Tumor-induced osteomalacia: A systematic literature review.

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

The activity of psoriatic arthritis with axial involvement correlates with the PsAID12.

OBJECTIVE: To determine the impact of the disease in patients with PsA in daily clinical practice and to evaluate its relationship with its axial activity. METHODS: A cross-sectional study was conducted in consecutive patients attended from January 2021 to December 2021 who met the CASPAR criteria, with clinical of inflammatory back pain and positive axial imaging, with or without peripheral involvement. Demographic, clinical, analytical data, HAQ index, PsAID12 and activity index (BASDAI and ASDAS-PCR) were also collected. Patients were divided into two groups, those with high impact and those with low impact according to PsAID results. Continuous variables are shown as median (Q1-Q3) and categorical variables as percentages and frequencies. RESULTS: Of the 269 patients evaluated with PsA, 72 patients with axial involvement were included, 40 men (55.6%), with a median age of 54.1 years and disease duration of 7 years. 28.3% of the patients were obese and serum CRP level was 0.45 mg/dl (0.08-1.10). BASDAI was 4.2 (2.0-6.2) and ASDAS-PCR was 2.4 (1.5-3.2), which translates into 39.6% of patients in low activity or remission. The median PsAID total score was 3.9 (1.6-5.4), evaluated in 61 patients. The patients who achieved a PsAID12 ≤ 4 were 63%, mostly men and with lower CRP levels than PsAID ≥ 4 patients. In addition, low impact measured by the PsAID12 was associated with low results in BASDAI and ASDAS-PCR. CONCLUSIONS: Axial involvement reflected lower impact of the disease measured by PsAID12 and it is correlated with low activity measured by BASDAI and ASDAS-PCR.

Secukinumab as Biological Treatment for Psoriatic Arthritis in Real Clinical Practice. / Secukinumab como tratamiento biológico en la artritis psoriásica en práctica clínica real.

INTRODUCTION: Clinical trials of secukinumab have demonstrated their efficacy and safety in psoriatic arthritis as biological first choice or after inadequate response to other biological treatments. OBJECTIVE: To analyze the efficacy and safety of secukinumab in peripheral psoriatic arthritis over 12 months in real clinical practice. MATERIAL AND METHODS: Patients with active peripheral psoriatic arthritis who started treatment with secukinumab according to the technical specifications were included. Efficacy and safety were evaluated from baseline to 12 months comparing naive and non-naive to biological therapy patients. RESULTS: A total of 76 patients were included (22 naive and 54 non-naive to biological) with an age of 51.9 years (10.3) and duration of the disease of 9.5 years (7.1). Of them, 31.6% with dactylitis, 51.3% with enthesitis and the baseline DAPSA was 19.0 (9.8). The retention rate was high, 90.9% in naive and 81.5% in non-naïve patients, and the percentage of patients with a DAPSA less than or equal to 14 was higher in the naive patients even after adjusting for age, sex and FAMEsc (P=.016). The safety data were similar to those described in the clinical trials. CONCLUSIONS: Secukinumab is effective and safe in 12-month treatment in peripheral active psoriatic arthritis in real clinical practice, after inadequate response to TNF or as first biological treatment.

Epidemiological Characteristics and Adverse Events of Patients with Psoriatic Arthritis Undergoing Treatment with Biological Therapies in Galicia. / Características epidemiológicas y eventos adversos de los pacientes con artritis psoriásica en tratamiento con terapias biológicas en Galicia.

Patients with severe forms of psoriatic arthritis (PsA) usually require treatment with biological agents. A greater knowledge of this subgroup of patients and their treatment enables better decision making in real clinical practice. METHODS: Longitudinal, multicentric observational study. We included all patients older than 16 years diagnosed with PsA in treatment with biological therapies from January 1, 2011 to December 31, 2015 treated in 6 Galician hospitals. RESULTS: Six hundred and fourpatients with PsA received biological therapies. Etanercept was the most used biological treatment. The average time of follow-up was 2.5 years and 67.9% were being treated with the first biological treatment. They were mostly patients with the peripheral subtype and met the criteria for clinical remission. Thirty-two percent had positive HLA-B27 and it was associated with axial PA subtypes. The prevalence of tuberculosis treated previously was 5.9%, and 23% of patients received chemoprophylaxis for latent tuberculosis. Twenty-four patients had undergone a prosthetic replacement. Hip prosthesis was the most frequent. Ninety-nine cases were treated for affective disorders. A diagnosis of fibromyalgia was established in 11 cases mostly women. Of the cases, 6.6% had episodes of serious infections, with respiratory infections being the most frequent. Sixteen tumours were detected (2.9%). Prostate cancer and gynaecological tumours were the most frequent. As with infections, the greater the age the greater the risk of presenting a tumour. CONCLUSIONS: We describe the epidemiological and safety characteristics in real life of a Galician multicentre cohort of patients with psoriatic arthritis under biological treatment.

Quality standard for the management of patients with psoriatic arthritis: QUANTUM Project. / Norma de calidad para el manejo del paciente con artritis psoriásica: proyecto QUANTUM.

OBJECTIVE: To generate a quality standard for the management of patients with psoriatic arthritis (PsA). METHODS: We employed qualitative methodology that included: 1) Two focus groups (one with patients with PsA and another with non-rheumatologist specialists involved in the care of PsA patients); 2) A narrative literature review of published documents related to the quality of care in PsA; 3) A nominal group meeting in which 15 expert rheumatologists generated and reached a consensus on a series of quality criteria, as well as formulas or quantifiable objective measures to evaluate them; 4) The Delphi method to establish the feasibility, priority and agreement with the quality criteria; 5) A final generation of standards of care and their attributes. A descriptive analysis of the results was carried out. RESULTS: A total of 59 standards of care was generated, 18 of mandatory compliance, grouped into 4 blocks according to specific objectives: 1) early diagnosis (n=6); 2) optimizing the management of the disease (n=26); 3) multidisciplinary collaboration (n=9); 4) monitoring improvement (n=18). To assess compliance with these standards of care, in many cases, the medical records will be reviewed. Other sources will be the records of the service and hospital and bibliographic databases. Regarding the level of compliance, for some of the standards of care this is yes/no; for others, compliance ranges from 50% to 100% and, in this range, in many cases, compliance was 80%. CONCLUSIONS: This set of standards of care should help improve quality of care in PsA patients.

Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients. / Supervivencia a largo plazo de los fármacos biológicos anti-TNF subcutáneos administrados durante los años 2008-2012 en una cohorte de pacientes con artritis reumatoide.

OBJECTIVE: To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. MATERIAL AND METHODS: Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. RESULTS: Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). CONCLUSIONS: In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy.

[Prevalence of osteoporosis, estimation of probability of fracture and bone metabolism study in patients with newly diagnosed prostate cancer in the health area of Lugo]. / Prevalencia de osteoporosis, estimación de la probabilidad de fractura y estudio del metabolismo óseo en pacientes con reciente diagnóstico de cáncer de próstata en el área sanitaria de Lugo.

OBJECTIVE: To study the prevalence of osteoporosis and fracture probability in patients diagnosed with prostate cancer. DESIGN: Observational descriptive transversal study. SITE: Study performed from Primary Care of Lugo in collaboration with Rheumatology and Urology Services of our referral hospital. PARTICIPANTS: Patients diagnosed with prostate cancer without bone metastatic disease from January to December 2012. MAIN MEASUREMENTS: Epidemiologic, clinical, laboratory and densitometric variables involved in osteoporosis were collected. The likelihood of fracture was estimated by FRAX® Tool. RESULTS: Eighty-three patients met the inclusion criteria. None was excluded. The average age was 67 years. The Body Mass Index was 28.28. Twenty-five patients (30.1%) had previous osteoporotic fractures. Other prevalent risk factors were alcohol (26.5%) and smoking (22.9%). Eighty-two subjects had vitamin D below normal level (98.80%). Femoral Neck densitometry showed that 8.9% had osteoporosis and 54% osteopenia. The average fracture risk in this population, estimated by FRAX®, was 2.63% for hip fracture and 5.28% for major fracture. Cut level for FRAX® major fracture value without DXA >5% and ≥7.5% proposed by Azagra et al. showed 24 patients (28.92%) and 8 patients (9.64%) respectively. CONCLUSIONS: The prevalence of osteoporosis in this population was very high. The more frequent risk factors associated with osteoporosis were: previous osteoporotic fracture, alcohol consumption, smoking and family history of previous fracture. The probability of fracture using femoral neck FRAX® tool was low. Vitamin D deficiency was very common (98.8%).

Anti-TNF-alpha-adalimumab therapy is associated with persistent improvement of endothelial function without progression of carotid intima-media wall thickness in patients with rheumatoid arthritis refractory to conventional therapy.

To determine whether treatment with the anti-TNF-alpha blocker adalimumab yields persistent improvement of endothelial function and prevents from morphological progression of subclinical atherosclerosis in patients with rheumatoid arthritis (RA) refractory to conventional therapy, a series of 34 consecutive RA patients, attending hospital outpatient clinics and who were switched from disease modifying antirheumatic drug therapy to anti-TNF-alpha-adalimumab treatment because of severe disease, were assessed by ultrasonography techniques before the onset of adalimumab therapy (at day 0) and then at day 14 and at month 12. Values of flow-mediated endothelium-dependent vasodilatation at day 14 and at month 12 were significantly higher (mean ± standard deviation (SD): 6.1 ± 3.9%; median: 5.7% at day 14, and mean ± SD: 7.4 ± 2.8%; median: 6.9% at month 12) than those obtained at day 0 (mean: 4.5 ± 4.0%; median: 3.6%; P = 0.03 and P < 0.001, resp.). Endothelium-independent vasodilatation results did not significantly change compared with those obtained at day 0. No significant differences were observed when carotid artery intima-media wall thickness values obtained at month 12 (mean ± SD: 0.69 ± 0.21 mm) were compared with those found at day 0 (0.65 ± 0.16 mm) (P = 0.3). In conclusion, anti-TNF-alpha-adalimumab therapy has beneficial effects on the development of the subclinical atherosclerosis disease in RA.

[Synovial sarcomas in Lugo between 2002-2006]. / Sarcomas sinoviales en el área sanitaria de Lugo en el período de 2002 a 2006.

OBJECTIVE: To study the clinical and epidemiological characteristics of all adults patients as having synovial sarcoma in the Hospital Xeral-Calde (Lugo) between 2002 and 2006. PATIENTS AND METHOD: We conducted a retrospective study of the case records of all adults patients diagnosed with synovial sarcoma from January 2002 through December 2006. Patients were considered to be adults if they were more than 18. In all cases a tissue-biopsy sample showing synovial sarcoma was required. The Hospital Xeral-Calde is the only referral center for a population of almost 250.000 people. RESULTS: Four cases (3 women) met the classification criteria for this study. The mean age was 35 years old (range, 22-41). The most common presentation was a palpable mass (mean 6.7cm.) associated with pain in lower extremities. The mean delay for the diagnosis was 17 months, but in one case has been noted as long as 2.5 years. Unlike the neck synovial sarcoma case, a long delay in the diagnosis implied a major tumor size and a higher histologic grade. The mean follow-up was 25.5 months; one patient died 1.5 years after the diagnosis. CONCLUSIONS: The overall annual incidence rate of synovial sarcoma in the Lugo region between January 2002 and 2006 for the population older than 18 years was a minimum estimate 0.32/10(5). Better physician awareness may contribute to the progressive increase in the recognition of this condition, especially in young people presenting with palpable mass. A long delay at the diagnosis implied a poor prognosis.

Late onset undifferentiated spondyloarthritis presenting with polymyalgia rheumatica features: description of seven cases.

To underline the importance of considering a diagnosis of undifferentiated spondyloarthritis (uSpA) in patients presenting polymyalgia rheumatica (PMR) features. All patients with late onset uSpA meeting criteria for PMR at the onset of their disease seen in the Rheumatology Division of Xeral-Calde Hospital of Lugo, Spain during a 5 year period, and in the Rheumatology Department of Lucania, Italy in a two and a half year period, were studied. Six patients with late onset uSpA showing PMR symptoms at the onset were seen during the study periods in the two centres. Another patient had previously been observed in Lugo in a study dealing with the spectrum of conditions mimicking PMR. Of the seven patients, five had manifestations of SpA at the beginning of the disease and two developed these in the following 6 months. All seven met the Amor and/or the ESSG criteria for classifying and diagnosing SpA. The possibility that late onset uSpA may have PMR-like features at the beginning of the disease should be taken into account. The diagnosis is not difficult if the entire clinical spectrum of SpA is considered.

Endothelial dysfunction in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors.

OBJECTIVE: To determine whether endothelial dysfunction was present in a cohort of patients with psoriatic arthritis (PsA) without overt cardiovascular disease or classic cardiovascular risk factors attended to in a community hospital. METHODS: Fifty patients with PsA who fulfilled the Moll and Wright criteria were recruited from Hospital Xeral-Calde (Lugo, Spain). Patients seen during the period of recruitment who had classic cardiovascular risk factors or had experienced cardiovascular or cerebrovascular events were excluded. Fifty healthy matched controls were also studied. In all patients and controls, endothelial function was determined by measuring flow-mediated endothelial dependent vasodilatation (FMD%) and endothelial independent vasodilatation (GTN%) by brachial ultrasonography. RESULTS: FMD% was significantly impaired in patients compared with controls (mean, median [range] 6.3%, 6.1% [0.3-13.4%] versus 8.2%, 8.2% [0.0-21.2%]; P = 0.008). However, no significant difference existed between patients and controls in GTN% or baseline diameter. A significant correlation between C-reactive protein level and erythrocyte sedimentation rate at the time of disease diagnosis and FMD% was found (P < 0.04). No significant FMD% and GTN% differences were observed when patients with PsA with polyarticular pattern were compared with the remaining patients with PsA. CONCLUSION: The present study demonstrates that patients with PsA without cardiovascular risk factors or clinically evident cardiovascular disease also exhibit endothelial dysfunction. These observations provide a basis for the potential association between PsA and atherosclerotic disease.

HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis.

OBJECTIVE: Cardiovascular (CV) disease is the most common cause of mortality in patients with rheumatoid arthritis (RA). We assessed the contribution of epidemiologic features, clinical features, routine laboratory markers of inflammation, and HLA-DRB1 alleles to CV mortality in patients with RA prospectively followed at a single referral center in Spain. METHODS: Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiologic data, and clinical data were assessed at that time. Patients were prospectively followed and clinical records were examined until patient's death or September 1, 2005. RESULTS: A total of 182 consecutive patients were assessed. Compared with the general Spanish population, the age- and sex-standardized mortality ratio by CV cause was 1.78. CV mortality adjusted by age at disease onset and sex was associated with chronic inflammation determined by C-reactive protein level (CRP; hazard ratio [HR] 1.14, P < 0.001) and erythrocyte sedimentation rate (ESR; HR 1.05, P = 0.003). Patients with HLA-DRB1*04 shared epitope alleles (HR 4.15, P = 0.030), in particular those HLA-DRB1*0404 positive (HR 6.65, P = 0.002), had increased risk of CV mortality. Increased risk of CV events was also associated with CRP level (HR 1.09, P = 0.001), ESR (HR 1.03, P = 0.003), and HLA-DRB1*0404 (HR 4.47, P = 0.002). CONCLUSION: Our results suggest that a chronically high inflammatory response in genetically predisposed individuals promotes an increased risk of CV events and CV mortality in RA.

Cardiovascular disease in rheumatoid arthritis.

Epidemiological studies have disclosed an increased mortality due to cardiovascular (CV) complications in patients with rheumatoid arthritis (RA). Patients with this disease have an increased risk of left ventricular diastolic dysfunction and congestive heart failure that is unrelated to the presence of traditional atherosclerosis risk factors or ischemic heart disease. Endothelial dysfunction, an early step in the atherogenesis process, is observed in both early and long-standing actively treated patients with RA. High-resolution B-mode ultrasound studies of the common carotid artery have shown the presence of subclinical atherosclerosis, manifested by increased carotid intima-media thickness and carotid plaques, in patients with RA. Association between HLA-DRB1*04 shared epitope alleles, in particular with HLA-DRB1*0404, and endothelial dysfunction and CV mortality has also been observed in these patients. Chronic inflammation plays a pivotal role in the mechanisms associated with atherogenesis in RA. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine implicated in the initiation and progression of inflammation as well as in the mechanisms associated with accelerated atherosclerosis in this disease. Anti-TNF-alpha therapy has proved to be clinically effective in patients with severe RA. Recent studies have also emphasized the positive effect of anti-TNF-alpha blockade in improving endothelial dysfunction in RA patients. However, this effect seems to be transient and in line with the persistence of chronic inflammation.

Giant cell arteritis and polymyalgia rheumatica: pathophysiology and management.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often concurrent diseases in Western countries in individuals aged >50 years. Clinical features of GCA are mainly due to involvement of the cranial arteries. PMR is clinically characterised by pain, aching and morning stiffness involving the neck, shoulder and hip girdles. Both conditions are generally associated with elevation of erythrocyte sedimentation rate and C-reactive protein. A temporal artery biopsy is the gold standard test for the diagnosis of GCA. Some diseases may mimic PMR or present with polymyalgic symptoms. Corticosteroids are the cornerstone of the management of GCA and PMR. An initial dosage of prednisone 10-20 mg/day yields a dramatic improvement of PMR symptoms in most cases. In GCA, the initial prednisone dosage required is higher (40-60 mg/day). However, once established, visual loss, which is the most feared complication of GCA, does not usually improve following corticosteroid therapy. Some patients exhibit a chronic-relapsing course and may need low doses of corticosteroids for several years. Alternative corticosteroid-sparing therapies and some therapeutic agents aimed at restoring balanced bone cell activity in patients taking corticosteroids are potentially useful in the management of GCA and PMR.

Giant cell arteritis: diagnosis and therapeutic management.

Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly in Western countries. Anemia and very high erythrocyte sedimentation rates are associated with lower incidence of severe ischemic events. Temporal artery biopsy is the gold standard in the diagnosis of GCA. A threshold size of 1 cm of post-formalin fixed segment of the temporal artery was associated with increased diagnostic yield of GCA. Other tools such as ultrasound, MRI, and fluorodeoxyglucose positron emission tomography are useful in the diagnosis of GCA. Corticosteroids are the cornerstone treatment of GCA. Studies using other drugs have yielded contradictory results.