Salmonella Typhi Infection Complicated by Rhabdomyolysis ... - AJNT

Arab Journal of Nephrology and Transplantation. 2011 May;4(2):91-3
Case Report
* Corresponding author; consultant nephrologist, UAQ Hospital, UAE;
E mail: medhatali10@hotmail.com
AJNT
Salmonella Typhi Infection Complicated by Rhabdomyolysis, Pancreatitis
and Polyneuropathy
Medhat Ali * and Hosam Abdalla
Department of Internal Medicine and Nephrology, UAQ Hospital, UAE
Abstract
Introduction: Typhoid is a common infection that can
have serious complications. Here we present a severe
case of Salmonella typhi infection complicated by
rhabdomyolysis and acute kidney injury.
Case report: A 42-year-old male presented with
shortness of breath, generalized body aches and upper
abdominal pain two weeks after returning from India.
Investigations revealed severe metabolic acidosis
(arterial blood pH 6.9), high serum creatinine (12.7 mg/
dl), hyperuricemia (16.4 mg/dl), hypocalcemia (4.1 mg/
dl), hyperphosphatemia (16.1 mg/dl), high serum amylase
(1458 u/L), thrombocytopenia (59,000/mm 3 ) and disturbed
coagulation profile. The diagnosis of rhabdomyolysis was
confirmed by an elevated creatine phosphokinase level
of 17,000 U/L. The patient was started on hemodialysis,
and two days later he developed broncho-pneumonia
and required mechanical ventilation. Blood cultures
grew Salmonella typhi; parenteral imipenem-cilastin
and ciprofloxacin were initiated. After one week, the
patient continued to have fever despite improvement
of biochemical parameters and negative blood and
stool cultures. Antibiotic drug-fever was suspected and
antibiotics were stopped. Subsequently, fever and rash
disappeared and the patient was switched to ceftazidime
two days later. The patient eventualy regained normal
kidney function but continued to have weakness in
both lower limbs. Electromyography (EMG) and nerve
conduction studies revealed diffuse axonal sensorimotor
polyneuropathy that progressively improved over time.
Conclusion: Common infective agents, including
salmonella typhi, can present in unusual ways. The
possibility of a severe systemic infection being the
underlying cause of rhabdomyolysis should not be
overlooked.
Keywords: Acute Kidney Injury; Neuropathy;
Rhabdomyolysis; Salmonellosis; Typhoid
The authors declared no conflict of interest
Introduction
Rhabdomyolysis is the breakdown of muscle fibers with
leakage of potentially toxic cellular contents into the
systemic circulation. Clinical sequelae of rhabdomyolysis
include hypovolemia due to sequestration of plasma water
within injured myocytes, hyperkalemia due to release of
cellular potassium into the systemic circulation, metabolic
acidosis due to release of cellular phosphate and sulfate,
acute kidney injury (AKI) due to the nephrotoxic effects
of liberated myocyte components, and disseminated
intravascular coagulation (DIC) due to thromboplastin
release from injured myocytes [1]. Muscle damage may
be caused by physical, chemical, or biological factors.
The clinical presentation is often subtle, underscoring the
need for a high index of suspicion. Classical risk factors
include alcohol abuse, recent soft tissue compression,
seizure activity, drug abuse, metabolic derangements and
sepsis [2]. More recently, illicit drugs, alcohol and some
prescription medications were reported to be responsible
for almost half the cases [3].
Typhoid fever is a systemic disease caused by
Salmonella typhi and paratyphi. It is a common disease
in India. Gastrointestinal bleeding, intestinal perforation,
pancreatitis, hepatitis, pericarditis, endocarditis, orchitis,
meningitis, myocarditis, parotitis, pneumonia, arthritis
and osteo-myelitis are complication associated with
typhoid fever [4]. Rhabdomyolysis has been reported
infrequently with salmonella species infection, and only
rarely with Salmonella typhi [5-8]. Here we present a
severe case of Salmonella typhi infection complicated by
rhabdomyolysis and acute kidney injury.
91

Medhat Ali and Hosam Abdalla
Case Report
A 42-year-old male was admitted to our hospital because
of severe shortness of breath that developed over few
days. He also complained of generalized body aches,
tremulousness, upper abdominal pain, vomiting and
dysuria. He had returned from India two weeks earlier
and had no history of trauma, illicit drug or alcohol
abuse.
His blood pressure was 140/80 mmHg, pulse 100 beats/
minute, temperature 37°C and respiratory rate 40/
minute. His breathing was deep and labored but with
normal oxygen saturation. He had generalized expiratory
wheezes on chest examination. Abdominal examination
revealed epigastric tenderness. There was generalized
muscle weakness and tenderness and he was unable to
get up from the bed. There was no skin rash.
Investigations revealed normal total leukocyte count and
hemoglobin level but he had thrombocytopenia (59000/
mm3 ). His serum creatinine was 12.7 mg/dl, serum
sodium 115 mmol/L (n. 135-145), serum potassium 3.8
mmol/L (n. 3.5-5.3), serum bicarbonate 4.9 mmol/L
(n. 21-31), pH 6.9 (high anion gap metabolic acidosis)
serum uric acid 16.4 mg/dl (n. 2.6-7.2), serum calcium
4.1 mg/dl (n. 8.8-10.4), and serum phosphorus 16.1 mg/
dl (n. 2.5-5). Liver function tests showed: serum albumin
2.4 g/dl (n. 3.5-5.0); liver enzymes (ALT) 268 iu/L (n.
10-40), serum bilirubin 1.8 mg/dl (n. 0.2-1) and disturbed
coagulation profile. He had high serum amylase at 1458
u/L (n. 25-125) and high C-reactive protein (CRP) at
192 ng/L (n. 0-9). Rhabdomyolysis was considered and
the serum muscle enzymes revealed elevated creatine
phosphokinase (CPK) at 17,000 U/L (n. 38-174) and
elevated lactate dehydrogenase (LDH) at 3050 U/L (n.
91-180). The serum and urine myoglobin assays were not
available at that time. Ultrasonography of the abdomen
and chest X ray were normal.
The patient was admitted to the intensive care unit (ICU)
and hemodialysis was started. His condition deteriorated
and fever appeared two days later with the development
of bronchopneumonia. Toxicological screening was
negative. Blood cultures grew Salmonella typhi while
urine and stool cultures were sterile. Mechanical
ventilation was started and parenteral imipenem-cilastin
and ciprofloxacin were initiated. After one week, the
patient continued to have fever (40°C) associated with
skin rash but with improvement of biochemical blood
tests (liver function tests, coagulation profile, LDH, CRP
and platelet counts) and negative blood and stool cultures.
Antibiotic drug-fever was suspected and antibiotics were
stopped. Both fever and skin rash disappeared; also
muscle enzymes and serum amylase levels improved.
Two days later, the patient was switched to ceftazidime.
Arab Journal of Nephrology and Transplantation
92
The patient was weaned from ventilation but continued
on intermittent hemodialysis for two weeks after which
his renal function showed progressive improvement. He
was discharged from hospital one month after the initial
hospitalization in a satisfactory condition. His renal
function normalized but he continued to have weakness
in both lower limbs. He underwent electromyography
(EMG) and nerve conduction studies which showed
diffuse axonal sensorimotor polyneuropathy, mainly in
the lower limbs. The muscle weakness progressively
improved over time.
Discussion
Rhabdomyolysis is a term used to describe the rapid
breakdown of striated muscles that results in the release
of cell breakdown products into the bloodstream. The
classic triad of symptoms includes muscle pain, weakness
and dark urine. However, only half of the patients may
complain of muscle pain initially, and a minority report
dark discoloration of the urine [2].
The laboratory diagnosis is based essentially on the
measurement of creatine kinase (CK) in serum. This assay
is widely available and 100% sensitive. Rhabdomyolysis
has been variously defined as total CK levels 5-10 times
above normal in a patient with typical symptoms and/or
risk factors. Plasma and urine myoglobin measurements
might be useful in the early stages of the syndrome and
for identifying a subset of patients with minor skeletal
muscle injury. A positive urine dipstick test for blood in
the absence of red blood cells suggests myoglobinuria
or hemoglobinria. Urine dipstick findings are positive
in fewer than 50% of patients with rhabdomyolysis;
therefore, a normal urine dipstick test does not rule out
this condition [9].
Patient monitoring is pivotal since the mortality rate
is as high as 8%, and should focus on preventing the
detrimental consequences that often include acute kidney
injury and coagulopathy [10]. The patient presented
here had a very complicated course of Salmonella typhi
infection: broncho-pneumonia, acute pancreatitis, hepatic
impairment, DIC, rhabdomyolysis and neuropathy. The
mechanisms of salmonella-induced rhabdomyolysis may
include tissue hypoxia caused by sepsis, toxin release,
direct bacterial invasion of muscle fibers and metabolic
derangement. Hyperkalemia is often present in cases of
rhabdomyolysis, but might have been balanced in this
case by significant gastrointestinal losses of potassium.
Our patient had diffuse sensorimotor neuropathy that
might have been a consequence of his severe renal
dysfunction or might have been a complication of
Salmonella typhi infection. A similar complication has
been reported by Khan et al [11]; they described a patient

who presented with Guillain-Barré syndrome (GBS)
accompanying Salmonella paratyphi infection.
Although a wide variety of drugs can cause drug fever,
certain medications should be considered with a higher
level of suspicion, anticonvulsants, antiarrythmics,
certain antihypertensives and antibiotics are commonly
associated with drug fever [12]. A history of allergy,
skin rashes, or peripheral eosinophilia is often absent
in cases of drug fever. Neither the fever pattern nor the
duration of previous therapy is helpful in establishing the
diagnosis. Stopping the causative drug generally leads to
defervescence within two days, as happened in this case.
Conclusion
Salmonella typhi can present in unusual ways. The
possibility of a severe systemic infection being the
underlying cause of rhabdomyolysis should not be
overlooked.
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