A case of secondary hypertrophic osteoarthropathy from medieval Tuscany (central Italy, 10th-12th centuries CE).

OBJECTIVES: This study aims to provide a detailed evaluation of a case of secondary hypertrophic osteoarthropathy (HOA) and to explore insights into the presence and consequences of disease in medieval rural Italy. MATERIALS: The skeleton of a male (US 4405) with an estimated age at death of 51-69 years excavated from the medieval rural site of Pieve di Pava (Siena, Italy). METHODS: Macroscopic and radiological (x-ray, CT) analyses were performed. RESULTS: Symmetrical extensive periosteal new bone formation on the diaphyseal and metaphyseal regions of this individual's long bones; the lower limbs were more extensively and severely affected than the upper limbs and the distal segments were more severely altered in comparison to the proximal ones. CONCLUSIONS: The macroscopic and radiological features are highly consistent with a diagnosis of secondary HOA. SIGNIFICANCE: The excellent state of preservation allowed the evaluation of rarely noted skeletal manifestations of HOA and provided insight into aspects of rural life in medieval Italy. LIMITATIONS: Molecular analysis was not successful in sequencing the aDNA of tuberculosis, therefore the underlying primary cause of secondary HOA, whether pulmonary or extrapulmonary, remains obscure in this case. SUGGESTION FOR THE FUTURE RESEARCH: It is advisable to regularly revisit the data available from osteoarchaeological collections in order to identify further cases of HOA, along with to further investigate the known cases to search for the underlying primary disease.

Co-morbidity with hypertrophic osteoarthropathy: A possible Iron Age Sarmatian case from the Volga steppe of Russia.

PURPOSE: Hypertrophic osteoarthropathy (HOA) is a condition that can be inherited or acquired. It causes diffuse periosteal new bone formation on the long bones, with a predilection for the appendicular skeleton. When acquired, it is a nonspecific indicator of systemic disease that arises following a primary condition. This paper reviews the palaeopathological literature associated with this rare condition. It also describes the first possible case of co-morbidity associated with hypertrophic osteoarthropathy in an adult skeleton (cal. BC 170 - 1 cal. AD) from the mobile pastoralist Sarmatian culture of the Volga steppes of Russia. METHODS: Macroscopic and radiological examination provide differential diagnoses of the lesions, while clinical and bioarchaeological analyses offer insights into the possible experience of disease and social implications of care among the nomadic populations of Iron Age Russia. RESULTS: The analysis of Sk. 6524.102 displays lesions that may be due to both hypertrophic osteoarthropathy and osteomalacia. The man was physically impaired and his participation in physically challenging activities would have been limited. CONCLUSIONS: The study stresses that co-morbidity is a key parameter when interpreting disease in past populations, particularly when the diagnosis involves hypertrophic osteoarthropathy. SIGNIFICANCE: This is the first case of hypertrophic osteoarthropathy identified in Eurasian prehistoric populations. The research emphasises the significance of co-morbidity in the past. LIMITATIONS: The diagnosis of co-morbid diseases in human remains is extremely complex and the conditions were identified as most probable by a process of elimination. SUGGESTIONS FOR FURTHER RESEARCH: Further studies should be dedicated to understanding co-morbidity in the past.

Secondary hypertrophic osteoarthropathy in a male from the Early Medieval settlement of Lauchheim, Germany.

Hypertrophic osteoarthropathy (HOA) is rarely diagnosed in archaeological human skeletons. Here, we report on the well-preserved skeleton of a middle-adult man from the early Medieval settlement site of Lauchheim (Germany) that exhibits pronounced multi-layered shell-like periosteal new bone formation in a bilaterally symmetric fashion on the long bones, the skeletal elements of the pelvis and those of the pectoral girdle. In addition, the two distal phalanges recovered show signs of osteoclastic resorption on their distal tuberosities. The distribution and morphology of the observed lesions are consistent with a diagnosis of HOA. The adult age at death of the individual and the co-occurrence of "healed" and "active" lesions suggest a secondary form of HOA. Given that only skeletal remains were available for study, the underlying (pulmonary or non-pulmonary) primary disease cannot be definitively ascertained in the present case. No osseous changes were found on the ribs, but signs of osteoclastic resorption were observed on the dorsal surface of the sternal body, which might indicate a retrosternal or mediastinal location of the primary disease. Thus far, only a few archaeological case studies of secondary HOA reported signs of the presumed underlying primary disease, which was of a pulmonary nature in each of the individuals.

Hypertrophic osteoarthropathy in a young adult male from Berber, Sudan (2nd-3rd century CE).

Hypertrophic osteoarthropathy (HOA) is a pathological condition characterised by extensive periosteal new bone formation (NBF) on the diaphyses of the long bones, metacarpal and metatarsal bones. In modern clinical contexts, the secondary form of the disease is common and most often occurs secondary to intra-thoracic cancer and other forms of chronic pulmonary disease. Paleopathological evidence for HOA on the other hand has only occasionally been reported. Here we report a young adult male from the Meriotic cemetery at Berber in Sudan (2nd-3rd century CE) displaying widespread NBF on the diaphyses of the upper and lower limb bones, metacarpal and metatarsal bones, as well as the pelvis and scapulae. While several pathological conditions have to be considered as differential diagnostic options for NBF in the post-cranial skeleton, HOA is the most likely diagnosis, based on the distribution of the changes observed in this individual, as well as their macroscopic and radiographic characteristics. A chronic pulmonary condition as indicated by NBF on the visceral side of the ribs may represent the underlying cause for the HOA. This individual represents the first paleopathological case of HOA reported from an archaeological site in Africa.

[The role of medical imaging in paleoanthropology]. / Apports de l'imagerie médicale en paléoanthropologie.

Study of the health status of ancient populations relies on the detection and analysis of bone or dental lesions from skeletons. In the absence of clinical or biological data, the identification of a pathology relies on anatomic and radiographic findings. Three paleopathological cases are presented and macroscopic and imaging findings are discussed. These include one case of eosinophilic granuloma, one case of Ewing sarcoma, and one case of secondary hypertrophic osteoarthropathy. Each case illustrates the value and limitations of retrospective diagnosis; an etiologic diagnosis can either be possible, suggested or unknown. Multiple biases, related to specimen preservation and the frequent non-specific nature of bony changes, make paleopathological diagnosis challenging. As such, the use of medical imaging seems valuable in the evaluation of such lesions. It allows non-invasive evaluation of the bone, underlying pathology, and lesion comparison to finally narrow the differential diagnosis.

Exploring the cause of the most ancient clinical sign of medicine: finger clubbing.

OBJECTIVE: Digital clubbing is regarded as the oldest clinical sign of medicine. The cause of this unique finger deformity has remained elusive throughout the centuries. For 3 decades our group has studied the etiology of this acropachy. This article reviews the current knowledge on the cause of digital clubbing. METHODS: PubMed database (www.pubmed.gov) was accessed. In clinical queries/clinical study service we entered "clubbing" or "hypertrophic osteoarthropathy," choosing the "etiology" category with a "broad sensitive" search scope. The time span was from January 1975 to August 2006. Additionally, this article narrates the chronology of our research on the pathogenesis of clubbing. RESULTS: The many dreadful internal illnesses associated with digital clubbing have in common enhanced platelet/endothelial cell activation. Emerging evidence suggests that, in hypoxic conditions with extrapulmonary shunting of blood, large megakaryocyte fragments fail to enter the pulmonary circulation. Instead they gain access to the systemic circulation impacting at the most distal sites, there releasing growth factors and thus inducing clubbing. In cases of lung cancer, the purported growth factor could gain direct entrance to the systemic circulation. Vascular endothelial growth factor (VEGF) may play a central role in the development of digital clubbing. It is a platelet-derived factor induced by hypoxia, and it is also abnormally produced by diverse malignant tumors fostering their uncontrolled growth. On the other hand VEGF produces vascular hyperplasia, edema, and fibroblast/osteoblast proliferation. Such are clubbing histologic characteristics. Enhanced VEGF expression has been reported in practically all internal illnesses associated with this type of finger deformity. Recent studies have demonstrated high circulating levels as well as increased local expression of VEGF in different groups of patients with digital clubbing. CONCLUSION: Abnormal expression of VEGF may be the cause of digital clubbing.

Evidence of hypertrophic osteoarthropathy in human skeletal remains from pre-Hispanic Mesoamerica.

Hypertrophic osteoarthropathy is one of the earliest recognized disease entities in the history of medicine. It has a peculiar periosteal proliferation distinctive from other bone diseases. In its advanced stage, it leaves an indelible mark on the skeleton. It has been recently shown that digital clubbing is accompanied by a bone remodeling process of the underlying phalanges. Thus, theoretically, this entity can be recognized in ancient human skeletal remains. We studied part of the collection of skeletal remains from pre-Hispanic Mesoamerica preserved at the National Museum of Anthropology of Mexico City. We examined 1000 specimens and found 2 skeletons with widespread, bilateral, symmetric periosteal proliferation of the tubular bones in addition to the bone remodeling changes of the distal phalanges. One of the specimens was from the Formative period (2000 B.C. to 100 A.D.). We conclude that hypertrophic osteoarthropathy can be recognized in ancient human skeletal remains and that this disease was present in Mesoamerica near the time of the original description of clubbing by Hippocrates about 2500 years ago.

History of hypertrophic osteoarthropathy (HOA).

Hypertrophic osteoarthropathy (HOA) was first described in 1868 as "hyperostosis of the entire skeleton". It has also been mistaken for acromegaly. In 1887-1888 the first description was given of a dermatological disorder "cutis verticis girata" which coexisted with the peculiar bone anomalies of HOA. In 1890 HOA was named "osteoarthropatie hypertrophiante pneumique". Later a distinction was made between the rare idiopathic (or primary) form, also called "pachydermoperiostosis" and the more common secondary form due to concomitant disorders involving the lungs and pleura. The primary form usually develops shortly after puberty or during adolescence and has not been found associated with underlying disease. Secondary HOA was initially called "hypertrophic pulmonary osteoarthropathy" because it is frequently associated with various malignancies or chronic infections of the lung and pleura. Later, since the site of primary disease may be elsewhere, involving the gut and the cardiovascular, hepatobiliary and endocrine systems, this designation fell into disuse. In some cases of secondary HOA, the osteoarthropatic and facial skin changes subside after pneumonectomy or other procedures. A disease resembling human HOA has been also described in dogs.

[Osteoarticular diseases from J.M. Charcot to the present time]. / Les affections ostéo-articulaires de J.M. Charcot à nos jours.

In foreign countries Charcot's main contribution in the field is known as Charcot's joint. A special paper is devoted to this topic by Dr Hubault in this issue of the Revue. It is perhaps less widely known that Charcot's thesis was devoted to rheumatoid arthritis and that he wrote also interesting observations on gout. Pierre Marie gave many famous contributions to bones and joints diseases. In 1886 he described acromegaly. In 1890 he described hypertrophic pulmonary osteoarthropathy which he correctly linked with lung diseases although some of the cases he had collected in the literature were instances of pachydermo-periostosis. In 1900 he gave a brilliant description of achondroplasia in 2 of his patients: Anatole and Claudius. On the 11th of February 1898 he reported 2 patients which were the basis of a historical description of ankylosing spondylitis, on which papers by Strümpell and von Bechterew had appeared in 1884 and 1893. The subsequent works at the Clinique des Maladies du Système Nerveux de la Salpêtrière on sciatica and herniated disks are related in Professor de Seze's paper in this issue of the Revue.