Background

Bartonella infections are an obscure group of diseases to most practitioners of Western medicine. However, the advent of AIDS has thrust this organism into the forefront of infectious disease research. In its classic form, Bartonellosis or Oroyo Fever, is an acute, often fatal human disease characterized by high fevers and progressive anemia with a case-fatality rate of from 10 to 90%.

Bartonella is named after the Peruvian bacteriologist, Alberto Barton, who in 1909, noted organisms in red blood cells (RBC’s) of patients suffering from Oroya fever. It has been known by several names (see outline below) depending upon which epidemic site the disease arose from (Oroya, Peru, Guáitira, Colombia). Daniel Alcides Carrión, was a medical student in Peru, who sacrificed his life to prove that inoculation with lesions of Verruga peruana caused the disease.

Bartonellosis refers to the infection caused by B. bacilliformis. After the bite of an infected sand fly, acute disease usually occurs after 16 to 22 days, with the incubation period ranging up to 3-4 months. Acute disease is characterized by fever, headache, musculoskeletal pain, and enlargement of lymph nodes. A progressive anemia develops due to the attachment by B. bacilliformis organisms and their destruction of up to 90% of red blood cells. Secondary superinfections due protozoan and Salmonella are common. Recovery may be complete, but may lead to a carrier state, or development of Verruga peruana.

Verruga peruana is a chronic manifestation of bartonellosis that may be preceded by Oroya fever or develop without previous acute illness. Prior to the onset of dermatological lesions, victims may experience irregular bouts of musculoskeletal pain. Skin lesions appear on the face and extremities and may be either a multiple, discrete reddish lesions or larger, cherry-pink grape-like nodules that may develop within the mouth, esophagus, and linings of the gastrointestinal tract, urinary bladder, uterus and vagina. One complication of these internal lesions is internal bleeding. The largest nodular lesions which may measure up to 4 cm may develop on the knees and elbows. They are highly vascularized and may rupture, bleed or ulcerate, eventually sloughing off.

Neurobartonellosis, is recognized during the acute stage, and is due to invasion of central nervous system (CNS) by the bacteria that cause meningoencephalitis leading to seizures, spastic and flaccid paralysis and death.

Bacillary angiomatosis and cat-scratch disease are two diseases that have also been linked to Bartonella infection. However, the arrival of HIV infection and AIDS has thrust these diseases to the forefront of many infectious disease research. Bacillary angiomatosis was first reported in 1983, described in a patient with advanced HIV disease who developed disseminated subcutaneous nodules that resolved completely aftertreatment with erythromycin. The clinical appearance of cutaneous lesions of three additional patients resembled Kaposi's sarcoma. However, both the histologic and electron microscopic examination of the lesions revealed small, gram-negative rods interspersed among proliferating endothelial cells. In 1987, a report described five HIV-seropositive patients with cutaneous vascular neoplasms that were called epithelioid angiomatosis. The lesions were papular, nodular, or polypoid; numbered few or in the hundreds; and were often mistaken for KS. Two of the patients died due to widespread dissemination of these lesions. In 1988, four additional HIV-infected patients with vascular lesions were described. When many of these vascular lesions were later discovered to contain numerous bacilli, the disease became known as bacillary angiomatosis, to reflect both the infectious and vascular proliferative nature of the disease.

Cat-scratch disease is closely related to bacillary angiomatosis. It is also caused by Bartonella henselae and is a benign and self-limited illness lasting 6 to 12 weeks in the absence of antibiotic therapy. Regional tender lymphadenopathy (axillary, head and neck, inguinal) which is occasionally pustular, is the predominant clinical feature of CSD. A careful history and physical examination may reveal a primary cutaneous inoculation lesion (0.5- to 1-cm papule or pustule) at the site of a cat scratch or bite. This may be elicited in 25% and 60% of patients. The skin lesions typically develop 3 to 10 days after injury and precede the onset of lymphadenopathy by 1 to 2 weeks. Low-grade fever and malaise accompany lymphadenopathy in up to 50% of patients. In addition constitutional symptoms such as headache, anorexia, weight loss, nausea and vomiting along with sore throat, and splenomegaly may develop. In addition, short-lived, non-specific maculopapular eruptions, erythema nodosum, figurate erythemas, and thrombocytopenic purpura have been observed.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS-Bartonellosis	Oroya fever Guáitira Fever Verruga peruana Carrión’s disease
SYNONYMS-Bacillary angiomatosis	Epithelioid angiomatosis
INCIDENCE	5-10% of individuals living in endemic zones have these bacteria in their circulating blood Nodules of recovering victims may be the source of continuing transmission by sand flies
GEOGRAPHY	2,000 and 9,200 feet in the Andes Mountains of Peru, Ecuador and Colombia Recent outbreaks have now documented a more extensive distribution by longitude, latitude and altitude
EPIDEMIOLOGIC ASSOCIATIONS	CHARACTERIZATION
Bartonellosis is considered a unique disease of humans, transmitted from human to human by the bite of a vector, a blood-sucking insect, a sand fly.	Invertebrate and vertebrate reservoir hosts have not been demonstrated New Bartonella species have been discovered which infect a variety of warm blooded (dogs, rodents) and cold blooded (reptiles, amphibians) vertebrates.
Bartonelosis (Carrion's Disease) in the pediatric population of Peru: an overview and update. Huarcaya E, Maguina C, Torres R, Rupay J, Fuentes L. Alexander von Humboldt Tropical Medical Institute, Cayetano Heredia University of Peru, Lima, Peru.	Braz J Infect Dis. 2004 Oct;8(5):331-9. Epub 2005 Mar 17. Abstract quote   Bartonellosis, or Carrion's Disease, is an endemic and reemerging disease in Peru and Ecuador. Carrion's Disease constitutes a health problem in Peru because its epidemiology has been changing, and it is affecting new areas between the highland and the jungle. During the latest outbreaks, and previously in endemic areas, the pediatric population has been the most commonly affected. In the pediatric population, the acute phase symptoms are fever, anorexia, malaise, nausea and/or vomiting. The main signs are pallor, hepatomegaly, lymphadenopathies, cardiac murmur, and jaundice. Arthralgias and weight loss have also commonly been described. The morbidity and mortality of the acute phase is variable, and it is due mainly to superimposed infections or associated respiratory, cardiovascular, neurological or gastrointestinal complications. The eruptive phase, also known as Peruvian Wart, is characterized by eruptive nodes (which commonly bleed) and arthralgias. The mortality of the eruptive phase is currently extremely low. The diagnosis is still based on blood culture and direct observation of the bacilli in a blood smear. In the chronic phase, the diagnosis is based on biopsy or serologic assays. There are nationally standardized treatments for the acute phase, which consist of ciprofloxacin, and alternatively chloramphenicol plus penicillin G. However, most of the treatments are based on evidence from reported cases. During the eruptive phase the recommended treatment is rifampin, and alternatively, azithromycin or erythromycin.

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
High seroprevalence to Bartonella quintana in homeless patients with cutaneous parasitic infestations in downtown Paris	J Am Acad Dermatol 2001;44:219-23 Prospectively studied the prevalence of and the factors associated with a positive serology to B quintana in the homeless population of downtown Paris The following data were recorded: ongoing cutaneous parasitic infestation, years of homelessness, living status, previous episodes of body pediculosis and scabies, alcoholism, intravenous drug use, known immunodepression (including undernutrition and known HIV infection), and contacts with animals. B quintana serology was performed in 57 patients and in 53 age- and sex-frequency-matched downtown Paris volunteer blood donors Thirty-one patients (54%; 95% confidence interval [CI], 41%-68%) had a positive B quintana serology as compared with 2% in the control group (P < .0001) 8 of 57 patients (14%; 95% CI: 6%-26%) had a serologic profile of an evolving infection Age and years of homelessness were independently associated with a positive B quintana serology with adjusted relative risks (RRs) of 2.9 (95% CI, 1.4-5.9) for age 40 years and older and 1.7 (95% CI, 1.1-2.7) for years of homelessness 3 or more Suggest a high prevalence of past and recent infections with B quintana in the downtown Paris homeless population with cutaneous parasitic infestations
	N Engl J Med 1995;332:419-23 N Engl J Med 1995;332:424-8 J Infect Dis 1996;173:1023-6. B quintana endocarditis and bacteremia have been reported in homeless patients living in downtown Seattle and Marseille and a serologic retrospective study has found antibodies to B quintana in 25% of the homeless population of Seattle compared with only 2% of the control group

 

PATHOGENESIS	CHARACTERIZATION
Gram negative rod	There is a close relationshiop between Bartonella organism and Rochalimaea quintana, the agent of trench fever Originally named Rochalimaea henselae in 1992 but became Bartonella henselae when the entire genus of Rochalimaea was merged with the genus of Bartonella in 1993 Gram negative bacillary organism measuring 2 X 0.5mm Giemsa stain shows both rods and in chains of rods Electron microscopy shows a flagella
B. henselae
B. quintana
B. bacilliformis
B. elizabethae
Old World	Old World (family Psychodidae, genus Phlebotimae) sand flies transmit various diseases in Europe, Asia, and Africa
New World	New World sand flies (Lutzomyia and Brumptomyia) transmit various diseases in North, Central and South America and the Caribbean Islands
Sand Fly Lifecycle	Its life cycle consist of four stages (egg, larva, pupa, adult) with an egg-to-egg cycle of seven to ten weeks Breeding places vary widely depending on genus and species, and include underneath stones, in masonry cracks, beneath leaves, in animal burrows, and under natural and man-made structures (tree stumps, buildings, etc) -- all of which provide darkness, humidity and organic matter for larvae to develop (20). Microenvironment for egg and larva development require 100% humidity. Adults measure 1.5-4 mm and are considered weak fliers. Feeding activity is restricted to dusk, at night and dawn, presumably due to less wind currents Only adult females take blood meals from a variety of warm and cold-blooded animals. Frequency of re-feeding habits of females determines, in part, likelihood of disease transmission.
Bacillary angiomatosis and Cat-scratch disease	JAMA. 1993 Feb 10;269(6):770-5. Significant epidemiologic association with traumatic cat exposure (cat bite or cat scratch) B. henselae has been isolated from a domestic cat and was isolated from the blood of all seven cats belonging to four patients with BA due to B. henselae. Thus, pet cats are a major reservoir for B. henselae and probably also the principle vector of B. henselae to humans, because most patients presenting with CSD still have a visible infected scratch The cat flea readily transmits B. henselae between cats, and thus the potential exists for flea-borne transmission of B. henselae to humans Another possible arthropod vector of Bartonella species is the ticks, where tick bites preceded diagnosis of B. henselae bacteremia in two patients

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
CULTURES
Culture of blood to recover B. henselae	NOTE: Not all patients with bacillary angiomatosis or peliosis hepatis are bacteremic Optimally isolated from blood using the lysis-centrifugation tubes and plating onto fresh chocolate or heart infusion agar with 5% rabbit blood, without antibiotics. B. henselae also has been isolated from blood collected in tubes containing EDTA and subsequently stored frozen The degree of bacteremia reported for Bartonella varies from 0.7 to greater than 1,000 colony-forming units per milliliter of blood Plates inoculated with blood should be incubated at 35°C for at least 3 weeks in 5% CO2 and high humidity until colonies appear, usually after 5 to 15 days Colonies are rough, cauliflower-like, and usually deeply embedded in the agar The bacilli are small (2 mm x 0.5 mm) and stain best with Gimenez stain with gram-staining, Bartonella species are only weakly counterstained with safranin
B. quintana colonies	B. quintana colonies are smooth, flat, and shiny and do not pit the agar
PCR AMPLIFICATION
Rapid polymerase chain reaction-based confirmation of cat scratch disease and Bartonella henselae infection. Margolis B, Kuzu I, Herrmann M, Raible MD, Hsi E, Alkan S. Department of Pathology, Loyola University Medical Center, Maywood, Ill 60153, USA.	Arch Pathol Lab Med 2003 Jun;127(6):706-10 Abstract quote CONTEXT: Cat scratch disease (CSD) commonly occurs secondary to Bartonella henselae infection, and the diagnosis has traditionally been made by microscopic findings, the identification of organisms by cytochemistry, and clinical history. However, cytochemical analysis tends to be very difficult to interpret, and histology alone may be insufficient to establish a definitive diagnosis of CSD. OBJECTIVE: To demonstrate the presence of B henselae in tissue suspected of involvement by CSD, using a novel polymerase chain reaction (PCR) assay. DESIGN: Isolates of B henselae (American Tissue Culture Collection 49793) and Afipia felis (American Tissue Culture Collection 49714) were cultured on blood agar and buffered charcoal yeast extract agar, respectively. DNA was isolated from these organisms and from formalin-fixed, paraffin-embedded tissue sections with involvement by CSD (8 patients). Negative controls included water, human placental tissue, and lymph node specimens from 6 patients with reactive lymphoid hyperplasia and from 2 patients with granulomatous lymphadenitis. A primer complementary to B henselae citrate synthase gltA gene sequence was designed to perform a seminested PCR amplification. For restriction fragment length polymorphism analysis, PCR products were digested by TaqI restriction enzyme and analyzed by gel electrophoresis. RESULTS: Seminested PCR analysis of the cultured isolates of B henselae, but not of A felis, showed specific amplification. However, nonnested PCR did not provide consistently positive results in tissue sections with CSD. Therefore, we used a seminested PCR, which revealed positivity in all of the cases with clinicopathologic diagnoses of CSD. None of the negative controls showed positivity. Restriction enzyme provided confirmation of the specific PCR amplification of the B henselae sequence. CONCLUSIONS: Since the amplification product has a low molecular size (<200 base pairs), this assay is useful for detection of B henselae in formalin-fixed, paraffin-embedded tissues. The seminested PCR protocol described here can be used for rapid and reliable confirmation of B henselae in samples that are histologically suggestive of CSD.
DNA Amplification for the Diagnosis of Cat-Scratch Disease in Small-Quantity Clinical Specimens Boaz Avidor, PhD, Merav Varon, BsC, Sylvia Marmor, MD, Beatriz Lifschitz-Mercer, MD, Yehudith Kletter, PhD, Moshe Ephros, MD, and Michael Giladi, MD	Am J Clin Pathol 2001;115:900-909 Abstract quote Diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) of lymph node fine-needle aspiration (FNA) and primary lesion specimens can be difficult owing to the minute amount of available material. A PCR assay specifically suited to test these specimens was developed. First, small-quantity (10 µL) samples were prepared from 17 CSD-positive and 16 CSD-negative specimens, and DNA extraction and amplification from these samples were compared using 3 methods. Sensitivity and specificity of PCR were 100% using material collected on glass microscope slides and by using Qiagen (Hilden, Germany) columns for DNA extraction. Then, this method was used to test 11 archival glass microscope slides of FNA (7 malignant neoplasms, 4 undiagnosed lymphadenitis) and 2 primary lesion specimens. Two of the 4 lymphadenitis samples and the 2 primary lesion specimens were PCR positive. The technique presented could facilitate CSD diagnosis from a wider range of clinical samples.
SEROLOGY
Widening of the clinical spectrum of Bartonella henselae infection as recognized through serodiagnostics. Massei F, Messina F, Talini I, Massimetti M, Palla G, Macchia P, Maggiore G. Dipartimento di Medicina della Procreazione e della Eta Evolutiva, Universita di Pisa, Italy	Eur J Pediatr 2000 Jun;159(6):416-9 Abstract quote The recently improved diagnostics have widened, in children, the spectrum of clinical manifestations recognisable as Bartonella henselae infection. We report here the clinical features of 20 (14 males) consecutive children with serologically proved B. henselae infection observed within 12 months in the Paediatric Department of the University of Pisa. The patients had a mean age of 7 years 4 months (range 1.1-14.1 years). All children but one had a history of contact with kittens. Clinical manifestations included regional lymphadenopathy in 14 patients, representing in five the only clinical manifestation at onset, infectious mononucleosis-like syndrome in six, erythema nodosum in three, and Parinaud oculoglandular syndrome in one. In five patients a severe disorder was first suspected: fever of unknown origin in two with multiple hepatosplenic granulomatosis in one; osteolytic lesion suggesting bone neoplasm, marked inguinal lymph-node enlargement, suggesting Burkitt lymphoma, and an acute encephalopathy in one each. Bartonella henselae IgG antibody was positive in all patients with a titre ranging from 1:128 to 1:8590. IgM antibody was present in all except one child with an IgG titre of 1:2048. All patients recovered, some spontaneously. CONCLUSION: Bartonella henselae infection is frequent in Tuscany and probably underdiagnosed due to the high frequency of atypical onset of the clinical manifestations. An accurate clinical history and a reasonably wide use of the serological test may allow a rapid and accurate diagnosis, reassuring the family of the patient and avoiding invasive and expensive diagnostic procedures.

 

GROSS APPEARANCE/CLINICAL VARIANTS	CHARACTERIZATION
VARIANTS OF CAT-SCRATCH DISEASE	Occur in up to 14% of patients
Perinaud's oculoglandular syndrome (6%)	Manifested by conjunctival granuloma, periauricular lymphadenopathy, and nonsuppurative conjunctivitis
Encephalopathy (2%),	Fever and coma that progress to convulsions, may last for days to weeks Cerebrospinal fluid is unremarkable Optic neuritis with transient blindness may also occur
Hepatic granulomas (0.3%)
Osteomyelitis (0.3%)
Pulmonary disease (0.2%)
ADDITIONAL CLINICAL VARIANTS
BACTEREMIA
Chronic paucisymptomatic bacteremia
BONE
Osteomyelitis
CNS
Myelitis
HEART
Endocarditis	Am J Clin Pathol 2000;114:880-889
LIVER
Granulomatous hepatitis
Peliosis hepatis
Chronic Active Myocarditis Following Acute Bartonella henselae Infection (Cat Scratch Disease) Glenn R. Meininger, M.D.; Tibor Nadasdy, M.D.; Ralph H. Hruban, M.D.; Robert C. Bollinger, M.D.; Kenneth L. Baughman, M.D.; Joshua M. Hare, M.D. From the Departments of Medicine, Division of Cardiology (G.R.M., K.L.B., J.M.H.), Division of Infectious Diseases (R.C.B.), and the Department of Pathology (T.N., R.H.H.), Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.	Am J Surg Pathol 2001;25:1211-1214 Abstract quote An association between Bartonella infection and myocardial inflammation has not been previously reported. We document a case of a healthy young man who developed chronic active myocarditis after infection with Bartonella henselae (cat scratch disease). He progressed to severe heart failure and underwent orthotopic heart transplantation. Bartonella henselae, therefore, should be included among the list of infectious agents associated with chronic active myocarditis.
LYMPH NODE
Chronic lymphadenopathy

 

HISTOLOGICAL TYPES	CHARACTERIZATION
BACILLARY ANGIOMATOSIS
Bacillary Angiomatosis Associated With Pseudoepitheliomatous Hyperplasia. Amsbaugh S, Huiras E, Wang NS, Wever A, Warren S. From the *University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and daggerMedical College of Wisconsin, Milwaukee, Wisconsin.	Am J Dermatopathol. 2006 Feb;28(1):32-35. Abstract quote   Bacillary angiomatosis is an opportunistic bacterial infection caused by either Bartonella henselae or B. quintana. The classic histologic presentation of bacillary angiomatosis involves three components: a lobular proliferation of capillaries with enlarged endothelial cells, neutrophilic debris, and clumps of finely granular material identified as bacteria with staining techniques. Pseudoepitheliomatous hyperplasia is a histologic reaction pattern characterized by epithelial proliferation in response to a variety of stimuli, including mycobacterial, fungal, and bacterial infections. We describe a case of bacillary angiomatosis associated with pseudoepitheliomatous hyperplasia in an immunocompromised patient with Acquired Immunodeficiency Syndrome. Histologic examination of a finger lesion demonstrated a capillary proliferation with neutrophilic debris and characteristic amorphous granular deposits. Warthin-Starry and Giemsa staining revealed clumps of coccobacilli. Cervical lymph node tissue also revealed organisms identified as Bartonella with PCR techniques. Stains and cultures for acid fast bacilli, fungus, and bacteria were negative. To our knowledge, there has been only one other report of bacillary angiomatosis presenting with pseudoepitheliomatous hyperplasia. We conclude that the differential diagnosis of entities associated with pseudoepitheliomatous hyperplasia should be expanded to include bacillary angiomatosis.
	Lobular proliferation of small, capillary-sized blood vessels with protuberant, cuboidal, or polygonal endothelial cells containing abundant cytoplasm, with or without cytologic atypia A mixed inflammatory infiltrate, including lymphocytes and neutrophils with leukocytoclasis and areas of focal necrosis, is often present Granular, fibrillary amphophilic material, revealing bacilli on silver staining or electron microscopy may be scattered throughout myxoid connective tissue, typically in close proximity to vascular lumina surrounded by neutrophilic aggregates Lymph node, bone, and brain BA lesions may demonstrate a less lobular pattern than cutaneous BA and have a less prominent neutrophilic infiltrate Liver or spleen show a spectrum ranging from dilated capillaries to multiple dilated, thin-walled, blood-filled peliotic spaces with surrounding myxoid stroma and parenchymal cells-Stromal areas contain a mixture of inflammatory cells and clumps of granular amphophilic material representing well-visualized bacillary organisms on silver staining and electron microscopy
CAT SCRATCH DISEASE	Palisading necrobiotic granuloma formation with small areas of frank necrosis surrounded by concentric layers of histiocytes, lymphocytes, and nucleated giant cells
VERRUGA PERUANA	Am J Dermatopathol 1987;9:279-291 Epidermal hyperplasia
Verruga peruana mimicking malignant neoplasms. Arias-Stella J, Lieberman PH, Garcia-Caceres U, Erlandson RA, Kruger H, Arias-Stella J Jr.	Am J Dermatopathol. 1987 Aug;9(4):279-91. Abstract quote     We have shown that in some cases fully developed florid verruga peruana nodules, as well as late-resolving, deeply situated lesions, can histologically suggest a variety of tumors to experienced pathologists. The compact proliferation of endothelial cells characteristic of florid verruga lesions can give rise to two pseudoneoplastic histologic patterns. One consists of sheets or islands of cells arranged in an epithelioid or pseudoepithelioid pattern (cases 1 and 2) in which the following histologic diagnoses were considered: squamous carcinoma, sweat gland carcinoma, epithelioid hemangioendothelioma, epithelioid sarcoma, melanoma and metastatic carcinoma. The other pattern of the florid lesion is characterized by a predominantly spindle cell arrangement (case 3) and in it the following diagnoses were made: Kaposi's sarcoma, fibrosarcoma, melanoma and leiomyosarcoma. The dense lymphoplasmacytic and histiocytic infiltrates of the late-resolving, deeply situated nodules (case 4) suggested the following histologic conditions: malignant lymphoma, nodular Hodgkin's disease, reticuloendotheliosis, and reticulosarcomatosis. Some histologic features thought to be of value to help in the differential diagnoses are discussed. It is emphasized that only the finding of Rocha-Lima's inclusions on light-microscopic studies and/or the demonstration of bartonella organisms in the lesions by electron-microscopic studies can objectively establish a diagnosis in a given lesion. However, knowledge of the epidemiologic data and particularly the presence of other lesions in the patient make it relatively easy to rule out neoplasia.
Histology, immunohistochemistry, and ultrastructure of the verruga in Carrion's disease. Arias-Stella J, Lieberman PH, Erlandson RA, Arias-Stella J Jr.	Am J Surg Pathol. 1986 Sep;10(9):595-610. Abstract quote   Twenty-six verruga peruana nodules were studied. The presence of Factor VIII-related antigen and Ulex europaeus lectin binding, and the ultrastructural finding of rudimentary cell junctions and pinocytotic vesicles establish the endothelial character of the proliferating cells in the verruga nodules. Whereas superficial lesions could show an angiomatoid pattern, deep-situated nodules tended to present a compact type of growth. Electron-microscopic studies have shown that Bartonella bacilliformis was found abundantly in the extracellular spaces in the florid lesions and that no organisms were present in the late, resolving subcutaneous nodules. Although no true intracellular "viable" microorganisms were noted, pseudopods of cytoplasm entrapping one or two bacteria and surrounding matrix substance were seen often. The characteristics of cytoplasmic inclusions previously described in verruga cells as "chlamydozoa" were detailed. The ultrastructure of the inclusions corresponded to endothelial phagocytic cells in which complex invaginations of the cell surface had produced a labyrinth of interconnected channels and vacuoles containing degraded bacteria, extracellular matrix components, or both. We conclude that in light microscopy the finding of Rocha-Lima's inclusions is the only definite morphologic evidence of the presence of bartonella in verruga lesions.
ADDITIONAL VARIANTS
ENDOCARDITIS
Bartonella Endocarditis	Am J Clin Pathol 2000;114:880-889 Cardiac valve pathology was evaluated in 15 patients 10 infected with B. quintana and 5 infected with B. henselae In comparison with other causes of infective endocarditis, these cases are more fibrotic and calcified, less vascularized, with less extensive vegetation and chronic inflammation
SKIN
Granuloma Annulare Another Manifestation of Bartonella Infection? Bruce R. Smoller, M.D.; Kunapali T. Madhusudhan, Ph.D.; Margie A. Scott, M.D.; Thomas D. Horn, M.D. From the Departments of Pathology (B.R.S., K.T.M., M.A.S.) and Dermatology (B.R.S., T.D.H.), University of Arkansas for Medical Sciences, Little Rock, Arkansas.	Am J Dermatopathol 2001;23:510-513 Abstract quote Granuloma annulare (GA) is a common cutaneous eruption whose pathogenesis remains unknown. Recent literature has suggested a relation between Borrelia infection and GA, a relation that has not been widely accepted. Earlier works attempted unsuccessfully to implicate various other infectious agents. Some reports have demonstrated the increased frequency of GA in patients with human immunodeficiency virus infection, again raising the possibility of an infectious etiology. Using polymerase chain reaction amplification, we examined 19 biopsy specimens from 19 patients with GA (14 with classic palisading GA and 5 with an interstitial pattern) for the presence of a 153–base pair sequence specific for Bartonella henselae or Bartonella quintana. None of our patients were known to be human immunodeficiency virus–positive. These primers failed to detect B. henselae and B. quintana DNA in any of the specimens examined. Our findings do not support the hypothesis that GA represents a granulomatous reaction pattern to cutaneous Bartonella infection. Nevertheless, we cannot exclude the possibility that there may be a relation in other geographic locations or in immunocompromised patients or that GA represents an autosensitization reaction in response to a distant site of infection. Additional studies are needed to address these hypotheses.

 

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
Special stains	Warthin-Starry stain positive Organism in extracellular location
Immunoperoxidase	Polyclonal and monoclonal antibodies against the bacteria are available
Electron microscopy (EM)	On electron microscopy these bacilli possess a trilaminar cell wall and contain electron-dense granular material

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Angiosarcoma
HEMANGIOMA
Kaposi's sarcoma

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Clin Infect Dis. 1995 Aug;21 Suppl 1:S94-8. HIV-infected patients should avoid rough play that may lead to cat scratches, wash any scratches immediately, control flea infestation, and, if a new cat is brought into the home, a mature cat rather than a kitten is preferred
Survival
Recurrence	Most often reported when a shorter course, usually only a few weeks, of antibiotic therapy was administered
TREATMENT
Bacillary angiomatosis and peliosis hepatis	B. quintana and B. henselae are usually susceptible in vitro to erythromycin, doxycycline, and tetracycline Erythromycin is usually administered orally (500 mg four times a day) but should be administered intravenously to patients with severe disease or who are unable to tolerate oral medication Oral doxycycline Minocycline After the first several doses of an appropriate antibiotic, the patient may experience a Jarisch-Herxheimer-like reaction, with exacerbation of systemic symptoms and fever-pretreatment with an antipyretic may attenuate this response

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