Mediterranean Spotted Fever (Boutonneuse Fever) Clinical Presentation

Updated: Sep 15, 2021
  • Author: D Matthew Shoemaker, DO, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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The incubation period for Mediterranean spotted fever (MSF), also known as boutonneuse fever (BF), is approximately 5 to 7 days after the infecting tick bite, which is typically painless and often goes unnoticed. About 37% of patients give a history of a tick bite; about 89% report having had contact with a dog; and some give a history of travel to an endemic area.

Because there is no test that can reliably confirm MSF in its early stages, the diagnosis is commonly made on the basis of clinical findings. [25] The clinical diagnosis is supported when a history of travel to an endemic area is coupled with the following triad:

  • Fever
  • Exanthem (maculopapular rash)
  • Eschar (tache noire) at site of tick bite

More specifically, patients commonly report the following:

  • Fever of 39 to 41°C
  • Nonpruritic skin rash, mainly on the lower legs, occurring 2 to 6 days after the fever appeared
  • Myalgia, arthralgia, or both

MSF cases are on the increase all over the world and should be considered in all febrile patients returning from abroad, especially from endemic areas (eg, the Mediterranean region). About 88% of MSF cases are diagnosed between June and September (as a reflection of the reproduction cycle of Rhipicephalus); however, physicians should be aware that climate changes are leading to increases in the number of off-season MSF cases. Spotless fever and cases appearing in the winter also may be due to Rickettsia infection. Therefore, a high degree of clinical suspicion is required so as not to miss the diagnosis.


Physical Examination

Findings that may be observed in a patient with MSF include the following:

  • High fever
  • Maculopapular rash
  • Eschar (tache noire) at site of tick bite
  • Stupor
  • Pulmonary infiltrates
  • Bradycardia
  • Coma
  • Jaundice
  • Gastrointestinal bleeding
  • Arthralgic and myalgic arthritis
  • Hepatomegaly and splenomegaly
  • Orchitis
  • Conjunctival hyperemia
  • Meningism [26]
  • Meningitis
  • Local lymphadenopathy
  • Retinopathy, [27] sensorineural hearing loss, [28] 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 specific laboratory test results (see DDx).



Complications of MSF tend to occur mainly in patients who are immunocompromised or elderly and who present with the malignant form of the disease. In Spain, complications are observed in about 22% of BF cases. Generally, however, the complication rate is estimated to be in the range of 1 to 20%.

The following complications have been reported [19] :

  • Renal failure - This is mainly due to renal vasculitis, acute tubular necrosis, or perivascular interstitial glomerulonephritis
  • Respiratory failure
  • GI bleeding
  • Stroke
  • Deep venous thrombosis (DVT) - This is observed in about 9% of patients during the late acute phase and the early convalescent phase of MSF
  • Arthromyalgia (16 to 76% of patients) and arthritis (rare)
  • Pulmonary complications (very rare)
  • Meningoencephalitic involvement - This may occur during the acute phase (lymphocytic coma or meningitis)
  • Myelitis - This tends to occur early in the convalescent phase as acute-onset paraplegia involving the lumbosacral spinal cord (very rare)
  • Septic shock
  • Multiorgan failure
  • Hepatosplenomegaly
  • Autoimmune anemia