Multiple Muscle Melt: severe atorvastatin-induced hepatitis associated with rhabdomyolysis and leiomyolysis
Authors
Department of Gastroenterology and Hepatology, Monash Medical Centre, Clayton, Victoria, Australia
Introduction
HMG-CoA reductase inhibitor (statin) use
is becoming more and more common.
With an increasing breadth of indications,
it has become the one of the top most
prescribed classes in developed
countries. In Australia, atorvastatin is the
most commonly prescribed PBS-
subsidised medication. Lipid lowering
agents are the most commonly prescribed
class. Hepatitis and myositis are both
recognised side effects of statin therapy .
Severe hepatitis, however, is less
common. Visceral myopathy is also a
very rare and perhaps under-recognised
adverse event.
We present an unusual case of both
paralytic ileus and urinary retention
associated with severe rhabdomyolysis
with diaphragmatic involvement and
hepatitis after an increase in dose of
atorvastatin.
Case Report
A 51 year old man with known alcohol abuse was
admitted with a 5 day history of jaundice without
abdominal pain, fevers or rigors on a background
of generalised myalgia and lethargy, with no
associated bladder or bowel dysfunction.
His past history included alcoholic pancreatitis ,
hypertension and hyperlipidaemia.
The myalgia corresponded to a change in dose of
atorvastatin from 20mg to 40mg daily. The patient
was also taking rabeprazole 20mg twice daily,
candesartan 16mg daily and thiamine 100mg daily.
Nil other substances including herbal supplements
or illicit drugs were taken.
Examination revealed jaundice, non-tender
hepatomegaly, no evidence of decompensation or
stigmata of chronic liver disease. Mild proximal
muscle weakness limiting ambulation to 10m was
also noted. There were no other abnormal
neurological signs. His cardiorespiratory findings
were unremarkable.
Discussion
Our patient also had an extremely aggressive form of
progressive myositis involving not only axial muscles but
also his muscles of respiration.
Similarly to liver impairment, factors that increase the
likelihood of myopathy include co-administration of
drugs metabolised by subgroup CYP3A4 as well as
fibrates.
From the experience in treating other myopathies,
steroids show normalisation of creatine kinase over
time, however efficacy is best shown in dermatomyositis
and polymyositis .
Myositis involving both skeletal and smooth muscle has
been documented in inflammatory myopathies
previously in several case studies. Smooth muscle
myositis associated with statin therapy however is very
rare, with only a few case studies noted in the literature.
MRI of thighs showing T2 hyperintensity These case studies suggest that it is associated with
more severe hepatitis or rhabdomyolysis (figure 1). Our
respiratory function tests suggested diaphragmatic
involvement which has not been previously described.
Though no definitive histology was available, the severe
ileus which culminated in bowel perforation was
Within 24 hours of admission, he developed severe muscle weakness, suspected to have been caused by leiomyolysis. Bowel
with a pronounced proximal emphasis. Neck flexor and proximal arm function improved concomitantly with recovery of
muscles were weak at MRC Grade 3/5, and hip flexor, gluteal and skeletal muscle and liver function. There was no clinical
quadriceps groups had 2/5 weakness. A creatinine kinase (CK) done at evidence of peripheral or autonomic neuropathy. Other
this time was found to be elevated at 9923IU/ml. reports of intestinal pseudo-obstruction are scarce. One
Atorvastatin was ceased, but weakness and CK increased over the case occurred after the addition of cerivastatin to
next three days. He was bed-bound and unable to move his limbs, cyclosporine resulting in a paralytic ileus,
head or trunk against gravity. Vital capacity decreased. Two days after rhabdomyolysis and severe hepatitis. Another case
admission, he went into acute urinary retention of 831mL. MRI showed
T2 signal change in gluteal, thigh adductor and hamstring muscle
reports the addition of erythromycin to existing statin
therapy, with subsequent multi-organ failure and ileus .
groups (Figure 1). A myositic screen was negative. Histopathological In both these cases, combination therapy was the
evaluation of a percutaneous vastus lateralis muscle biopsy revealed a precipitant. Our case illustrates that dose escalation
diffuse toxic rhabdomyolysis affecting all muscle layers consistent with a can also be the trigger.
drug-related myositis . Urinary retention postulated to be due to bladder
Abdominal Xray on Day 8 of admission showing ileus
It appeared he was starting to have diaphragmatic involvement and smooth muscle involvement has been described
oxygen saturations also decreased. Due to these concerns, he was previously. Our case, however, shows that this can
commenced on empiric intravenous hydrocortisone (100mg IV qid) on occur along with severe skeletal and bowel myositis.
day 3. Whether urodynamics in the acute setting is helpful
5 days after admission, he developed acute severe abdominal remains unclear.
distension associated with nausea, vomiting and absolute constipation.
An abdominal X-ray revealed grossly dilated large and small bowel
loops with no transition point (figure 3) and a gastrograffin follow- Conclusion
through confirmed no mechanical no obstruction. On sigmoidoscopy an In the setting of a recently introduced or dose
irregular, oedematous, congested mucosa was seen, however no cause escalated statin therapy, severe skeletal myositis
was found for this abnormality, nor any mass lesion. Ileus continued and
should prompt the treating clinician to monitor
he once again underwent emergent decompression, this time with
respiratory status carefully, ideally with daily vital
colonoscopy which was aborted due to the high risk of perforation.
Unfortunately, he developed a transverse colon perforation post- capacities. Monitoring of bladder and bowel
procedure and proceeded to laparotomy with formation of defunctioning function is also necessary to look for any smooth
colostomy. muscle involvement and the use of steroids may
aid in both skeletal and smooth muscle recovery.