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The antiquity of the spondyloarthritides: Presentation of one of the oldest Neolithic cases in Western Europe
International Journal of Paleopathology 24 (2019) 229–235
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The antiquity of the spondyloarthritides: Presentation of one of the oldest Neolithic cases in Western Europe
T
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Richard Donata, , Fatima-Zohra Mokranea,b,c, Hervé Rousseaub, Fabrice Dedouita,d, Norbert Telmona,e, Éric Crubézya a Laboratory of Molecular Anthropology and Image Synthesis (AMIS), University of Toulouse, French National Centre for Scientific Research (CNRS), UMR 5288, Faculty of Medicine Purpan, 37, Allées Jules Guesde, 31000, Toulouse, France b Department of Radiology, CHU Toulouse-Rangueil, 1, avenue du Pr Jean Poulhès TSA 50032, 31059, Toulouse Cedex 9, France c Department of Radiology, New York-Presbyterian, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY, 10032, USA d University Center of Legal Medicine, Lausanne-Geneva, Forensic Imaging and Anthropology Unit, Chemin de la Vulliette 4, CH-1000, Lausanne 25, Switzerland e Department of Forensic Medicine, CHU Toulouse-Rangueil, 1, avenue du Pr Jean Poulhès TSA 50032, 31059, Toulouse Cedex 9, France
A R T I C LE I N FO
A B S T R A C T
Keywords: Axial spondyloarthritis Neolithic Epidemiological transition
In humans, little is yet known about the origins of the inflammatory rheumatisms of the spondyloarthritides group, especially regarding the period of their emergence. However, a better knowledge of their history would help to clarify their aetiology. We report a paleopathological case of European origin, dated from the late Neolithic (3621-3023 cal BC), consisting of an isolated vertebral block combining erosion, ossification and severe anterior and posterior ankylosis. The lesional presentation is very suggestive of a severe form of axial spondyloarthritis. This specimen and some other rare cases from the same period found in Western Europe suggest that these diseases appeared, in this geographical region, in evolving groups of humans as part of the demographic and epidemiological transition that constituted the Neolithic period. The emergence of infectious agents and the profound dietary changes that occurred during this period of human history may have favoured the appearance of the spondyloarthritides.
1. Introduction The concept of spondyloarthritis (SpA) defines a distinct nosological entity that includes different phenotypic presentations of chronic inflammatory rheumatism. This heterogeneous group of diseases is based on the existence of common clinical and imaging characteristics: axial lesions (pelvispinal syndrome) and/or peripheral lesions (arthritis, enthesitis, dactylitis), possible extra-articular manifestations (uveitis, psoriasis, balanitis, urethritis, diarrhoea, inflammatory bowel disease) and a preferred pathological target represented by enthesitis and the absence of rheumatoid factor (Dougados et al., 1991; Rudwaleit et al., 2009a, b, 2011; Zochling et al., 2005). In addition, there is a particular genetic tendency: a strong familial aggregation, and association with the HLA B27 antigen and other susceptibility loci, such as the interleukin-1 gene cluster (Brown et al., 2000; Reveille, 2011; Robinson and Brown, 2014). The standard nosological forms of this group are represented by ankylosing spondylitis (AS), psoriatic arthritis (PsA), enteropathic arthritis/arthritis associated with inflammatory bowel
disease (IBD), reactive arthritis (ReA) and all undifferentiated spondyloarthritis (USpA). The different clinical expressions of these disorders explain the several successive classification systems (Rome criteria, New York criteria, modified New-York criteria, etc.), of which the most recent, defined by the Assessment of SpondyloArthritis International Society (ASAS), distinguishes: 1) the predominantly axial spondyloarthritides (ax-SpA), with early involvement of the sacroiliac joint (sacroiliitis) and vertebral structural lesions (erosion, ossification, ankylosis) (Rudwaleit et al., 2009a, b); 2) the predominantly peripheral spondyloarthritides, which include articular forms (monoarthritis or asymmetric oligoarthritis, erosive or non-erosive) as well as enthesitic forms (inflammatory involvement of the enthesis) (Rudwaleit et al., 2011). In the current global population, the overall estimated prevalence of SpA varies between 0.01% and 2.5%, depending on the geographical distribution of the HLA B27 antigen, the sensitivity of diagnostic criteria and the methodology of epidemiological investigations (Stolwijk et al., 2012). In ancient populations, rare epidemiological data also testify to a great variability in prevalence, which may be
⁎ Corresponding author at: Laboratoire AMIS (Anthropologie Moléculaire et Imagerie de Synthèse), CNRS, UMR 5288, Université Toulouse III Paul Sabatier, Bât. 4R3 (1er étage), 118, Route de Narbonne, 31062, Toulouse Cedex 9, France. E-mail addresses: [email protected], [email protected] (R. Donat).
https://doi.org/10.1016/j.ijpp.2018.12.005 Received 15 June 2018; Received in revised form 21 December 2018; Accepted 21 December 2018 1879-9817/ © 2018 Elsevier Inc. All rights reserved.
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Natica etc.) and limestone beads (Donat et al., 2014). The typology and technological characteristics of the furnishings reveal their origin in the early and intermediate phases of the late Neolithic period of the Paris Basin (3600-3000 cal BC) as it has been defined in the north-central part of France (notably from the furnishings discovered in the Marne hypogea; Augereau et al., 2007; Cottiaux and Salanova, 2014). Moreover, they are identical to those found in another hypogeum (located 30 m from hypogeum I) whose radiocarbon dates are centred in the middle of the 4th millennium BC (3600-3400 cal BC) (Donat et al., 2014). The human remains discovered in the Mont-Aimé hypogeum I were subjected to three radiometric datings (three left femurs attributable to adult individuals), which indicate measurements between 3621 and 3023 cal BC: 3621-3356 cal BC (GrN-31025: 4650 ± 40 BP), 34913102 cal BC (GrN-31026: 4560 ± 40 BP) and 3344-3023 cal BC (GrN31027: 4470 ± 40 BP) (CALIB radiocarbon calibration program 7.04 (Stuiver and Reimer, 1993), using the IntCal13 atmospheric calibration curve (Reimer et al., 2013), with corresponding 95% HPD (Highest Posterior Density) regions). The specimen presented in this study comes from the posterior part of the burial chamber, which had the oldest date (3621-3356 cal BC). However, considering the context (dislocated bones), it seems necessary to retain a broader chronological interval (3621-3023 cal BC). The very ancient dates obtained designate the Mont-Aimé hypogeum I as one of the oldest known collective burials of the Paris Basin The bone specimen was examined macroscopically and radiologically. Sectional imaging was performed on a multi-slice CT scanner (Siemens Sensation 16, Erlangen, Germany). The physical acquisition parameters are as follows: voltage: 120 KVp; tube current: 650 mAs; slice thickness: 0.75 mm. Several reconstructions were made, using bone and smoothing filters.
elevated in certain populations: for example, in a collection of skeletons of individuals of Portuguese origin from the 19th-20th centuries, the percentage of SpA cases was 6.7% (Martin-Dupont et al., 2006). However, the spondyloarthritides are not limited to humans or non-human primates (gorilla, chimpanzees, orangutan etc; Rothschild and Woods, 1992a). In fact, these diseases affect a wide variety of fossil animal species (mammal-like reptiles, dinosaurs, Cenozoic crocodiles, etc.), current wild species (great apes, bears, rhinoceroses, elephants, etc.) and domestic species (dogs, cows, horses etc.) (Rothschild and Feldtkeller, 2016; Rothschild and Martin, 2006: 49–62). At present, the spondyloarthritides are an essentially trans-mammalian phenomenon whose prevalence has increased over time (Rothschild, 2017). Fossil zoological data reveal that SpAs have a long history, occurring in the Early Permian, nearly 300 million years ago (Rothschild and Feldtkeller, 2016). In humans, the history of these diseases does not seem to date back beyond a few millennia, covering only part of the Holocene (Rothschild and Feldtkeller, 2016). In Western Europe, the oldest human cases of SpA seem contemporary with the development of Neolithic agropastoral communities (5700/5500-2000 cal BC) (Ortner, 2003a; Zorab, 1961). For this period, which ushered in a change in the way of life and subsistence for human populations marked by a major economic and demographic transition, reported cases of SpA remain extremely rare and isolated, however. In the study of past populations, the state of conservation and representation of the skeletons, which are sometimes dislocated and incomplete, makes retrospective diagnosis difficult, whilst certain equivocal paleopathological manifestations clearly raise the possibility of a differential diagnosis (Martin-Dupont et al., 2006). This situation explains, in part, the difficulty in identifying paleopathological disorders such as SpA, which currently have different phenotypic forms (Rudwaleit et al., 2009a, b, 2011) and whose diagnostic criteria are based, moreover, on a collection of clinical, laboratory and medical imaging findings not applicable to dry bone, apart from certain directly super-imposable radiological signs. The purpose of our presentation is to contribute to the knowledge of the origin and the history of these diseases through the paleopathological presentation of an ancient case of European origin, dated from the late Neolithic (36213023 cal BC), having a lesional presentation very suggestive of axial spondyloarthritis. A review of the paleopathological literature can better contextualize the specimen, describing it in light of the oldest known human cases of SpA.
3. Results The bone specimen consists of a segmental vertebral block (preserved in its near entirety) resulting from the complete fusion of three lumbar vertebrae (L2-L4) by a severe ankylosis process involving the vertebral bodies and arches, at the expense of the tendon-ligament system (Figs. 3,4 ). Ankylosis of the body is the culmination of a process of sub-ligamentous interbody ossification due to the development of bony bridges covering the anterior and lateral surfaces of the vertebral bodies and the periphery of the intervertebral disc spaces (spaces lacking any bone production can be seen at the anterior portions of the L2-L3 and L3-L4 joint spaces and the posterolateral L3-L4 joint space). Anterior and anterolateral bony bridges can also be observed on the superior endplate of L2 (L1-L2 joint space) and inferior L4 (L4-L5 joint space), but without fusion. Bone productions mainly consist of vertically-oriented ossifications on a homogeneous and compact surface, but there are also more localized exuberant proliferations with a horizontal trajectory (L3 left anterolateral inferior angle) (Fig. 3). The modifications of the anterosuperior and anteroinferior body edges contribute to the loss of anterior concavity of the vertebral body, giving it a rectilinear aspect on the lateral view ("squaring") (Fig. 3). In addition, there are signs of ossification of the intervertebral disc combined with destructive lesions, in the form of mirror-image macro-geodes on the anterior portion of the inferior L2 endplate and superior L3 endplate (Fig. 5). The vertebral endplates also have a sclerotic appearance, predominantly at the superior L4 endplate. There is no clear sign of osteoporosis. Fusion of the posterior arches results from an ossification process extending to the joint capsules of the facet joints, which are completely fused together (the joint spaces are no longer visible), as well as accessory ligaments, uniting: 1) the vertebral laminae: the yellow ligaments are completely ossified and subsumed by amorphous bone production; 2) the costiform processes: the insertions of the intertransverse ligaments are covered with bone outgrowths, formed of small
2. Materials and methods The reported case consists of an isolated bone specimen, a vertebral block attributable to an adult (over 20 years old) collected in the MontAimé hypogeum I (Val-des-Marais, Marne, France), a Neolithic collective tomb located in the Champagne region, 40 km south of Reims, on the eastern margin of the Paris Basin (Fig. 1). The Mont-Aimé hypogeum I belongs to a group of 160 artificial cavities spread over a limited area (less than 40 km2). These hypogea were used as collective burial sites during the late Neolithic period (3600-3000 cal BC) (Bailloud, 1974; Chambon, 2003). Discovered and excavated in 1982 (Champagne-Ardenne Regional Archaeology Service; Chertier, 1983), the Mont-Aimé hypogeum I included an access corridor and an elongated burial chamber (17 m2) dug in the local chalk. The grave contained the skeletal remains of nearly sixty individuals (25 adults, 32 children and adolescents), whose skeletons were found on excavation to be completely dislocated: none had retained its anatomical coherence, the human remains having been displaced and regrouped during successive burials (Fig. 2). Among the human bones, 272 artifacts were discovered, examples of: 1) the lithic industry (102 elements, mostly in local flint: arrowheads, blades, axes and scrapers), with predominantly transverse arrowheads (78 items) (Langry-François, 2004); 2) bone and antler artifacts (13 items: axe sheaths, smoothing tools and bone bodkins); and 3) personal ornaments, with 157 items, essentially shell ornaments (Dentalium, Oliva, 230
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Fig. 1. Geographical location of the Mont-Aimé hypogeum I (Marne, France).
remodelling of the entheses is also reflected in the ossification of all insertion areas of the posterior ligamentous complex and by ankylosis of the facet joint capsules. In this context, the observed destructive lesions, which are associated with disc calcifications, suggest a spondylodiscitis (Andersson lesion), which can result from inflammatory and/ or mechanical factors (Bron et al., 2009).
enthesophytes and amorphous bone production; and 3) the spinous processes: the interspinous ligaments are ossified, in the form of compact and homogeneous layers, which form a thin wall connecting the adjacent spinous processes, with the notable exception of the fourth lumbar vertebra, whose facet joint mass reveals bilateral isthmic lysis (spondylolysis) (Fig. 3). Destroyed post mortem, the apices of the spinous processes (insertion of the supraspinous ligaments) are not observable.
4.2. Differential diagnosis 4. Discussion
Diffuse idiopathic skeletal hyperostosis (DISH) represents the main differential diagnosis in axial forms of SpA, with which it shares apparent radiological similarities and a privileged target: the enthesis. DISH represents a distinct clinical entity, a non-inflammatory syndrome characterized by an ossification of the peripheral entheses and by axial manifestations consisting in the calcification and ossification of the anterior longitudinal ligament, forming bony bridges that finally merge with each other (Mader et al., 2013; Resnick et al., 1975; Resnick and Niwayama, 1976). The appearance of bone spurs, which creates anterolateral bone moulding (predominantly right), is mainly localized to the middle and lower thoracic levels of the spine but differs from the syndesmophytes of the spondyloarthritides (Baraliakos et al., 2012; Olivieri et al., 2009). The process of entheses ossification can extend to all syndesmoses of the vertebral arch, but without erosion, subchondral sclerosis or fusion of the facet joints (Resnick and Niwayama, 1976). The appearance and combination of the observed structural lesions also make it possible to rule out infectious spondylodiscitis, which may be suggested by the mirror-image intra-somatic macro-geodes. The typical or suggestive signs of spinal tuberculosis (Pott's disease), which can cause anterior and posterior ankylosis, are also absent here (extensive destruction with collapse, osteomyelitis or periosteal reactions, etc.) (Ortner, 2003b). Ochronotic arthropathy can also progress to
4.1. Retrospective diagnosis The spinal structural changes observed include severe multifocal involvement combining erosion, ossification and ankylosis, in which entheseal remodelling predominates (tendon insertion areas, ligaments and joint capsules at the bone) (Claudepierre and Voisin, 2005). The lesional presentation is very suggestive of a progressive axial form of spondyloarthritis, whose paleopathological diagnostic criteria have been summarized by various authors (for a review of the paleopathological diagnostic criteria, see, for example, Martin-Dupont et al., 2006; Samsel et al., 2014). The anterior and lateral interbody bony bridges reproduce the typical image of bridging syndesmophytes, corresponding to ossification of the periphery of the annulus fibrosus (Resnick and Niwayama, 1983). In the spondyloarthritides, the formation of syndesmophytes consists of the apposition of reactive bone that follows the initial erosive lesion (Romanus lesions in early spondylitis) in the enthesitis process involving the peripheral insertion of the annulus fibrosus (Ball, 1971; Claudepierre and Voisin, 2005): these modifications result in the loss of anterior concavity of the vertebral bodies (Jacobson et al., 2008). On the examined bone specimen, the 231
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Fig. 2. Plan of the funeral chamber of the Mont-Aimé hypogeum I, with distribution of human skeletal remains.
documented, if not equivocal. They consist of isolated vertebral blocks (two to three vertebrae), which were found in collective burial sites attributed to the Neolithic period, without further clarification. These consist of two bone parts discovered in Sweden (Hemmor, Gotland and Mysinge, Öland) and described by Fürst (1914: 25, Figs. 10, 11), as well as a specimen presented by Pales (1930: 117; pl. XXIV, Figs. 1,2) found in the Baumes-Chaudes cave (Lozère, France). Fürst (1914) advanced the diagnosis of "arthritis deformans anchylopoiëtica". Pales (1930), whose arguments are convincing, concluded on a case of "rhyzomelic spondylosis". In an article devoted to the antiquity of rheumatic diseases, Snorrason (1942) succinctly cites two cases of "spondylarthritis anchylopaetica". These were probably isolated vertebral blocks, one of which was presented as belonging to the French Neolithic period and the other to the Danish Neolithic period. These previously described different bone parts would require a review in light of current knowledge. Similarly, the chrono-cultural context remains to be clarified. In another geographical context, that of West Africa and the Near East, the oldest known specimen of SpA comes from the Hassi el Abiod region in the Malian Sahara. It corresponds to a Neolithic skeleton dated about 7000 BP, which presents signs suggestive of peripheral articular spondyloarthritis, with asymmetrical ankylosis of the wrist
multi-stage disc calcification and ankylosis of the body, but without formation of syndesmophytes or facet joint fusion (Lagier and Sit'aj, 1974; Phornphutkul et al., 2002). Finally, severe forms of skeletal fluorosis may produce more or less extensive vertebral ankylosis in the form of periosteal hyperostosis, whose appearance differs from the structural changes in the spondyloarthritides, which preferentially affects the entheses (Littleton, 1999; Ortner, 2003c).
4.3. Contribution to the history of spondyloarthritides In Western Europe, in addition to the Mont-Aimé hypogeum I specimen presented in this study (3621-3023 cal BC), one of the oldest cases of SpA described to date comes from the Neolithic Hoguette cairn at Fontenay-le-Marmion (Calvados, France), dated from the first half of the 4th millennium BC (4000-3500 cal BC). It corresponds to the remains of a man with axial involvement compatible with ankylosing spondylitis (AS): bilateral ankylosis of the sacroiliac joints and ankylosis of the vertebral bodies and facet joints of all conserved vertebrae (T10 to L4), demonstrating the classic "bamboo spine" appearance (Torre and Dastugue, 1976). Described previously, other cases of prehistoric spondyloarthritides of European origin are rare and poorly 232
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Fig. 3. Macroscopic presentation in anterior (a), right lateral (b) and posterior (c) views of the lumbar vertebral block showing severe ankylosis involving the body and vertebral arches. The anterior view image (a) shows the anterior and lateral interbody bony bridges with vertical orientation (white arrows) and the more localized presence of horizontally developing bone spurs (white circle). The lateral view (b) highlights the rectilinear aspect ("squaring") of the vertebrae. The posterior view (c) shows ankylosis of the facet joint capsules and ossification of all insertion areas of the ligamentous complex.
these diseases, the oldest of which is attributed to the 3rd dynasty (2700-2600 cal BC). In North America, the oldest possible case of SpA (Modoc rock shelter, Illinois, USA) is attributed to a broad time interval, between 6219-2765 BC (Neumann, 1966, cited by Arriaza, 1993). Among the oldest cases in this part of the American continent are also four skeletons (4/87 = 4.6%; Rothschild and Woods, 1992b) from the Frontenac Island site (New York, USA) occupied between 4900 and 3700 BP (Ellis et al., 1990: 106). In a sample of various North American prehistoric populations (1657 individuals in total, including those of Frontenac Island), dated between 4900 and 400 BP, Rothschild and Woods (1992b) noted thirty-five cases of SpA, with frequencies varying between 0.7 and 5.1%, depending on the groups of humans considered. The authors did not observe a significant increase in the prevalence of these diseases over time (Rothschild and Martin, 2006; Rothschild and Woods, 1992b). In South America, in a sample of mummies from different prehistoric groups of humans (7000 BC-1530 AD) having populated the northern part of present-day Chile, at least 4.4% of the examined individuals (15/340) presented signs of SpA (Arriaza, 1993). The oldest cases are dated between 2200-1000 BC (Chinchorro culture; 2/ 51 = 3.9%). Moreover, the study of this sample revealed an increase in the prevalence of SpA over time and, notably, in human groups having acquired an agropastoral economy (Arriaza, 1993). Finally, in comparison with the age of some known specimens in Western Europe, West Africa, the Middle East and the American continent, the Asian continent does not contain such ancient cases of SpA, except for a possible peripheral form discovered in Japan, dated between 3650-3000 BC (Inoue et al., 2005).
Fig. 4. Sagittal view of the Volume Rendering Technique (VRT) reconstruction, which allows a better visualization of bone spur reliefs.
and erosive lesions of the proximal interphalangeal joints (Rothschild et al., 1999). In Upper Egypt, the oldest identified cases of SpA come from the Nile Valley and are attributable to the predynastic era (4000/ 3900-2900 cal BC; Hendrickx, 2006). The best-dated specimens have been discovered in the predynastic necropolis of Adaïma; there are two individuals: one, with an axial form of SpA, is attributed to the Naqada IIIA period (3600-3350 cal BC), and the other individual, with a possible peripheral form, is attributed to a broader chronological interval, between 3600-2900 cal BC (Crubézy, 2017: 90–94). In the same chrono-cultural context (predynastic period), but without precise dating, two cases identified by Bourke (1971) are added; one from the Naqada "Great Cemetery" and the other case from Cemetery B of Hu. Finally, we note that Ruffer (1921: 212–267) described several cases of
5. Conclusion The paleopathological study of a vertebral block collected in a Neolithic collective grave, Mont-Aimé hypogeum I, testifies to the existence of an advanced axial form of spondyloarthritis dated from the second half of the 4th millennium BC, or even a little earlier (36213023 cal BC). This specimen represents, with that of the Neolithic Hoguette Cairn in Fontenay-le-Marmion (Calvados, France), one of the oldest cases of this type of inflammatory rheumatism reported in Western Europe. In this geographical region, no cases of 233
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Fig. 5. Coronal reconstructions passing through: a) the anterior third of the vertebral bodies: presence of mirrorimage macro-geodes on the anterior part of the inferior L2 endplate and superior L3 endplate (white arrows); b) the middle third of the vertebral bodies: visualization of anterior and anterolateral bone spurs (fused syndesmophytes, white arrows) and ossification of the intervertebral disc (red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
spondyloarthritis are known in the groups of hunter-gatherers who preceded the agropastoral societies of the Neolithic period (Villotte, 2009). The paleopathological data thus suggest that the profound changes during the Neolithic period (sedentarization and concentration of human groups, population growth, domestication of plants and animals, and transformed diets) constituted, in Western Europe, a fertile ground for the development of inflammatory rheumatisms similar to the current forms of spondyloarthritides. The causes are to be sought in, among others, the emergence and the increased transmissibility of certain infectious agents (zoonoses) and the change of diet: these two factors are involved in the modifications of the intestinal microbiota (dysbiosis) (Harper and Armelagos, 2013), whose role is suspected in the aetiopathogenesis of SpA (Breban, 2016; Breban et al., 2017). It is possible that this pattern has prevailed in human groups of different geographical origins (Western Europe, Nile Valley, Northern Chile, etc.). On the other hand, zoological data, showing the extent of the phenomenon and its increasing prevalence over time, regardless of lifestyle and means of subsistence (e.g., wild versus domestic, carnivorous versus herbivore etc; Rothschild, 2017), suggest a more comprehensive explanatory model.
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Acknowledgements We would like to sincerely thank the Champagne-Ardenne Regional Archaeology Service, in the person of its Director, Mr. Yves Desfossés, for placing at our disposal the important unpublished documentation relating to the archaeological excavation of the Mont-Aimé hypogeum I. These data were used as part of a scientific thesis (Biology-Health) prepared for the University of Toulouse, UMR 5288, Faculty of Medicine Purpan. Our thanks also go to the translator of this article, Dr. James Herbert, as well as to Yaramila Tchérémissinoff (INRAP) for his proofreading of the archaeological portion. Finally, we thank the Editor-in-Chief of this journal and the two anonymous reviewers for their constructive comments that have helped to significantly improve the content of this article. References Arriaza, B.T., 1993. Seronegative spondyloarthropathies and diffuse idiopathic skeletal hyperostosis in ancient northern Chile. Am. J. Phys. Anthropol. 91, 263–278.
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changing microbe-scape: time to revisit some old tales and tell some new ones. Am. J. Phys. Anthropol. 57, 135–152. Hendrickx, S., 2006. Predynastic–early dynastic chronology. In: Hornung, E., Krauss, R., Warburton, D.A. (Eds.), Ancient Egyptian Chronology. Brill, Leiden, pp. 55–93. Inoue, K., Takigawa, W., Sato, M., Kumagai, M., Dodo, Y., Katayama, K., 2005. A possible case of spondyloarthropathy in a prehictoric Japanese skeleton. Int. J. Osteoarchaeol. 15, 186–195. Jacobson, J.A., Girish, G., Jiang, Y., Resnick, D., 2008. Radiographic evaluation of arthritis: inflammatory conditions. Radiology 248, 378–389. Lagier, R., Sit’aj, S., 1974. Vertebral changes in ochronosis. Ann. Rheum. Dis. 33, 86–92. Langry-François, F., 2004. Le mobilier lithique des sépultures en hypogée du département de la Marne. Anthropologica et Præhistorica 115, 91–102. Littleton, J., 1999. Paleopathology of skeletal fluorosis. Am. J. Phys. Anthropol. 109, 465–483. Mader, R., Verlaan, J.J., Buskila, D., 2013. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat. Rev. Rheumatol. 9, 741–750. Martin-Dupont, S., Cunha, E., Rougé, D., Crubézy, E., 2006. Spondylarthropathy striking prevalence in a 19th–20 th century Portuguese collection. Joint Bone Spine 73, 303–310. Neumann, H.W., 1966. A preliminary survey of the paleopathology of an archaic American Indian population. Bull. Tulane Univ. Med. Fac. 25, 195–206. Olivieri, I., D’Angelo, S., Palazzi, C., Padula, A., Mader, R., Khan, M.A., 2009. Diffuse idiopathic skeletal hyperostosis: differentiation from ankylosing spondylitis. Curr. Rheumatol. Rep. 11, 321–328. Ortner, D.J., 2003a. Erosive arthropathies, enthesopathies, and miscellaneous pathological conditions of joints. Identification of Pathological Conditions in Human Skeletal Remains, second ed. Academic Press, USA, pp. 561–587. Ortner, D.J., 2003b. Infectious diseases: tuberculosis and leprosy. Identification of Pathological Conditions in Human Skeletal Remains, second ed. Academic Press, USA, pp. 227–271. Ortner, D.J., 2003c. Metabolic disorders. Identification of Pathological Conditions in Human Skeletal Remains, second ed. Academic Press, USA, pp. 383–418. Pales, L., 1930. Paléopathologie et pathologie comparative. Masson, Paris. Phornphutkul, C., Introne, W.J., Perry, M.B., Bernardini, I., Murphey, M.D., Fitzpatrick, D.L., Anderson, P.D., Huizing, M., Anikster, Y., Gerber, L.H., Gahl, W.A., 2002. Natural history of alkaptonuria. N. Engl. J. Med. 347, 2111–2121. Reimer, P.J., Bard, E., Bayliss, A., Beck, J.W., Blackwell, P.G., Bronk Ramsey, C., Buck, C.E., Cheng, H., Edwards, R.L., Friedrich, M., Grootes, P.M., Guilderson, T.P., Haflidason, H., Hajdas, I., Hatté, C., Heaton, T.J., Hoffmann, D.L., Hogg, A.G., Hughen, K.A., Kaiser, K.F., Kromer, B., Manning, S.W., Niu, M., Reimer, R.W., Richards, D.A., Scott, E.M., Southon, J.R., Staff, R.A., Turney, C.S.M., van der Plicht, J., 2013. IntCal13 and Marine13 radiocarbon age calibration curves 0–50,000 years cal BP. Radiocarbon 55, 1869–1887. Resnick, D., Niwayama, G., 1976. Radiographic and pathologic features of spinal involvement in Diffuse Idiopathic Skeletal Hyperostosis (DISH). Radiology 119, 559–568. Resnick, D., Niwayama, G., 1983. Entheses and enthesopathy. Anatomical, pathological, and radiological correlation. Radiology 146, 1–9. Resnick, D., Shaul, S.R., Robins, J.M., 1975. Diffuse idiopathic skeletal hyperostosis (DISH): Forestier’s disease with extraspinal manifestations. Radiology 115, 513–524. Reveille, J.D., 2011. The genetic basis of spondyloarthritis. Ann. Rheum. Dis. 70, 44–50. Robinson, P.C., Brown, M.A., 2014. Genetics of ankylosing spondylitis. Mol. Immunol. 57, 2–11. Rothschild, B.M., 2017. Transcending human spondyloarthritis: implications of the
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The antiquity of the spondyloarthritides: Presentation of one of the oldest Neolithic cases in Western Europe
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Richard Donata, , Fatima-Zohra Mokranea,b,c, Hervé Rousseaub, Fabrice Dedouita,d, Norbert Telmona,e, Éric Crubézya a Laboratory of Molecular Anthropology and Image Synthesis (AMIS), University of Toulouse, French National Centre for Scientific Research (CNRS), UMR 5288, Faculty of Medicine Purpan, 37, Allées Jules Guesde, 31000, Toulouse, France b Department of Radiology, CHU Toulouse-Rangueil, 1, avenue du Pr Jean Poulhès TSA 50032, 31059, Toulouse Cedex 9, France c Department of Radiology, New York-Presbyterian, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY, 10032, USA d University Center of Legal Medicine, Lausanne-Geneva, Forensic Imaging and Anthropology Unit, Chemin de la Vulliette 4, CH-1000, Lausanne 25, Switzerland e Department of Forensic Medicine, CHU Toulouse-Rangueil, 1, avenue du Pr Jean Poulhès TSA 50032, 31059, Toulouse Cedex 9, France
A R T I C LE I N FO
A B S T R A C T
Keywords: Axial spondyloarthritis Neolithic Epidemiological transition
In humans, little is yet known about the origins of the inflammatory rheumatisms of the spondyloarthritides group, especially regarding the period of their emergence. However, a better knowledge of their history would help to clarify their aetiology. We report a paleopathological case of European origin, dated from the late Neolithic (3621-3023 cal BC), consisting of an isolated vertebral block combining erosion, ossification and severe anterior and posterior ankylosis. The lesional presentation is very suggestive of a severe form of axial spondyloarthritis. This specimen and some other rare cases from the same period found in Western Europe suggest that these diseases appeared, in this geographical region, in evolving groups of humans as part of the demographic and epidemiological transition that constituted the Neolithic period. The emergence of infectious agents and the profound dietary changes that occurred during this period of human history may have favoured the appearance of the spondyloarthritides.
1. Introduction The concept of spondyloarthritis (SpA) defines a distinct nosological entity that includes different phenotypic presentations of chronic inflammatory rheumatism. This heterogeneous group of diseases is based on the existence of common clinical and imaging characteristics: axial lesions (pelvispinal syndrome) and/or peripheral lesions (arthritis, enthesitis, dactylitis), possible extra-articular manifestations (uveitis, psoriasis, balanitis, urethritis, diarrhoea, inflammatory bowel disease) and a preferred pathological target represented by enthesitis and the absence of rheumatoid factor (Dougados et al., 1991; Rudwaleit et al., 2009a, b, 2011; Zochling et al., 2005). In addition, there is a particular genetic tendency: a strong familial aggregation, and association with the HLA B27 antigen and other susceptibility loci, such as the interleukin-1 gene cluster (Brown et al., 2000; Reveille, 2011; Robinson and Brown, 2014). The standard nosological forms of this group are represented by ankylosing spondylitis (AS), psoriatic arthritis (PsA), enteropathic arthritis/arthritis associated with inflammatory bowel
disease (IBD), reactive arthritis (ReA) and all undifferentiated spondyloarthritis (USpA). The different clinical expressions of these disorders explain the several successive classification systems (Rome criteria, New York criteria, modified New-York criteria, etc.), of which the most recent, defined by the Assessment of SpondyloArthritis International Society (ASAS), distinguishes: 1) the predominantly axial spondyloarthritides (ax-SpA), with early involvement of the sacroiliac joint (sacroiliitis) and vertebral structural lesions (erosion, ossification, ankylosis) (Rudwaleit et al., 2009a, b); 2) the predominantly peripheral spondyloarthritides, which include articular forms (monoarthritis or asymmetric oligoarthritis, erosive or non-erosive) as well as enthesitic forms (inflammatory involvement of the enthesis) (Rudwaleit et al., 2011). In the current global population, the overall estimated prevalence of SpA varies between 0.01% and 2.5%, depending on the geographical distribution of the HLA B27 antigen, the sensitivity of diagnostic criteria and the methodology of epidemiological investigations (Stolwijk et al., 2012). In ancient populations, rare epidemiological data also testify to a great variability in prevalence, which may be
⁎ Corresponding author at: Laboratoire AMIS (Anthropologie Moléculaire et Imagerie de Synthèse), CNRS, UMR 5288, Université Toulouse III Paul Sabatier, Bât. 4R3 (1er étage), 118, Route de Narbonne, 31062, Toulouse Cedex 9, France. E-mail addresses: [email protected], [email protected] (R. Donat).
https://doi.org/10.1016/j.ijpp.2018.12.005 Received 15 June 2018; Received in revised form 21 December 2018; Accepted 21 December 2018 1879-9817/ © 2018 Elsevier Inc. All rights reserved.
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Natica etc.) and limestone beads (Donat et al., 2014). The typology and technological characteristics of the furnishings reveal their origin in the early and intermediate phases of the late Neolithic period of the Paris Basin (3600-3000 cal BC) as it has been defined in the north-central part of France (notably from the furnishings discovered in the Marne hypogea; Augereau et al., 2007; Cottiaux and Salanova, 2014). Moreover, they are identical to those found in another hypogeum (located 30 m from hypogeum I) whose radiocarbon dates are centred in the middle of the 4th millennium BC (3600-3400 cal BC) (Donat et al., 2014). The human remains discovered in the Mont-Aimé hypogeum I were subjected to three radiometric datings (three left femurs attributable to adult individuals), which indicate measurements between 3621 and 3023 cal BC: 3621-3356 cal BC (GrN-31025: 4650 ± 40 BP), 34913102 cal BC (GrN-31026: 4560 ± 40 BP) and 3344-3023 cal BC (GrN31027: 4470 ± 40 BP) (CALIB radiocarbon calibration program 7.04 (Stuiver and Reimer, 1993), using the IntCal13 atmospheric calibration curve (Reimer et al., 2013), with corresponding 95% HPD (Highest Posterior Density) regions). The specimen presented in this study comes from the posterior part of the burial chamber, which had the oldest date (3621-3356 cal BC). However, considering the context (dislocated bones), it seems necessary to retain a broader chronological interval (3621-3023 cal BC). The very ancient dates obtained designate the Mont-Aimé hypogeum I as one of the oldest known collective burials of the Paris Basin The bone specimen was examined macroscopically and radiologically. Sectional imaging was performed on a multi-slice CT scanner (Siemens Sensation 16, Erlangen, Germany). The physical acquisition parameters are as follows: voltage: 120 KVp; tube current: 650 mAs; slice thickness: 0.75 mm. Several reconstructions were made, using bone and smoothing filters.
elevated in certain populations: for example, in a collection of skeletons of individuals of Portuguese origin from the 19th-20th centuries, the percentage of SpA cases was 6.7% (Martin-Dupont et al., 2006). However, the spondyloarthritides are not limited to humans or non-human primates (gorilla, chimpanzees, orangutan etc; Rothschild and Woods, 1992a). In fact, these diseases affect a wide variety of fossil animal species (mammal-like reptiles, dinosaurs, Cenozoic crocodiles, etc.), current wild species (great apes, bears, rhinoceroses, elephants, etc.) and domestic species (dogs, cows, horses etc.) (Rothschild and Feldtkeller, 2016; Rothschild and Martin, 2006: 49–62). At present, the spondyloarthritides are an essentially trans-mammalian phenomenon whose prevalence has increased over time (Rothschild, 2017). Fossil zoological data reveal that SpAs have a long history, occurring in the Early Permian, nearly 300 million years ago (Rothschild and Feldtkeller, 2016). In humans, the history of these diseases does not seem to date back beyond a few millennia, covering only part of the Holocene (Rothschild and Feldtkeller, 2016). In Western Europe, the oldest human cases of SpA seem contemporary with the development of Neolithic agropastoral communities (5700/5500-2000 cal BC) (Ortner, 2003a; Zorab, 1961). For this period, which ushered in a change in the way of life and subsistence for human populations marked by a major economic and demographic transition, reported cases of SpA remain extremely rare and isolated, however. In the study of past populations, the state of conservation and representation of the skeletons, which are sometimes dislocated and incomplete, makes retrospective diagnosis difficult, whilst certain equivocal paleopathological manifestations clearly raise the possibility of a differential diagnosis (Martin-Dupont et al., 2006). This situation explains, in part, the difficulty in identifying paleopathological disorders such as SpA, which currently have different phenotypic forms (Rudwaleit et al., 2009a, b, 2011) and whose diagnostic criteria are based, moreover, on a collection of clinical, laboratory and medical imaging findings not applicable to dry bone, apart from certain directly super-imposable radiological signs. The purpose of our presentation is to contribute to the knowledge of the origin and the history of these diseases through the paleopathological presentation of an ancient case of European origin, dated from the late Neolithic (36213023 cal BC), having a lesional presentation very suggestive of axial spondyloarthritis. A review of the paleopathological literature can better contextualize the specimen, describing it in light of the oldest known human cases of SpA.
3. Results The bone specimen consists of a segmental vertebral block (preserved in its near entirety) resulting from the complete fusion of three lumbar vertebrae (L2-L4) by a severe ankylosis process involving the vertebral bodies and arches, at the expense of the tendon-ligament system (Figs. 3,4 ). Ankylosis of the body is the culmination of a process of sub-ligamentous interbody ossification due to the development of bony bridges covering the anterior and lateral surfaces of the vertebral bodies and the periphery of the intervertebral disc spaces (spaces lacking any bone production can be seen at the anterior portions of the L2-L3 and L3-L4 joint spaces and the posterolateral L3-L4 joint space). Anterior and anterolateral bony bridges can also be observed on the superior endplate of L2 (L1-L2 joint space) and inferior L4 (L4-L5 joint space), but without fusion. Bone productions mainly consist of vertically-oriented ossifications on a homogeneous and compact surface, but there are also more localized exuberant proliferations with a horizontal trajectory (L3 left anterolateral inferior angle) (Fig. 3). The modifications of the anterosuperior and anteroinferior body edges contribute to the loss of anterior concavity of the vertebral body, giving it a rectilinear aspect on the lateral view ("squaring") (Fig. 3). In addition, there are signs of ossification of the intervertebral disc combined with destructive lesions, in the form of mirror-image macro-geodes on the anterior portion of the inferior L2 endplate and superior L3 endplate (Fig. 5). The vertebral endplates also have a sclerotic appearance, predominantly at the superior L4 endplate. There is no clear sign of osteoporosis. Fusion of the posterior arches results from an ossification process extending to the joint capsules of the facet joints, which are completely fused together (the joint spaces are no longer visible), as well as accessory ligaments, uniting: 1) the vertebral laminae: the yellow ligaments are completely ossified and subsumed by amorphous bone production; 2) the costiform processes: the insertions of the intertransverse ligaments are covered with bone outgrowths, formed of small
2. Materials and methods The reported case consists of an isolated bone specimen, a vertebral block attributable to an adult (over 20 years old) collected in the MontAimé hypogeum I (Val-des-Marais, Marne, France), a Neolithic collective tomb located in the Champagne region, 40 km south of Reims, on the eastern margin of the Paris Basin (Fig. 1). The Mont-Aimé hypogeum I belongs to a group of 160 artificial cavities spread over a limited area (less than 40 km2). These hypogea were used as collective burial sites during the late Neolithic period (3600-3000 cal BC) (Bailloud, 1974; Chambon, 2003). Discovered and excavated in 1982 (Champagne-Ardenne Regional Archaeology Service; Chertier, 1983), the Mont-Aimé hypogeum I included an access corridor and an elongated burial chamber (17 m2) dug in the local chalk. The grave contained the skeletal remains of nearly sixty individuals (25 adults, 32 children and adolescents), whose skeletons were found on excavation to be completely dislocated: none had retained its anatomical coherence, the human remains having been displaced and regrouped during successive burials (Fig. 2). Among the human bones, 272 artifacts were discovered, examples of: 1) the lithic industry (102 elements, mostly in local flint: arrowheads, blades, axes and scrapers), with predominantly transverse arrowheads (78 items) (Langry-François, 2004); 2) bone and antler artifacts (13 items: axe sheaths, smoothing tools and bone bodkins); and 3) personal ornaments, with 157 items, essentially shell ornaments (Dentalium, Oliva, 230
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Fig. 1. Geographical location of the Mont-Aimé hypogeum I (Marne, France).
remodelling of the entheses is also reflected in the ossification of all insertion areas of the posterior ligamentous complex and by ankylosis of the facet joint capsules. In this context, the observed destructive lesions, which are associated with disc calcifications, suggest a spondylodiscitis (Andersson lesion), which can result from inflammatory and/ or mechanical factors (Bron et al., 2009).
enthesophytes and amorphous bone production; and 3) the spinous processes: the interspinous ligaments are ossified, in the form of compact and homogeneous layers, which form a thin wall connecting the adjacent spinous processes, with the notable exception of the fourth lumbar vertebra, whose facet joint mass reveals bilateral isthmic lysis (spondylolysis) (Fig. 3). Destroyed post mortem, the apices of the spinous processes (insertion of the supraspinous ligaments) are not observable.
4.2. Differential diagnosis 4. Discussion
Diffuse idiopathic skeletal hyperostosis (DISH) represents the main differential diagnosis in axial forms of SpA, with which it shares apparent radiological similarities and a privileged target: the enthesis. DISH represents a distinct clinical entity, a non-inflammatory syndrome characterized by an ossification of the peripheral entheses and by axial manifestations consisting in the calcification and ossification of the anterior longitudinal ligament, forming bony bridges that finally merge with each other (Mader et al., 2013; Resnick et al., 1975; Resnick and Niwayama, 1976). The appearance of bone spurs, which creates anterolateral bone moulding (predominantly right), is mainly localized to the middle and lower thoracic levels of the spine but differs from the syndesmophytes of the spondyloarthritides (Baraliakos et al., 2012; Olivieri et al., 2009). The process of entheses ossification can extend to all syndesmoses of the vertebral arch, but without erosion, subchondral sclerosis or fusion of the facet joints (Resnick and Niwayama, 1976). The appearance and combination of the observed structural lesions also make it possible to rule out infectious spondylodiscitis, which may be suggested by the mirror-image intra-somatic macro-geodes. The typical or suggestive signs of spinal tuberculosis (Pott's disease), which can cause anterior and posterior ankylosis, are also absent here (extensive destruction with collapse, osteomyelitis or periosteal reactions, etc.) (Ortner, 2003b). Ochronotic arthropathy can also progress to
4.1. Retrospective diagnosis The spinal structural changes observed include severe multifocal involvement combining erosion, ossification and ankylosis, in which entheseal remodelling predominates (tendon insertion areas, ligaments and joint capsules at the bone) (Claudepierre and Voisin, 2005). The lesional presentation is very suggestive of a progressive axial form of spondyloarthritis, whose paleopathological diagnostic criteria have been summarized by various authors (for a review of the paleopathological diagnostic criteria, see, for example, Martin-Dupont et al., 2006; Samsel et al., 2014). The anterior and lateral interbody bony bridges reproduce the typical image of bridging syndesmophytes, corresponding to ossification of the periphery of the annulus fibrosus (Resnick and Niwayama, 1983). In the spondyloarthritides, the formation of syndesmophytes consists of the apposition of reactive bone that follows the initial erosive lesion (Romanus lesions in early spondylitis) in the enthesitis process involving the peripheral insertion of the annulus fibrosus (Ball, 1971; Claudepierre and Voisin, 2005): these modifications result in the loss of anterior concavity of the vertebral bodies (Jacobson et al., 2008). On the examined bone specimen, the 231
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Fig. 2. Plan of the funeral chamber of the Mont-Aimé hypogeum I, with distribution of human skeletal remains.
documented, if not equivocal. They consist of isolated vertebral blocks (two to three vertebrae), which were found in collective burial sites attributed to the Neolithic period, without further clarification. These consist of two bone parts discovered in Sweden (Hemmor, Gotland and Mysinge, Öland) and described by Fürst (1914: 25, Figs. 10, 11), as well as a specimen presented by Pales (1930: 117; pl. XXIV, Figs. 1,2) found in the Baumes-Chaudes cave (Lozère, France). Fürst (1914) advanced the diagnosis of "arthritis deformans anchylopoiëtica". Pales (1930), whose arguments are convincing, concluded on a case of "rhyzomelic spondylosis". In an article devoted to the antiquity of rheumatic diseases, Snorrason (1942) succinctly cites two cases of "spondylarthritis anchylopaetica". These were probably isolated vertebral blocks, one of which was presented as belonging to the French Neolithic period and the other to the Danish Neolithic period. These previously described different bone parts would require a review in light of current knowledge. Similarly, the chrono-cultural context remains to be clarified. In another geographical context, that of West Africa and the Near East, the oldest known specimen of SpA comes from the Hassi el Abiod region in the Malian Sahara. It corresponds to a Neolithic skeleton dated about 7000 BP, which presents signs suggestive of peripheral articular spondyloarthritis, with asymmetrical ankylosis of the wrist
multi-stage disc calcification and ankylosis of the body, but without formation of syndesmophytes or facet joint fusion (Lagier and Sit'aj, 1974; Phornphutkul et al., 2002). Finally, severe forms of skeletal fluorosis may produce more or less extensive vertebral ankylosis in the form of periosteal hyperostosis, whose appearance differs from the structural changes in the spondyloarthritides, which preferentially affects the entheses (Littleton, 1999; Ortner, 2003c).
4.3. Contribution to the history of spondyloarthritides In Western Europe, in addition to the Mont-Aimé hypogeum I specimen presented in this study (3621-3023 cal BC), one of the oldest cases of SpA described to date comes from the Neolithic Hoguette cairn at Fontenay-le-Marmion (Calvados, France), dated from the first half of the 4th millennium BC (4000-3500 cal BC). It corresponds to the remains of a man with axial involvement compatible with ankylosing spondylitis (AS): bilateral ankylosis of the sacroiliac joints and ankylosis of the vertebral bodies and facet joints of all conserved vertebrae (T10 to L4), demonstrating the classic "bamboo spine" appearance (Torre and Dastugue, 1976). Described previously, other cases of prehistoric spondyloarthritides of European origin are rare and poorly 232
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Fig. 3. Macroscopic presentation in anterior (a), right lateral (b) and posterior (c) views of the lumbar vertebral block showing severe ankylosis involving the body and vertebral arches. The anterior view image (a) shows the anterior and lateral interbody bony bridges with vertical orientation (white arrows) and the more localized presence of horizontally developing bone spurs (white circle). The lateral view (b) highlights the rectilinear aspect ("squaring") of the vertebrae. The posterior view (c) shows ankylosis of the facet joint capsules and ossification of all insertion areas of the ligamentous complex.
these diseases, the oldest of which is attributed to the 3rd dynasty (2700-2600 cal BC). In North America, the oldest possible case of SpA (Modoc rock shelter, Illinois, USA) is attributed to a broad time interval, between 6219-2765 BC (Neumann, 1966, cited by Arriaza, 1993). Among the oldest cases in this part of the American continent are also four skeletons (4/87 = 4.6%; Rothschild and Woods, 1992b) from the Frontenac Island site (New York, USA) occupied between 4900 and 3700 BP (Ellis et al., 1990: 106). In a sample of various North American prehistoric populations (1657 individuals in total, including those of Frontenac Island), dated between 4900 and 400 BP, Rothschild and Woods (1992b) noted thirty-five cases of SpA, with frequencies varying between 0.7 and 5.1%, depending on the groups of humans considered. The authors did not observe a significant increase in the prevalence of these diseases over time (Rothschild and Martin, 2006; Rothschild and Woods, 1992b). In South America, in a sample of mummies from different prehistoric groups of humans (7000 BC-1530 AD) having populated the northern part of present-day Chile, at least 4.4% of the examined individuals (15/340) presented signs of SpA (Arriaza, 1993). The oldest cases are dated between 2200-1000 BC (Chinchorro culture; 2/ 51 = 3.9%). Moreover, the study of this sample revealed an increase in the prevalence of SpA over time and, notably, in human groups having acquired an agropastoral economy (Arriaza, 1993). Finally, in comparison with the age of some known specimens in Western Europe, West Africa, the Middle East and the American continent, the Asian continent does not contain such ancient cases of SpA, except for a possible peripheral form discovered in Japan, dated between 3650-3000 BC (Inoue et al., 2005).
Fig. 4. Sagittal view of the Volume Rendering Technique (VRT) reconstruction, which allows a better visualization of bone spur reliefs.
and erosive lesions of the proximal interphalangeal joints (Rothschild et al., 1999). In Upper Egypt, the oldest identified cases of SpA come from the Nile Valley and are attributable to the predynastic era (4000/ 3900-2900 cal BC; Hendrickx, 2006). The best-dated specimens have been discovered in the predynastic necropolis of Adaïma; there are two individuals: one, with an axial form of SpA, is attributed to the Naqada IIIA period (3600-3350 cal BC), and the other individual, with a possible peripheral form, is attributed to a broader chronological interval, between 3600-2900 cal BC (Crubézy, 2017: 90–94). In the same chrono-cultural context (predynastic period), but without precise dating, two cases identified by Bourke (1971) are added; one from the Naqada "Great Cemetery" and the other case from Cemetery B of Hu. Finally, we note that Ruffer (1921: 212–267) described several cases of
5. Conclusion The paleopathological study of a vertebral block collected in a Neolithic collective grave, Mont-Aimé hypogeum I, testifies to the existence of an advanced axial form of spondyloarthritis dated from the second half of the 4th millennium BC, or even a little earlier (36213023 cal BC). This specimen represents, with that of the Neolithic Hoguette Cairn in Fontenay-le-Marmion (Calvados, France), one of the oldest cases of this type of inflammatory rheumatism reported in Western Europe. In this geographical region, no cases of 233
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Fig. 5. Coronal reconstructions passing through: a) the anterior third of the vertebral bodies: presence of mirrorimage macro-geodes on the anterior part of the inferior L2 endplate and superior L3 endplate (white arrows); b) the middle third of the vertebral bodies: visualization of anterior and anterolateral bone spurs (fused syndesmophytes, white arrows) and ossification of the intervertebral disc (red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
spondyloarthritis are known in the groups of hunter-gatherers who preceded the agropastoral societies of the Neolithic period (Villotte, 2009). The paleopathological data thus suggest that the profound changes during the Neolithic period (sedentarization and concentration of human groups, population growth, domestication of plants and animals, and transformed diets) constituted, in Western Europe, a fertile ground for the development of inflammatory rheumatisms similar to the current forms of spondyloarthritides. The causes are to be sought in, among others, the emergence and the increased transmissibility of certain infectious agents (zoonoses) and the change of diet: these two factors are involved in the modifications of the intestinal microbiota (dysbiosis) (Harper and Armelagos, 2013), whose role is suspected in the aetiopathogenesis of SpA (Breban, 2016; Breban et al., 2017). It is possible that this pattern has prevailed in human groups of different geographical origins (Western Europe, Nile Valley, Northern Chile, etc.). On the other hand, zoological data, showing the extent of the phenomenon and its increasing prevalence over time, regardless of lifestyle and means of subsistence (e.g., wild versus domestic, carnivorous versus herbivore etc; Rothschild, 2017), suggest a more comprehensive explanatory model.
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