How rare is rare? A literature survey of the last 45 years of paleopathological research on ancient rare diseases.

OBJECTIVE: This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this. MATERIALS: A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus. METHODS: Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage. RESULTS: Studies of ancient rare diseases (ARD) are mostly published as case reports in specialized journals and their number did not benefit from the introduction of biomolecular studies. The higher frequency of cases of achondroplasia suggests that not all rare diseases are equally under-represented. CONCLUSIONS: Rare diseases are still largely under-represented in bioarchaeological literature. Their marginality likely results from a combination of taphonomic, methodological and public visibility factors. SIGNIFICANCE: This article is the first attempt to provide a quantitative assessment of the under-representation of ARD and to outline the factors behind it. LIMITATIONS: Rare diseases are an etiologically heterogeneous group. The number of surveyed journals and articles, as well as targeted diseases might be limiting factors. SUGGESTIONS FOR FURTHER RESEARCH: Increasing collection and dissemination of data on ARD; opening a wide-ranging debate on their definition; implementation of biomolecular studies.

A possible case of Langerhans-cell histiocytosis? Differential diagnosis in a rare case from the Late Antiquity Bavaria (Germany).

OBJECTIVE: To outline the importance of accurate diagnosis in ancient rare diseases by presenting a possible case of Langerhans-cell histiocytosis. MATERIALS: Skeletal elements from a well-preserved skeleton of a nine to eleven-year-old, probably female child who lived around 300-400 AD Late Roman Neuburg / Donau (Germany). METHODS: Macroscopic, radiologic, light and scanning-electron microscopic and physical techniques were used. RESULTS: Resorptive defects, particularly in the cranium, but also in the left hip bone and the right femur, suggest the presence of Langerhans-cell histiocytosis macroscopically and radiologically. The presence of morphological changes along the edges of osteolytic lesions and in the diploic spaces appear to be post-mortem artifacts based on microscopic investigation and elemental analysis. CONCLUSIONS: Re-evaluation of morphological structures and elemental constitution of lesions is critical to differential diagnosis. In the case examined here, the identification of post-mortem structures rules out the former diagnosis of Langerhans-cell histiocytosis. Re-evaluation of cases of rare diseases require applying a range of methods during the analysis, as every single case makes a difference in the numbers of this very small group of diseases. SIGNIFICANCE: This study emphasizes the importance of utilizing different analytical techniques to avoid false diagnoses. LIMITATIONS: Not all morphological features can reliably be diagnosed using microscopic and elemental techniques. SUGGESTIONS FOR FURTHER RESEARCH: In the case of rare diseases that are difficult to diagnose, the widest possible spectrum of techniques should always be used, particularly microscopy.