Although numerous parts of the world have shown to be potential sites where Rickettsia conorrii can be contracted (India, Pakistan, Israel, Ukraine, Russia, Kenya, Morocco, South Africa and countries of Northern Europe), Boutonneuse fever is most frequently diagnosed in the Mediterranean basin, which is why the terms "Mediterranean spotted fever" or "Marseilles fever" are frequently used [1] [2]. Boutonneuse fever is a zoonotic disease that develops after a tick bite, specifically by Rhipicephalus sanguineus, the common dog tick [3]. The infection is usually diagnosed in the warmer months (July-September) [1] [3], and the clinical presentation is similar to other rickettsioses - fever, a maculopapular rash and the presence of an eschar (known as "tache noir") at the site of the tick bite [3]. Only one eschar is found in virtually all infected individuals, but their absence or even the appearance of more than one eschar has been documented [1]. Moreover, patients will often not remember being bitten by a tick as the transmission of bacteria by ticks may occur while the ticks are in the stages of larvae or nymph, which are rarely noticed [2]. Myalgias, dyspnea, cough, and hepatosplenomegaly are less common symptoms [2]. The course of the disease is generally self-limiting, especially in children, and the rash, as well as fever, resolves spontaneously in the majority of individuals, but a more severe form of the disease is encountered in approximately 6% of cases [3] [4]. Dehydration, tachycardia, obtundation, stupor and electrolyte imbalance are hallmarks of severe infection that may eventually lead to thrombocytopenia, myocarditis, gastric bleeding, renal failure and multiple organ damage [5] [5]. Additionally, central nervous system infection (meningitis or encephalitis), although rare, is an important cause of mortality in patients suffering from this form of Boutonneuse fever [4] [5]. Several risk factors for clinical deterioration have been described, including diabetes mellitus, preexisting cardiac or renal insufficiency, glucose-6-phosphate dehydrogenase deficiency (G6PD), and alcoholism [2] [3]. Overall mortality rates are around 2.5% [2].

• Fever

  Boutonneuse fever (also called Mediterranean spotted fever, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, African tick-bite fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium [en.wikipedia.org]

  […] diagnosed in the Mediterranean basin, which is why the terms "Mediterranean spotted fever" or "Marseilles fever" are frequently used. [symptoma.com]

  fever-group Rickettsiae present in those areas. [ncbi.nlm.nih.gov]

• Fatigue

  Kradin has a number of clinical interests including Chronic Fatigue Syndrome, Interstitial Lung Disease, Multiple Chemical Sensitivity and Pulmonary Immunology. He also holds an Associate Professor position of Pathology at Harvard Medical School. [books.google.de]

  At the early onset, this condition manifests in fever, nausea, vomiting, extremely hard headache, pain and fatigue in the muscles, decreased appetite and sometimes even in inflammation of one or major salivary glands. [ic.steadyhealth.com]

  However, a significant fatigue persisted in most patients. An additional 14 days of doxycycline therapy was prescribed to achieve complete cure, because it was not possible to reassess the patients' health at the third week. [doi.org]

• Tachycardia

  Dehydration, tachycardia, obtundation, stupor and electrolyte imbalance are hallmarks of severe infection that may eventually lead to thrombocytopenia, myocarditis, gastric bleeding, renal failure and multiple organ damage. [symptoma.com]

  Examination findings included resting tachycardia and melenic stool. Blood pressure was 95/50 mm Hg. Multiple raised, soft, bluish 0.3 to 1 cm lesions were noted on the trunk and extremities. [consultant360.com]

• Photophobia

  After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black, ulcerous crust (tache noire). [en.wikipedia.org]

• Arthralgia

  The patient came to our notice after nine days of high fever, headache, arthralgia with no history of tick-bite. [biomedcentral.com]

  […] is coupled with the following triad: Fever Rash (exanthem) Tache noire More specifically, patients commonly report the following: Fever of 39-41 C Nonpruritic skin rash, mainly on the lower legs, occurring 2-6 days after the fever appeared Myalgia, arthralgia [emedicine.medscape.com]

• Suggestibility

  In one couple, the more seriously ill patient had antibodies of the IgM class, suggesting that this was his first exposure to Rickettsia conorii. [ncbi.nlm.nih.gov]

• Headache

  All three patients developed similar symptoms of disease, including high fever, headache, maculopapular exanthem, and conjunctivitis, and none had tache noire. [ncbi.nlm.nih.gov]

  After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black, ulcerous crust (tache noire). [en.wikipedia.org]

  Diagnosis One of the tick borne spotted fevers starts, with a black ulcer (tache noir for you Francophiles) and proceeds to fevers, chills, headache, myalgias and a rash. [pusware.com]

  […] bou·ton·neuse fever \ ˌbü-tȯ-ˈnœ̅z- \ : a tick-borne illness of the Mediterranean region, central Asia and especially India, and Africa that is typically marked by mild symptoms including fever, headache, and red rash with both raised and flat lesions [merriam-webster.com]

• Meningism

  Additionally, central nervous system infection (meningitis or encephalitis), although rare, is an important cause of mortality in patients suffering from this form of Boutonneuse fever. [symptoma.com]

  [18] Meningitis Local lymphadenopathy Retinopathy, [19] sensorineural hearing loss, [20] and other neurologic manifestations (rare) The presence of malignant BF is indicated when 2 or more specific clinical symptoms occur in conjunction with 2 or more [emedicine.medscape.com]

  Meningitis, or inflammation of the membrane covering the brain and spinal cord; and pneumonitis, or inflammation in the lungs, have also been reported as complications Prompt treatment of Rocky Mountain Spotted Fever with antibiotics is recommended, if [dovemed.com]

  The patient had a severely-affected central nervous system with obtunded consciousness, facial nerve deficit and meningeal signs. Examination of cerebrospinal fluid did not reveal any significant findings. [biomedcentral.com]

The diagnosis of Boutonneuse fever relies on three main factors - a thorough patient history, a detailed physical examination and microbiological investigation. Firstly, patients must be asked about their recent travel (or whether they are residents of the Mediterranean), as well as recent tick bites. A meticulous physical examination should follow, which may identify the site of the tick bite by detecting the typical eschar. More importantly, if signs and symptoms suggestive of more severe infection (hepatosplenomegaly, jaundice, petechial rash, meningismus) are detected during the exam, electrolyte and liver transaminase levels need to be assessed, as hyponatremia and increased aspartate aminotransferase or AST, can be seen, respectively [2]. Because of the risk for coagulopathy and thrombocytopenia, a complete blood count (CBC) and a full coagulation panel should also be drawn during workup. Although clinical criteria supported by data from patient history may be sufficient to make the diagnosis, the confirmation of Rickettsia conorrii and Boutonneuse fever as the underlying cause of symptoms can be made after isolating the bacteria by some of the recommended microbiological techniques. Cultivation using the shell vial system, indirect immunofluorescence, and polymerase chain reaction (PCR) seem to be most efficient, but PCR and immunofluorescence are favored due to their faster turnaround time, and they are performed whenever possible [2] [4] [5].

1. Rovery C, Brouqui P, Raoult D. Questions on Mediterranean Spotted Fever a Century after Its Discovery. Emerging Infectious Diseases. 2008;14(9):1360-1367.
2. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
3. Cascio A, Iaria C. Epidemiology and clinical features of Mediterranean spotted fever in Italy. Parassitologia. 2006;48(1-2):131-133.
4. Colomba C, Saporito L, Polara VF, Rubino R, Titone L. Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children. BMC Infect Dis. 2006;6:60.
5. Aliaga L, Sánchez-Blázquez P, Rodríguez-Granger J, Sampedro A, Orozco M, Pastor J. Mediterranean spotted fever with encephalitis. J Med Microbiol. 2009;58(4):521-525.