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Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art
IJCA-24654; No of Pages 3 International Journal of Cardiology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art Francesco M. Galassi a,⁎, Claudio Borghi b, Roberta Ballestriero c,d, Michael E. Habicht a,e, Maciej Henneberg a,f, Frank J. Rühli a a
Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland Medical and Surgical Sciences Department, University of Bologna, Via Massarenti 9, Bologna, Italy University of the Arts, Central Saint Martins, Granary Building, 1 Granary Square, King's Cross, London N1C 4AA, UK d The Gordon Museum of Pathology, Kings College London, Guy's Campus, St. Thomas' Street, London SE1 9RT, UK e School of Humanities and Creative Arts (Department of Archaeology), Flinders University, Adelaide 5001, Australia f Biological Anthropology and Comparative Anatomy Unit, University of Adelaide, Adelaide 5005, Australia b c
a r t i c l e
i n f o
Article history: Received 6 January 2017 Accepted 24 February 2017 Available online xxxx Keywords: Frank's sign Earlobe crease Cardiovascular pathology Prevention Palaeopathology Mantegna Renaissance
a b s t r a c t Several studies have associated the earlobe crease sign, discovered by Sanders T. Frank in 1973, with cardiovascular pathology, yet very few studies have focused on the antiquity of this trait, with the most ancient one thought to date back to the Roman Emperor Hadrian (76–138 CE). This article presents two more cases from the Italian Renaissance in the works of the artist Andrea Mantegna (1431–1506) and examines them in a multidisciplinary fashion. © 2017 Elsevier B.V. All rights reserved.
1. Introduction: theoretical background and aim Cardiovascular diseases are responsible for about 31% of all deaths worldwide every year, which amount to 17.5 million casualties per annum [1]. Considered multifactorial nosological entities, they involve complex levels of interaction between environmental stressors and genetic background [2]. For this reason the possibility of identifying early visible signs of potential vascular deterioration has been stressed in an attempt to improve the overall diagnostic and preventive impact on patients' prognosis [3]. Of these, one of the most intriguing, and at the same time controversial, sign is the earlobe crease (ELC), also known as Frank's sign, named after its discoverer, Sanders T. Frank (1938–1998) [4]. It consists of a deep wrinkle, presenting either bilaterally or unilaterally and extending backwards from the intertragic notch to the auricle at an angle of about 45° [5]. Since the introduction of ELC in medical theory, a possible relation between coronary heart disease (CAD) has been sought for, with contrasting interpretations, either confirming or refuting this link [5]. A recent meta-analysis of existing literature on the matter, both clinical and necroscopic, has come to the conclusion that the hypothesis that ELC could represent a marker for ⁎ Corresponding author. E-mail address: [email protected] (F.M. Galassi).
CAD is very strong [6]. From a palaeopathological perspective, the first recorded evidence of this sign dates back the classical world, in particular to Emperor Hadrian (76–138 CE). Patrakis noticed the earlobe crease sign on a series of busts of the Emperor (Athens National Museum, Museo Nazionale Romano in Rome, Prado Museum in Madrid and the Uffizi Gallery in Florence) [7], which belong mostly to the Terminitype bust sculpted for his accession in 117 CE (when he was 41) and used until c. 121 CE. Patrakis established a link between this type of highly accurate form of art and literary evidence from the ancient sources suggesting that Hadrian suffered from epistaxis and ultimately developed dropsy, which he reinterpreted as a sign of a potentially underlying hypertension, also corroborated by the Emperor's behaviour as derived from the ancient sources, considered by Patrakis as clearly type A [7]. As an ex post commentary, it may be added that the accuracy of Patrakis's sculptural observation can be additionally confirmed by the presence of the sign in other busts of Hadrian not considered by the scholar, such as the one exhibited in the Vatican Museum. Moreover, similar observations were later made in ancient statues exhibited in the Louvre Museum in Paris, namely Hadrian again, the pseudoSeneca and the Greek orator Demosthenes (384–322 BCE) [8]. Recently Charlier and Deo have identified bilateral earlobe creases in the 1880made death mask of the famous French novelist Gustave Flaubert (1821–1880) [9]. This highlights the existence of a great hiatus between
http://dx.doi.org/10.1016/j.ijcard.2017.02.128 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128
2
F.M. Galassi et al. / International Journal of Cardiology xxx (2017) xxx–xxx
the ancient world and the late modern period which leads to the question whether this sign was ever noted in the intercurring centuries and potentially related to unfavourable pathological outcomes. 2. Materials and methods An answer may be attempted by re-examining Italian Renaissance art, known to show a high level of accuracy [10]. In particular, here two pictorial representations of the earlobe crease by Andrea Mantegna (1431–1506) are presented: the tempera paintings Portrait of Cardinal Ludovico Trevisan (later renamed Ludovico Scarampi Mezzarota, 1459–1460) (Fig. 1) exhibited in the Berlin Gemäldegalerie [inventory number: 9], and Portrait of a Man in Profile (c. 1460), exhibited in the Milan “Poldi Pezzoli” collection [inventory number: 1592] (Fig. 2). The depictions are examined using a combination of traditional artistic and retrospective clinical analyses, when possible (1 of the 2 cases), strengthened by further medical data derived from the portrayed individuals' biographical accounts [11].
3. Results Both depictions show two aged male individuals in all their attributes of gravitas conveyed by the seriousness of their visual expressions, facial morphology and bearing. In the first portrait (Fig. 1), the cardinal's left earlobe (Fig. 1b) shows a well-defined crease highlighted by the chiaroscuro effect which gives depth to the sulcus crossing the soft tissue. While the profile view does not allow one to determine whether the subject presented the same sign contralaterally, it can furthermore be remarked how the generally mature and slightly aged look, as well as the three fatty folds on the external surface of the anterior cervical compartment originating from the submental area, point to a certain corpulence of the portrayed figure. As far as the second portrait (Fig. 2) is concerned, a different variant of septation can be appreciated in the left earlobe (Fig. 2b) – the right-sided one being once again invisible – broader and seemingly consisting of a double branching which roughly gives the anatomical conformation the morphology of a “V”. 4. Discussion Mantegna, a master of drawing and perspective, represented his figures as solid, tangible beings following the lead given by Masaccio (1401–1428). Solemn and statuesque, his figures look somewhat hard and harsh, almost wooden. The late art historian Ernst Gombrich
Fig. 1. a Portrait of Cardinal Ludovico Trevisan. (1459–1460, tempera on panel painting, 44.8 × 33.9 cm) Gemäldegalerie, Berlin, Germany. Image in the public domain from wikisource: https://it.wikipedia.org/wiki/Ritratto_del_cardinale_Ludovico_Trevisan#/ media/File:Ludovico_trevisano_portrait_by_andrea_mantegna.jpg. 1b. Magnified detail of the cardinal's left ear, showing a crease across his auricular lobe.
Fig. 2. a Portrait of a Man in Profile (c. 1460, tempera on panel painting, 32.3 × 28.8 cm). “Poldi Pezzoli” Museum, Milan, Italy. Image in the public domain from wikisource: https://it.wikipedia.org/wiki/Profilo_d'uomo#/media/File:Andrea_Mantegna_114.jpg. 2b. Detail of the unidentified individual's left ear, showing two sulci which resemble the shape of the letter “V”.
(1909–2001) suggested that “[the] more conscientiously we copy a figure line by line and detail by detail, the less we can imagine that it ever really moved and breathed” [12]. Even though a full naturalness of representation would only be achieved later through Leonardo da Vinci's (1452–1519) sfumato technique [13], for his precision in copying reality, Mantegna is to be regarded a trustworthy portrayer of reality. Furthermore, with specific reference to pathology, he is well documented to have accurately represented conditions – often before their actual scientific discoveries – such as goitre [14], Down syndrome [15], turgidity of the temporal artery suggestive of Horton's disease and ricketts [16], and dwarfism [17], the latter recently proposed to be representative of an ancient case of type 1 neurofibromatosis [18]. Therefore, the eventuality that, albeit without a strictly scientific purpose, but rather wishing to highlight the signs of mature age, Mantegna truly represented earlobe creases is likely. As far as Cardinal Trevisan is concerned, additional information can be retrieved from his historical record: the cardinal's death, which occurred five to six years after the portrait was made, in Rome on 22nd March 1465, might very well have been the result of oedema [19], once known by the currently obsolete term “dropsy”, a common final pathophysiological step of several organ failures such as hepatic and renal, and well known to be associated with cardiovascular disease. Support for such a retrospective diagnosis is to be found in a letter by the humanist Iacopo Ammannati (1422–1472), who reports that, as the newly elected, and former political enemy, pope Paulus II (born Pietro Barbo, 1417–1471) paid Trevisan a visit after his election, found him, diseased in his feet (“aeger pedibus”) and unable to move from his chair (“e sella se movere non poterat”) [20]. While these words do not allow a clear-cut semiological reassessment and further peripheral etiologies (e.g. rheumatological or orthopaedic conditions, thromboflebitis, varicose veins) should be taken into account, they clearly convey the chronic nature of the cardinal's ailments, underlined also by his seemingly nullified locomotion. A cardiac oedema may very well explain this clinical picture and would likely cause the cardinal's inability to move not only as a result of lower limb impairment but also potentially as a result of a generalised oedema (e.g. ascites) causing the body size to increase as result of fluid retention. Such a clinical scenario thus provides an interesting comparison with Emperor Hadrian's case.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128
F.M. Galassi et al. / International Journal of Cardiology xxx (2017) xxx–xxx
As far as the second portrait is concerned, a different variant of septation can be appreciated in the left earlobe – the right-sided one being once again invisible – broader and seemingly consisting of a double branching which roughly gives the anatomical conformation the morphology of a “V”. The identity of the character is mysterious, which makes it impossible to retrieve primary documental and biographical information which would be essential to form a more precise retrospective diagnosis. The subject's advanced age and the eyecatching arborisation present on his left temple have already been subjected to retrospective diagnostics allowing the production of a rheumatological hypothesis, namely giant-cell (Horton's) arteritis [16], whose pictorial record appears to be rather established in Renaissance art [21]. While cardiac and rheumatological diseases can logically coexist, additional monopathological vascular retrospective diagnoses of the temporal artery reflecting a more general underlying cardiovascular pathological background, of which the earlobe creases can be seen as an external marker, may be cautiously suggested. In particular, arteriosclerosis and atherosclerosis, or even medial arterial calcification, are nosological entities which can mimick temporal arteritis making temporal artery biopsy necessary in order to resolve the diagnostic uncertainty [22,23]. However, unlike in Cardinal Trevisan's case, the purely morphological nature of this observation in the aged individual portrayed by Mantegna, unsupported by further historical and archival evidence on the patient's medical condition, reasonably leaves the subject open to debate. 5. Conclusion While its association with coronary heart disease was first put forward only in 1973, the earlobe crease sign has been almost continuously recorded throughout history, potentially and more realistically just as a sign of advanced or old age. However – when possible – if one reexamines the historical accounts of the portrayed characters (e.g. Hadrian and Cardinal Trevisan) references to cardiovascular pathologyinduced or -contributed demises are to be found. This allows one to backdate this clinical association by hundreds of years. The possibility in the future to increase the sample size of these observations, preferably combining both palaeo-pathographic (artistic and documental) evidence with hard biological evidence from palaeopathological and biomedical analysis of mummies [24], will make it possible to better clarify the antiquity as well as phenotypic and genotypic characteristic of cardiovascular pathologies, as well as the presentation and morphology of their externally visible markers, hence enriching the cultural stock of cardiovascular research. Furthermore, the implementation of such multidisciplinary analyses will help science clarify how a mismatch between an evolved bodily constitution and the modern environment may determine diseases of civilisation, thus making it also possible to evaluate epidemiological variations in cardiovascular diseases throughout history. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
3
Informed consent No informed consent is required for this study.
Acknowledgements The authors wish to thank the Mäxi Foundation (Switzerland) for supporting this research and Mr. Owen Burke (Aylesbury, UK) for helping with the graphics and for carefully revising the English. References [1] WHO cardiovascular diseases fact sheet, http://www.who.int/mediacentre/ factsheets/fs317/en/ 2016 (accessed 10.11.2016). [2] F. Rühli, K. van Schaik, M. Henneberg, Evolutionary medicine: the ongoing evolution of human physiology and metabolism, Physiology (Bethesda) 31 (6) (2016) 392–397. [3] A. Uliasz, M. Lebwohl, Cutaneous manifestations of cardiovascular diseases, Clin. Dermatol. 26 (3) (2008) 243–254. [4] S.T. Frank, Aural sign of coronary-artery disease, N. Engl. J. Med. 289 (6) (1973) 327–328. [5] A.P. Agouridis, M.S. Elisaf, D.R. Nair, D.P. Mikhailidis, Ear lobe crease: a marker of coronary artery disease? Arch. Med. Sci. 11 (6) (2015) 1145–1155. [6] E. Lucenforte, M. Romoli, G. Zagli, G.F. Gensini, A. Mugelli, A. Vannacci, Ear lobe crease as a marker of coronary artery disease: a meta-analysis, Int. J. Cardiol. 175 (1) (2014) 171–175. [7] N.L. Patrakis, Diagonal earlobe creases, type A behavior and the death of Emperor Hadrian, West. J. Med. 132 (1) (1980) 87–91. [8] I.A. Guţiu, E. Galeţescu, L.I. Guţiu, L. Răducu, Diagonal earlobe crease: a coronary risk factor, a genetic marker of coronary heart disease, or a mere wrinkle. Ancient GrecoRoman evidence, Rom. J. Intern. Med. 34 (3–4) (1996) 271–278. [9] P. Charlier, S. Deo, Modern diagnosis of Flaubert's death mask, Lancet Neurol. 16 (1) (2017) 31. [10] J. Dunkerton, Giotto to Dürer: Early Renaissance Painting in the National Gallery, Yale University Press — National Gallery Publications, New Haven and London, 1991. [11] F.J. Rühli, F.M. Galassi, M. Haeusler, Palaeopathology: current challenges and medical impact, Clin. Anat. 29 (7) (2016) 816–822. [12] E.H. Gombrich, The Story of Art, Phaidon Press, London, 2006 300. [13] M. Kemp, Leonardo da Vinci: The Marvellous Works of Nature and Man, Oxford University Press, Oxford, 2006. [14] M. Traversari, R. Ballestriero, F.M. Galassi, A likely case of goiter in the Madonna col Bambino dormiente (1465/1470) by Andrea Mantegna (1431–1506), J. Endocrinol. Investig. 40 (2) (2017) 237–238. [15] N. Bukvic, J.W. Elling, Genetics in the art and art in genetics, Gene 555 (1) (2015) 14–22. [16] F.M. Galassi, S. Galassi, A case of Horton's disease (with its potential neurological symptoms) depicted in a portrait by Andrea Mantegna, Neurol. Sci. 37 (1) (2016) 147–148. [17] J. Battin, Art and the history of medicine. The dwarf pointed by Mantegna of Montua and the Morgante of Florence, Vesalius 15 (1) (2009) 5–8. [18] R. Bianucci, A. Perciaccante, O. Appenzeller, Painting neurofibromatosis type 1 in the 15th century, Lancet Neurol. 15 (11) (2016) 1123. [19] S. Miranda. The Cardinals of the Holy Roman Church. Biographical Dictionary. Entry: (21) 1. TREVISANO, Ludovico (1401–1465). Florida International University Libraries: (http://www2.fiu.edu/~mirandas/bios1440.htm (accessed 04.12.2016), reference 4). [20] I. Ammannati, Epistolae et Commentarii, apud Alexandrum Minutianum, Mediolani, 1506, p. 348. [21] J. Dequeker, Paleopathology of rheumatism in paintings, in: D.J. Ortner, A.C. Aufderheide (Eds.), Human Paleopathology: Current Syntheses and Future Options, Smithsonian Institution Press, Washington 1991, pp. 216–220. [22] C.J. Allsop, P.J. Gallagher, Temporal artery biopsy in giant-cell arteritis. A reappraisal, Am. J. Surg. Pathol. 5 (4) (1981) 317–323. [23] A.I. Al-Absi, B.M. Wall, C.R. Cooke, Medial arterial calcification mimicking temporal arteritis, Am. J. Kidney Dis. 44 (4) (2004) e73–e78. [24] R.C. Thompson, et al., Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations, Lancet 381 (2013) 1211–1222.
Ethical approval This paper does not contain any studies with human participants or animals performed by any of the authors.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art Francesco M. Galassi a,⁎, Claudio Borghi b, Roberta Ballestriero c,d, Michael E. Habicht a,e, Maciej Henneberg a,f, Frank J. Rühli a a
Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland Medical and Surgical Sciences Department, University of Bologna, Via Massarenti 9, Bologna, Italy University of the Arts, Central Saint Martins, Granary Building, 1 Granary Square, King's Cross, London N1C 4AA, UK d The Gordon Museum of Pathology, Kings College London, Guy's Campus, St. Thomas' Street, London SE1 9RT, UK e School of Humanities and Creative Arts (Department of Archaeology), Flinders University, Adelaide 5001, Australia f Biological Anthropology and Comparative Anatomy Unit, University of Adelaide, Adelaide 5005, Australia b c
a r t i c l e
i n f o
Article history: Received 6 January 2017 Accepted 24 February 2017 Available online xxxx Keywords: Frank's sign Earlobe crease Cardiovascular pathology Prevention Palaeopathology Mantegna Renaissance
a b s t r a c t Several studies have associated the earlobe crease sign, discovered by Sanders T. Frank in 1973, with cardiovascular pathology, yet very few studies have focused on the antiquity of this trait, with the most ancient one thought to date back to the Roman Emperor Hadrian (76–138 CE). This article presents two more cases from the Italian Renaissance in the works of the artist Andrea Mantegna (1431–1506) and examines them in a multidisciplinary fashion. © 2017 Elsevier B.V. All rights reserved.
1. Introduction: theoretical background and aim Cardiovascular diseases are responsible for about 31% of all deaths worldwide every year, which amount to 17.5 million casualties per annum [1]. Considered multifactorial nosological entities, they involve complex levels of interaction between environmental stressors and genetic background [2]. For this reason the possibility of identifying early visible signs of potential vascular deterioration has been stressed in an attempt to improve the overall diagnostic and preventive impact on patients' prognosis [3]. Of these, one of the most intriguing, and at the same time controversial, sign is the earlobe crease (ELC), also known as Frank's sign, named after its discoverer, Sanders T. Frank (1938–1998) [4]. It consists of a deep wrinkle, presenting either bilaterally or unilaterally and extending backwards from the intertragic notch to the auricle at an angle of about 45° [5]. Since the introduction of ELC in medical theory, a possible relation between coronary heart disease (CAD) has been sought for, with contrasting interpretations, either confirming or refuting this link [5]. A recent meta-analysis of existing literature on the matter, both clinical and necroscopic, has come to the conclusion that the hypothesis that ELC could represent a marker for ⁎ Corresponding author. E-mail address: [email protected] (F.M. Galassi).
CAD is very strong [6]. From a palaeopathological perspective, the first recorded evidence of this sign dates back the classical world, in particular to Emperor Hadrian (76–138 CE). Patrakis noticed the earlobe crease sign on a series of busts of the Emperor (Athens National Museum, Museo Nazionale Romano in Rome, Prado Museum in Madrid and the Uffizi Gallery in Florence) [7], which belong mostly to the Terminitype bust sculpted for his accession in 117 CE (when he was 41) and used until c. 121 CE. Patrakis established a link between this type of highly accurate form of art and literary evidence from the ancient sources suggesting that Hadrian suffered from epistaxis and ultimately developed dropsy, which he reinterpreted as a sign of a potentially underlying hypertension, also corroborated by the Emperor's behaviour as derived from the ancient sources, considered by Patrakis as clearly type A [7]. As an ex post commentary, it may be added that the accuracy of Patrakis's sculptural observation can be additionally confirmed by the presence of the sign in other busts of Hadrian not considered by the scholar, such as the one exhibited in the Vatican Museum. Moreover, similar observations were later made in ancient statues exhibited in the Louvre Museum in Paris, namely Hadrian again, the pseudoSeneca and the Greek orator Demosthenes (384–322 BCE) [8]. Recently Charlier and Deo have identified bilateral earlobe creases in the 1880made death mask of the famous French novelist Gustave Flaubert (1821–1880) [9]. This highlights the existence of a great hiatus between
http://dx.doi.org/10.1016/j.ijcard.2017.02.128 0167-5273/© 2017 Elsevier B.V. All rights reserved.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128
2
F.M. Galassi et al. / International Journal of Cardiology xxx (2017) xxx–xxx
the ancient world and the late modern period which leads to the question whether this sign was ever noted in the intercurring centuries and potentially related to unfavourable pathological outcomes. 2. Materials and methods An answer may be attempted by re-examining Italian Renaissance art, known to show a high level of accuracy [10]. In particular, here two pictorial representations of the earlobe crease by Andrea Mantegna (1431–1506) are presented: the tempera paintings Portrait of Cardinal Ludovico Trevisan (later renamed Ludovico Scarampi Mezzarota, 1459–1460) (Fig. 1) exhibited in the Berlin Gemäldegalerie [inventory number: 9], and Portrait of a Man in Profile (c. 1460), exhibited in the Milan “Poldi Pezzoli” collection [inventory number: 1592] (Fig. 2). The depictions are examined using a combination of traditional artistic and retrospective clinical analyses, when possible (1 of the 2 cases), strengthened by further medical data derived from the portrayed individuals' biographical accounts [11].
3. Results Both depictions show two aged male individuals in all their attributes of gravitas conveyed by the seriousness of their visual expressions, facial morphology and bearing. In the first portrait (Fig. 1), the cardinal's left earlobe (Fig. 1b) shows a well-defined crease highlighted by the chiaroscuro effect which gives depth to the sulcus crossing the soft tissue. While the profile view does not allow one to determine whether the subject presented the same sign contralaterally, it can furthermore be remarked how the generally mature and slightly aged look, as well as the three fatty folds on the external surface of the anterior cervical compartment originating from the submental area, point to a certain corpulence of the portrayed figure. As far as the second portrait (Fig. 2) is concerned, a different variant of septation can be appreciated in the left earlobe (Fig. 2b) – the right-sided one being once again invisible – broader and seemingly consisting of a double branching which roughly gives the anatomical conformation the morphology of a “V”. 4. Discussion Mantegna, a master of drawing and perspective, represented his figures as solid, tangible beings following the lead given by Masaccio (1401–1428). Solemn and statuesque, his figures look somewhat hard and harsh, almost wooden. The late art historian Ernst Gombrich
Fig. 1. a Portrait of Cardinal Ludovico Trevisan. (1459–1460, tempera on panel painting, 44.8 × 33.9 cm) Gemäldegalerie, Berlin, Germany. Image in the public domain from wikisource: https://it.wikipedia.org/wiki/Ritratto_del_cardinale_Ludovico_Trevisan#/ media/File:Ludovico_trevisano_portrait_by_andrea_mantegna.jpg. 1b. Magnified detail of the cardinal's left ear, showing a crease across his auricular lobe.
Fig. 2. a Portrait of a Man in Profile (c. 1460, tempera on panel painting, 32.3 × 28.8 cm). “Poldi Pezzoli” Museum, Milan, Italy. Image in the public domain from wikisource: https://it.wikipedia.org/wiki/Profilo_d'uomo#/media/File:Andrea_Mantegna_114.jpg. 2b. Detail of the unidentified individual's left ear, showing two sulci which resemble the shape of the letter “V”.
(1909–2001) suggested that “[the] more conscientiously we copy a figure line by line and detail by detail, the less we can imagine that it ever really moved and breathed” [12]. Even though a full naturalness of representation would only be achieved later through Leonardo da Vinci's (1452–1519) sfumato technique [13], for his precision in copying reality, Mantegna is to be regarded a trustworthy portrayer of reality. Furthermore, with specific reference to pathology, he is well documented to have accurately represented conditions – often before their actual scientific discoveries – such as goitre [14], Down syndrome [15], turgidity of the temporal artery suggestive of Horton's disease and ricketts [16], and dwarfism [17], the latter recently proposed to be representative of an ancient case of type 1 neurofibromatosis [18]. Therefore, the eventuality that, albeit without a strictly scientific purpose, but rather wishing to highlight the signs of mature age, Mantegna truly represented earlobe creases is likely. As far as Cardinal Trevisan is concerned, additional information can be retrieved from his historical record: the cardinal's death, which occurred five to six years after the portrait was made, in Rome on 22nd March 1465, might very well have been the result of oedema [19], once known by the currently obsolete term “dropsy”, a common final pathophysiological step of several organ failures such as hepatic and renal, and well known to be associated with cardiovascular disease. Support for such a retrospective diagnosis is to be found in a letter by the humanist Iacopo Ammannati (1422–1472), who reports that, as the newly elected, and former political enemy, pope Paulus II (born Pietro Barbo, 1417–1471) paid Trevisan a visit after his election, found him, diseased in his feet (“aeger pedibus”) and unable to move from his chair (“e sella se movere non poterat”) [20]. While these words do not allow a clear-cut semiological reassessment and further peripheral etiologies (e.g. rheumatological or orthopaedic conditions, thromboflebitis, varicose veins) should be taken into account, they clearly convey the chronic nature of the cardinal's ailments, underlined also by his seemingly nullified locomotion. A cardiac oedema may very well explain this clinical picture and would likely cause the cardinal's inability to move not only as a result of lower limb impairment but also potentially as a result of a generalised oedema (e.g. ascites) causing the body size to increase as result of fluid retention. Such a clinical scenario thus provides an interesting comparison with Emperor Hadrian's case.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128
F.M. Galassi et al. / International Journal of Cardiology xxx (2017) xxx–xxx
As far as the second portrait is concerned, a different variant of septation can be appreciated in the left earlobe – the right-sided one being once again invisible – broader and seemingly consisting of a double branching which roughly gives the anatomical conformation the morphology of a “V”. The identity of the character is mysterious, which makes it impossible to retrieve primary documental and biographical information which would be essential to form a more precise retrospective diagnosis. The subject's advanced age and the eyecatching arborisation present on his left temple have already been subjected to retrospective diagnostics allowing the production of a rheumatological hypothesis, namely giant-cell (Horton's) arteritis [16], whose pictorial record appears to be rather established in Renaissance art [21]. While cardiac and rheumatological diseases can logically coexist, additional monopathological vascular retrospective diagnoses of the temporal artery reflecting a more general underlying cardiovascular pathological background, of which the earlobe creases can be seen as an external marker, may be cautiously suggested. In particular, arteriosclerosis and atherosclerosis, or even medial arterial calcification, are nosological entities which can mimick temporal arteritis making temporal artery biopsy necessary in order to resolve the diagnostic uncertainty [22,23]. However, unlike in Cardinal Trevisan's case, the purely morphological nature of this observation in the aged individual portrayed by Mantegna, unsupported by further historical and archival evidence on the patient's medical condition, reasonably leaves the subject open to debate. 5. Conclusion While its association with coronary heart disease was first put forward only in 1973, the earlobe crease sign has been almost continuously recorded throughout history, potentially and more realistically just as a sign of advanced or old age. However – when possible – if one reexamines the historical accounts of the portrayed characters (e.g. Hadrian and Cardinal Trevisan) references to cardiovascular pathologyinduced or -contributed demises are to be found. This allows one to backdate this clinical association by hundreds of years. The possibility in the future to increase the sample size of these observations, preferably combining both palaeo-pathographic (artistic and documental) evidence with hard biological evidence from palaeopathological and biomedical analysis of mummies [24], will make it possible to better clarify the antiquity as well as phenotypic and genotypic characteristic of cardiovascular pathologies, as well as the presentation and morphology of their externally visible markers, hence enriching the cultural stock of cardiovascular research. Furthermore, the implementation of such multidisciplinary analyses will help science clarify how a mismatch between an evolved bodily constitution and the modern environment may determine diseases of civilisation, thus making it also possible to evaluate epidemiological variations in cardiovascular diseases throughout history. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
3
Informed consent No informed consent is required for this study.
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Ethical approval This paper does not contain any studies with human participants or animals performed by any of the authors.
Please cite this article as: F.M. Galassi, et al., Palaeopathology of the earlobe crease (Frank's sign): New insights from Renaissance art, Int J Cardiol (2017), http://dx.doi.org/10.1016/j.ijcard.2017.02.128