A 23-year-old Man with Leptospirosis and Acute Abdominal Pain

Momal Mazhar MD; Janet J. Kao MD; and Dennis Thomas Bolger Jr. MD, MPH

Abstract Case Report

Leptospirosis is a zoonosis caused by the spirochete Leptospira interrogans. A 23-year-old Caucasian man from the continental United States
Most cases of leptospirosis are mild to moderate, and self-limited. The course residing in Hawai‘i presented to the emergency department
of disease, however, may be complicated by multiorgan dysfunction such (ED) three days prior to admission with a two-day history of
as in Weil’s disease. We present a case of Weil’s disease with pancreatitis
in a young Caucasian man residing in Hawai‘i. Although leptospirosis is fever (104F/40C), chills, headache, neck stiffness, productive
common in Hawai‘i, few patients present with pancreatitis. This report of cough, nausea, and diffuse myalgias. At that time, he denied
leptospirosis-induced pancreatitis should help raise awareness of clinicians photophobia, rash, abdominal pain, and diarrhea. On exam,
to assess for pancreatitis when evaluating a patient with leptospirosis and he was found to be tachycardic (119 beats per minute [bpm])
acute abdominal pain. and febrile (101.4F/38.5C). He received 2 L normal saline.
He was reassessed and found to be hemodynamically stable.
Keywords He was discharged by the ED physician with prescriptions for
Leptospirosis, Weil’s disease, pancreatitis, multiorgan dysfunction, acetaminophen and ondansetron. The patient reported that his
hyperbilirubinemia, acute abdominal pain fever was controlled with acetaminophen, however, his nausea
was unremitting.
Introduction Two days after his first ED visit, the patient developed symp-
Leptospirosis is a zoonosis caused by the spirochete Leptospira toms of photophobia, non-bloody, watery stools, non-bloody,
interrogans. Compared to temperate regions, the incidence of non-bilious emesis up to seven times per day, bloody sputum,
this disease is significantly higher in tropical and subtropical and dark tea-colored urine. On the night prior to his second ED
regions.1 In the United States, an estimated 100-200 lepto- visit, the patient also noticed yellowing of his eyes and face and
spirosis cases are identified annually, of which 50% occur in onset of abdominal pain prompting him to return to the ED.
Hawai‘i.2 The infection is primarily transmitted to humans The patient reported swimming in freshwater 2 weeks prior to
through direct contact with water, mud, or soil contaminated admission, but denied skin abrasions and water ingestion. He
with the urine of chronically infected mammals and rodents.3 An further denied history of recent travel, sick contacts, eating
incubation period of 5-14 days is typical. During this time, the uncooked foods, animal bites, and positive purified protein
spirochetes proliferate in the bloodstream and then disseminate derivative (PPD) status. Upon questioning, the patient admit-
hematogenously. The clinical manifestations of leptospirosis in ted to recreational alcohol consumption, his last episode being
humans vary from a subclinical infection to severe illness with consumption of 4 beers (48 fluid ounces) twelve days prior to
multiorgan dysfunction. Usual disease presentation includes a onset of illness.
flu-like illness with mild hepatic and renal impairment, whereas
severe disease forms are characterized by hepatorenal failure,
encephalopathy, and pulmonary hemorrhage.4-6 The illness
itself has a biphasic nature: an initial septicemia phase and
consequent immune phase. During septicemia, patients will
present with fever, headache, myalgia, conjunctival suffu-
sion, and various non-specific findings such as mild cough, Abbreviations
rash, lymphadenopathy, nausea, and vomiting.7 Subsequently,
ALT: alanine aminotransferase
patients may have a brief afebrile period of variable duration AST: aspartate aminotransferase
whereafter they develop organ derangements, most commonly bpm: beats per minute
of the liver and kidneys. In rare cases, it is reported to directly CDC: Center for Disease Control
CT: Computerized tomography
affect other organs such as the eye, bone marrow, and pancreas. ED: Emergency Department
Weil’s disease, the most severe form of illness, is character- ICU: Intensive Care Unit
ized by jaundice, renal failure, and hemorrhage with a variable IgM: Immunoglobulin M
INR: International Normalized Ratio
clinical course.4 Infected patients with acute renal failure may PPD: Purified Protein Derivative
demonstrate elevated serum amylase levels, however, clinical PT: Prothrombin Time
symptoms of pancreatitis are uncommon.4 We present a case PTT: Partial Thromboplastin Time
of Weil’s disease accompanied by pancreatitis.

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 Upon admission, the patient’s vital signs were significant for transferase (AST) were elevated (184 mEq/L and 144 mEq/L,
hypertension (149/81 mmHg), tachycardia (120 bpm), pyrexia respectively), and there was significant hyperbilirubinemia
(101.1F/38.4C), and tachypnea (24 breaths per minute); he also (total 13.0 mEq/L, direct 9.9 mEq/L, indirect 3.1 mEq/L).
demonstrated pulse oximetry of 94% on room air, and BMI 22 Coagulation studies demonstrated prothrombin time (PT) 13.2
kg/m2. In addition, he was icteric, with conjunctival injection seconds, partial thromboplastin time (PTT) 28.9 seconds, and
but no suffusion. He had decreased breath sounds bilaterally, international normalized ratio (INR) of 1.0. Urinalysis revealed
abdominal rigidity, and arthralgias of his hips, knees, and large amounts of blood and bilirubin. Troponin I was not el-
ankles, but no effusions. Kernig’s and Brudzinski’s signs were evated. Computed tomography (CT) scan of the chest (Figure
absent. On abdominal exam, bowel sounds were hyperactive. 1) revealed diffuse, bilateral peribronchial thickening and
Abdominal organomegaly could not be assessed because the consolidation with extensive bud nodular opacities. Abdominal
patient had severe rigidity and tenderness to palpation and ultrasound was performed and did not demonstrate gallblad-
percussion. There was no rebound tenderness. der inflammation, common bile duct dilatation, or evidence of
Laboratory studies demonstrated leukocytosis (approximately gallstones. CT scan of the abdomen was performed without
18,000/mm3) with neutrophil predominance (83%), thrombocy- oral or intravenous contrast, due to the patient’s acute kidney
topenia (42,000/mm3), hyponatremia (132 mEq/L), hypokalemia injury, and demonstrated hepatosplenomegaly without biliary
(3.0 mEq/L), respiratory acidosis, metabolic alkalosis, and wide dilatation and an unremarkable pancreas.
anion gap acidosis, as well as acute kidney injury (creatinine The patient was admitted for systemic inflammatory response
levels 4.4 mg/dL). Total creatine kinase was elevated (1162 syndrome with suspicion for infection or inflammation in the
IU/ml), alanine aminotransferase (ALT) and aspartate amino- hepatobiliary system. Differential diagnoses included chol-

Figure 1. Computed tomography (CT) scan of the chest demonstrating diffuse, bilateral peribronchial thickening and consolidation with extensive bud nodular opacities.

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angitis, pancreatitis, hepatitis (viral, autoimmune, drug- or has been related to toll-like receptor (TLR) activation from
toxin-associated), leptospirosis, dengue, murine typhus, and Leptospira lipoproteins.4,5 Cardiac involvement may present
typhoid fever. As such, he was started on empiric intravenous with non-specific electrocardiogram abnormalities or findings
antibiotics (doxycycline, ceftriaxone, and metronidazole) while consisting with pericarditis or myocarditis (PR interval prolon-
awaiting blood/sputum/urine/stool cultures, gram stains, and gation, T-wave inversion, first degree atrioventricular block).4
serological test results. Acute renal failure, also associated with TLR activation, is
Shortly after admission to the medical floor, the patient reported in 16%-40% of cases where oliguria is a significant
developed respiratory distress. He was found to have oxygen predictor of death.4,9
saturation of 80% on room air. He was tachycardic, tachypneic,
Although acute pancreatitis has been recognized as a rare
and expectorated a large volume of blood. The patient quickly involvement of the multiorgan dysfunction of leptospirosis,
became less responsive to verbal stimuli. Given his acute respi- most reported cases are of patients who developed hemor-
ratory failure, the patient was transferred to the intensive care rhagic or necrotizing pancreatitis several days after the onset
unit (ICU) where he was supported with supplemental high flow of disease. Furthermore, most reports deal with leptospirosis
oxygen via Venturi mask and close monitoring. At this time, the cases occurring in under-developed countries and involving
patient’s serum lipase was found to be 1750 Units/Liter (normal mainly elderly patients.10-13 The case presented herein adds to
range 13-60 U/L). The patient became increasingly lethargic the body of knowledge in that leptospirosis-induced pancreatitis
and he was unable to tolerate oral intake. The patient’s condi- occurred in a young patient and at the early onset of disease. This
tion slowly improved with intravenous fluids and empiric triple patient developed acute abdominal pain and rigidity coupled
antibiotic therapy. He was weaned to supplemental oxygen via with high lipase level and inadequate pancreatic imaging.
nasal cannula and had no further respiratory distress or evidence He became critically ill from a combination of acute kidney
of recurrent pulmonary hemorrhage. injury, acute respiratory failure, pancreatitis, acute cholestatic
Back on the hospitalist ward team, the patient demonstrated hepatitis, and immune dysfunction. In the context of this report,
jaundice, decreased abdominal rigidity, and tenderness to palpa- it is important to consider alcohol consumption as a possible
tion predominantly in the right upper quadrant and epigastric cause of pancreatitis. However, the patient reported last inges-
region. Laboratory values demonstrated down-trending hepatic tion 12 days prior to disease onset, decreasing the likelihood of
transaminases, serum creatinine, and creatine kinase. However, alcohol-induced pancreatitis. Also, patients often minimize the
serum bilirubin levels were increased (total 18.7 mEq/L, direct amount consumed. Animal studies suggest alcohol consumption
16.5 mEq/L, indirect 2.2 mEq/L). Abdominal ultrasound was is usually not associated with pancreatitis unless 5 drinks or
repeated and showed an unremarkable pancreas and gallblad- more per day (60 g of ethanol) are consumed.14 Nonetheless,
der, but demonstrated hepatomegaly without evidence of biliary such results suggest that ethanol could sensitize the pancreas to
dilatation or ascites. The patient was started on a clear liquid injury while additional factors may trigger the development of
diet and continued to demonstrate nausea and epigastric pain overt pancreatitis. In the setting of leptospirosis, this may be Lep-
without emesis. Serological tests returned significant only for tospira antigen-associated vascular endothelial damage, which
leptospira immunoglobulin M (IgM). The Center for Disease has been associated with the various other organ dysfunctions
Control (CDC) would define a positive leptospira IgM as a of leptospirosis.4 Vascular injury most likely causes ischemic
probable case. The patient’s antibiotics were narrowed to intra- effects on the pancreas such as through decreased removal
venous doxycycline. The patient was discharged after demon- of reactive oxygen species, intracellular enzymes and toxins,
strating clinical improvement on completion of seven-days of and increased stasis of injurious elements that, together, may
intravenous doxycycline. At the time of discharge, the patient manifest as acute pancreatitis. Leptospira interrogans-induced
was able to tolerate a regular diet without nausea. The patient acute pancreatitis seems rare. However, because of the high
was educated that his illness was likely related to freshwater mortality rate associated with pancreatitis, clinicians should
exposure to the infectious agent and counseled on methods for keep in mind the possibility of Leptospira-induced pancreatitis
decreasing risk. when confronted with leptospirosis.15

Discussion Conclusions
Leptospirosis is a disease with a variable grade of severity and Leptospirosis is a frequently encountered infectious disease
organ involvement. Neurologic injury is seen in up to 25% in Hawai‘i and certain other parts of the world. Weil’s disease
of all cases and is most commonly associated with aseptic represents the most severe form of leptospirosis. While multi-
meningitis; however, intracranial hemorrhages, cerebellitis, organ dysfunction is common, pancreatitis is rare. Furthermore,
and myelitis have been reported as well.4,8 Hepatic injury is significant alcohol consumption may predispose leptospirosis
associated with disruption of cellular cohesion, plugging of bile patients to pancreatitis. Acute pancreatitis is associated with
canaliculi, and occasional acute inflammatory infiltrates.4 This significant morbidity and mortality, resulting in the death of
pathophysiology is consistent with the laboratory findings of 20% of patients.16 Thus, it is essential to assess risk factors for
hypertransaminemia, and direct hyperbilirubinemia. Pulmonary pancreatitis, such as alcohol consumption and gallstones, in
injury often presents with hemorrhage, as in our patient, and patients presenting with leptospirosis.

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Conflict of Interest 6. Yew KL, Go CS, Razali F. Pancreatitis and myopericarditis complication in leptospirosis infec-
tion. Journal of the Formosan Medical Association. 2014.doi: 10.1016/j.jfma.2014.01.021
None of the authors identify any conflict of interest. 7. Bal AM. Unusual clinical manifestations of leptospirosis. Journal of Postgraduate Medicine.
2005;51(3):179-183.
Authors’ Affiliation: 8. Vale TC, Santos GC, Santurnino SF, et al. Weil syndrome: a rare cause of cerebral venous
thrombosis. JAMA Neurol. 2014;71(2):238-239.
- John A. Burns School of Medicine, University of Hawai‘i, Honolulu, HI 9. Chakrabarti A, Nandy M, Pal D, Mallik S. A rare case of Weil’s disease with alveolar hemorrhage.
Asian Pac J Trop Biomed. 2014;4(Suppl 1):S66-S69. Available at http://www.ncbi.nlm.nih.gov/
Correspondence to: pmc/articles/PMC4025278/. Accessed December 28, 2014.
Dennis Thomas Bolger Jr. MD, MPH; Department of Medicine, 10. Popa D, Vasile D, Ilco A. Severe acute pancreatitis - a serious complication of leptospirosis. J
John A. Burns School of Medicine, University of Hawai‘i, 1356 Lusitana Street #702, Med Life. 2013;6(3):307-309.
11. Boonpucknavig V, Douangchawee G, Niwattaykul K. Infectious diseases and tropic disease
Honolulu, HI, 96813; Email: dbolger@hawaii.edu pathology: SY16-2A pathology of leptospirosis: autopsy study. Pathology. 2014;46(Suppl 2):S27.
Available at http://journals.lww.com/pathologyrcpa/pages/articleviewer.aspx?year=2014&issu
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