On the history of gout: paleopathological evidence from the Medici family of Florence.

OBJECTIVES: Throughout history, gout has been referred to as the "disease of the kings", and has been clearly associated with the lifestyle of the aristocratic social classes. According to the written sources, several members of the famous Medici family of Florence suffered from an arthritic disease that contemporary physicians called "gout". A paleopathological study carried out on the skeletal remains of some members of the family, exhumed from their tombs in the Church of San Lorenzo in Florence, offered a unique opportunity to directly investigate the evidence of the arthritic diseases affecting this elite group. METHODS: The skeletal remains of several members of the family were examined macroscopically and submitted to x-ray investigation. RESULTS: The results of the study allowed us to ascertain that the so-called "gout of the Medici" should be considered the clinical manifestation of three different joint conditions: diffuse idiopathic skeletal hyperostosis, rheumatoid arthritis and uratic gout. In particular, uric acid gout was diagnosed in the Grand Duke Ferdinand I (1549-1609). Recently, a new case of this disease was diagnosed in Anton Francesco Maria (1618-1659), a probable illegitimate member of the family. CONCLUSIONS: With this new case, uratic gout was observed in 2 out of 9 adult males, leading to suppose that the disease should have been a common health problem within the family. The aetiology of the disease has to be searched in environmental factors, since both historical and paleonutritional studies demonstrated that the diet of this aristocratic court was rich in meat and wine.

The ossification diathesis in the Medici family: DISH and other features.

The Medici family ruled Florence for most of the period from the 1430s to the 1730s, with the senior (primogenito) branch predominating until the line ended in the 1530s and the cadet (secondogenito) branch predominating thereafter. Recent studies have identified a familial syndrome consisting of cutaneous symptoms, peripheral arthropathy and spinal ankylosis in the primogenito branch of the family, and the presence of diffuse idiopathic skeletal hyperostosis (DISH) in two members of the secondogenito branch. These findings raise the question of whether DISH was also a component of the primogenito familial syndrome. The present study provides a further specification of the ossification diathesis in the familial syndrome of the primogenito branch of the Medici family. Recently discovered photographs of exhumed Medici skeletons from the primogenito line are examined, with a focus on spinal, sacro-iliac and peripheral ossifications. These observations are supplemented with published reports of radiological, histological and macroscopic studies of the skeletons. Our interpretations of the ossification data relating to the primogenito branch of the Medici family are supportive of a diagnosis of DISH. DISH was one component of the triple pathology identified as a syndrome in the fifteenth century primogenito Medici line. As a diagnosis of DISH has recently been proposed for two sixteenth century members of the secondogenito branch of the family, it appears that the same condition affected both branches of the Medici lineage, without excluding other forms of undifferentiated joint and spondylarthropathies.

The 'gout' of the Medici, Grand Dukes of Florence: a palaeopathological study.

OBJECTIVE: According to the written sources several members of the famous Medici family of Renaissance Florence suffered from an arthritic disease, called 'gout' by contemporary physicians; a palaeopathological study allowed verification of the true nature of the 'gout of the Medici' referred by archive document data. METHODS: The skeletal remains of the Grand Dukes and their families, buried in the Basilica of San Lorenzo in Florence, were examined macroscopically and submitted to X-ray investigation. RESULTS: Out of 15 investigated individuals, two cases of diffuse idiopathic skeletal hyperostosis (DISH), with ossification of the anterior longitudinal ligament and massive hyperostotic changes of the extra-spinal ligaments, were detected in the skeletons of the Grand Dukes Cosimo I (1519-74) and his son Ferdinand I (1549-1609). The left foot of Ferdinand also revealed typical lesions of the uratic gout, confirming the archive data, which describe the disease in detail. CONCLUSIONS: The association between DISH and elite status, highlighted in recent research, receives further confirmation in the present study, furnishing evidence to the significance of this disorder as a lifestyle indicator, linked specifically with a high-caloric diet, consequent obesity and type II diabetes mellitus. Furthermore, the coexistence between DISH and gout observed in Ferdinand represents the first documentation of this association in the palaeopathological literature.

[Rheumatic diseases at the court of the Medici of Florence: the so-called "gout" of the Medici]. / Le malattie reumatiche alla corte medicea di Firenze: la cosiddetta "gotta" dei Medici.

According to the archive documents several members of the Medici family of Florence suffered from gout. The word "gout", with which the Renaissance physicians indicated pain episodes localised to hands, feet, spine and shoulders, was in general improperly used, and hint other nosological entities. A paleopathological investigation carried out on the skeletal remains of the Grand Dukes of Florence and their relatives, revealed the true nature of the diseases they suffered from, allowing to diagnose two cases of diffuse idiopathic skeletal hyperostosis (DISH), a case of rheumatoid arthritis in an advanced stage, and a case of gout.

Brief communication: paleopathology of the Kiik-Koba 1 Neandertal.

The Kiik-Koba 1 Neandertal partial skeleton (canine, partial hands, partial leg, and feet), of a approximately 40-year-old probable male, exhibits a suite of pathological lesions, including hypercementosis, minor fibrous ossifications, pedal phalangeal fracture, and pronounced enthesopathies on the patella and calcanei in the context of no articular degenerations. The first two sets of lesions are related to age in the context of advanced dental attrition and physical strains. The third lesion joins a series of healed minor traumatic lesions among the Neandertals. The last represents either pronounced tendinous inflammation, albeit in the context of no articular degenerations, or a case of diffuse idiopathic skeletal hyperostosis (DISH) in the Late Pleistocene. Kiik-Koba 1 therefore adds to the high incidence of pathological lesions among the Neandertals and, if a diagnosis of DISH is correct, to a high frequency of this disorder among older Neandertals.

Extracapsular fracture of the femur in an elderly male from the Church of Nossa Senhora da Anunciada (Setúbal, Portugal).

In modern populations, hip fractures in older people are associated with high morbidity and mortality. Their incidence is rising; notwithstanding, fractures of the proximal femur are still relatively uncommon in archeological contexts. This case study represents a well-healed hip fracture in an aged male skeleton from Church of Nossa Senhora da Anunciada (16th-19th centuries AD) in Setúbal (Portugal). The individual was also diagnosed with diffuse idiopathic skeletal hyperostosis. Fractures of the proximal femur are usually associated with bone loss but in this case other causes are proposed, including the anatomy of the proximal femur, and the potential combined effect of diffuse idiopathic skeletal hyperostosis, cardiovascular disease, diabetes mellitus and falls.

A recording form for differential diagnosis of arthropathies.

The present study is focused on a group of arthropathies that may have very similar bone manifestations (rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, osteoarthritis and diffuse idiopathic skeletal hyperostosis), which makes it more difficult to diagnose them in human remains from archaeological contexts. A stepwise recording form was designed in order to improve the identification and differential diagnosis of these pathological conditions in bone remains, particularly in joint manifestations of the spine, pelvis, hands, feet and other limb joints. This recording form was applied in the analysis of two medieval individuals from the Basque Country (Spain) who presented very severe arthropathic manifestations. The use of this recording form allowed the researchers the diagnosis of ankylosing spondylitis in one of them and diffuse idiopathic skeletal hyperostosis in the other.

Enfermedad de Forestier-Rotés Querol: un proceso continuo desde la Atenas de Pericles hasta el mundo de Almodóvar / Forestier-Rotés Querol disease: a continuous process from the Athens of Pericles to the world of Almodóvar

Se presentan 2 casos, separados por un intervalo de más de 2500 años, de Enfermedad de Forestier - Rotés-Querol, uno de ellos procedentes de un enterramiento de la Atenas de Pericles y el otro actual para ejemplificar su presencia continua en la historia de la patología humana. Se realiza una sucinta revisión histórica sobre su separación de las espondilopatías inflamatorias anquilosantes, se revisan sus posibles manifestaciones clínicas y radiológicas y se menciona su importante papel en el desarrollo de la última película de Pedro Almodóvar, Dolor y Gloria

We present two cases of Forestier-Rotés-Querol disease, separated by an interval of more than 2500 years, one of them coming from a burial in the Athens of Pericles and the other from the present. This exemplify its continuous presence in the history of human pathology. A brief historical review of their separation from ankylosing inflammatory spondylopathies is carried out their possible clinical and radiological manifestations are reviewed, and it is mentioned an important role in the development of the latest film by Pedro Almodóvar, Dolor y Gloria

A paleoepidemiologic study of diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: To investigate the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in ancient populations. MATERIAL AND METHODS: We studied 38 women and 61 men aged at least 30 years at death, whose remains were recovered from four cemeteries of the High Middle Ages (VIth to VIIIth century) located in Lorraine (eastern France). Criteria previously developed by Crubézy and Crubézy-Ibanez for paleopathological studies were used to determine whether the skeletal remains exhibited definite, possible, probable, or no DISH. RESULTS: Definite DISH with flowing ossification along the thoracic spine and ossification of peripheral enthesopathies was seen in 2.8 to 3.7% of the subjects from two cemeteries and in none from the other two cemeteries. Identical figures were found for possible DISH. The prevalence and male predominance s (nine of 13 subjects in any DISH category were males) were similar to those reported in contemporary studies and in other paleopathological studies. CONCLUSION: In the absence of clinical data on the metabolic status of the study subjects, our results suggest that DISH in our subjects was a marker for older age at death.

Diffuse idiopathic skeletal hyperostosis.

The ubiquitous nature of spinal ligamentous calcification in the paleontologic record provides additional support for the suggestion that DISH is a protective phenomenon rather than a musculoskeletal disease, and perhaps represents a normal variant. Clinical assessment of contemporary DISH suggests a protective mechanical effect, paradoxically associated with increased risk of hypertension and cerebrovascular accident. DISH should probably not be considered a satisfactory explanation for back pain, but the presence of spinal ligamentous calcification requires that the patient be assessed for hypertension and that aggressive therapy be instituted for any found.

Diffuse idiopathic skeletal hyperostosis from Roman Hungary.

This paper deals with cases of diffuse idiopathic skeletal hyperostosis (DISH) found at the Late Roman Age necropolis in Pécs, Hungary (4th century AD). The skeletal remains of two male individuals, aged between 60-70 years and 45-55 years, displayed right-sided ossification of the anterior longitudinal ligament with extra-spinal manifestations typical in DISH cases. It is presumed that both male individuals were middle-class citizens. Their social status was supplemented with trace element analysis in order to reconstruct the dietary habits of the urban population. Concentrations of Sr and Zn indicated a predominantly vegetal diet. Potential DISH risk factors and associations were subsequently discussed and compared with our findings.

The "gout of the Medici": making the modern diagnosis using paleopathology.

Documentary sources show that painful joint disease afflicted several members of the Medici family, which dominated Renaissance Florence in Italy. The term frequently reported in contemporary archives to indicate these morbid episodes is "gout." Paleopathology allows us to verify the nosological information obtained from the written documents and to clarify the nature of the rheumatological condition that afflicted the Medici. A paleopathological study carried out on the skeletal remains of several members of the Medici family buried in the basilica of S. Lorenzo in Florence demonstrated that the "gout" of the Medici was truly a uric acid gout only in Ferdinand I (1549-1609), whose left foot showed peculiar lesions. Genetic and environmental factors, with particular regard to diet, may have been involved in the etiology of this disease, which in Ferdinand was associated with diffuse idiopatic skeletal hyperostosis (DISH). DISH was observed also in the column of Cosimo the Elder (1389-1464) and Cosimo I (1519-1574); a link between the incidence of DISH and high social status, especially in terms of lifestyle and nutritional patterns, has been suggested and the present study seems to further confirm this association. Finally, rheumatoid arthritis (RA) was diagnosed in Cosimo the Elder, Piero "the Gouty" (1416-1469) and Cardinal Carlo (1596-1666); as for Carlo, macroscopic and radiological findings were supported by molecular results which revealed that he was bearing the specificity HLA-DR4 predisposing to RA. The coexistence of DISH and RA attested in Cosimo the Elder can be interpreted as coincidental. In conclusion, the term "gout" as used in Renaissance texts has to be regarded as the clinical manifestation of a number of different joint diseases. In the case of the Medici family in Florence, these included DISH, rheumatoid arthritis and uric acid gout.

Diffuse idiopathic skeletal hyperostosis: diagnosis in a palaeopathological context.

Clinically, the presence of diffuse idiopathic skeletal hyperostosis (DISH) has been linked to a disturbance of glucose and insulin metabolism, hypertension, dyslipidemia and obesity associated with a rich diet. The prevalence of DISH in archaeological skeletal samples may therefore be a valuable indicator of their socio-economic status when compared to other contemporary groups. However, various methods are currently being used to diagnose DISH. The purpose of this study was therefore to assess the comparability of results obtained using four different diagnostic methods to estimate the prevalence of DISH in a skeletal sample, and to discuss the implications of the results in relation to palaeopathological health assessments. Four different diagnostic criteria were applied to 127 male and 113 female skeletons to diagnose DISH. Skeletal remains were obtained from two 16th century samples from Delft and one modern sample from the anatomy dissection hall of the Leiden University Medical Centre. The estimated prevalences were statistically compared. Special attention was also given to the distribution of extra-spinal enthesophytes described in diagnostic criteria, in order to assess their diagnostic value. The prevalence of DISH observed in the skeletal samples varied significantly depending on the criteria used for diagnosis. Furthermore, extra-spinal enthesophytes, suggested as being indicative of DISH, proved to be variable and unreliable. It was concluded that it is of great importance to explicitly state and adhere to criteria employed for diagnosing DISH in both palaeopathological and clinical investigations in order to ensure reliable comparisons between studies. Also, DISH cannot be positively diagnosed solely based on the presence of extra-spinal enthesophytes.

Coexistence of melorheostosis and DISH in a female skeleton from Magna Graecia (Sixth Century BC).

This paper reports on a case of massive hyperostotic alterations observed in the skeleton of an adult woman from the necropolis of Montescaglioso Belvedere (Basilicata, Southern Italy) attributed to the Enotrian culture and dated to the 6th century BC. Hyperostotic changes involve joints, the vertebral column, and the lower limbs. In particular, the large flowing ossification in both the thoracic (T6-T10) and lumbar (L2-L5) tracts, the sacralization of L5, accompanied by sacroiliac fusion on the left side, and the proliferative bone production on both the metaphyseal portion of the left tibia and the left third metatarsal are described. The vertebral antero-lateral ossification and the sacroiliac fusion support a diagnosis of diffuse idiopathic skeletal hyperostosis (DISH), while the flowing bone formation on the lower limbs supports a diagnosis of melorheostosis. The pathological conditions described here were already described in the literature, but this is the first reported case of the coexistence of DISH and the very rare melorheostosis. Furthermore, the skeleton from Montescaglioso Belvedere represents the first case of this disease described for ancient Europe, therefore adding a valuable contribution to the reconstruction of the antiquity and distribution of skeletal dysplasias.

Shanidar 1: a case of hyperostotic disease (DISH) in the middle Paleolithic.

The Shanidar 1 Neandertal partial skeleton presents osteophytic lesions on its vertebrae and appendicular skeleton which appear independent of the multiple traumatic and degenerative joint disease lesions on the individual. In particular, the large flowing osteophyte on the L3 body, a smaller one on the L5 body, and enthesopathic osteophytes on both calcaneal tuberosities, both patellae and the left ulnar olecranon, support a diagnosis of hyperostotic disease (DISH). The diagnosis is supported by small enthesopathic osteophytes on the preserved femoral greater trochanter and scapular corocoid process. This diagnosis would make it the oldest hominid specimen clearly presenting this systemic condition.