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Boutonneuse Fever

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


Boutonneuse fever (BF), also known as Mediterranean spotted fever (MSF), is transmitted by the dog tick Rhipicephalus sanguineus. The tick bite causes a characteristic rash and a distinct mark—namely, a tache noire (black spot) at the site of the bite.

The etiologic agent for BF is Rickettsia conorii, an organism that is endemic in the Mediterranean basin and is also associated with Marseilles fever, Kenya tick typhus, South African tick bite fever, Indian tick typhus, and Israeli tick typhus. Persons with Israeli spotted fever seldom, if ever, develop the tache noire at the site of the tick bite. BF and African tick bite fever are separate illnesses that occur in the same geographic area. Unlike BF, African tick bite fever causes local adenopathy and multiple eschars.

The major clinical features of BF are as follows:

  • Fever
  • Exanthem (rash)
  • Tache noire

In some patients, the eruption is papulovesicular; this form is more common in adults in Africa. In other patients, the only symptom is an isolated lymphadenopathy. R conorii infection should be considered in patients with lymphadenopathy who live in or have traveled to an endemic area, even when other more specific features are not present.

Although BF is usually a mild disease, severe complications with neurologic involvement can occur in about 6-10% of cases, often resulting from delayed diagnosis of BF and the common practice of prescribing beta-lactam antibiotics as empiric therapy. Complications of BF are more common in patients with underlying disease or in elderly persons (the so-called malignant form of BF). Mild forms of the disease are usually observed in children.

Treatment relies on antibiotic therapy. Prevention is important. Patients should be educated about avoiding tick bites and minimizing contact with dogs in areas that are endemic for BF. For patient education resources, see the First Aid and Injuries Center, as well as Ticks.



Once introduced through a tick bite, R conorii invades and proliferates in the endothelial cells of small vessels, causing endothelial injury and tissue necrosis, as illustrated by the tache noire at the bite site. Activation of the acute-phase response with changes in the coagulation state follows. Thrombosis is not an important pathogenic mechanism in this infection, but deep venous thrombosis can occur late in the course of illness.

BF patients have an alteration in cell-mediated immunity, together with a reduction in CD4 cells and a considerable alteration in the cytokine profile.[1] The incubation time of BF is usually 4-15 days but can be longer (reportedly, 5-28 days in German travelers).

Fractalkine (CX3CL1) is a chemokine expressed mainly by endothelial cells. Its peak of expression on day 3 of infection reportedly coincides with the time of infiltration of macrophages into infected tissues and precedes the peak of rickettsial content in tissues.[2]

Induction of the endothelial cyclooxygenase (COX)-2 system and the ensuing release of vasoactive prostaglandins may contribute to the regulation of inflammatory responses and vascular permeability changes.[3] Expression of type I cytokines may correlate with milder disease expression.[4, 5]

The course of the illness may be divided into stages as follows:

  • The first day of fever is recognized as the first day of the disease
  • The acute stage extends from day 2 to day 14
  • Week 3 (days 15-21) is the borderline period between the acute stage and the convalescent stage
  • The convalescent stage starts after day 21


Rickettsiae are obligate, intracellular gram-negative coccobacilli that measure 1 ´ 0.3 µm and are found within the cytoplasm and occasionally the nucleus of eukaryotic cells. A member of this genus, R conorii, is the organism responsible for BF.

R sanguineus (the brown dog tick) is the most common vector for R conorii. In Cyprus, 3.8% of ticks are infected with R conorii. In Crimea (Ukraine), 8% of ticks are infected with R conorii. In Cyprus, 8.16% of Hyalomma ticks are infected with R conorii.

In addition, the following 6 species or subspecies within the spotted fever group in the genus Rickettsia have been described as emerging pathogens[6] :

  • Rickettsia slovaca
  • Rickettsia sibirica subsp mongolitimonae
  • Rickettsia massiliae
  • R conorii subsp israelensis
  • R conorii subsp caspia
  • Rickettsia aeschlimannii


United States statistics

BF is uncommon in the United States. About 50 imported cases of BF have been reported and confirmed by the US Centers for Disease Control and Prevention (CDC).[7] A disease similar to BF, Rocky Mountain spotted fever, is found in the United States. Rocky Mountain spotted fever is caused by Rickettsia rickettsii, for which the ixodid tick is the vector.

International statistics

BF is known to be prevalent in southern Europe, Africa, and central Asia, including India. The frequency of travel-associated BF has increased worldwide because of increased travel to endemic areas, including ecotourism. However, the true incidence of BF is unknown. In many endemic areas, mild infection is common, underdiagnosed, and underreported.

In the Mediterranean region, the incidence of BF is estimated to be about 50 cases per 100,000 inhabitants per year. In the Leon province of Spain, antibodies to R conorii were discovered in 1% of humans and in 14% of dogs.[8] In the Valles Occidental in Spain, a population without a previous history of BF, antibodies to R conorii were detected in 4.6-13.5% (mean, 8%) of humans and in 26.1% of dogs.[9]

In southern Portugal, 7.6% of the population have antibodies to R conorii; nationally as many as 20,000 cases are estimated to occur each year, but only about 5% are reported.[10] In Sicily, almost 400 cases are reported every year (mainly from June to September).[11] In Croatia, 51.6% of a studied population with a recent history of a tick bite had antibodies to R conorii. On the Mediterranean coast of Turkey, immunoglobulin G (IgG) antibodies against R conorii were detected in 13.3% of the healthy population.[12]

In Zambia, the seroprevalence of antibodies against R conorii is estimated to be 16.7% in the human population and higher in cattle-breeding areas.

In Germany, Norway, and the Netherlands, sporadic cases of so-called imported BF (eg, disease acquired via infected dogs or as a holiday souvenir) are described. BF and other rickettsial infections are reported from Korea.[13] In the United Kingdom, spotted fever group rickettsial species were detected in 9.7% of Ixodes ricinus ticks and 27% of Dermacentor reticularis ticks.[14]

Age-, sex-, and race-related demographics

People of all ages are susceptible to R conorii infection. In published reports, most BF patients present at the mean age of about 50 years if a cohort of adult patients is examined. The male-to-female ratio for BF is 1.7:1. This condition affects people of all races.



Traditionally, BF was characterized as a benign rickettsiosis; however, Guillain-Barré syndrome, polyneuropathy, altered mental status, hepatomegaly, acute renal failure, thrombocytopenia, hypoxemia, and death have been reported.[15] Factors associated with more severe disease include older age, alcoholism, immune compromise, and glucose-6-phosphatase dehydrogenase (G6PD) deficiency.

Such complications notwithstanding, BF is still a benign condition in most cases, carrying a low mortality (in the range of 2-5%). The prognosis is especially good in cases of mild disease; the main concern is malignant (severe) BF developing in patients who are immunocompromised, elderly, or both.[16]

In one series, 2.5% of BF patients died of the malignant form. In another series, 33% of BF patients with underlying disease (eg, chronic liver disease, alcoholism, diabetes mellitus, G6PD deficiency, end-stage renal disease, or cardiac disease) died of malignant BF. Death from malignant BF has been associated with delays in diagnosis (>5 days) and treatment (>10 days).

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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