The clinical history of the Medici family is well known [1]. It emerges that several members of the Medici family suffered from arthritic diseases. The term frequently reported by contemporary sources to indicate these morbid episodes, is “gout”. It should be remembered that the term “gout” was used in those times to indicate several pathological conditions of rheumatic origin [2].This disease seems to have been a family disease among the Medici, as attested by the nickname “the gouty” attributed to Piero (1416-1469). In particular, gout is reported in the clinical history of Cosimo I (1519-1574), Ferdinand I (1549-1609), Cardinal Carlo (1596-1666), Lorenzo (1599-1648), Cosimo II (1590-1621), Cardinal Giovanni Carlo (1611-1663), Prince Matthias (1613-1667), Cardinals Leopoldo (1617-1675) and Francesco Maria (1660-1711). The archive data refer that Cosimo I suffered from several illnesses, including an acute articular disorder of the right knee, named “gout” by the court physicians, which appeared at the age of 49 and 52-53 [1]. The palaeopathological study of Cosimo’s remains reveals a series of lesions of the axial and appendicular skeleton. The skull shows hyperostosis frontalis interna. The anterior longitudinal ligament on the right-hand side of the column is ossified at the level of the T6, T7 and T8 vertebral bodies; this flowing ossification forms a bony bridge between the vertebrae, appearing as a continuous line of bumps. Two other vertebrae, L2 and L3, are fused on the left-hand side through a bony bridge. Several thoracic and lumbar vertebrae present syndesmophytes, but without vertebral fusion. Marked bone spurs at the insertion of the ligamenta flava are also visible. Intervertebral disks and articular surfaces are normal. Ligament and tendon attachments of the appendicular skeleton show enthesopathies, in particular at the level of clavicles, humeri, ulnae, radii, coxal bones, femurs, patellae, tibiae and calcanei. A diffuse and severe arthritis affecting the lower thoracic and lumbar spine and the great joints is also visible. For Ferdinand I, the historic documentation attests that he suffered from many acute attacks of gout, generally of the left foot, typically positioned in the big toe, from the age of 33 until death. The first attack seems to have been dated back to 1582, when Ferdinand wrote to his brother, the Grand Duke Francesco I, referring that he was confined to bed or chair because of “…some catarrh has fallen down to my left foot. By God’s grace, may it not be podagra!”. In 1591 the court physician Giulio Angeli accurately describes a typical gout attack: “yesterday the gout started to pinch the big toe of the Grand Duke’s left foot and then continued to advance rapidly! Overnight the toe has become swollen, inflamed and painful”. The crises afflicted the Grand Duke also in the following years; furthermore, he started to become obese at the age of 41 [1]. The paleopathological investigation carried out on the skeleton of Ferdinand I reveals pathological features similar to those observed in his father. The vertebral bodies from T5 to T11 are fused in a unique block for the ossification of the right anterior ligament, conferring the typical aspect of a “candle wax” to this spine segment. The body of several cervical and thoracic vertebrae presents partial ossification of the right anterior ligament, but with no formation of bony bridges between the vertebrae. The intervertebral spaces and the apophyseal joints are normal. Ossifications of ligamenta flava, interspinal and supraspinal ligament insertions are largely present. The extra-spinal ligaments show massive hyperostotic changes. Enthesopathies were present at the muscular insertion of clavicles, scapulae, humeri, ulnae, coxal bones, femurs, patellae, tibiae and calcanei. The thyroid cartilage and the epiglottis are ossified and well preserved. Large rough bilateral calcifications of the sterno-costal cartilages of the first and of the last ribs are present, leading to a sternum with multiple ribs attached. Ferdinand I was affected by diffuse osteoarthritis, involving not only the spine and major joints, but also several articulations of his hands and feet. Furthermore, the skeleton of Ferdinand shows a peculiar lesion in the left foot. The interphalangeal joint of the big toe presents cavitations, erosions and osteophytic margins. At the peri-articular and articular surface of the joint a “scooped-out” defect, with partial destruction of the sub-chondral plate, is also visible. X-ray examination reveals an evident sclerotic margin, which involves both bones of the joint. The changes observed in Cosimo I and Ferdinand I meet the standard major criteria established for the diagnosis of DISH (Diffuse Idiopathic Skeletal Hyperostosis) [3]. Both skeletons showed hyperostosis of the column, with the involvement of at least three contiguous vertebrae in Cosimo I, and up to seven vertebrae in Ferdinand. Such changes were limited to the right side of the thoracic segment and diffuse ossifications of the articular ligaments and entheses. Features often associated with DISH, such as hyperostosis frontalis interna, ossification of the neck and rib cartilages and massive osteoarthritis, confirm the diagnosis. The lack of evidence of these diseases in the written sources may be due to the fact that, despite the dramatic radiological aspect, DISH is generally asymptomatic, as its manifestations are limited to back stiffness and mild pain. Paleopathological literature has reported several cases of DISH from different geographical sites and different periods [4, 5]. The aetiology of this condition remains uncertain, but has been related to various metabolic disorders, in particular obesity and type II diabetes mellitus. Recent studies have highlighted a link between the incidence of diffuse idiopathic skeletal hyperostosis and high social status, with particular regard to life style and nutritional patterns. A palaeonutritional study performed recently on the Medici Grand Dukes and their families confirmed the written sources. Carbon and nitrogen stable isotope analysis revealed a diet very rich in meat, as demonstrated by the δ15N high values at the level of the carnivores. The δ13C values, related to the consumption of fish, revealed an intake of marine proteins at 14-30% [6]. The present study seems to further confirm the association between DISH and elite status. Among the five individuals belonging to the Medici family of more than 40 years of age that have been studied so far, two were affected by DISH. Furthermore, it is worth mentioning the case of Cosimo “the Elder” (1389- 1464), whose remains showed the stigmata of this condition as well [7]. Despite the narrowness of the sample, the high incidence of DISH in the Medici family is remarkable and a significant life style indicator, supporting the link between social status and risk of developing DISH in mature age. Furthermore, the case of Ferdinand I is of particular interest for the diagnosis of gout, of which very little evidence has been found in palaeopathology [8]. An alimentation rich in animal proteins, as attested by the palaeonutritional investigation carried out on the Medici family [6], may have favoured the onset of this disease. An association with obesity, diabetes and hyperinsulinemia is ascertained [9]. Modern clinical studies report a significant association between diffuse idiopathic skeletal hyperostosis and gout [10]. As the aetiology of DISH has also been related to obesity and hyperinsulinemia, it has been proposed that the link factor between these two rheumatic diseases could be hyperinsulinemia, possibly related to obesity. Not only do the typical skeletal and radiological features observed in the bone remains of Ferdinand I confirm the data reported by the written sources regarding the arthritic left foot gout which affected the Grand Duke, but this represents the first documentation of the coexistence between diffuse idiopathic skeletal hyperostosis and gout attested in palaeopathological literature. References 1. Pieraccini G. La stirpe dei Medici di Cafaggiolo. vol. 2. Firenze: Nardini Editore, 1986. 2. Nuki G, Simkin P A. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 2006; 8 (Suppl. 19); S1. 3. Rogers J, Waldron T. DISH and the monastic way of life, International Journal of Osteoarchaeology 2001; 11: 357-365. 4. Aufderheide C, Rodriguez-Martin C. The Cambridge encyclopedia of human paleopathology. Cambridge: Cambridge University Press, 1998. 5. Ortner DJ. Identification of pathological conditions in human skeletal remains. New York: Smithsonian Institution Press, 2003. 6. Fornaciari G. Food and disease at the Renaissance courts of Naples and Florence: a paleonutritional study. Appetite 2008; 51: 10-14. 7. Costa A, Weber G. Le alterazioni morbose del sistema scheletrico in Cosimo dei Medici il Vecchio, in Pier oil Gottoso, in Lorenzo il Magnifico, in Giuliano Duca di Nemours. Arch de Vecchi Anat Patol 1955; 23: 1-69. 8. Roberts C, Manchester K. The archaeology of disease. Ithaca, New York: Cornell University Press, 2007. 9. Cohen MG, Emmerson BT. Gout. In: Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed., Vol.2, London: Mosby, 1998: 8.14. 10. Littlejohn GO, Hall S. Diffuse idiopathic skeletal hyperostosis and new bone formation in male gouty subjects. Rheumatol Int 1982; 2: 83-86.

The "gout" of the Medici: a paleopathological approach

FORNACIARI, GINO
2009

Abstract

The clinical history of the Medici family is well known [1]. It emerges that several members of the Medici family suffered from arthritic diseases. The term frequently reported by contemporary sources to indicate these morbid episodes, is “gout”. It should be remembered that the term “gout” was used in those times to indicate several pathological conditions of rheumatic origin [2].This disease seems to have been a family disease among the Medici, as attested by the nickname “the gouty” attributed to Piero (1416-1469). In particular, gout is reported in the clinical history of Cosimo I (1519-1574), Ferdinand I (1549-1609), Cardinal Carlo (1596-1666), Lorenzo (1599-1648), Cosimo II (1590-1621), Cardinal Giovanni Carlo (1611-1663), Prince Matthias (1613-1667), Cardinals Leopoldo (1617-1675) and Francesco Maria (1660-1711). The archive data refer that Cosimo I suffered from several illnesses, including an acute articular disorder of the right knee, named “gout” by the court physicians, which appeared at the age of 49 and 52-53 [1]. The palaeopathological study of Cosimo’s remains reveals a series of lesions of the axial and appendicular skeleton. The skull shows hyperostosis frontalis interna. The anterior longitudinal ligament on the right-hand side of the column is ossified at the level of the T6, T7 and T8 vertebral bodies; this flowing ossification forms a bony bridge between the vertebrae, appearing as a continuous line of bumps. Two other vertebrae, L2 and L3, are fused on the left-hand side through a bony bridge. Several thoracic and lumbar vertebrae present syndesmophytes, but without vertebral fusion. Marked bone spurs at the insertion of the ligamenta flava are also visible. Intervertebral disks and articular surfaces are normal. Ligament and tendon attachments of the appendicular skeleton show enthesopathies, in particular at the level of clavicles, humeri, ulnae, radii, coxal bones, femurs, patellae, tibiae and calcanei. A diffuse and severe arthritis affecting the lower thoracic and lumbar spine and the great joints is also visible. For Ferdinand I, the historic documentation attests that he suffered from many acute attacks of gout, generally of the left foot, typically positioned in the big toe, from the age of 33 until death. The first attack seems to have been dated back to 1582, when Ferdinand wrote to his brother, the Grand Duke Francesco I, referring that he was confined to bed or chair because of “…some catarrh has fallen down to my left foot. By God’s grace, may it not be podagra!”. In 1591 the court physician Giulio Angeli accurately describes a typical gout attack: “yesterday the gout started to pinch the big toe of the Grand Duke’s left foot and then continued to advance rapidly! Overnight the toe has become swollen, inflamed and painful”. The crises afflicted the Grand Duke also in the following years; furthermore, he started to become obese at the age of 41 [1]. The paleopathological investigation carried out on the skeleton of Ferdinand I reveals pathological features similar to those observed in his father. The vertebral bodies from T5 to T11 are fused in a unique block for the ossification of the right anterior ligament, conferring the typical aspect of a “candle wax” to this spine segment. The body of several cervical and thoracic vertebrae presents partial ossification of the right anterior ligament, but with no formation of bony bridges between the vertebrae. The intervertebral spaces and the apophyseal joints are normal. Ossifications of ligamenta flava, interspinal and supraspinal ligament insertions are largely present. The extra-spinal ligaments show massive hyperostotic changes. Enthesopathies were present at the muscular insertion of clavicles, scapulae, humeri, ulnae, coxal bones, femurs, patellae, tibiae and calcanei. The thyroid cartilage and the epiglottis are ossified and well preserved. Large rough bilateral calcifications of the sterno-costal cartilages of the first and of the last ribs are present, leading to a sternum with multiple ribs attached. Ferdinand I was affected by diffuse osteoarthritis, involving not only the spine and major joints, but also several articulations of his hands and feet. Furthermore, the skeleton of Ferdinand shows a peculiar lesion in the left foot. The interphalangeal joint of the big toe presents cavitations, erosions and osteophytic margins. At the peri-articular and articular surface of the joint a “scooped-out” defect, with partial destruction of the sub-chondral plate, is also visible. X-ray examination reveals an evident sclerotic margin, which involves both bones of the joint. The changes observed in Cosimo I and Ferdinand I meet the standard major criteria established for the diagnosis of DISH (Diffuse Idiopathic Skeletal Hyperostosis) [3]. Both skeletons showed hyperostosis of the column, with the involvement of at least three contiguous vertebrae in Cosimo I, and up to seven vertebrae in Ferdinand. Such changes were limited to the right side of the thoracic segment and diffuse ossifications of the articular ligaments and entheses. Features often associated with DISH, such as hyperostosis frontalis interna, ossification of the neck and rib cartilages and massive osteoarthritis, confirm the diagnosis. The lack of evidence of these diseases in the written sources may be due to the fact that, despite the dramatic radiological aspect, DISH is generally asymptomatic, as its manifestations are limited to back stiffness and mild pain. Paleopathological literature has reported several cases of DISH from different geographical sites and different periods [4, 5]. The aetiology of this condition remains uncertain, but has been related to various metabolic disorders, in particular obesity and type II diabetes mellitus. Recent studies have highlighted a link between the incidence of diffuse idiopathic skeletal hyperostosis and high social status, with particular regard to life style and nutritional patterns. A palaeonutritional study performed recently on the Medici Grand Dukes and their families confirmed the written sources. Carbon and nitrogen stable isotope analysis revealed a diet very rich in meat, as demonstrated by the δ15N high values at the level of the carnivores. The δ13C values, related to the consumption of fish, revealed an intake of marine proteins at 14-30% [6]. The present study seems to further confirm the association between DISH and elite status. Among the five individuals belonging to the Medici family of more than 40 years of age that have been studied so far, two were affected by DISH. Furthermore, it is worth mentioning the case of Cosimo “the Elder” (1389- 1464), whose remains showed the stigmata of this condition as well [7]. Despite the narrowness of the sample, the high incidence of DISH in the Medici family is remarkable and a significant life style indicator, supporting the link between social status and risk of developing DISH in mature age. Furthermore, the case of Ferdinand I is of particular interest for the diagnosis of gout, of which very little evidence has been found in palaeopathology [8]. An alimentation rich in animal proteins, as attested by the palaeonutritional investigation carried out on the Medici family [6], may have favoured the onset of this disease. An association with obesity, diabetes and hyperinsulinemia is ascertained [9]. Modern clinical studies report a significant association between diffuse idiopathic skeletal hyperostosis and gout [10]. As the aetiology of DISH has also been related to obesity and hyperinsulinemia, it has been proposed that the link factor between these two rheumatic diseases could be hyperinsulinemia, possibly related to obesity. Not only do the typical skeletal and radiological features observed in the bone remains of Ferdinand I confirm the data reported by the written sources regarding the arthritic left foot gout which affected the Grand Duke, but this represents the first documentation of the coexistence between diffuse idiopathic skeletal hyperostosis and gout attested in palaeopathological literature. References 1. Pieraccini G. La stirpe dei Medici di Cafaggiolo. vol. 2. Firenze: Nardini Editore, 1986. 2. Nuki G, Simkin P A. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther 2006; 8 (Suppl. 19); S1. 3. Rogers J, Waldron T. DISH and the monastic way of life, International Journal of Osteoarchaeology 2001; 11: 357-365. 4. Aufderheide C, Rodriguez-Martin C. The Cambridge encyclopedia of human paleopathology. Cambridge: Cambridge University Press, 1998. 5. Ortner DJ. Identification of pathological conditions in human skeletal remains. New York: Smithsonian Institution Press, 2003. 6. Fornaciari G. Food and disease at the Renaissance courts of Naples and Florence: a paleonutritional study. Appetite 2008; 51: 10-14. 7. Costa A, Weber G. Le alterazioni morbose del sistema scheletrico in Cosimo dei Medici il Vecchio, in Pier oil Gottoso, in Lorenzo il Magnifico, in Giuliano Duca di Nemours. Arch de Vecchi Anat Patol 1955; 23: 1-69. 8. Roberts C, Manchester K. The archaeology of disease. Ithaca, New York: Cornell University Press, 2007. 9. Cohen MG, Emmerson BT. Gout. In: Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed., Vol.2, London: Mosby, 1998: 8.14. 10. Littlejohn GO, Hall S. Diffuse idiopathic skeletal hyperostosis and new bone formation in male gouty subjects. Rheumatol Int 1982; 2: 83-86.
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