Junais Koleri
Assistant Professor, Infectious Disease
Unit, Dept of General Medicine, Govt Medical College,
Kozhikode, Kerala
Address for Correspondence: Dr.
Junais Koleri, MBBS, MD, MRCP (UK), Assistant Professor,
Infectious Disease Unit, Dept of General Medicine, Govt
Medical College, Kozhikode, Kerala, India. E- mail:
drjunais@gmail.com
Abstract
Cloxacillin, a commonly prescribed antibiotic for MSSA,
can rarely cause cholestatic hepatitis. Case fatalities have
also been reported. Liver injury can be delayed upto several
weeks after stopping the drug, thus causing difficulty in
making the diagnosis and also an array of unnecessary
investigations. Hence a high index of suspicion is required.
We are presenting a case of cloxacillin induced cholestatic
hepatitis which occurred in a young male after 4 weeks of
taking the drug and persisted for 5 weeks.
Keywords: cholestatic hepatitis, Cloxacillin
Introduction
Cloxacillin is a penicillinase resistant semisynthetic
penicillin used for the treatment of methicillin sensitive
Staphylococcus infections. There were case reports from
Australia, Netherlands and Scandinavia of cholestatic liver
injury of unknown cause in cloxacillin users (1-4).
Subsequently the clinical picture was better delineated with
clinical case series. There occurs a prolonged painless
jaundice and pruritus with elevation in liver enzymes, 2 to 6
weeks after cloxacillin use.
We present a case of cloxacillin induced hepatitis four weeks
after consumption of the drug.
Case report
Middle aged person presented with generalised pruritus of five
days duration and two days of yellowish discolouration of
urine. There was no fever, anorexia, nausea, or vomiting.
There were no significant past illnesses. Not on any long term
medication. No family history of jaundice. No sexual
promiscuity or IV drug abuse. Never consumed alcohol. On
examination there was jaundice and generalised excoriation
marks. No signs of chronic liver disease. No hepatomegaly or
splenomegaly.
A provisional diagnosis of viral hepatitis was made and
baseline investigations showed elevated liver enzymes and
bilirubin. There was no relief of pruritus with UDCA. All the
viral markers came out negative. Repeated liver function tests
showed reduction in SGPT, but the ALP and bilirubin remained
high. As the viral markers were negative a USG of the abdomen
was done which showed Normal liver except for a diffuse
increase in echo texture.
Meanwhile due to the intractable pruritus, cholestyramine was
given, following which there was some relief.
As the cause of the predominantly cholestatic form of jaundice
was not found, the history was retaken. Old documents showed
history of cloxacillin intake for a minor wound infection one
month before the onset of pruritus. Cloxacillin was taken for
ten days at a dose of 500 mg four times a day.
Hence the diagnosis of cloxacillin induced hepatitis was made
and was kept under observation. Further tests were deferred.
There was gradual improvement and became totally asymptomatic
over a period of five weeks.
Discussion
Cholestatic hepatitis as a side effect of cloxacillin is well
described, though rare [1-5]. The risk is estimated to be
about 7 per 100,000 users [6], reported mostly in the first
six weeks of drug intake [7]. Fatal reactions are rarely
reported [2,4,5]. Prolonged use of cloxacillin (more than two
weeks) and increasing age (more than 55 years) are the major
risk factors [1]. Illness usually presents as jaundice and
pruritus which are severe and protracted [1]. Diagnosis of
drug induced liver injury (DILI) can be difficult because of
the delay in presentation and the concomitant presence of
other risk factors like alcoholism and non alcoholic fatty
liver disease (NAFLD). The cause of cholestatic hepatitis can
be attributed to the culprit drug if there is a prior exposure
(latent period may vary) and after exclusion of other possible
causes [8]. Injury may improve after stopping the drug and
recur more rapidly with worsened severity on further exposure
[9].
Histopathology shows centrizonal bile stasis with portal tract
inflammation and variable loss of bile ducts [1,4,17]. It may
also resemble autoimmune hepatitis [10]. A genome-wide
association study using more than 8 lakh markers found
HLA-B*5701 to be the main common genetic risk factor [11]. A
delay in the onset of symptoms and identification of human
leukocyte antigen (HLA)-B*57:01 as a susceptibility factor are
indicative of an immune pathogenesis, with largely T cell
involvement. [12,13].
Other drugs which can cause similar picture are
amoxicillin-clavulanate, captopril, carbamazepine,
chlorpromazine, efavirenz, ezetimibe, estradiol, flutamide,
diclofenac, erythromycin estolate, nafcillin, ketoconazole,
nevirapine, rifampin, rosiglitazone,
trimethoprim-sulfamethoxazole, troglitazone, and amiodarone
[14,15,16].
Cloxacillin is the drug of choice for methicillin sensitive
staphylococcus aureus. This case is reported to create
awareness of such possible complications.
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