Also, since diagnosis relied in almost all series on serological testing (paired serology or single serology GSK-3 phosphorylation with suggestive MSF features), species other than R conorii may have been included due to cross reaction, like for

example R aeschlimannii in Spanish series16 or R slovaca in Sicilian studies.8 This could even explain that subsets of patients were observed with atypical MSF features like multiple eschars or eschars on children scalps. Beyond the uncertainties due to different study definitions, reported rates of severe organ involvement varied extremely, from less than 1% in pediatric series to 5% in large French studies, and up to 15% to 20% in some reports from the Iberian Peninsula and from Algeria. Mortality rates ranged from 0% to 3% in all published series, except in one retrospective hospital-based study from Portugal (with clinical diagnosis) where 20% of fatalities were reported (with a peak of 33% of admitted patients PR 171 in 1997).9 Complications and death have been associated with advanced age, debilitating underlying conditions and delay in appropriate treatment.17 It is however established that disease severity varies according to time and geographic location.4 Reasons are unclear but differences may be due to variability in defining a complicated

course, recruitment bias, changes in R conorii conorii virulence,4 or local contribution of R conorii subspecies possibly more pathogenic.18–22 Meningitis and encephalitis have been classically reported as possible complications of MSF. However, a recent literature review has identified only seven cases properly documented.23 Similarly to our first case, all patients presented with complications like kidney failure, respiratory distress or hypotension besides the neurological manifestations. Dysfunction of the central nervous system included signs as diverse as stupor (n = Pregnenolone 5), seizure (n = 3), incontinence (n = 2), ataxia, aphasia, flaccid quadriplegia or paraplegia

(n = 1 for each sign). Three patients died and three of those four who survived developed severe sequels. In a recent study, 7% of Algerian patients diagnosed with MSF presented with “major neurological manifestations”, and the fatality rate exceeded 50% in this subgroup.13 Lung embolism has been exceptionally described in MSF,2 although pulmonary involvement seems rather frequent (infiltrates and pleural effusion in up to 25% of the Algerian cases).13 In our second case, the lung thromboses might have been due to the rickettsia-induced vasculitis (evidenced also in the skin biopsy) or to some thrombophilic phenomenon precipitated by the systemic inflammation and the protein C deficiency. No deep venous thrombosis could be found and the angiographic findings did not allow a clear-cut conclusion.