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The Reply

  • Gino Fornaciari
    Affiliations
    Division of Paleopathology, Department of History of Medicine and Paleopathology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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      The finding of a document with a description of the conditions of Francesco I in the last moments of his life is of particular interest, as it allows us to further clarify the causes of the Grand Duke's death.
      In this document the symptoms presented by Francesco are petechiae, fever, and swollen neck. Prof. Lippi concludes that this account “supports the conclusion of poisoning” of a previous work
      • Mari F.
      • Polettini A.
      • Lippi D.
      • Bertol E.
      The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder?.
      , because “skin eruption (such as petechiae), fever and swelling are symptoms of acute arsenic poisoning.”
      In acute arsenic poisoning, skin rash is described, but only in the form of flushing erythema or maculopapular eruption.
      • Uede K.
      • Furukawa F.
      Skin manifestations in acute arsenic poisoning from the Wakayama curry-poisoning incident.
      These findings are totally different from petechiae, historically associated with infectious diseases such as epidemic typhus, which the 16th-century physicians could certainly distinguish. On the contrary, these dermatological manifestations are described among the symptoms of malaria, and are mainly seen with falciparum species.
      • White N.J.
      • Breman J.G.
      Malaria.
      The skin lesions consist of petechiae, which are small (1–2 mm) red or purple spots on the body and are caused by minor hemorrhages.
      • Khan A.
      • Chaudhry A.A.
      • Khan U.
      Falciparum—the masquerader.
      The incidence of malaria manifesting with purpura (diffused petechiae) is reported in the range 1.33% to 25.6%.
      • Godse K.V.
      • Zawar V.
      Malaria presenting as urticaria.
      The second symptom mentioned in the document is fever, which is never described in acute arsenic poisoning and is instead typical of malaria.
      • White N.J.
      • Breman J.G.
      Malaria.
      With regard to the “swollen neck,” although it is a very generic symptom that is not helpful in the diagnosis, it is well known that swollen neck lymph nodes are a common sign of many infections, not of intoxication.
      Finally, as already discussed in the comments to the original paper,
      • Mari F.
      • Polettini A.
      • Lippi D.
      • Bertol E.
      The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder?.
      there are no evidences of arsenic poisoning of Francesco I, simply because the toxicological analyses were carried out on very questionable soft tissue remains,
      • Fornaciari G.
      The mystery of beard hairs.
      • Ottini L.
      Who is who, that is the question.
      which most likely cannot be attributed to Francesco.
      On the contrary, ancient Plasmodium falciparum proteins were detected in the skeletal remains of the Grand Duke, demonstrating without any doubt that he was affected by falciparum malaria at the time of his death.
      • Fornaciari G.
      • Giuffra V.
      • Ferroglio F.
      • Gino S.
      • Bianucci R.
      Plasmodium falciparum immunodetection in bone remains of members of the Renaissance Medici family (Florence, Italy, sixteenth century).
      I am grateful to Prof. Lippi for having found the Vatican document, which further supports the diagnosis of severe, acute malaria as the cause of death of Francesco I de' Medici.

      References

        • Mari F.
        • Polettini A.
        • Lippi D.
        • Bertol E.
        The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic murder?.
        BMJ. 2006; 333: 1299-1301
        • Uede K.
        • Furukawa F.
        Skin manifestations in acute arsenic poisoning from the Wakayama curry-poisoning incident.
        Br J Dermatol. 2003; 149: 757-762
        • White N.J.
        • Breman J.G.
        Malaria.
        in: Kasper D.L. Fauci A.S. Hauser S.L. Longo D.L. Jameson J.L. Loscalzo J. Harrisons Principles of Internal Medicine. 17th ed. McGraw-Hill, New York2008: 1281-1289
        • Khan A.
        • Chaudhry A.A.
        • Khan U.
        Falciparum—the masquerader.
        J Pak Med Assoc. 2012; 62 (2012): 62-63
        • Godse K.V.
        • Zawar V.
        Malaria presenting as urticaria.
        Indian J Dermatol. 2012; 57: 237-238
        • Fornaciari G.
        The mystery of beard hairs.
        BMJ. 2006; 333: 1299
        • Ottini L.
        Who is who, that is the question.
        BMJ. 2006; 333: 1299
        • Fornaciari G.
        • Giuffra V.
        • Ferroglio F.
        • Gino S.
        • Bianucci R.
        Plasmodium falciparum immunodetection in bone remains of members of the Renaissance Medici family (Florence, Italy, sixteenth century).
        Trans R Soc Trop Med Hyg. 2010; 104: 583-587

      Linked Article

      • Still About Francesco de' Medici's Poisoning (1587)
        The American Journal of MedicineVol. 128Issue 10
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          In 2010, Fornaciari et al1 detected Plasmodium falciparum in the skeletal remains of Francesco I de' Medici (1541-1587), Grand Duke of Tuscany. Francesco and his wife died within a few hours of each other, with the official report giving the cause as pernicious malaria. However, others suspected they had been poisoned by Francesco's brother and successor as Grand Duke, Ferdinando. The Fornaciari group argued that their findings confirmed the official explanation of Francesco's death and removed any suggestion of poisoning, although toxicologic studies published in 2006 had found arsenic concentrations within the lethal range in the remains of Francesco and his wife.
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