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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Clinical History 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 Click to view with ImageScope Click to view with a Web-Based Viewer 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. Case 2 - Figure 4 The triads were normal except for some mild lymphocytic infiltrate. Case 2 - Figure 5 Necrotic granuloma with thick fibrous rim. Case 2 - Figure 6 Higher power of the necrosis. Introduction: 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. Pathologic Findings: 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. Differential Diagnosis: The diagnoses considered during the evolution of this case included hepatic adenoma (pre-operatively), fungal infection, amebiasis, and bacterial abscess. Final Diagnosis: Hepatic granulomas and peliosis with hepatic rupture due to infection with Bartonella. Case Discussion: 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 with granulomas. 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 effective. Conclusions: 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 or PCR. 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