Jpn. J. Infect. Dis.

, 68, 407–409, 2015

Short Communication

Severe Toxoplasmic Hepatitis in an Immunocompetent Patient

Aynur AT_ILLA1*, Saliha AYDIN1, Ayºse Nurten DEM_IRDOVEN
Ä 2, and S. Sƒrrƒ KILIC
º 1
1Department of Infectious Diseases and Clinical Microbiology, Samsun Training and Research Hospital, Samsun;
and 2Private Demird äoven Pathology Laboratory, Samsun, Turkey

SUMMARY: Acute Toxoplasma gondii infection causes different clinical courses in 10–20z of cases.
In immunocompetent patients, toxoplasmosis most often presents as asymptomatic cervical lymph-
adenopathy. Clinical manifestations such as pneumonia, myocarditis, hepatitis, and encephalitis are
rarely reported. We present the case of an immunocompetent patient with a serious and complicated
clinical course of toxoplasmic hepatitis with a maculopapular rash. The diagnosis was confirmed by
serology and identification of bradyzoites in liver biopsy samples.

Toxoplasmosis is caused by infection with the ob-
ligate intracellular parasite Toxoplasma gondii. Primary
infection is usually subclinical, but cervical lymph-
adenopathy or ocular disease can occur. Infections ac-
quired during pregnancy may cause severe damage to
the fetus (1). Some patients develop severe symptoms,
including high fever (39–409 C), myalgias, arthralgias,
fatigue, dry cough, dyspnea, generalized lymphadeno-
pathy, hepatosplenomegaly, and maculopapular rash
(2). Clinical manifestations such as pneumonia, my-
ocarditis, hepatitis and encephalitis are rarely reported
(3).
Toxoplasmosis can be fatal in immunodeficient or
immunocompromised patients. Immunocompromised
hosts often experience a life-threatening involvement of
one or more organs during primary infections and can
suffer reactivation of pre-existing tissue cysts due to a
deficient of the immune system (3). We present a case of
toxoplasmic hepatitis in an immunocompetent woman,
highlighting the need for increased awareness of the
etiology in cases of severe unknown conditions despite
their presumed relative rarity.
46 yr-old woman was admitted for complaints of
fever, nausea, vomiting, fatigue, loss of appetite, and
myalgia since 2 days. She reported having consumed
raw meat since childhood. She had used paracetamol
for her high fever. Physical examination revealed a
fever of 39.59 C, with a pulse of 102 beats/min, and
blood pressure of 120/70 mmHg. She did not have neck
stiffness, lymphadenopathy, or cardiac or respiratory
abnormalities. Disseminated maculopapular rashes,
hepatomegaly, and pain on the right upper abdominal
quadrant with palpation were noted. Laboratory analy-
sis showed values and concentrations as follows:
hemoglobin (Hb): 13.4 g/dL, hematocrit: 41.1z,
platelet count (Plt): 218 × 103/mL, white blood count
(Wbc): 13.94 × 103/mL (36z granulocytes, 40z lym-
phocytes, and 16z eosinophiles), aspartate trans-
Received October 3, 2014. Accepted December 12, 2014.
J-STAGE Advance Publication March 13, 2015.
DOI: 10.7883/yoken.JJID.2014.422
*Corresponding author: Mailing address: Department of
Infectious Diseases and Clinical Microbiology, Samsun
Training and Research Hospital, Samsun, Turkey. Tel:
＋90 532 5568767, E-mail: aynur.atilla＠gmail.com
aminase (AST): 633 U/L (normal: 0–38 U/L), alanine
transaminase (ALT): 698 U/L (normal: 0–49 U/L),
alkaline phosphatase: 260 U/L (normal: 45–129 U/L),
lactate dehydrogenase: 848 U/L (normal: 120–246 U/
L), gamma glutamyl transpeptidase: 140 U/L (normal:
0–38 U/L), albumin: 3.0 g/dL (normal: 3.2–4.8 g/dL),
total serum protein: 5.6 g/dL, IgE: 1,050 IU/mL (nor-
mal: 100), rheumatoid factor: 15.7 IU/mL (normal:
15), ferritin 210 ng/mL (normal: 13–150 ng/mL),
and C-reactive protein: 124 mg/L (normal: 0–5 mg/L).
Electrolyte, blood urea nitrogen, creatinine, calcium
phosphate, and bilurubin levels as well as sedimentation
rates were within normal limits. Abdominal ultrasono-
graphy revealed hepatomegaly (195 mm). However,
there was no evidence of steatosis, biliary canal dilata-
tion, or lymphadenopathy. Skin lesions were believed to
be eruptions due to paracetamol use. Methylpredniso-
lone treatment (60 mg/day) was initiated. However, her
high fever (39–409 C), maculopapular rashes, and itch-
ing persisted under this treatment.
Further testing revealed laboratory values as follows:
Wbc: 30.98 × 103/mL, Hb: 13.2 g/dL, and Plt were
160 × 103/mL. Bilirubin levels had increased, with total
bilirubin (TB) and direct bilirubine (DB) levels reaching
3.1 mg/dL and 2.6 mg/dL, respectively. Based on her
high fever, leukocytosis, TB and DB levels, and pain in
the right upper quadrant, the patient was preliminary
diagnosed with acute cholangitis, and piperacillin
tazobactam (3 × 4.5 g) treatment was started. In order
to investigate the source of her fever and the hepatitis
etiology, the patient was tested for hepatitis B, C, and
E; human immunodeficiency virus, cytomegalovirus,
Epstein-Barr virus, rubella, herpes simplex virus, and
brucella. The patient was negative for anti-nuclear
antibodies, anti-mitocondrial antibodies, anti-dsDNA,
perinuclear anti-neutrophil cytoplasmic antibodies,
anti-smooth muscle antibodies, and liver-kidney micro-
somes antibodies. Chest X-rays, cranial magnetic reso-
nance imaging, ophthalmic examination, and echocar-
diography were normal.
T. gondii serology findings revealed anti-Toxoplasma
IgM and IgG antibodies (result: 2, cut off: 0.9 and
result: 83.4, cut off: 8, respectively) (Capture ELISA
system, Chorus). Therefore, based on these laboratory
findings as well as her history of eating raw meat, the
patient was diagnosed with toxoplasmosis, and clin-

407
 Fig. 1. (Color online) Toxoplasma gondii bradyzoites seen in hepatocyte stained by PAS.
damycin treatment (4 × 600 mg) was started. Two
weeks later, there was a 4-fold increase in anti-
Toxoplasma IgG titers (result: 464).
Liver and skin biopsies were performed to assess the
persistence of increased liver enzyme values and itchy
maculopapular rashes. Liver biopsy revealed mixed in-
flammatory cell infiltration with fewer eosinophil leuco-
cytes in the sinusoids and portal regions. Focal necrosis,
cholestasis in the periportal regions, and cloudy swell-
ings along with widening in the sinusoids were noted.
Pathological examination with hematoxylin-eosin,
Giemsa, and Periodic Acid Schiff (PAS) stains revealed
T. gondii bradyzoites and hepatitis (Fig. 1). Skin biopsy
showed chronic vasculitis. The piperacillin/tazobactam
treatment was discontinued on day 14. AST and ALT
levels decreased to 44 U/L and 141 U/L, respectively,
on the 8th day of clindamycin treatment. The patient
was discharged on clindamycin treatment (4 × 600 mg)
in a generally healthy condition. On follow-up, her
clinical and laboratory findings had ameliorated. Treat-
ment was discontinued on day 21.
Toxoplasmosis is mainly acquired by ingestion of
food or water contaminated with oocysts shed by cats or
by eating undercooked or raw meat containing tissue
cysts (1). Our patient reported a history of eating raw
meat. Acute T. gondii infection causes different clinical
courses in 10–20z of cases. In immunocompetent
patients, toxoplasmosis most often presents as asymp-
tomatic cervical lymphadenopathy (3). However, pneu-
monitis, myocarditis, and myositis may also occur.
Rarely, hepatitis has been reported in immunocompe-
tent and immunodeficient patients (4–8). Vischer et al.
reported 2 cases of hepatitis due to T. gondii in 1967 (9).
408
Severe cases of toxoplasmosis have been previously
reported in French Guiana, Suriname, and Brazil
(10–12). Patients commonly develop a generalized infec-
tious syndrome with visceral involvement such as mild
hepatitis, jaundice, atypical pneumonia, enlarged lym-
ph nodes, and, less frequently, myositis and chorioreti-
nitis (8,10). Patients are often admitted with fever, rash-
es, and a clinical picture of hepatitis.
Diagnosis of acute toxoplasmosis typically requires
amplification of parasite DNA from blood and body
fluids, revealing and isolating T. gondii bradyzoites in
histopathological examination of biopsy materials
(direct), or detection of antibodies against parasites in
blood (indirect). Bradyzoites are rarely seen in stained
tissue sections during histopathological examination.
Bradyzoites are present in primary and reactive infec-
tions and indicate active infection (3). We detected
bradyzoites in the liver tissue of our patient. Therefore,
diagnosis was confirmed by histopathologic and sero-
logic means.
The standard treatment for acquired toxoplasmosis in
both immunocompetent and immunodeficient patients
is the synergistic combination of pyrimethamine and
sulphonamides. However, because of toxicity, the ther-
apeutic efficacy of pyrimethamine-sulphonamide com-
binations may be limited. Alternatively, newer macro-
lides and clindamycin may be used (3). Due to severe
clinical signs and visceral involvement in our patient
(maculopapular rash and hepatitis), we initiated clin-
damycin treatment, although this therapy is rarely indi-
cated in immunocompetent patients. We preferred
clindamycin due to being easier to reach and because
pyrimethamine and sulfadiazine combination were not
 Toxoplasmic Hepatitis
available in our regional market. A 21-day treatment
regimen managed the disease and cured the infection.
In conclusion, in order to provide prompt treatment,
the potential for toxoplasmosis should be considered for
patients with hepatitis, especially those presenting with
fever and rashes.
Conflict of interest None to declare.
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