Cuff tear arthropathy in the nineteenth century: 'chronic rheumatic arthritis' with 'partial luxation upwards' of the humeral head.

INTRODUCTION: Cuff tear arthropathy of the shoulder is a common indication for insertion of an increasing number of reverse shoulder arthroplasties. It is widely believed that this condition was unknown to medical practitioners and writers prior to the introduction of the term cuff tear arthropathy by Charles Neer in 1977. PURPOSE: To search nineteenth-century written sources for pathoanatomical and biomechanical descriptions of the typical changes found in cuff tear arthropathy. METHODS: A historical review. Nineteenth-century medical textbooks, reviews, case series, autopsy reports and illustrations were systematically searched and retrieved for relevance. References were hand-searched. Illustrations were reproduced and interpreted. RESULTS: A richly illustrated nineteenth-century literature was identified. The typical changes in cuff tear arthropathy were termed 'chronic rheumatic arthritis' of the shoulder with 'partial luxation upwards' of the humeral head and interpreted within a pathoanatomical and biomechanical framework. Detailed descriptions and illustrations of massive rotator cuff tears, biceps pathology and the osseous changes were identified and presented. CONCLUSION: The pathoanatomical and biomechanical changes later termed cuff tear arthropathy were well understood and nicely described in nineteenth-century medical literature.

Auguste Renoir, Sculptor With Hired Hands: A Masterful Artistic Cooperation Overshadowed by Legal Issues and Copyright Infringement.

The coping with rheumatoid arthritis of the famous French impressionist painter Pierre-Auguste Renoir (1841-1919) is described in former publications. The heavily handicapped painter has in his last years created sculptures in cooperation with the sculptor Richard Guino (1890-1973). The extraordinary genesis of the sculptures through a masterful artistic cooperation, as well as the resulting legal issues and shameful copyright infringements, is reported. Renoir's decision to create sculptures with the help of Guido can be attributed to his remarkable artistic vision, vitality, optimistic nature, and strong will and is also a further testimonial of creative coping of an artist overcoming the physical handicap due to rheumatoid arthritis of his final years, so far not described in detail in the medical literature.

Lost in Translation? Cortisone and the Treatment of Rheumatoid Arthritis in Britain, 1950-1960. [corrected].

Cortisone, initially known as 'compound E' was the medical sensation of the late 1940s and early 1950s. As early as April 1949, only a week after Philip Hench and colleagues first described the potential of 'compound E' at a Mayo Clinic seminar, the New York Times reported the drug's promise as a 'modern miracle' in the treatment of rheumatoid arthritis (RA). Given its high profile, it is unsurprising that historians of medicine have been attracted to study the innovation of cortisone. It arrived at the end of a decade of 'therapeutic revolutions', kicked off by penicillin transforming the treatment of bacterial infections and ending with hopes of a revolution in the treatment of non-infectious, chronic inflammatory diseases. Despite these studies of cortisone's introduction, few historians have taken the story forward and considered how cortisone was adopted and adapted into clinical practice. This article tells the longer of how the drug and its derivatives were taken from research laboratories and integrated into clinical practice; what has in recent decades become known as translational medicine (TM). In exploring cortisone's first decade in Britain, we focus specifically on its role in the treatment of RA. Our approach is always to consider cortisone's use in the context of other treatments available to clinicians, and at local and national institutional settings. We do not discuss the many other therapeutic uses of cortisone, which ranged for topical applications for skin diseases to the management of cancers, especially childhood leukaemia, nor do we discuss its close analogue ACTH-AdenoCorticoTropic Hormone. We think there are lessons in our study for TM policies today.

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.

No rheumatoid arthritis in ancient Egypt: a reappraisal.

Antiquity of rheumatoid arthritis (RA) remains controversial, and its origins in Americas or in the Old World are disputed. Proponents of the latter frequently refer to RA in ancient Egypt, but validity of those claims has never been examined. Review of all reported RA cases from ancient Egypt revealed that none of them represent real RA, instead being either examples of changing naming conventions or of imprecise diagnostic criteria. Most cases represented osteoarthritis or spondyloarthropathies. Also review of preserved ancient Egyptian medical writings revealed many descriptions of musculoskeletal disorders, but none of them resembled RA. This suggests that RA was absent in ancient Egypt and supports the hypothesis of the New World origin of RA and its subsequent global spread in the last several centuries.

Approach to the diagnosis of unusual carpal ankylosis from ancient Egypt.

OBJECTIVES: Carpal fusion is not an uncommon finding in archaeological bones. The majority of cases are due to inflammatory or infectious diseases and those are usually associated with other major alterations in the skeleton. METHODS: Two distinct individual cases, both adult females recovered from the Necropolis of Sharuna in the Middle Egypt from the Ptolemaic Period (IV to I BC) are presented in this study. Specimen 4323/1 shows a fusion of the scaphoid, lunate and triquetral bones in the right wrist. Specimen 4323/2 is a very rare fusion of a dysplastic lunate bone with the radius in the left wrist. In the proximal end of that left wrist, two possible remains of the flattened scaphoid and triquetral bones are also present. RESULTS: A differential diagnosis of both abnormalities as well as broad research into similar paleopathological cases were carried out: the most probable diagnosis for the specimen 4323/1 is an uncommon carpal coalition of three bones from the same row; the diagnosis of the specimen 4323/2 is more dubious with both rheumatoid arthritis and septic arthritis being strong candidates. CONCLUSIONS: In archaeological remains, carpal fusion should be thoroughly studied in order to ensure an accurate differential diagnosis.

Development of anti-TNF therapy for rheumatoid arthritis.

The aetiology of systemic, autoimmune, chronic inflammatory diseases--such as rheumatoid arthritis--is not known, and their pathogenesis is complex and multifactorial. However, progress in the characterization of intercellular mediators--proteins that are now known as cytokines--has led to the realization that one cytokine, tumour-necrosis factor (TNF; previously known as TNF-alpha), has an important role in the pathogenesis of rheumatoid arthritis. This discovery heralded a new era of targeted and highly effective therapeutics for rheumatoid arthritis and, subsequently, other chronic inflammatory diseases.

Autoimmunity: from black water fever to regulatory function.

Autoimmunity is a field that has only been around for a little over a century. Initially, it was thought that autoimmunity could not happen, that the body would never turn on itself (i.e. "horror autotoxicus"). It was only around the First World War that autoimmunity was recognized as the pathogenesis of various diseases, including rheumatoid arthritis. The discovery of Compound E led to successful treatment of patients with autoimmune diseases, but it was not till later that the adverse effects of this class of drugs were elucidated. The "modern" age of autoimmunity began around 1945 with the description of blackwater fever, and most of the subsequent research on hemolytic anemia and the role of an autoantibody in its pathogenesis led to a description of the anti-globulin reaction. The lupus erythematous (LE) cell was recognized in the mid-1940s by Hargreaves. His research carried on into the 1960s. Rheumatoid factor was also first described in the 1940s as yet another serum factor with activity against globulin-coated sheep red blood cells. The concept of autoimmunity really gained a foothold in the 1950s, when autoimmune thyroid disease and idiopathic thrombocytopenia were first described. Much has happened since then, and our understanding of autoimmunity has evolved now to include mechanisms of apoptosis, signaling pathway derangements, and the discovery of subsets of T cells with regulatory activity. The modern day study of autoimmunity is a fascinating area of research, and full understanding of the pathogenesis of autoimmune diseases is far from being completely elucidated.

Max Schüller and an alleged microbial cause of rheumatoid arthritis.

Max Schüller (1843-1907) was a German surgeon and microbiologist. From 1884 to 1905, he published histopathologic and bacteriological research on bacterial infection of human joints. Beginning in 1892, he focused on a bacterium he had identified in joints of patients with rheumatoid arthritis and surmised that he had discovered the cause of this disease. He persisted in conducting various experiments, some original at the time, with which he convinced himself of the validity of his discovery, without considering the possibility that he was working on contaminants. Contemporaneous attempts to confirm Schüller's findings gave inconsistent results. A century of microbiological research with ever more sensitive techniques has not definitively answered the etiologic question. This history is a cautionary tale of the difficulty of disproving an erroneous premise.

A Renaissance Pope with arthritis following frostbite.

Pius II, a 15th century Pope, developed chronic foot pain following frostbite at age 30. Later in life he was progressively disabled by arthritis elsewhere and by colic, which may have been due to kidney stones. The differential diagnosis of his rheumatic disease and its effect on his career are discussed.

[Pharmacotherapy for rheumatoid arthritis in the early 21st century: Russian and international experience].

The paper summarizes the data of international and Russian studies concerning current approaches to the pharmacotherapy of rheumatoid arthritis. Particular emphasis is placed on the substantiation of the treat-to-target concept, on the efficacy and safety of genetically engineered biological agents, including the inhibitors of tumor necrosis factor, interleukin-6 receptors, T-lymphocyte co-stimulation, and anti-B-cell therapy.

Rheumatoid arthritis in Cardinal Carlo de' Medici (1595-1666): a confirmed macroscopic, radiologic and molecular diagnosis.

OBJECTIVES: The paleopathological study of the skeletal remains belonging to Cardinal Carlo de' Medici (1595-1666), son of Ferdinando I (1549-1609) and Cristina of Lorena (1565-1637), has been presented previously. A diagnosis of Klippel-Feil syndrome, tuberculosis and a polyarthopathy, interpreted as rheumatoid arthritis, was suggested. A revision of this case based on the analysis of the historical documents and of some radiological images of Carlo's bones has been proposed recently; according to the Authors, the Cardinal was affected by the 'Medici syndrome', a combined Psoriatic-DISH arthropathy. This revision offers us the opportunity to discuss this complex case, comparing different points of view, and to present the results of the molecular analyses carried out on Carlo's bone samples. We looked for the genetic risk factors of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We also searched for the primary candidate genes of RA and PsA, i.e. DR4 or DR1 and Cw6 or DR7 respectively, the latter predisposing also for psoriasis. METHODS: An original molecular protocol was applied to achieve an aDNA uncontaminated by exogenous sources and almost intact, starting from one of the Cardinal's rib pieces. The allele risk factors for both diseases were identified by PCR-SSP assay as HLA genotyping methodology. RESULTS: Our data assigned Carlo the genotype DRB1*04/*11 for HLA-DRB locus and Cw*04/*12 for HLA-C locus. CONCLUSIONS: Since Carlo was infected by M. tuberculosis during infancy and was carrying the DR4 variant but not the Cw6, he surely had a predisposition to RA, not to PsA and/or psoriasis. The diagnosis of RA is thus confirmed.

50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams.

2011 marks the 50th anniversary of the discovery of ibuprofen. This article is a focus on the personal reflections and career of Dr Stewart Adams OBE, the scientist whose research lead to the discovery of the cyclooxygenase inhibitor. When Dr Adams discovered ibuprofen, he was working as a pharmacologist in the Research Department for the Boots Pure Drug Company Ltd. Dr Adams was assigned to work on rheumatoid arthritis (RA) and chose in 1953 to search for a drug that would be effective in RA but would not be a corticosteroid. He was one of the first workers in this field that later became known as NSAIDs (Non-Steroidal Anti Inflammatory Drugs). In 1961, Dr Adams with John Nicholson, the organic chemist, filed a patent for the compound 2-(4-isobutylphenyl) propionic acid, later to become one of the most successful NSAIDs in the modern world, ibuprofen. In this article, Dr Adams gives his modest insight into the early stages and initial observations which led to this world-wide success.

Great artists with rheumatoid arthritis: what did their disease and coping teach? Part I. Pierre-Auguste Renoir and Alexej von Jawlensky.

The famous artists Pierre-Auguste Renoir (1841-1919) and Alexej von Jawlensky (1864-1941) had rheumatoid arthritis (RA). Both represent an outstanding example of successful coping with RA in former times when treatment was very limited, and these individuals took advantage of creative disease management. The most popular French impressionist painter Renoir used his creativity to develop his own exercises and assistive equipments for painting despite his disability. Thus, Renoir exemplifies an artistic life altered by RA over more than 25 years that he dedicated entirely to his art and the depiction of beauty and happiness testified by his own words: "The pain passes, but the beauty remains." Jawlensky, a Russian from origin, was one of the most important expressionist painter active in Germany and the first painter in the 20th century who created extensive series of paintings especially of human faces. From Jawlensky, we learned that his rapidly progressing, late-onset RA induced depression, disability, financial pressure, and social retreat. But the resulting artistic sublimation contributed to the change in his paintings, which we owe the more than 1000 series of the very unique, small-format "Meditations."For those interested in art, new insight will be opened into the life and work of the artists and increase the appreciation for their contribution to modern art.

Great artists with rheumatoid arthritis. What did their disease and coping teach? Part II. Raoul Dufy and Niki de Saint Phalle.

Raoul Dufy (1877-1953) and Niki de Saint Phalle (1930-2002) were 2 famous artists who suffered from rheumatoid arthritis (RA). Both artists represent an additional outstanding example of successful coping with RA in former times when, for the first time, corticosteroids were available, but nevertheless treatment was very limited in the pre-biological era. Dufy was one of the earliest patients with RA who received corticosteroids and regained his creativity to paint for a few additional years, but finally he died of massive intestinal hemorrhages, the adverse event of the combination of corticosteroid plus aspirin. Niki de Saint Phalle, a self-taught French painter and sculptor, was one of the most significant and unconventional female artists of the 20th century. Her eventful life was full of emotional burdens and lifelong lung disease in addition to RA. Niki de Saint Phalle came out from each physical and emotional crisis with new forces and new artistic ideas. Interestingly, it has been suggested that the occupational exposure to colors contributed to the development of RA in artists, which used significantly more bright and clear colors based on toxic heavy metals such as Renoir and Dufy. Moreover, these 2 were cigarette smokers, a recently described risk factor for developing RA and increasing the severity once it does develop. Niki de Saint Phalle produced her sculptures made of plastic material without protection while she assumed that exposition to polyester and toxic fumes of polystyrene caused severe damage to her lungs, resulting in recurrent health problems.

The origins, results and consequences of the 1995 Arthritis Research Campaign Low-Dose Glucocorticoid Study.

The discovery and subsequent therapeutic use of glucocorticoids, which took 30 years, was stimulated by clinical observation and achieved by persistent investigation. Early reports of the potential of glucocorticoids to modify the underlying course of rheumatoid arthritis (RA) were overshadowed by pharmaceutical innovations with symptom relieving non-steroidal anti-inflammatory drugs (NSAIDs), and it was not until 1995 that clear-cut evidence of a powerful glucocorticoid disease-modifying action was published as the Arthritis Research Campaign Low-dose Glucocorticoid Study. This review reports how the study came to be designed and implemented, adds some additional information from the study not previously published, and considers the subsequent impact of the 1995 paper. Eighty years after Hench and colleagues made their first suggestion of benefit the UK National Health Service suggested all patients newly diagnosed with RA should have early access to glucocorticoid treatment.