Boutonneuse Fever Workup

Updated: Mar 11, 2016
  • Author: Jason F Okulicz, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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Approach Considerations

Boutonneuse fever (BF), also known as Mediterranean spotted fever (MSF), is diagnosed primarily on the basis of clinical symptoms and epidemiologic data, along with laboratory evidence of recent exposure to rickettsial organisms. Both culture techniques and serologic tests are used to confirm the diagnosis. Currently, indirect immunofluorescence (IIF) is the most commonly used confirmatory test.

A magnetic resonance study can demonstrate multifocal white matter disturbances if the central nervous system is involved.

Characteristic histopathologic findings at the site of the primary lesion consist of epidermal ulceration, hyperplasia of the endothelium of the small dermal antinodes, and perivascular infiltrates in the dermis.


Laboratory Studies

Basic laboratory tests for BF include the following:

  • Complete blood count (CBC) with differential - Normochromic anemia; leukopenia and lymphopenia; thrombocytopenia (35% of patients)

  • Liver function tests - Increased liver enzymes (60.5-64.8% of patients)

  • Creatinine - Increased levels (29.7% of patients)

  • Urinalysis - Hematuria (35.9% of patients); proteinuria (56.4% of patients)

  • Fibrinogen - Increased levels during acute phase

  • Fibronectin - Decreased levels during acute phase

Culture of the organism may be considered the reference standard for diagnosis; however, it is rarely performed during the acute phase of the disease, and it cannot be performed retrospectively unless samples were appropriately collected and stored (at −70°C).

Serologic testing is commonly employed for confirmation of the diagnosis however, these tests are useful only after an acute infection because antibodies can be detected late (even >30 days after the onset of symptoms).

On IIF, the antibody titer in serum is increased only 2 weeks after the infection and reaches its peak level after 4 weeks. Afterward, the immunoglobulin M (IgM) level decreases and the immunoglobulin G (IgG) level remains high for several months. Titers of 1:64 or greater are diagnostic. [22]

With the Weil-Felix reaction (agglutination type), the result can become positive 40 days after the symptoms started, with OX19, OX2, and OXK strains of Proteus vulgaris antigens. This test is still used in clinical practice because of its convenience, but it has low sensitivity and specificity.

When R conorii is isolated by means of the centrifugation-shell vials technique, the result can become positive 14 days after inoculation. Results can be obtained within 2-3 days after receipt of the sample.

IIF of R conorii in circulating endothelial cells (CEC) isolated from whole blood can be performed by using immunomagnetic beads. This test is sensitive; 50% of results are positive. Results can be obtained in 3 hours. The initiation of the therapy has no influence on the results. This test can be used in all routine laboratories.

Enzyme-linked immunosorbent assay (ELISA) techniques were developed to detect antibodies to lipopolysaccharide (LPS) of R conorii. ELISA is a relatively simple and convenient way of serodiagnosing BF with a single serum dilution. It can be of use in laboratories that lack more sophisticated equipment (such as that needed for IIF).

Polymerase chain reaction (PCR) is not routinely used or universally available. Ergas et al reported early diagnosis using nested PCR. [23] Either PCR or Western blot studies can be used to differentiate R conorii from Rickettsia africae. Species isolation should be considered in patients with unusual presentations, including severe disease, and those traveling from areas with poorly defined rickettsial activity. [24]

Direct immunofluorescence of cutaneous biopsy specimens is diagnostic only during the acute phase of the disease. It reveals endothelial hyperplasia, intraluminal thrombosis, and lymphocytic perivascular infiltrate. This test is specific and sensitive if performed before the initiation of antimicrobial therapy and before the 10th day of the disease. It is not widely available, because it is time-consuming and requires an experienced pathologist with a well-equipped laboratory. Results can be obtained within 2-3 days after sample receipt.