was positive in 87 (87%) of the 101 patients tested including 43 of 50 biopsied patients. HCV RNA titres, measured by quantitative PCR, were significantly higher in HIV-positive patients compared with HIV-negative patients (P < 0.05) but were not related to HAI, mean factor concentrate usage, duration of HCV infection or HCV genotype. There was no relationship between HCV genotype and HAI. Qualitative HCV PCR was positive in 30 of 43 liver biopsies tested. Biopsy PCR-positive and -negative cohorts were not distinguished by HAI or serum HCV titre. We conclude that although serum HCV PCR is useful in confirming the presence of HCV infection in patients with bleeding disorders, little meaningful information concerning the severity of the disease can be obtained from serum HCV quantification.

Adult↗

PubMed1999

Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection.

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.

Adult↗

PubMed1999

Autoimmune liver disease in patients with neoplastic diseases.

BACKGROUND: Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. METHODS/RESULTS: In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1-76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related.

Adult↗

PubMed1999

Factors associated with progression of the disease before transplantation in patients with autoimmune hepatitis.

AIMS/BACKGROUND: Studies on transplanted patients may provide clinically useful data on factors influencing progression of autoimmune hepatitis (AIH) since transplantation rather than death may now be considered as the most likely end-point of the disease. The aim of this work was to analyze risk factors related to progression of AIH before transplantation and provide guidelines for further prognostication with regards to the timing of transplantation. METHODS: 80 liver transplants in 68 patients with AIH were performed in our unit. The diagnosis was established on conventional clinical criteria. Parameters such as sex, age at diagnosis and transplantation or duration of the disease were evaluated in relation to: patient HLA DR status, disease presentation (aggressive or non-aggressive), presence of anti-LKM antibodies and concurrent immune disease. RESULTS: AIH with concurrent immune disease occurred more commonly in females (90 vs. 61%; p = 0.0075) and was linked with markedly slower progression of the disease (125 vs. 66 mo; p = 0.002) as compared to subjects without such association. AIH without concurrent autoimmune disease occurred significantly more commonly in patients with DR3 phenotype (p = 0.01). Patients with positive anti-LKM autoantibodies were younger at transplantation (25.6 vs. 43.5 yr; p = 0.006) and had more rapid progression of their disease (14.3 vs. 103 mo; p = 0.001). Unlike previously reported series of non-transplanted patients, all anti-LKM positive subjects had no concurrent autoimmune disease. CONCLUSIONS: Coincidence with another autoimmune disease is associated with a significantly longer disease history prior to transplantation and may possibly reflect greater responsiveness to immunosuppressive therapy before grafting. AIH without concurrent autoimmune disease, particularly if associated with DR4 negative phenotype, male sex and anti-LKM antibodies may characterize patients with rapid progression of the disease. None of these factors had a significant influence on 5 year survival after surgery.

Adult↗

PubMed1999

Successful treatment of acquired perforating dermatosis with rifampicin in an Asian patient with sclerosing cholangitis.

Acquired perforating dermatosis (APD) is a very rare disorder which has been described in association with systemic diseases such as diabetes mellitus, HIV infection or lymphoma. In this report we describe a patient with APD associated with sclerosing cholangitis and diabetes mellitus who was successfully treated with rifampicin. A 33-year-old Indian woman with a history of extensive pancreatic surgery, sclerosing cholangitis and insulin dependent diabetes mellitus was referred to our unit with intractable pruritus. She was treated with cholestyramine, ursodeoxycholic acid, several analgesics, UVB therapy, topical steroids, sedative antihistamines and plasmapheresis without significant improvement. Increasingly severe itching was associated with papular skin changes limited initially to the lower limbs but which later involved her entire body. Biopsy of a representative lesion showed the changes of APD. She was subsequently treated with rifampicin which produced a dramatic resolution of pruritus within 3 weeks and the skin changes progressively resolved over subsequent months. In this newly described association of APD with sclerosing cholangitis, rifampicin treatment appeared to be efficient in ameliorating pruritus and the papular skin changes typical of APD.

Adult↗