Apremilast in refractory orogenital ulcers and other manifestations of Behçet's disease. A national multicentre study of 51 cases in clinical practice.

OBJECTIVES: The objective of the present study was to assess the efficacy of apremilast (APR) in the management of refractory oral and/or genital ulcers in patients with Behçet's disease (BD). METHODS: National multicentre open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. RESULTS: We included 51 patients (35 women/16 men; mean age 44.7±13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n=19) or genital (n=2) aphthous ulcers or both (n=30). Other manifestations found at APR onset were arthralgia/arthritis (n=16), folliculitis/pseudofolliculitis (n=14), erythema nodosum (n=3), furunculosis (n=2), paradoxical psoriasis induced by TNF-α-inhibitors (n=2), ileitis (n=2), deep venous thrombosis (n=2), leg ulcers (n=1), erythematosus and scaly skin lesions (n=1), fever (n=1), unilateral anterior uveitis (n=1) and neuro Behçet (n=1). After a mean follow-up of 8.5±6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. CONCLUSIONS: APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

The impact of information and communications technology and broadcasting on YouTube for improving attitude toward organ donation in secondary education with the creation of short films.

OBJECTIVE: There is a lack of awareness about organ donation among teenagers, a fact that could decrease future donation rates. The objective is to analyze the impact of an educational proposal based on the creation of short films. METHODS: Fifteen schools were randomly selected: ten for the experimental group (EG), and five for the control group (CG). In both groups all students from the selected classes participated (EG: n = 543, CG: n = 320). An intervention was undertaken in the EG, providing a website to make a short film about organ donation and transplantation (ODT) to be broadcast on YouTube. The students completed a questionnaire before and after the proposal. STATISTICS: Mann-Whitney test was conducted to compare the pre-test data, McNemar test compare the pre and post test results of each group, and Chi-square test to compare the change in responses between the two groups. RESULTS: The change to a more favorable response was greater in the EG in all variables. The YouTube channel received 104,912 viewings. CONCLUSIONS: An innovative educational intervention has a positive influence on teenage attitude and knowledge about ODT; it also has important social repercussions. PRACTICE IMPLICATIONS: Implementing this educational proposal about ODT could help improve future donation rates.

Assessing treatment tolerability for rheumatoid arthritis. Validation and practical applications of the 'TOL-AR-18 questionnaire'.

INTRODUCTION: Given the lack of standardized tools to assess tolerability from patient's perspective, we carried out the validation of a questionnaire to asses treatment tolerability for rheumatoid arthritis (RA): TOL-AR-18. METHODS: The TOL-AR-18 was validated in the cross-sectional observational study in adult patients with RA. Socio-demographic and clinical variables were collected. Patients completed the TOL-AR-18 and ARTS questionnaires and a question about their general health status. RESULTS: Data of 66 patients with a mean age (standard deviation; SD) of 56.71 (10.50) years were analyzed; 66.7% were women. Mean (SD) time to disease progression was 10.76 (8.23) years, and time from first treatment initiation was 9.24 (7.70) years. Patients did not report other adverse events rather than those included in the TOL-AR-18. The questionnaire was feasible with high internal consistency (Cronbach's α >0.90). Discriminant validity was moderate, with significant differences between patients in remission and all other, and between patients who did not report adverse events and the rest (P<.05). Convergent validity was moderate-low when correlated with the ARTS questionnaire. CONCLUSION: The TOL-AR-18 is valid for use in a clinical setting and useful as an additional tool for all professionals to manage and assess tolerability in RA.

Epidemiology of osteoporosis and its determinants in physically active Majorcan elderly.

OBJECTIVE: To estimate the prevalence and distribution of determinants of osteoporosis (OP) in a population of physically active Majorcans over 60. METHODS: Health survey in which consecutive women and men above 60 years old visiting sports facilities during a two-month period were recruited. All underwent a densitometry of the lumbar spine (LS) and femoral neck (FN). Osteoporosis was defined according to the World Health Organization densitometric criteria (T-score <2.5 SD in the LS or FN, and osteopenia if the result was between -2.5 and -1 SD). As osteoporosis shows substantial differences between genders, the study of its determinants was conducted independently for men and women. RESULTS: The sample included 731 subjects (86% female), with an average age of 70 (SD 5) among men and 65 (8) among women. The overall prevalence of osteoporosis was 35.7% in the LS, 8.9% in the FN and 39.4% in the LS and/or FN. The analysis by gender showed a higher prevalence of osteoporosis in women than in men (43.8 % vs. 11.1%). The presence of osteoporosis increased with age in men and women (7.8% for 61-75 years old vs 22.7% > 75 years old for men and 48.5% for 61-75 years old vs 62.7% > 75 for women). CONCLUSIONS: Densitometric osteoporosis is frequent among physically active elderly population, and higher than expected in a largely sunlight-exposed area.

Clinical Characterization and Diagnostic Approaches for Patients Reporting Hypersensitivity Reactions to Quinolones.

BACKGROUND: Quinolones are the second most frequent cause of hypersensitivity reactions (HSRs) to antibiotics. A marked increase in the number of patients with HSRs to quinolones has been detected. OBJECTIVE: To describe the clinical characteristics of patients with HSRs to quinolones and present methods for their diagnosis. METHODS: Patients attending the allergy unit due to reactions suggestive of HSRs to quinolones were prospectively evaluated between 2005 and 2018. Diagnosis was achieved using clinical history, skin tests (STs), basophil activation tests (BATs), and drug provocation tests (DPTs) if ST and BAT results were negative. RESULTS: We included 128 subjects confirmed as having HSRs to quinolones and 42 found to be tolerant. Anaphylaxis was the most frequent entity in immediate HSRs and was most commonly induced by moxifloxacin. Patients were evaluated a median of 150 days (interquartile range, 60-365 days) after the reaction. Of patients who underwent ST and BAT, 40.7% and 70%, respectively, were positive. DPT with a quinolone was performed in 48 cases, giving results depending on the culprit drug: when moxifloxacin was involved, 62.5% of patients gave a positive DPT result to ciprofloxacin, whereas none reacted to levofloxacin. The risk of HSR was 96 times higher in subjects who reported moxifloxacin-induced anaphylaxis and 18 times higher in those reporting immediate reactions compared with clinical entities induced by quinolones other than moxifloxacin and nonimmediate reactions. CONCLUSIONS: The diagnosis of HSR to quinolones is complex. The use of clinical history is essential as a first step. BAT shows higher sensitivity than STs. DPTs can be useful for finding safe alternative quinolones.

Pulmonary arterial hypertension in adult-onset Still's disease: A case series and systematic review of the literature.

OBJECTIVE: To investigate the prevalence, clinical characteristics and prognosis of pulmonary arterial hypertension (PAH) in adult onset Still's disease (AOSD). METHODS: We retrospectively reviewed all patients with AOSD diagnosed during a 33-year period in 2 referral tertiary care hospitals, selecting for analysis those who presented PAH confirmed as by right heart catheterization. A systematic review of the literature (PubMed 1990 to July 2018) was also performed, in order to determine the prognosis and the most appropriate treatment strategy for this complication. RESULTS: The overall prevalence of PAH in our AOSD population was 4.8% (2/41). Including our 2 cases, 20 well-documented patients have been reported. PAH may complicate AOSD at any time during its course, and usually occurs in patients who have persistent and severe disease, with a considerable frequency (35%) of previous or concomitant severe clinical complications. In all cases, the etiology of pulmonary hypertension was a group 1 PAH based on the 2015 ESC/ERS guidelines. Most patients in this series had advanced WHO functional classes III-IV at the time of PAH diagnosis, reflecting an important diagnostic delay. Thirty-three percent of patients had a poor outcome despite the therapy, with a mortality rate that reached 22%. The therapeutic strategy that achieved the best results was the use of glucocorticoids, immunosuppression and PAH-specific vasodilator therapy. CONCLUSION: HAP is an under-recognized complication of AOSD that should be kept in mind in the differential diagnosis of those patients who experience dyspnea on exertion or a decrease in exercise tolerance.

Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women.

OBJECTIVES: To analyze the clinical characteristics and the principal causes of osteoporosis in premenopausal women. METHODS: This study included 52 osteoporotic premenopausal women ages 20-51 years (mean 36.2 +/- 7) who were referred to an outpatient rheumatology department for osteoporosis evaluation. Bone mass assessment, automated biochemical profile, urinary calcium excretion, and bone marker assays were performed on all patients. Hormonal measurements were made when a specific etiology was not readily apparent. The diagnosis of osteoporosis was defined by the presence of atraumatic vertebral fractures and/or by densitometric criteria. Previous skeletal fractures, weight, height, body mass index (BMI), age at menarche, and family history of osteoporosis also were recorded. RESULTS: Twenty-nine patients (56%) had idiopathic osteoporosis and 23 (44%) had secondary osteoporosis. Fifteen patients (29%) had vertebral fractures and 12 had previous peripheral fractures. Patients with secondary osteoporosis showed higher BMI (23.2 +/- 3 v 21.2 +/- 2, P =.02) and lower femoral Z-scores of bone mineral density (BMD) (-2.1 +/- 0.6 v -1.5 +/- 0.9, P =.02) than those with idiopathic disease. The most frequent causes of secondary osteoporosis included Cushing syndrome, pregnancy osteoporosis, and osteogenesis imperfecta. Nearly half of the patients (48%) with idiopathic osteoporosis had a family history of osteoporosis. In addition, 11 patients (38%) with idiopathic osteoporosis had associated hypercalciuria. Except for an increase in urinary calcium excretion (248 +/- 53 v 143 +/- 47 mg/24 h, P <.0001), no other significant differences in the remaining variables analyzed were found between hypercalciuric and normocalciuric patients with idiopathic osteoporosis. CONCLUSIONS: Idiopathic osteoporosis was the most frequent diagnosis of pre-menopausal osteoporosis in our unit. These patients showed lower BMI and higher femoral neck Z-scores than patients with secondary causes. A family history of osteoporosis and hypercalciuria were factors frequently associated with this disorder.

Power Doppler ultrasonography assessment of entheses in spondyloarthropathies: response to therapy of entheseal abnormalities.

OBJECTIVE: To investigate the response to therapy of entheseal abnormalities assessed with power Doppler (PD) ultrasound (US) in spondyloarthropathies (SpA). METHODS: A total of 327 patients with active SpA who were starting anti-tumor necrosis factor (TNF) therapy were prospectively recruited at 35 Spanish centers. A PDUS examination of 14 peripheral entheses was performed by the same investigator in each center at baseline and at 6 months. The following elementary lesions were assessed at each enthesis (presence/absence): morphologic abnormalities (hypoechogenicity and/or thickening), entheseal calcific deposits, cortical abnormalities (bone erosion and/or proliferation), adjacent bursitis and intraenthesis and perienthesis (tendon body and/or bursa) PD signal. Response to therapy of each elementary lesion was assessed by calculating change in the cumulative presence from baseline to 6 months. Intraobserver reliability of PDUS was evaluated by blindly assessing the stored baseline images 3 months after the real-time examination. RESULTS: Complete data were obtained on 197 patients who received anti-TNF therapy for 6 months. In 91.4% of the patients there were gray-scale or PD elementary lesions at baseline and at 6 months. Cumulative entheseal morphologic abnormalities, intraenthesis PD, perienthesis PD, and bursitis showed a significant decrease from baseline to 6 months (p < 0.05). There was high intraobserver reliability for all elementary lesions (interclass correlation coefficient > 0.90, p < 0.0005). CONCLUSION: Entheseal morphologic abnormalities, PD signal, and bursitis were US abnormalities that were responsive to anti-TNF therapy in SpA. PDUS can be a reproducible method for multicenter monitoring of therapeutic response in enthesitis of SpA.

Dissection of the ascending aorta in a patient with HLA-B27 associated ankylosing spondylitis.

We describe a 38-year-old patient with ankylosing spondylitis complicated by a non-traumatic dissection of the ascending aorta without concomitant Marfan's syndrome.

Validity, reproducibility, and responsiveness of a twelve-joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis.

OBJECTIVE: To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. METHODS: A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. RESULTS: A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84-0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. CONCLUSION: A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.

[Spondylodiskitis caused by enterococcus: an unusual entity. A case report and literature review]. / Espondilodiscitis enterocócica: una entidad inusual. Descripción de un caso y revisión de la bibliografía.

Spondylodiskitis caused by enterococcus is an entity anecdoticaly described in medical literature. We report a case of lumbar spondylodiskitis caused by enterococcus faecalis of urinary origin in a male patient after being operated because of prostate benign hyperplasia. Clinical, radiologic and evolutive features were revised. Through a bibliographical search 9 cases have been found in medical literature, although 2 of them were included in etiologic series of infectious spondylodiskitis with no more information. Together with our case we describe briefly the published characteristics of the 7 patients.

Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis.

BACKGROUND: Since primary biliary cirrhosis (PBC) is usually diagnosed in postmenopausal women with minor cholestasis, it has been questioned whether PBC itself represents a further risk for osteoporosis. AIM: To assess the prevalence and risk factors for osteoporosis in an unselected series of women with PBC. PATIENTS AND METHODS: 142 women with PBC (age: 54.3+/-0.8 years) and an age-matched control group. Osteoporosis was established by densitometry (bone mineral density below -2.5 T-score). Age, duration and severity of PBC, body mass index, menopausal status, histological stage and markers of bone turnover were assessed. RESULTS: Prevalence of osteoporosis was higher in PBC (32.4%) than in normal women (11. 1%) (RR: 3.83, 95%CI: 2.59-5.67, P<0.001). Osteoporosis was associated with older age, menopausal status, body mass index, longer PBC duration, advanced histological stage, high bilirubin and alkaline phosphatase, and low albumin and prothrombin index. Regression analysis identified older age, higher Mayo risk score, lower body mass index and advanced histological stage but not menopause as the independent risk factors for osteoporosis. CONCLUSIONS: Osteoporosis is more prevalent in women with PBC than in the general population. Age and severity of the disease, but not menopausal status, are the main risk factors for osteoporosis in this liver disease.

Hypophosphatemic osteomalacia: a report of five cases and evaluation of bone markers.

In this study, we analyzed the changes in biochemical markers of bone turnover in five patients with hypophosphatemic osteomalacia. The following bone markers were evaluated: among bone formation markers, total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), osteocalcin (bone Gla protein, BGP) and procollagen type I N propeptide (PINP); among bone resorption markers, serum beta C-terminal cross-linked telopeptide of type I collagen (s-CTx), urinary hydroxyproline (HYP), and N-terminal and alpha and beta C-terminal cross-linked telopeptides of collagen (NTx and alpha- and beta-CTx). In addition, the alpha/beta-CTx ratio was evaluated. TAP and BAP were the markers with the highest increase in both frequency and magnitude. Conversely, BGP values were low in all patients. Collagen-related markers were slightly increased in nearly half of the patients. Among them, PINP showed the highest proportion of increased values. The alpha/beta-CTx ratio was within normal values in all patients. In conclusion, TAP and BAP seem to be the best bone markers in the diagnostic evaluation of hypophosphatemic osteomalacia. In addition, their high values associated with low levels of BGP provide an even more reliable biochemical profile of this disorder, when associated with the classic mineral and skeletal homeostasis abnormalities.

Alendronate is more effective than etidronate for increasing bone mass in osteopenic patients with primary biliary cirrhosis.

OBJECTIVES: Osteopenia increases the morbidity of primary biliary cirrhosis (PBC). In this study, we have compared two bisphosphonates, alendronate and cyclical etidronate, that inhibit osteoclast-mediated bone resorption and have examined their effects on bone mass in patients with this disease. METHODS: A total of 32 women with PBC were randomly assigned to receive alendronate (10 mg/day) or etidronate (400 mg/day) for 14 days every 3 months. Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months. Bone fractures and markers of bone mineral metabolism were also evaluated. RESULTS: Sixteen patients were allocated to each group, which were comparable with respect to the severity of PBC and osteopenia. Thirteen patients in each group completed the 2-yr trial. Both treatments increased bone mineral density after 2 yr, although the increase at the lumbar spine and at the proximal femur was significantly higher in patients receiving alendronate than in patients on etidronate. This higher effect of alendronate paralleled with changes in the biochemical markers of bone turnover. No patient developed new vertebral fractures, but new peripheral fractures were detected in two patients on alendronate and in one on etidronate. There were no serious adverse effects. Neither treatment impaired liver function or cholestasis. CONCLUSIONS: Alendronate effectively increases bone mass and has greater antiresorptive power than etidronate in patients with primary biliary cirrhosis, and is associated with minor or no side effects.

Effect of surgical menopause and Paget's disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy.

The objective of this study was to analyze the effect of surgical menopause and Paget's disease of bone, as well as the influence of therapy, on the isomerization of the carboxyterminal telopeptide of type I collagen (CTX). Fourteen women who had undergone surgical menopause and had begun hormone replacement therapy (HRT) after surgery were recruited. Results for these women were compared with those of 29 patients with Paget's disease of bone treated with tiludronate (400 mg/day) for 3 months, and with those of a group of 21 healthy premenopausal women (control group I). In addition, 14 healthy individuals with an age range similar to that of the pagetic patients (control group II) were included in the study. Urine samples were analyzed for levels of nonisomerized and beta-isomerized CTX (alpha-CTX and beta-CTX). Biochemical determinations were performed 3 months after surgical menopause and after 3 and 9 months of HRT, and at baseline, and 1 and 6 months after tiludronate treatment in the pagetic patients. The average levels of alpha-CTX and beta-CTX were higher in patients than in controls. In patients after surgical menopause, because of their greater increase of beta-CTX, the alpha-CTX/beta-CTX ratio was lower than that of control group I (0.881 +/- 0.3 vs 1.515 +/- 0.8; P < 0.05). In contrast, at baseline, pagetic patients showed marked increases in alpha-CTX levels, resulting in a higher alpha-CTX/beta-CTX ratio than that of control group II (2.879 +/- 1.3 vs 0.96 +/- 0.25; P < 0.0001). The average percent decrease in both markers after therapy was similar in both conditions (-60% for alpha-CTX and -44% for beta-CTX after 3 months of HRT in the surgical menopause group, vs -66% for alpha-CTX and -41% for beta-CTX in the pagetic group, 1 month after finishing tiludronate therapy; P, NS), resulting in a significant decrease of the alpha-CTX/beta-CTX ratio in pagetic patients (2.879 +/- 1.3 vs. 1.614 +/- 0.8; P < 0.001). In conclusion, surgical menopause is associated with a decrease in the urinary alpha-CTX/beta-CTX ratio because of the higher increase in the beta-CTX level after menopause. Pagetic patients show an increase in this ratio, compared with the control value, and the ratio decreases after bisphosphonate treatment. The response to therapy was similar in both conditions, with a comparable decrease of both markers. These findings show how bone markers may contribute to the understanding of pathophysiologic mechanisms in bone diseases.