Medscape is available in 5 Language Editions – Choose your Edition here.


Boutonneuse Fever Treatment & Management

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

Approach Considerations

The course of boutonneuse fever (BF), also known as Mediterranean spotted fever (MSF), can be shortened with appropriate treatment (ie, antibiotics). The illness sometimes takes a malignant form—for instance, in people who are elderly and especially in those who are immunocompromised. In a study of 142 patients hospitalized with BF, 5% of patients presented with malignant BF.

Tetracyclines, along with chloramphenicol and quinolones, may be considered first-line antibiotics for BF. After 2-4 days of first-line therapy, the fever decreases and the rash usually disappears. Patients already in good health are usually discharged after 7-8 days of treatment. Single-dose azithromycin can be used for prophylaxis of BF.

Because the differential diagnosis for BF includes many rare diseases, consultations with a dermatologist and an infectious disease specialist should be considered.


Pharmacologic Therapy

Patients with the benign form of BF are usually treated with antibiotics for 7 days; those with the malignant form of BF are usually treated with antibiotics for 2 weeks.

The preferred drug is doxycycline (100 mg PO q12hr). Other effective treatments include the following:

  • Ciprofloxacin (200 mg IV q12hr or 750 mg PO q12hr)
  • Levofloxacin (500 mg PO once daily)
  • Chloramphenicol (50-60 mg/kg/day PO in 4 divided doses)
  • Macrolides such as azithromycin (500 mg PO once daily) and clarithromycin (500 mg PO q12h) - These have been shown to be efficacious in children [25] and can be used as alternatives to doxycycline in adults, including pregnant women. A small randomized trial in children and adults showed a similar time to resolution of fever and other symptoms among those treated with clarithromycin versus doxycycline (or doxycycline plus josamycin in children). [26]

For children with malignant BF, tetracyclines (especially doxycycline) should be considered first; these are the most effective drugs for this potentially life-threatening disease. A single short (≤1 week) course of doxycycline should not result in cosmetically significant staining of teeth. In malignant BF, there is a narrow window of time during which effective antibiotic therapy delivered in an extremely efficient way can substantially reduce the risk of an unfavorable outcome.

In pregnant women, erythromycin should be administered; however, it is not as effective as the tetracyclines are.

In an analysis of risk factors for malignant BF, researchers noted that fluoroquinolones may have a deleterious effect.[27]

Josamycin, a newer macrolide antibiotic, seems to be effective against malignant BF (when available). Some have suggested that it may be the drug of choice for malignant BF in pregnant women.[28, 29, 30]

Rifampin, though designated by the US Food and Drug Administration (FDA) as a category C drug in pregnancy and tuberculosis, has also been used extensively in this setting and appears to be safe.



To prevent infection by rickettsiae, precautions should be taken to avoid exposure to ticks, in particular by refraining from close contact with ticks’ animal vectors (eg, dogs, goats, and sheep) when in endemic areas.

Protective clothing should be worn, preferably impregnated with permethrin or another pyrethroid. Topical repellents can be used on any exposed skin; however, these agents have a short duration of effect (~1-2 hours per application), and frequent application is therefore recommended. During travel, daily self-checks and removal of any ticks found should be performed.

At present, there is no vaccine for BF.

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.

  1. Popivanova NI, Murdjeva MA, Baltadzhiev IG, Haydushka IA. Dynamics in serum cytokine responses during acute and convalescent stages of Mediterranean spotted fever. Folia Med (Plovdiv). 2011 Apr-Jun. 53(2):36-43. [Medline].

  2. Valbuena G, Walker DH. Expression of CX3CL1 (fractalkine) in mice with endothelial-target rickettsial infection of the spotted-fever group. Virchows Arch. 2005 Jan. 446(1):21-7. [Medline].

  3. Rydkina E, Sahni A, Baggs RB, Silverman DJ, Sahni SK. Infection of human endothelial cells with spotted Fever group rickettsiae stimulates cyclooxygenase 2 expression and release of vasoactive prostaglandins. Infect Immun. 2006 Sep. 74(9):5067-74. [Medline]. [Full Text].

  4. de Sousa R, Ismail N, Nobrega SD, França A, Amaro M, Anes M, et al. Intralesional expression of mRNA of interferon- gamma , tumor necrosis factor- alpha , interleukin-10, nitric oxide synthase, indoleamine-2,3-dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis. J Infect Dis. 2007 Sep 1. 196(5):770-81. [Medline].

  5. Damås JK, Davì G, Jensenius M, Santilli F, Otterdal K, Ueland T, et al. Relative chemokine and adhesion molecule expression in Mediterranean spotted fever and African tick bite fever. J Infect. 2009 Jan. 58(1):68-75. [Medline].

  6. Brouqui P, Parola P, Fournier PE, Raoult D. Spotted fever rickettsioses in southern and eastern Europe. FEMS Immunol Med Microbiol. 2007 Feb. 49(1):2-12. [Medline].

  7. Palau LA, Pankey GA. Mediterranean Spotted Fever in Travelers from the United States. J Travel Med. 1997 Dec 1. 4(4):179-182. [Medline].

  8. Jufresa J, Alegre J, Suriñach JM, Aleman C, Recio J, Juste C, et al. [Study of 86 cases of Mediterranean boutonneuse fever hospitalized at a university hospital]. An Med Interna. 1997 Jul. 14(7):328-31. [Medline].

  9. Segura-Porta F, Diestre-Ortin G, Ortuño-Romero A, Sanfeliu-Sala I, Font-Creus B, Muñoz-Espin T, et al. Prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs from and endemic area of mediterranean spotted fever in Catalonia, Spain. Eur J Epidemiol. 1998 Jun. 14(4):395-8. [Medline].

  10. de Sousa R, Nóbrega SD, Bacellar F, Torgal J. Mediterranean spotted fever in Portugal: risk factors for fatal outcome in 105 hospitalized patients. Ann N Y Acad Sci. 2003 Jun. 990:285-94. [Medline].

  11. Cascio A, Iaria C. Epidemiology and clinical features of Mediterranean spotted fever in Italy. Parassitologia. 2006 Jun. 48(1-2):131-3. [Medline].

  12. Mert A, Ozaras R, Tabak F, Bilir M, Ozturk R. Mediterranean spotted fever: a review of fifteen cases. J Dermatol. 2006 Feb. 33(2):103-7. [Medline].

  13. Choi YJ, Jang WJ, Ryu JS, Lee SH, Park KH, Paik HS, et al. Spotted fever group and typhus group rickettsioses in humans, South Korea. Emerg Infect Dis. 2005 Feb. 11(2):237-44. [Medline]. [Full Text].

  14. Tijsse-Klasen E, Jameson LJ, Fonville M, Leach S, Sprong H, Medlock JM. First detection of spotted fever group rickettsiae in Ixodes ricinus and Dermacentor reticulatus ticks in the UK. Epidemiol Infect. 2011 Apr. 139(4):524-9. [Medline].

  15. Popivanova N, Hristova D, Hadjipetrova E. Guillain-Barré polyneuropathy associated with mediterranean spotted fever: case report. Clin Infect Dis. 1998 Dec. 27(6):1549. [Medline].

  16. Aliaga L, Sánchez-Blázquez P, Rodríguez-Granger J, Sampedro A, Orozco M, Pastor J. Mediterranean spotted fever with encephalitis. J Med Microbiol. 2009 Apr. 58:521-5. [Medline].

  17. Chipp E, Digby S. Rickettsia: an unusual cause of sepsis in the emergency department. Emerg Med J. 2006 Nov. 23(11):e60. [Medline]. [Full Text].

  18. Ezpeleta D, Muñoz-Blanco JL, Tabernero C, Giménez-Roldán S. [Neurological complications of Mediterranean boutonneuse fever. Presentation of a case of acute encephalomeningomyelitis and review of the literature]. Neurologia. 1999 Jan. 14(1):38-42. [Medline].

  19. Leone S, De Marco M, Ghirga P, Nicastri E, Lazzari R, Narciso P. Retinopathy in Rickettsia conorii infection: case report in an immunocompetent host. Infection. 2008 Aug. 36(4):384-6. [Medline].

  20. Tsiachris D, Deutsch M, Vassilopoulos D, Zafiropoulou R, Archimandritis AJ. Sensorineural hearing loss complicating severe rickettsial diseases: report of two cases. J Infect. 2008 Jan. 56(1):74-6. [Medline].

  21. Demeester R, Claus M, Hildebrand M, Vlieghe E, Bottieau E. Diversity of life-threatening complications due to Mediterranean spotted fever in returning travelers. J Travel Med. 2010 Mar-Apr. 17(2):100-4. [Medline].

  22. Broadhurst LE, Kelly DJ, Chan CT, Smoak BL, Brundage JF, McClain JB, et al. Laboratory evaluation of a dot-blot enzyme immunoassay for serologic confirmation of illness due to Rickettsia conorii. Am J Trop Med Hyg. 1998 Jun. 58(6):786-9. [Medline].

  23. Ergas D, Sthoeger ZM, Keysary A, Strenger C, Leitner M, Zimhony O. Early diagnosis of severe Mediterranean spotted fever cases by nested-PCR detecting spotted fever Rickettsiae 17-kD common antigen gene. Scand J Infect Dis. 2008. 40(11-12):965-7. [Medline].

  24. Giulieri S, Jaton K, Cometta A, Trellu LT, Greub G. Development of a duplex real-time PCR for the detection of Rickettsia spp. and typhus group rickettsia in clinical samples. FEMS Immunol Med Microbiol. 2012 Feb. 64(1):92-7. [Medline].

  25. Dzelalija B, Petrovec M, Avsic-Zupanc T, Strugar J, Milic TA. Randomized trial of azithromycin in the prophylaxis of Mediterranean spotted fever. Acta Med Croatica. 2002. 56(2):45-7. [Medline].

  26. Anton E, Muñoz T, Travería FJ, Navarro G, Font B, Sanfeliu I, et al. Randomized Trial of Clarithromycin for Mediterranean Spotted Fever. Antimicrob Agents Chemother. 2015 Dec 28. 60 (3):1642-5. [Medline].

  27. Botelho-Nevers E, Rovery C, Richet H, Raoult D. Analysis of risk factors for malignant Mediterranean spotted fever indicates that fluoroquinolone treatment has a deleterious effect. J Antimicrob Chemother. 2011 Aug. 66(8):1821-30. [Medline].

  28. Antón E, Font B, Muñoz T, Sanfeliu I, Segura F. Clinical and laboratory characteristics of 144 patients with mediterranean spotted fever. Eur J Clin Microbiol Infect Dis. 2003 Feb. 22(2):126-8. [Medline].

  29. Bentov Y, Sheiner E, Kenigsberg S, Mazor M. Mediterranean spotted fever during pregnancy: case presentation and literature review. Eur J Obstet Gynecol Reprod Biol. 2003 Apr 25. 107(2):214-6. [Medline].

  30. Cohen J, Lasri Y, Landau Z. Mediterranean spotted fever in pregnancy. Scand J Infect Dis. 1999. 31(2):202-3. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.