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Vanishing Bile Duct Syndrome
Mashhood Ali et al.
Case Report
Vanishing Bile Duct Syndrome
Abstract
A 33 year old male presented with 5 weeks history severe pruritis ,
anorexia, weight loss and malaise .He underwent extensive workup
including USG Abdomen ,MRCP, Viral serology and workup for
autoimmune diseases which were all normal. He then underwent ERCP and
findings on ERCP were consistent with Vanishing Bile Duct Syndrome
which a rare entity in itself. He underwent Liver biopsy and findings were
consistent with VBDS and he was subsequently followed up on outdoor
basis and his symptoms improved with medications.
Introduction
Vanishing bile duct syndrome refers to a group of
acquired disorders resulting in progressive destruction
and disappearance of the intrahepatic bile ducts and
ultimately cholestasis.
Ductopenia (a pathologic
description) refers to the associated reduction in the
number of intrahepatic bile ducts, a process that
ultimately leads to cholestasis.1-3
It’s a rare entity and many causes have been implicated
and causes maybe developmental (syndromatic or non
syndromatic
paucity
of
interlobular
bile
ducts),immunological(primary biliary cirrhosis ,graft
versus
host
disease,
primary
sclerosing
chloangitus)infective(Vascular
or
chemical
in
origin).Several
drugs
including
chlorpromazine,
carbamazepine,
ibuprofen,
clindamycin,
fluoroquinolones,
antifungal
drugs,
tricyclic
antidepressants and trimethopirim- sulfamethoxazole
have been showed to be associated with VBDS.VBDS
has also been reported in children with histiocytosis x
and adult non hodgkin lymphoma patient.4-9,10
We report a patient who presented with severe
progressive intrahepatic cholestasis due to VBDS for
which a cause was not found
Case Report
Mashhood Ali**
Haseeb Noor*
Yasir Rafique Rajwana*
Asif Imran*
*Resident,
**Senior Registrar,
Department of Gastroenterology,
Pakistan Institute of Medical
Sciences (PIMS), Islamabad
Address for Correspondence
Dr. Haseeb Noor
Department of Gastroenterology,
Pakistan Institute of Medical
Sciences (PIMS), Islamabad
Email: [email protected]
were added to his complaints for the last 4 weeks. He
had no history of previous jaundice, blood transfusion,
alcohol abuse or recent drug ingestion and no family
history of liver disease. On admission his physical
examination was remarkable for jaundice, itch marks all
over the body and shiny nails attributed to persistent
itching. There was no fever, hepatosplenomegaly or
lymphadenopathy.
Laboratory findings on admission revealed: White cell
count:9900/microlit, platelets 373000/microliter, ESR
90mm/h, INR 1.4,(decreased normal value after
treatment with vitamin k). Biochemical features
consistent with cholestasis: total bilirubin:36.39
mg/dl(NV 0.3-1.2), alkaline phosphatase:232 U/L(NV
40-1300),alanine aminotransferase:112 U/L(NV 4-42),
aspartate aminotransferase 110 U/L(10-42), g-glutamyltranspeptidase
400
U/L
(nv
7-60).
Serum
immunoglobulins and combs test were normal.
Serological tests for hepatitis A, B,C,E were negative.
Blood, urine and stool cultures for bacteria and fungi
were negative. Antimitochondrial antibody and
antinuclear tests were negative. Autoimmunehepatitis,
hemochromatosis and wilsons disease were ruled out .
Additionally C-ANCA and P-ANCAS were also negative.
Abdominal ultrasound revealed minimal hepatomegaly.
Magnetic resonance cholangiopancreatography did not
reveal any abnormality. (Figure 1)
A 33 year old male presented with 5 weeks history
severe pruritis, anorexia, weight loss and malaise.
Painless jaundice, dark coloured urine and pale stools
Ann. Pak. Inst. Med. Sci. 2014; 10(2):110-112
110
Vanishing Bile Duct Syndrome
Mashhood Ali et al.
started on cap ursodeoxycholic acid(750 mg
daily),rifampicin(150 mg daily),sertraline (50 mg daily)
for both pruritis and cholestasis. Within two weeks
patients symptoms improved though not settling
completely and owing to untreatable pattern of disease
he was discharged with follow up in outdoor clinic.
Figure 1: MRCP of the patient
Endoscopic
retrograde
cholangiopancreatography
demonstrated normal common bile duct with very small
intrahepatic ducts suggestive of vanishing bile duct
syndrome. (Figure 2)
Figure 3: Percutaneous liver biopsy findings in the
patient.
Discussion
Figure 2: ERCP of the patient.
Percutanous liver biopsy revealed seven portal tracts
with paucity of bile duts, marked cholestasis ,minimal
acute on chronic inflammation, no significant fibrosis
and mild to moderate steatosis. (Figure 3) Patient was
Ann. Pak. Inst. Med. Sci. 2014; 10(2): 110-112
The term “idiopathic adulthood ductopenia ” was first
mentioned by Ludwig, in 1988, to describe those
patients those patients with biliary ductopenia (the
absence of interlobular bile ducts in at least 50% of
small portal tracts)not associated with any specific
underlying cause.1-3
In VBDS HLA class 2 antigens are displayed on the bile
ducts and recognition of biliary antigens by cytotoxic Tcells leads to destruction of interlobular ducts. The
clinical course and clinical manisfestations are highly
variable reflecting the varied underlying causes.Disease
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Vanishing Bile Duct Syndrome
onset can be rapid as in acute cellular rejection; as in
our patient; or gradual ,as in primary biliary cirrhosis.
The diagnosis is established by liver biopsy in the
appropriate clinical setting.Evaluation should include
imaging tests to exclude extrahepatic biliary obstruction
and appropriate serological evaluation when there is
suspicion for a particular clinical diagnosis (e.g
antimitochondrial antibodyin patients suspected of
having primary biliary cirrhosis).A careful history
including all recent prescription and non prescription
drug use
is efabnorssential since drug induced
cholestasis is common and drug withdrawal is
essential.However in our patient all such causes were
ruled out.
There are generally two potential outcomes in patients
with ductopenia:progressive,irreversible bile duct loss
leading
to
extensive
ductopenia
and
biliary
cirrhosis(although
the
time
course
varies
considerably)or biliary epithelial regeneration and
clinical recovery over months to years as in our patient.
Few cases of VBDS have been published it being a rare
entity. All of the cases reported had an underlying cause
but we here have reported a case for which no cause
was found. Nationally only one case has been reported
and that too was associated Hodgkins Lymphoma. A
recent international study reported a patient of VBDS
secondary to Toxic epidermal Necrolysis (TEN). 1,3,7,8,11
The mechanism of VBDS is poorly understood. There is
no recognized treatment for VBDS. A few reports have
described the use of ursodeoxycholic acid in drug
induced VBDS. The above mentioned case report of
VBDS secondary to TEN first reported use of Infliximab
and plasmapharesis in addition to steroids and made
efforts to support a mechanism for why these modalities
could be effective treatments in the future. Since VBDS
is a relatively recent defined entity, clinicians may not
always be aware of its existence or its associations. This
report emphasizes that VBDS should be considered in a
patient with cholestatic jaundice.1,3
1.
2.
References
Schumaker AL, Okulicz JF. Meropenem-induced vanishing bile duct
syndrome. Pharmacotherapy 2010; 30: 953. PubMed Citation (60 year
old woman developed jaundice and pruritus while on meropenem and
3 weeks after course of ceftriaxone, metronidazole and vancomycin
[bilirubin 11.2 rising to 26 mg/dL, ALT 83 U/L, Alk P 1467 U/L], with
persistent jaundice and liver biopsy showing absence of bile ducts,
improving but not completely resolving over next 6 months on
ursodiol).
Kochar R, Nevah MI, Lukens FJ, Fallon MB, Machicao VI. Vanishing
bile duct syndrome in human immunodeficiency virus: nevirapine
hepatotoxicity revisited. World J Gastroenterol 2010; 16: 3335-
Ann. Pak. Inst. Med. Sci. 2014; 10(2): 110-112
Mashhood Ali et al.
8. PubMed Citation (28 year old pregnant woman with HIV infection
developed jaundice 4 weeks after starting zidovudine, lamivudine and
nevirapine to prevent perinatal transmission of HIV [bilirubin 10.5
mg/dL, ALT 179 U/L, Alk P 496 U/L], with persistent jaundice and liver
biopsy showing ductopenia; follow up not provided).
3. Gökçe S, Durmaz O, Celtik C, Aydogan A, Güllüoglu M, Sökücü S.
Valproic acid-associated vanishing bile duct syndrome. J Child Neurol
2010; 25: 909-11. PubMed Citation (8 year old girl developed
persistent jaundice and itching 2 months after starting valproic acid
[bilirubin rising to 20.2 mg/dL, ALT 118 U/L, Alk P 2787 U/L, normal
INR], liver biopsy showing severe bile duct loss, bilirubin falling to
normal after 8 months on ursodiol therapy but with persistence of Alk P
elevations).
4. Juricic D, Hrstic I, Radic D, Skegro M, Coric M, Vucelic B, Francetic I.
Vanishing bile duct syndrome associated with azithromycin in a 62year-old man. Basic Clin Pharmacol Toxicol 2010; 106: 62-5. PubMed
Citation (62 year old man developed Stevens Johnson syndrome 3
days after a 3 day course of azithromycin and became jaundiced
during recovery [bilirubin 15.2 mg/dL, ALT 1545 U/L, Alk P 545 U/L],
with persistent jaundice and pruritus and liver biopsy showing absence
of interlobular bile ducts at time of transplantation 10 months later).
5. Robinson W, Habr F, Manlolo J, Bhattacharya B. Moxifloxacin
associated vanishing bile duct syndrome. J Clin Gastroenterol 2010;
44: 72-3. PubMed Citation (82 year old man received azithromycin,
ceftriaxone and 7 days of moxifloxacin and developed jaundice
[bilirubin 15.3 rising to 25.8 mg/dL, ALT 441 U/L, Alk P 821 U/L], with
biopsy showing ductopenia with persistence of jaundice; outcome not
provided).
6. Bhayana H, Appasani S, Thapa BR, Das A, Singh K. Lamotrigine
induced vanishing bile duct syndrome in a child. J Pediatr
Gastroenterol Nutr 2011. PubMed Citation (12 year old boy developed
rash 2 weeks after starting lamotrigine followed by jaundice [bilirubin
14.8 mg/dL, ALT 321 U/L, Alk P 123 U/L], liver biopsy showing ductal
paucity with incomplete recovery on ursodiol and referral for
transplantation 2 years later).
7. Ichikawa T, Sato H, Kaira K, Oh-I S, Kakizaki S, Sato K, Takagi H,
Mori M. Prolonged intrahepatic cholestasis after exposure to
loxoprofen. Clin Ther 2008; 30: 2402-6.PubMed Citation (36 year old
woman developed jaundice 5 days after starting loxoprofen [bilirubin
27.5 mg/dL, ALT 470 U/L, Alk P 1082 U/L], liver biopsy showing
paucity of bile ducts, with protracted course and slow resolution 14
months after onset).
8. Orman ES, Conjeevaram HS, Vuppalanchi R, Freston JW, Rochon J,
Kleiner DE, Hayashi PH; DILIN Research Group. Clinical and
histopathologic features of fluoroquinolone-induced liver injury. Clin
Gastroenterol Hepatol. 2011; 9: 517-23. PubMed Citation (12 cases of
liver injury due to fluoroquinolones including one due to moxifloxacin
that resulted in VBDS and liver transplantation 16 months after onset
of acute cholestatic hepatitis).
9. Farouj NE, Cadranel JF, Mofredj A, et al. Ductopenia related liver
sarcoidosis. World J Hepatol 2011; 3:170
10. Yusuf MA, Elias E, Hubscher SG. (2000) Jaundice caused by the
vanishing bile duct syndrome in a child with Hodgkin lymphoma. J
Pediatr Hematol Oncol. 22(2):154-157
11. Jason C. White and Stephanie Appleman. Infliximab/Plasmapheresis
in Vanishing Bile Duct Syndrome Secondary to Toxic Epidermal
Necrolysis. September 22, 2014;Pediatrics;Official journal of the
American academy of Pedriatics.
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