Case 2 -
Hepatic Granulomas and Peliosis with Hepatic Rupture Due to Infection with Bartonella
Frank A. Mitros, University of Iowa, Iowa City, IA
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The patient is a 30 year old woman from rural Iowa who had been in good health until 3 days before admission. At that time she developed the sudden onset of right upper quadrant pain. She was evaluated at her local Emergency Room and was given an analgesic and was sent home. She returned the next day with persistent pain, now radiating to her chest and back. An ultrasound revealed a mass in the right lobe of her liver. A CT revealed a 9 by 12 cm mass with hematoma in the right lobe of liver. Her hemoglobin was 10.8 g/dl with a hematocrit of 32%. Her AST was 298 u/l. She had a past history of tonsillectomy and wisdom teeth extraction in the remote past without incident. She is on no medication other than oral contraceptives.
She was transferred to the University of Iowa Hospitals and Clinics, and a right hepatic lobectomy was performed. The pathology report described the gross appearance as follows:
"The liver lobe surface is dark red-purple and shiny. The capsule is ruptured and there is a 13.0 cm by 15.5 cm subcapsular hematoma. The specimen had been previously excised. This incision displays a subcapsular cavity measuring 7.0 cm by 3.5 cm by 3.0 cm. It is lined by an irregular hemorrhagic surface. The liver parenchyma away from the cavity is dark red and hemorrhagic." (this was not one of our finest gross descriptions !)
Case 2 - Slide 1
Case 2 - Figure 1
Large dilated vessels surrounded by hemorrhage into the parenchyma with subsequent necrosis of hepatocytes
Case 2 - Figure 2
Blood filled space with no endothelial lining typical for peliosis.
Case 2 - Figure 3
Note the dilated and congested sinusoids.
There are a variety of diseases caused by Bartonella, and it is highly likely that
Bartonella related illnesses are significantly under-recognized. The most commonly recognized of theses
diseases is cat scratch disease (CSD) which is a zoonosis in which the domestic cat is the main mammalian
reservoir. Even patients with CSD may have some systemic illness, and systemic involvement is quite
common with other species of Bartonella, especially (but not always) in immunocompromised patients. When
the liver is involved, neoplasia is often simulated, as was true in this case, which was thought to be a
hepatic adenoma pre-operatively.
At the time of surgery an ill-defined hemorrhagic "mass" measuring 17.0 by 15.0 by 5.5
cm was removed. Frozen section revealed granulomas with necrosis and calcification, but no neoplasm.
Multiple permanent sections showed granulomas with necrosis and focal calcification. The granulomas were
confluent and surrounded by a thick fibrous rim. Special stains, including AFB, GMS, Gram, Giemsa, and
Warthin-Starry did not reveal organisms. The surrounding liver showed a mild to moderate portal
lymphocytic infiltrate. There were prominent peliosis type changes, including dilated sinusoids and
variable sized areas of hemorrhage, the larger ones being associated with necrosis. Serologic tests for
Histoplasmosis, Coccidiomycosis and Blastomycosis were negative. Serologic testing done by the CDC was
positive for Bartonella quintana.
The diagnoses considered during the evolution of this case included hepatic adenoma
(pre-operatively), fungal infection, amebiasis, and bacterial abscess.
Hepatic granulomas and peliosis with hepatic rupture due to infection with Bartonella.
There are at least 22 species of Bartonella (formerly Rochalimaea) currently recognized,
but only three of them commonly cause disease in humans. These are Bartonella bacilliformis (BH) the
agent of Oroya fever in the Andes, Bacilliformis quintana (BQ) implicated as causing trench fever during
WWI and WWII, and Bartonella henselae (BH) the agent causing cat scratch disease. The organisms are
small pleomorphic gram negative flagellate rods that are fastidiously aerobic. One of their main
characteristics is the ability to adhere or invade red blood cells (dependent on the species of the
host). An apparently unique feature is the ability to stimulate profound vasoproliferation by their
action on endothelial cells. They are closely related to the Rickettsiae and to Brucellosis.
BH has a limited range in certain altitudes in the Andes, the restriction likely related
to the range of its vector, the sandfly. It produces severe fever and hemolysis in its initial phases,
and an elevated skin lesion, verruga peruana (Peruvian wart) in its later stages. It is often fatal, and
seriously interfered with development in its endemic area. There is evidence that it has existed for
centuries, and some feel it contributed to the decline of the Inca Empire.
BQ has been identified for some time as the etiologic agent of trench fever. Its
mammalian reservoir is man, and the main vector is the body louse. Cramped conditions with poor hygiene
led to it affecting large numbers of troops during the wars. Fever is the main symptom, and has a
tendency to recur at regular intervals, usually about every 5 days, (hence the name quintana). A
peculiar feature is intense pain in the long bones, usually manifest as extremely painful shins. In
fact, it is present widely in many countries and is often not diagnosed. Outbreaks amongst homeless
alcoholic men have been reported, but even those with a high standard of living can be affected (here
mites have been incriminated as a vector). In immunocompromised hosts in particular, systemic
involvement, including bacillary angiomatosis (ba) and peliosis (bp), have been described. Skin, liver
and bone are the common sites for ba, which may simulate neoplasm. The awareness of this capability was
brought to light in the early days of the HIV epidemic.
BH was identified as the causative agent of CSD in the early 1990's. It usually affects
immunocompetent individuals, particularly children and young adults. The main mammalian reservoir is the
domestic cat; many studies have shown 50% or more of pet cats in the US to be infected. Young cats and
kittens are more likely to be bacteremic, and are most capable of spreading disease to humans via a bite
or scratch. Cat to cat transmission is by the cat flea. There is usually a lesion, typically tender
swelling, at the site of inoculation in the host, and regional lymphadenopathy develops in the drainage
region. Characteristic granulomas with stellate micrabscesses are often present in the nodes.
Warthin-Starry or Giemsa stains have the best chance of visualizing the organisms. However stains are
often negative, and the diagnosis is established with serologic or PCR studies. In the
immunocompromised, ba and bh can occur. However, it is not commonly realized that CSD can produce
systemic involvement even in immunocompetent individuals, particularly in children and young adults. In
one study of 101 pediatric patients with CSD, 30 had probable hepatosplenic involvement. There were 19
of the 30 in which serologic confirmation was obtained. In all 19 there were positive titers for both BH
and BQ; in 9 of the 19 the titers for BQ were higher than those for BH. In a review dealing with
systemic involvement by BH, 15 of 23 immunologically intact individuals had hepatic granulomas. In the
immunocompromised individuals 4 of 19 had hepatic granulomas; 12 of these 19 had peliosis, two concurrent
Review and treatment:
A high index of suspicion is necessary for diagnosis. Bartonella related disease will be
encountered in the general population. Antibiotic treatment can be effective, but can be difficult
because of the ability of organisms to live intracellularly. Rifampin and Ciprofloxacin have proven
Bartonella infections are more common than generally realized, and can present in a number
of ways, both as a regional or a systemic disease. A history of typical exposure (pets, occupation,
travel, socioeconomic conditions) is important. The histologic findings are fairly characteristic (
granulomas, stellate microabscesses, angiomatous lesions, peliosis). Diagnosis is confirmed by serology
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