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Boutonneuse Fever Workup

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

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.

Contributor Information and Disclosures

Jason F Okulicz, MD, FACP, FIDSA Director, HIV Medical Evaluation Unit, Infectious Disease Service, San Antonio Military Medical Center; Associate Professor of Medicine, F Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences; Clinical Associate Professor of Medicine, University of Texas Health Science Center at San Antonio; Adjunct Clinical Instructor, Feik School of Pharmacy, University of the Incarnate Word

Jason F Okulicz, MD, FACP, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America

Disclosure: Nothing to disclose.


Pierre A Dorsainvil, MD Medical Director, HIV Specialist, Palm Beach County Main Detention Center; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Lake Ida Medical Center

Disclosure: Nothing to disclose.

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, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mark S Rasnake, MD, FACP Assistant Professor of Medicine, Program Director, Internal Medicine Residency, University of Tennessee Graduate School of Medicine; Consulting Staff, Department of Infectious Diseases, University of Tennessee Medical Center at Knoxville

Mark S Rasnake, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.


David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joseph Richard Masci, MD Professor of Medicine, Professor of Preventive Medicine, Mount Sinai School of Medicine; Director of Medicine, Elmhurst Hospital Center

Joseph Richard Masci, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Association of Professors of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Robin Travers, MD Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians

Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Medical Dermatology Society, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Anna Zalewska, MD, PhD Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

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