QJM: An International Journal of Medicine, 2015, 967968
doi: 10.1093/qjmed/hcv077
CASE REPORT
Leptospirosis and JarischHerxheimer reaction
S. Takamizawa1, H. Gomi2, Y. Shimizu1, H. Isono1, T. Shirokawa1,2 and
M. Kato1
From the 1Department of Medicine and 2Center for Global Health, Mito Kyodo General Hospital, University of
Tsukuba, Ibaraki, Japan
Address correspondence to Dr H. Gomi, Center for Global Health, Mito Kyodo General Hospital, University of Tsukuba, 3-2-7 Miyamachi, Mito, Ibaraki 310-
0015, Japan. email: hgomi-oky@umin.org
Learning points for clinicians
Although not commonly seen in Japan, the incidence of
leptospirosis reported in 2014 was the highest in the past
6 years. It is important to consider leptospirosis among
patients who traveled to Okinawa, Japan, and to keep in
mind JarischHerxheimer reaction when administering
antimicrobial agents to patients with leptospirosis.
Case report
A 59-year-old Japanese man with a history of hypertension pre-
sented with a complaint of fever and watery diarrhea. He
climbed mountains, got lost accidentally and drunk 2 l of fresh
water in the swamp in Okinawa, Japan 2 weeks prior to
admission.
Physical examinations showed blood pressure 129/
89 mmHg, heart rate 112/min, respiratory rate 30/min, tempera-
ture of 38.5 C and oxygen saturation of 97% on room air. His bi-
lateral palpebral conjunctivas were significantly injected with
jaundice. The patient had tenderness to bilateral thighs and
lower legs. Table 1 shows the laboratory data on admission.
He was admitted to our intensive care unit for severe sepsis
and significant hypokalemia. He was also started on ceftriaxone
1 g intravenously every 12 h and levofloxacin 250 mg intraven-
ously every 24 h with a working diagnosis of leptospirosis given
his travel history and fresh water exposure. Two hours after ad-
ministration of ceftriaxone, he started to have shaking chills
and fever of 40 C. Systolic blood pressure decreased to
80 mmHg, and diffuse maculopapular skin rash appeared on the
trunk and upper and lower extremities. He was immediately
intubated and resuscitated with fluids and vasopressors
Submitted: 24 March 2015; Revised (in revised form): 29 March 2015
C The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians.
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Case report
vigorously. At the bedside, this reaction was thought to be most
likely JarischHerxheimer reaction, not septic shock due to dif-
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ferent organisms. The patient got stabilized successfully. The
serum taken on admission was sent to the National Institute of
Infectious Diseases in Japan, and leptospirosis due to Leptospira
kirschneri serovar Grippotyphosa was confirmed by polymerase
chain reaction and serology.
Discussion
In Japan, 2030 cases per year have been reported since 2004.1
In 2014, a total of 28 cases were reported in Okinawa, which was
the highest in the past 6 years.2 The serotype of Leptospira de-
tected in this patient was one of the strains found in the previ-
ous outbreak in 1999.3 This may suggest that the same strain of
Leptospira has been prevalent since 1999. This patients clinical
course was consistent with Weils disease, the most severe dis-
ease type of leptospirosis.
JarischHerxheimer reaction is known that fever, chills and
decreased blood pressure can occur within a few hours after ad-
ministration of b-lactam antimicrobial agents in patients with
infection due to spirochetes. This reaction can be severe enough
for significant morbidity and mortality. It is much more often
found in the treatment of patients with syphilis. It is relatively
rare in patients with leptospirosis. It is reported in 92 people out
of 1 228 people (7.49%) who were treated for leptospirosis from
1955 to 2012.4 It is also very difficult to distinguish from other
critical illness among returning travelers from endemic areas
for multiple diseases such as typhoid and Rickettsial disease. In
this patient, we had expected this reaction before administra-
tion of antimicrobial treatment in advance, and continued the
same treatment without changing antimicrobial agents when
he turned into a shock state. When we treat leptospirosis, we
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Table 1. Laboratory data

Variable On admission Variable On admission

Hemoglobin (g/dl) 13.0 Lactate dehydrogenase (IU/l) 290

Platelets (per ml) 8.4  104 Creatine phosphokinase (IU/l) 599
White blood cell count (per ml) 6600 Total bilirubin (mg/dl) 3.5
Differential count (%) Direct bilirubin (mg/dl) 2.3
Stab cells 23.0 C-reactive protein (mg/dl) 18.97
Segmented cells 62.0 Prothrombin time (sec) 14.5
Eosinophils 2.0 PT-INR 1.27
Monocytes 3.0 PT% (%) 64.8
Sodium (mEq/l) 137 Activated partial thromboplastin time (sec) 47.5
Potassium (mEq/l) 2.8 Fibrinogen (mg/dl) 923
Chloride (mEq/l) 100 Blood fibrinogen/fibrin degradation products (mg/ml) 12.9
Calcium (mg/dl) 7.8 D-dimer (mg/ml) 3.1
Blood urea nitrogen (mg/dl) 70 Urine test
Creatinine (mg/dl) 3.25 Urinary protein (mg/dl) 100
Glucose (mg/dl) 107 Occult blood reaction 3
Uric acid (mg/dl) 11.2 Blood gases
Protein (g/dl) pH 7.459
Total 6.2 Partial pressure of carbon dioxide (mmHg) 25.8
Albumin 2.4 Partial pressure of carbon oxygen (mmHg) 85.5
Alkaline phosphatase (IU/l) 651 Bicarbonate (mmol/l) 18.0
c-glutamyltransferase (IU/l) 338 Base excess (mmol/l) 3.5
Asparate aminotransferase (IU/l) 104 Lactate (mmol/l) 1.40
Alanine aminotransferase (IU/l) 84

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need to expect this reaction in advance. This reaction is an im- References
portant reminder for clinicians.
1. Infectious Disease Surveillance Center, Okinawa. Incidence
Although not common in Japan, the increasing incidence of
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requires prompt diagnosis and treatment to prevent adverse out-
cessed) (in Japanese).
comes. It is necessary to manage patients with potentially fatal ill-
2. Infectious Disease Surveillance Center, Okinawa. Incidence
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of leptospirosis. http://www.idsc-okinawa.jp/news/leptospir
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(in Japanese).
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endemic areas. This case provides an instructive reminder to clin-
recreational exposure to water in the Yaeyama islands, Japan.
icians to consider leptospirosis among patients with a travel his-
Am J Trop Med Hyg 2005; 73:6526.
tory to Okinawa, Japan, and JarischHerxheimer reaction when
4. Guerrier G, DOrtenzio E. The Jarisch-Herxheimer reac-
managing patients with leptospirosis.
tion in leptospirosis: a systematic review. PLoS One 2013; 8:
Conflict of interest: None declared. e59266.