Musculoskeletal manifestations in polymyalgia rheumatica and temporal arteritis.

To evaluate the incidence and characteristics of musculoskeletal manifestations in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS The records of 163 cases of PMR or TA diagnosed over a 15 year period in one area of Spain were reviewed for the presence and type of musculoskeletal manifestations. RESULTS Of 163 patients, 90 had isolated PMR and 73 had TA. Eighteen of the 90 patients (20%) with isolated PMR developed distal peripheral arthritis either at diagnosis or during the course of the disease. When it occurred, synovitis was mild, monoarticular or pauci-articular, asymmetrical, transient, and not destructive. Other distal manifestations observed in these patients were carpal tunnel syndrome and distal extremity swelling with pitting oedema. In all cases these manifestations occurred in conjunction with active PMR. As expected, PMR was the most frequent musculoskeletal manifestation in patients with TA, occurring in 56% of cases. On the contrary, only 11% of patients with TA developed peripheral arthritis. An important finding was that peripheral arthritis in these patients appears to be linked only temporally to the presence of simultaneous PMR and is not observed in its absence. Distal extremity swelling or defined polyarthritis were not observed. CONCLUSION The spectrum of distal musculoskeletal manifestations of PMR in our series is similar to that reported in other populations. By contrast, distal musculoskeletal symptoms are uncommon in TA. The almost complete absence of distal musculoskeletal manifestations in patients with pure TA suggests different mechanisms of disease in PMR and TA, supporting the view of two separate conditions or one common disease in which host susceptibility influences the clinical expression.

Musculoskeletal pain in female asylum seekers and hypovitaminosis D3

Résumé de l'article L'hypovitaminose D3 est bien connue et courante chez la population âgée en Occident. Toutefois, elle est probablement sous-diagnostiquée chez les jeunes femmes immigrantes, bien qu'elle soit bien documentée, principalement en Angleterre dans la population Indo-Pakistanaise. Lorsque ce déficit est diagnostiqué, le traitement substitutif est simple et bon marché. Nous avons suspecté une haute prévalence chez de jeunes femmes requérantes d'asile, surtout chez celles provenant de cultures différant quant à l'exposition solaire et la diète. Nous publions donc une série de 11 cas de patientes avec une hypovitaminose D symptomatique issues de la consultation générale de la Policlinique Médicale Universitaire. Toutes les patientes présentaient une anamnèse d'une faible exposition solaire et de douleurs osseuses diffuses, d'une fatigue, d'une faiblesse musculaire ou des modifications de la marche. Toutefois, les premiers diagnostics évoqués par les médecins étaient une possible somatisation (3 patientes), des douleurs dorso-lombaires chroniques (4 patientes) et des symptômes somatiques multiples et inexpliqués (3 patientes). Le diagnostic a été posé d'emblée chez une patiente seulement. La durée moyenne des plaintes avant la pose du diagnostic était de 38 mois et 5 jours. Avec le traitement de cholecalciférol et de calcium, les symptômes disparaissaient entre 1 et 3 mois, chez une patiente ils ont duré sept mois. Le taux moyen de 250H vitamine D3 était de 10.9 nmol/l (IR 21-131). Le taux moyen de calcium était de 2.19 mmol/l (2.15-2.55) et quatre patientes présentaient une hypocalcémie. Nous pensons donc que les femmes requérantes d'asile sont à risque d'une durée prolongée de symptômes, de part la possible haute prévalence de cette condition et la difficulté chez les médecins à la reconnaître. Le diagnostic d'hypovitaminose devrait être recherché chez les femmes requérantes d'asile souffrant de douleurs musculo-squelettiques de longue durée. Le premier diagnostic souvent évoqué, dans un contexte psychosocial souvent difficile, était de l'ordre d'un trouble somatoforme douloureux ou de somatisations. Toutefois, les douleurs liées à l'hypovitaminose D3 sont relativement bien définies ; elles sont symétriques, osseuses, débutent souvent dans la région lombaire pour ensuite s'étendre au bassin, aux membres inférieures proximalement et à la cage thoracique. Le traitement substitutif est simple, peu onéreux et il serait judicieux d'initier d'autres études pour évaluer le besoin d'une substitution de routine dans la population présentée. Abstract: Deficiency of vitamin D, which can lead to osteomalacia, is common in elderly patients in Western countries. However, it is still widely underdiagnosed in young immigrant women, even though the condition has been extensively reported in the immigrant Indo- Asian population in the United Kingdom since the 1960s. A recent study reports an average 59 months before diagnosis was established, and another study found a prevalence of 78% of hypovitaminosis D3 (compared with 58% in controls) in an Indo-Asian population attending a UK rheumatology clinic. When recognised, hypovitaminosis D3 is easily treatable. A study on osteomalacic myopathy in veiled Arabic women in Denmark found that muscle strength returned to normal (except in maximal voluntary con-traction) after six months' treatment. We expected to see this disease in female asylum seekers, especially in those from societies with different customs regarding exposure to sunlight and diet We report 11 cases of symptomatic hypovitaminosis D3 in female asylum seekers (table 1). We focus on the pathology encountered by the primary care doctors caring for these 11 patients, the length of time between the appearance of symptoms, and the establishment of the diagnosis of hypovitaminosis D3 as well as the women's response to treatment by the improvement of a wide range of clinical symptoms-bone pain, muscular weakness, and fatigue.

Persistent association of nailfold capillaroscopy changes and skin involvement over thirty-six months with duration of untreated disease in patients with juvenile dermatomyositis.

OBJECTIVE: To determine the association of changes on nailfold capillaroscopy with clinical findings and genotype in children with juvenile dermatomyositis (DM), in order to identify potential differences in disease course over 36 months. METHODS: At diagnosis of juvenile DM in 61 children prior to the initiation of treatment, tumor necrosis factor alpha (TNFalpha) -308 allele and DQA1*0501 status was determined, juvenile DM Disease Activity Scores (DAS) were obtained, and nailfold capillaroscopy was performed. The disease course was monitored for 36 months. Variations within and between patients were assessed by regression analysis. RESULTS: At diagnosis, shorter duration of untreated disease (P = 0.05) and a lower juvenile DM skin DAS (P = 0.035) were associated with a unicyclic disease course. Over 36 months, end-row loop (ERL) regeneration was associated with lower skin DAS (P < 0.001) but not muscle DAS (P = 0.98); ERL regeneration and decreased bushy loops were associated with a shorter duration of untreated disease (P = 0.04 for both). At 36 months, increased ERL regeneration (P = 0.007) and improvement of skin DAS (P < 0.001) and muscle DAS (P = 0.025) were associated with a unicyclic disease course. CONCLUSION: Early treatment of juvenile DM may lead to a unicyclic disease course. The non-unicyclic disease course usually involves continuing skin manifestations with persistent nailfold capillaroscopy changes. The correlation of nailfold capillaroscopy results with cutaneous but not with musculoskeletal signs of juvenile DM over a 36-month period suggests that the cutaneous and muscle vasculopathies have different pathophysiologic mechanisms. These findings indicate that efforts to identify the optimal treatment of cutaneous features in juvenile DM require greater attention.

Tumeurs de l'appareil locomoteur: de la simple "bosse" a la prise en charge multidisciplinaire [Tumors of the musculoskeletal system: from the "lumps" to multidisciplinary care].

Management of musculoskeletal tumours usually begins with the appearance of a lump or bump, or the onset of unspecific symptoms. A poor initial work-up, a faulty biopsy or an inadequate resection may have a severe impact on the prognosis, including re-interventions, amputation, local recurrence or systemic spread of the disease. The patient with a suspicious lesion should be referred to a "sarcoma centers" where a planned and well-performed diagnostic work-up will allow a precise diagnosis in terms of histology and staging. After a multidisciplinary discussion of the case, an accurate treatment plan is established. Such an approach allows an adequate patient management, often with a positive impact on the survival and functional outcome.

Leri's pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis.

OBJECTIVES: Leri's pleonosteosis (LP) is an autosomal dominant rheumatic condition characterised by flexion contractures of the interphalangeal joints, limited motion of multiple joints, and short broad metacarpals, metatarsals and phalanges. Scleroderma-like skin thickening can be seen in some individuals with LP. We undertook a study to characterise the phenotype of LP and identify its genetic basis. METHODS AND RESULTS: Whole-genome single-nucleotide polymorphism genotyping in two families with LP defined microduplications of chromosome 8q22.1 as the cause of this condition. Expression analysis of dermal fibroblasts from affected individuals showed overexpression of two genes, GDF6 and SDC2, within the duplicated region, leading to dysregulation of genes that encode proteins of the extracellular matrix and downstream players in the transforming growth factor (TGF)-β pathway. Western blot analysis revealed markedly decreased inhibitory SMAD6 levels in patients with LP. Furthermore, in a cohort of 330 systemic sclerosis cases, we show that the minor allele of a missense SDC2 variant, p.Ser71Thr, could confer protection against disease (p<1×10(-5)). CONCLUSIONS: Our work identifies the genetic cause of LP in these two families, demonstrates the phenotypic range of the condition, implicates dysregulation of extracellular matrix homoeostasis genes in its pathogenesis, and highlights the link between TGF-β/SMAD signalling, growth/differentiation factor 6 and syndecan-2. We propose that LP is an additional member of the growing 'TGF-β-pathies' group of musculoskeletal disorders, which includes Myhre syndrome, acromicric dysplasia, geleophysic dysplasias, Weill-Marchesani syndromes and stiff skin syndrome. Identification of a systemic sclerosis-protective SDC2 variant lays the foundation for exploration of the role of syndecan-2 in systemic sclerosis in the future.

Diffusion-weighted MR imaging in musculoskeletal diseases: Current concepts.

MR imaging is currently regarded as a pivotal technique for the assessment of a variety of musculoskeletal conditions. Diffusion-weighted MR imaging (DWI) is a relatively recent sequence that provides information on the degree of cellularity of lesions. Apparent diffusion coefficient (ADC) value provides information on the movement of water molecules outside the cells. The literature contains many studies that have evaluated the role of DWI in musculoskeletal diseases. However, to date they yielded conflicting results on the use and the diagnostic capabilities of DWI in the area of musculoskeletal diseases. However, many of them have showed that DWI is a useful technique for the evaluation of the extent of the disease in a subset of musculoskeletal cancers. In terms of tissue characterization, DWI may be an adjunct to the more conventional MR imaging techniques but should be interpreted along with the signal of the lesion as observed on conventional sequences, especially in musculoskeletal cancers. Regarding the monitoring of response to therapy in cancer or inflammatory disease, the use of ADC value may represent a more reliable additional tool but must be compared to the initial ADC value of the lesions along with the knowledge of the actual therapy.

Extraintestinal Manifestations of Inflammatory Bowel Disease.

Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD.

A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co- ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

Computed tomography findings of paracoccidiodomycosis in musculoskeletal system

Objective: To evaluate musculoskeletal involvement in paracoccidioidomycosis at computed tomography. Materials and Methods: Development of a retrospective study based on a review of radiologic and pathologic reports in the institution database. Patients with histopathologically confirmed musculoskeletal paracoccidioidomycosis and submitted to computed tomography were included in the present study. The imaging findings were consensually described by two radiologists. In order to avoid bias in the analysis, one patient with uncountable bone lesions was excluded from the study. Results: A total of seven patients were included in the present study. A total of 18 bone lesions were counted. The study group consisted of 7 patients. A total number of 18 bone lesions were counted. Osteoarticular lesions were the first manifestation of the disease in four patients (57.14%). Bone lesions were multiple in 42.85% of patients. Appendicular and axial skeleton were affected in 85.71% and 42.85% of cases, respectively. Bone involvement was characterized by well-demarcated osteolytic lesions. Marginal osteosclerosis was identified in 72.22% of the lesions, while lamellar periosteal reaction and soft tissue component were present in 5.55% of them. One patient showed multiple small lesions with bone sequestra. Conclusion: Paracoccidioidomycosis can be included in the differential diagnosis of either single or multiple osteolytic lesions in young patients even in the absence of a previous diagnosis of pulmonary or visceral paracoccidioidomycosis

Magnetic resonance imaging and BMB score in the evaluation of bone involvement in Gaucher’s disease patients

AbstractObjective:To evaluate by magnetic resonance imaging changes in bone marrow of patients undergoing treatment for type I Gaucher’s disease.Materials and Methods:Descriptive, cross-sectional study of Gaucher’s disease patients submitted to 3 T magnetic resonance imaging of femurs and lumbar spine. The images were blindly reviewed and the findings were classified according to the semiquantitative bone marrow burden (BMB) scoring system.Results:All of the seven evaluated patients (three men and four women) presented signs of bone marrow infiltration. Osteonecrosis of the femoral head was found in three patients, Erlenmeyer flask deformity in five, and no patient had vertebral body collapse. The mean BMB score was 11, ranging from 9 to 14.Conclusion:Magnetic resonance imaging is currently the method of choice for assessing bone involvement in Gaucher’s disease in adults due to its high sensitivity to detect both focal and diffuse bone marrow changes, and the BMB score is a simplified method for semiquantitative analysis, without depending on advanced sequences or sophisticated hardware, allowing for the classification of the disease extent and assisting in the treatment monitoring.

The burden of disease in Spain: results from the global burden of disease study 2010

BackgroundWe herein evaluate the Spanish population¿s trends in health burden by comparing results of two Global Burden of Diseases, Injuries, and Risk Factors Studies (the GBD studies) performed 20 years apart.MethodsData is part of the GBD study for 1990 and 2010. We present results for mortality, years of life lost (YLLs), years lived with disability, and disability-adjusted life years (DALYs) for the Spanish population. Uncertainty intervals for all measures have been estimated.ResultsNon-communicable diseases accounted for 3,703,400 (95% CI 3,648,270¿3,766,720) (91.3%) of 4,057,400 total deaths, in the Spanish population. Cardiovascular and circulatory diseases were the main cause of mortality among non-communicable diseases (34.7% of total deaths), followed by neoplasms (27.1% of total deaths). Neoplasms, cardiovascular and circulatory diseases, and chronic respiratory diseases were the top three leading causes for YLLs. The most important causes of DALYs in 2010 were neoplasms, cardiovascular and circulatory diseases, musculoskeletal disorders, and mental and behavioral disorders.ConclusionsMortality and disability in Spain have become even more linked to non-communicable diseases over the last years, following the worldwide trends. Cardiovascular and circulatory diseases, neoplasms, mental and behavioral disorders, and neurological disorders are the leading causes of mortality and disability. Specific focus is needed from health care providers and policy makers to develop health promotion and health education programs directed towards non-communicable disorders.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

A retrospective study of the epidemiological and clinic-pathological aspects of cattle and buffaloes with degenerative joint disease (DJD) was conducted in the state of Pará, Brazil. From 1999 to 2014, eleven cattle and 24 buffaloes were evaluated. All the treated animals with suspected DJD underwent a clinical examination of the musculoskeletal system. In seven cattle and eight buffaloes with clinical signs of the disease postmortem examination was performed. The common clinical signs observed in both species were chronic lameness, stiff gait, postural changes, audible crackles in the affected limb, prolonged recumbency, difficulty in getting up and progressive weight loss. The lesions observed at necropsy were: irregular articular surfaces, erosion of the articular cartilage and the underlying bone tissue, and proliferation of the periarticular bone tissue with formation of osteophytes. The most affected joints in cattle and buffaloes wereof the hind limb. In buffaloes, the main predisposing factor to the onset of DJD was phosphorus deficiency. In cattle, defects of the anatomical conformation of the hind limbs, chronic trauma due to the activities performed, such as semen collection, and advanced age possibly contributed to the emergence of the disease.

Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer's disease: A controlled trial

Aim: The objective of the present study was to investigate the effect of a multimodal exercise intervention on frontal cognitive functions and kinematic gait parameters in patients with Alzheimer's disease. Methods: A sample of elderly patients with Alzheimer's disease (n=27) were assigned to a training group (n=14; aged 78.0±7.3years) and a control group (n=13; aged 77.1±7.4years). Multimodal exercise intervention includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week for 16weeks, and the control participants maintained their regular daily activities during the same period. The frontal cognitive functions were evaluated using the Frontal Assessment Battery, the Clock Drawing Test and the Symbol Search Subtest. The kinematic parameters of gait-cadence, stride length and stride speed were analyzed under two conditions: (i) free gait (single task); and (ii) gait with frontal cognitive task (walking and counting down from 20 - dual task). Results and discussion: The patients in the intervention group significantly increased the scores in frontal cognitive variables, Frontal Assessment Battery (P<0.001) and Symbol Search Subtest (P<0.001) after the 16-week period. The control group decreased the scores in the Clock Drawing Test (P=0.001) and increased the number of counting errors during the dual task (P=0.008) after the same period. Conclusion: The multimodal exercise intervention improved the frontal cognitive functions in patients with Alzheimer's disease. © 2012 Japan Geriatrics Society.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

Foi realizado um estudo retrospectivo sobre os aspectos epidemiológicos e clínico-patológicos em bovinos e búfalos com doença articular degenerativa (DAD) no estado do Pará, Brasil. Durante os anos de 1999 a 2014 foram avaliados 11 bovinos e 24 bubalinos. Todos os animais atendidos com suspeita clínica de DAD foram submetidos a exame clínico do sistema locomotor. Foram necropsiados sete bovinos e oito bubalinos com sinais clínicos da enfermidade. Os sinais clínicos comuns observados em ambas as espécies foram claudicação crônica, andar rígido, alterações posturais, crepitações audíveis no membro acometido, decúbito prolongado, dificuldade para levantar, e emagrecimento progressivo. As lesões articulares evidenciadas na necropsia consistiram em irregularidade da superfície articular, presença de erosão na cartilagem articular e no tecido ósseo subjacente, proliferação de tecido ósseo periarticular com formação de osteófitos. Tanto nos bovinos como nos bubalinos as articulações mais acometidas foram as dos membros posteriores. Nos bubalinos, possivelmente o principal fator predisponente ao surgimento de DAD foi à deficiência de fósforo, ao contrário dos bovinos, nos quais os defeitos de conformação anatômica dos membros posteriores, traumas crônicos em virtude da atividade exercida, como a coleta de sêmen e a idade avançada, foram o que, possivelmente, contribuíram para surgimento da enfermidade.

Degenerative joint disease in cattle and buffaloes in the Amazon region: a retrospective study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)