eMedicine Specialties > Dermatology > Bacterial Infections

Boutonneuse Fever

Author: Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Jul 7, 2009

Introduction

Background

Boutonneuse fever (BF) is usually a mild rickettsial disease caused by Rickettsia conorii (endemic in the Mediterranean basin); however, severe complications with neurologic involvement can occur in about 6-10% of boutonneuse fever patients. Boutonneuse fever complications are more common in patients with underlying disease or in elderly persons (so-called malignant form of boutonneuse fever). Mild forms are usually observed in children. Also see Mediterranean Spotted Fever.

The major clinical features of boutonneuse fever are fever, exanthem, and tache noire (eschar, necrotic plaque). 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. Consider R conorii infection in patients with lymphadenopathy who live in or have traveled to an endemic area even when other more specific features are not present.

Pathophysiology

The pathogen for boutonneuse fever is introduced through the bite of a tick. The organism, R conorii, invades and proliferates in the endothelial cells of small vessels, destroying them. Activation of the acute-phase response with changes in the coagulation state follows. Boutonneuse fever patients have an alteration in cell-mediated immunity together with a reduction in CD4 cells and a considerable alteration in the cytokine profile. The incubation time of boutonneuse fever is usually 4-15 days, but it can be longer (reportedly 5-28 d in German travelers).

In recent years, 6 more species or subspecies within the spotted fever group within the genus Rickettsia have been described as emerging pathogens. They include Rickettsia slovaca, Rickettsia sibirica mongolitimonae, Rickettsia massiliae, Rickettsia conorii israelensis, Rickettsia conori caspia, and Rickettsia aeschlimannii.1

Fractalkine (CX3CL1) is a chemokine expressed mainly by endothelial cells, which are the major cellular targets of rickettsiae. The peak of expression of CX3CL1 on day 3 of infection reportedly coincided with the time of infiltration of macrophages into infected tissues and preceded the peak of rickettsial content in tissues.2

Induction of the endothelial cyclooxygenase-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

Frequency

United States

Boutonneuse fever is unrecognized in most cases. About 50 imported cases of boutonneuse fever have been reported and confirmed by the US Centers for Disease Control and Prevention (CDC).6

International

The true incidence of boutonneuse fever is unknown. In many endemic areas, mild infection is common, underdiagnosed, and underreported.

  • In the Mediterranean region, the incidence of boutonneuse fever is estimated at 50 cases per 100,000 inhabitants per year.
  • In Croatia, 51.6% of a studied population with a recent history of a tick bite had antibodies to R conorii.
  • In the Leon province of Spain, antibodies to R conorii were discovered in 1% of humans and in 14% of dogs.7
  • In the Valles Occidental in Spain, a population without a previous history of boutonneuse fever, antibodies against R conorii were detected in 4.6-13.5% (mean, 8%) of humans and in 26.1% of dogs.8
  • In southern Portugal, 7.6% of the population have antibodies to R conorii, and nationally as many as 20,000 cases are estimated to occur each year, but only about 5% are reported.9
  • In the Mediterranean coast of Turkey, immunoglobulin G (IgG) antibodies against R conorii were detected in 13.3% of the healthy population.10
  • 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 (eg, via infected dogs, as a holiday souvenir) boutonneuse fever are described.
  • On the Italian island of Sicily, almost 400 cases are reported every year (mainly from June to September).11
  • Boutonneuse fever and other rickettsial infections are reported from Korea.12

Mortality/Morbidity

Mortality is generally estimated to be less than 5%.

  • In one series, 2.5% of boutonneuse fever patients died from the malignant form.
  • In another series, 33% of boutonneuse fever patients with underlying disease (eg, chronic liver disease, alcoholism, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency end stage kidney disease, cardiac disease) died because of malignant boutonneuse fever.
  • Death from malignant (severe) boutonneuse fever has been associated with delay in diagnosis (>5 d) and treatment (>10 d).

Race

Boutonneuse fever affects all races.

Sex

The male-to-female ratio for boutonneuse fever is 1.7:1.

Age

People of all ages are susceptible to infection. In published reports, most boutonneuse fever patients present at the mean age of about 50 years if a cohort of adult patients is examined.

Clinical

History

No test reliably confirms boutonneuse fever in its early stages and diagnosis is often made based on clinical findings.13

About 88% of boutonneuse fever cases are diagnosed between June and September (reproduction cycle of Rhipicephalus species); however, because of climate changes, physicians should be aware of increasing off-season boutonneuse fever cases. 

  • About 37% of patients give a history of a tick bite.
  • About 89% of patients had contact with a dog.
  • Some patients give a history of travel to an endemic area.
  • Patients report the following:
    • Fever of 39-41°C
    • Nonpruritic skin rash mainly on the lower legs, occurring 2-6 days after fever appeared
    • Headache
    • Myalgia, arthralgia, or both

Physical

  • The following triad of symptoms are most characteristic for boutonneuse fever:
    • Fever 39-40°C is noted in 93-100% of patients.
    • Erythematous papules, mainly on the lower limbs, are observed in 94.5-100% of patients.
    • Purpura is present in about 45% of patients.
    • Tache noire (eschar) at the site of the tick bite is discovered in 71.8% of patients.
  • The malignant form of boutonneuse fever is diagnosed when patients present with at least 2 laboratory findings and 2 clinical symptoms of the following criteria:
    • Laboratory findings
      • Thrombocytopenia less than 100 G/L
      • Renal failure (creatinine level >150 mmol/L)
      • Hyponatremia (<130 mmol/L)
      • Hypocalcemia (<2.1 mmol/L)
      • Hypoxemia (arterial oxygen pressure <10.5 kPa)
    • Clinical symptoms
      • Purpuric rash
      • Stupor
      • Pneumonia
      • Bradycardia
      • Coma
      • Jaundice
      • Gastrointestinal bleeding
      • Arthralgic and myalgic arthritis
      • Hepatomegaly and splenomegaly
      • Orchitis
      • Conjunctival hyperemia
      • Meningism14
      • Meningitis
      • Local lymphadenopathy

Causes

The organism responsible for boutonneuse fever is the coccobacillus R conorii, an obligatory intracellular bacterium.

  • Vectors of R conorii
    • Rhipicephalus sanguineus (brown dog tick) is the most common vector. 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 species are infected with R conorii.

More on Boutonneuse Fever

Overview: Boutonneuse Fever
Differential Diagnoses & Workup: Boutonneuse Fever
Treatment & Medication: Boutonneuse Fever
Follow-up: Boutonneuse Fever
References
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References

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Further Reading

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Keywords

boutonneuse fever, BF, Mediterranean spotted fever, MSF, Carducci fever, Carducci's fever, tick typhus, South African tick typhus, Indian tick typhus, tick bite fever, rickettsial disease, Rickettsia conorii, R conorii

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Contributor Information and Disclosures

Author

Anna Zalewska, MD, PhD, Assistant Professor, Adjunct Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-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.

Medical Editor

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.

Pharmacy Editor

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.

Managing Editor

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

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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