eMedicine Specialties > Infectious Diseases > Bacterial Infections

Bartonellosis: Differential Diagnoses & Workup

Author: Kassem A Hammoud, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, University of Kansas Medical Center
Coauthor(s): Daniel Hinthorn, MD, Director, Division of Infectious Diseases, Professor, Departments of Internal Medicine, Pediatrics and Family Medicine, University of Kansas; Brian Edwards, MD, Consulting Staff, Department of Infectious Diseases, Cotton O'Neil Clinic
Contributor Information and Disclosures

Updated: Oct 13, 2008

Differential Diagnoses

Bacillary Angiomatosis
Catscratch Disease

Other Problems to Be Considered

Catscratch disease: Consider other causes of enlarged lymph nodes, such as localized infections with regional node swelling and systemic diseases. Examples include lymphoma, leukemia, other neoplasms, fungal infection, tularemia, tuberculosis, plague, lymphogranuloma venereum (LGV), AIDS, and syphilis.

Bacteremia and systemic illnesses: Culture-negative endocarditis is always difficult to diagnose. Consider this diagnosis when the Duke criteria for endocarditis are present with negative findings on routine blood cultures. If bartonellosis is suspected, obtain antibody titers for B henselae and B quintana. Other causes of culture-negative endocarditis that merit consideration include legionellosis, Q fever, HACEK group infections (Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae), and fastidious or slowly growing streptococci.

Bacillary angiomatosis: These lesions are often dark purple and resemble Kaposi sarcoma, pyogenic granuloma, or verruga peruana.

Oroya fever and verruga peruana: Febrile patients who have returned from travel to a developing country mandate consideration of a rather large number of possible illnesses depending on the itinerary, activities, and potential for exposures. Serious illnesses to consider include Dengue fever, malaria, tuberculosis, and babesiosis.

Workup

Laboratory Studies

  • Stains
    • Microscopic examination of Giemsa-stained blood smears is used to detect B bacilliformis in patients who may have Oroya fever.
    • Organisms are rod-shaped and slightly curved, similar to Campylobacter or Helicobacter species.
    • B bacilliformis organisms often appear to be adherent to erythrocytes, but they may actually be inside erythrocytes.
    • Other Bartonella species are visible only with silver stains (eg, Warthin-Starry, Steiner, Dieterle), if they stain at all. Bacillary forms also exist.
    • Immunostaining can also aid in the diagnosis of early lesions or atypical manifestations of catscratch disease.
    • Late in the course of B henselae infection, organisms may not be found in areas of necrotizing granulomas.
  • Cultures
    • Culture for Bartonella bacteria is not recommended for routine cases of patients with catscratch disease lymphadenopathy.
    • Cultures may be useful in patients who have other manifestations of either B henselae or B quintana infection, including fever of unknown origin, neuroretinitis, encephalitis, culture-negative endocarditis, and peliosis or bacillary angiomatosis. Fresh media is required to increase the chance of isolation.
    • A recent study suggests a novel chemically modified liquid medium that supports the growth of 7 Bartonella species.21
    • The lysis-centrifugation system (Isolator) is recommended for blood cultures.
    • Minced tissues may be cultured on chocolate agar plates in a humid atmosphere with carbon dioxide to facilitate growth.
    • Antibiotic susceptibility is not routinely tested in patients with bartonellosis because susceptibility studies may fail to predict response to therapy.
  • Serologic testing
    • Serologic testing is the most cost-effective method to confirm the diagnosis in most patients with bartonellosis; however, serologic testing can provide negative results or can be otherwise nondiagnostic in immunocompromised patients.
    • For catscratch disease and CNS or eye infections, serologic testing provides helpful data. Cross-reactions occur between antibodies for B henselae and B quintana and with both Chlamydia species and Coxiella burnetii.22
    • Recent studies have shown that Western immunoblotting appears to have very high sensitivity and specificity for diagnosing Bartonella endocarditis.8
    • An IgM titer of 1:16 or greater is usually considered evidence for early recent Bartonella infection. IgM levels may stay elevated for about 3 months in 50% of patients.
    • An IgG titer of greater than 1:256 is considered evidence of current or past Bartonella infection. Titers of 1:64 to 1:128 are considered equivocal. A titer of 1:800 or more for IgG antibodies to either B henselae or B quintana has a positive predictive value of 0.810 for the detection of chronic bartonellosis in the general population and a value of 0.955 for the detection of bartonellosis among patients with endocarditis.23
    • Patients with delayed decreases in antibody titers may be at risk for endocarditis relapse. When clinical suspicion is high, titers should be repeated in 10-14 days for comparison.
    • Evidence shows that some patients never mount a detectable antibody response. The serology results of some patients remain positive long after exposure and recovery from their illness.
  • Polymerase chain reaction
    • PCR is a molecular technique that involves amplification of Bartonella species genes.
    • PCR-based detection of various target genes of Bartonella species in tissue specimens is widely accepted in diagnosing catscratch disease and bacillary angiomatosis, but the results rely heavily on the quality of the laboratory in which the assays are conducted.
    • In cases of suspected Bartonella endocarditis, PCR on cardiac valve tissue is very sensitive and is not affected by antibiotics treatment prior to surgery.
    • Because of the cross-reactivity between Bartonella species and other bacteria, PCR analysis of tissue and body fluid is the most specific test, especially in identifying distinct genotypes among Bartonella species.
    • PCR has played an important role in the diagnosis of Bartonella endocarditis. This test amplifies a 296–base-pair fragment of the 16S ribosomal RNA. Investigators reported PCR results that were positive for Bartonella on cardiac valve tissue in more than 95% of patients with Bartonella endocarditis in one study, despite the fact that more than 60% of these patients underwent valve analyzation following the receipt of antibiotics.

Imaging Studies

  • CT scanning of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.
  • CT scanning or ultrasonography of the abdomen can demonstrate multiple hypodense lesions in the liver and/or spleen in patients with catscratch disease
  • In patients with bacillary angiomatosis/peliosis, CT scanning or MRI of the involved organ shows the enhancing lesions (eg, brain, liver). Radiography of the bone may show osteolytic lesions and bone destruction.
  • According to some reports, patients with catscratch disease may require echocardiography to assess for valvular lesions. Patients with valvulopathy and catscratch disease are at risk for Bartonella endocarditis.

Other Tests

  • The catscratch disease skin test is helpful. However, this test may transmit other infectious agents, as it is derived from human pus.
  • Silver stains and PCR can be performed on pus collected from a node via fine-needle aspiration, sparing the patient a surgical biopsy.

Histologic Findings

Catscratch disease: Lymph node biopsy demonstrates granulomas with stellate necrosis, which are characteristic of catscratch disease. Silver stains, such as Dieterle or Warthin-Starry, may show bacilli.

Bacillary angiomatosis and peliosis hepatitis: Both of these disorders show blood vessel proliferation. Bacillary angiomatosis refers to vascular tumors that readily bleed when cut. The microscopic appearance of neovascular proliferation is diagnostic. Silver stains may demonstrate clusters of Bartonella bacilli. Peliosis refers to blood-filled cystic lesions that may be microscopic or up to a few millimeters in diameter. These lesions are characteristically found in the liver but are occasionally found in the spleen. Bacilli may be visible on electron microscopy.

More on Bartonellosis

Overview: Bartonellosis
Differential Diagnoses & Workup: Bartonellosis
Treatment & Medication: Bartonellosis
Follow-up: Bartonellosis
References
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Further Reading

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Keywords

bartonellosis, Bartonella infection, catscratch disease, cat scratch disease, CSD, catscratch fever, cat scratch fever, trench fever, urban trench fever, bacillary angiomatosis, bacillary peliosis, peliosis hepatis, Parinaud oculoglandular syndrome, Parinaud's oculoglandular syndrome, Oroya fever, Carrión disease, Carrión’s disease, verruga peruana, Bartonella bacilliformis, B bacilliformis, Bartonella henselae, B henselae, Bartonella quintana, B quintana, Bartonella vinsonii, B vinsonii, Bartonella clarridgeiae, B clarridgeiae, Bartonella elizabethae, B elizabethae, Bartonella tamiae, B tamiae, Bartonella rochalimae, B rochalimae, Bartonella alsatica, B alsatica, Pediculus humanus, P humanus, Phlebotomus, Lutzomyia, Ctenocephalides felis, C felis, Bartonella endocarditis, Peruvian wart

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Contributor Information and Disclosures

Author

Kassem A Hammoud, MD, Fellow, Department of Internal Medicine, Division of Infectious Diseases, University of Kansas Medical Center
Kassem A Hammoud, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Daniel Hinthorn, MD, Director, Division of Infectious Diseases, Professor, Departments of Internal Medicine, Pediatrics and Family Medicine, University of Kansas
Daniel Hinthorn, MD is a member of the following medical societies: American Academy of Family Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Brian Edwards, MD, Consulting Staff, Department of Infectious Diseases, Cotton O'Neil Clinic
Disclosure: Nothing to disclose.

Medical Editor

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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