Long-term Use Of Glucocorticoids Research Articles

Long-term use of glucocorticoids for polymyalgia rheumatica: follow-up of the PMR Cohort Study.

ObjectivesPMR is a common inflammatory condition in older adults, characterized by bilateral hip and shoulder pain and stiffness. Reducing oral glucocorticoids, classically used for ≤2 years, are the mainstay of treatment. This study considers the factors early in the disease course that might be associated with prolonged treatment.MethodsSix hundred and fifty-two people with incident PMR were recruited from English general practices (2012–2014). Participants completed seven questionnaires over 2 years (used to allocate people to pain–stiffness trajectories) and a further long-term follow-up (LTFU) questionnaire a median of 5.16 years after diagnosis. Characteristics of those still taking and having ceased glucocorticoids were described and compared using Kruskal–Wallis and χ2 and Student’s 2-sample t-tests as appropriate.ResultsOf the 197 people completing the LTFUQ questionnaire, 179 people reported ever having taken glucocorticoids. Of these, 40.1% were still on treatment, with a median (quartile 1, quartile 3) daily dose of 5 (1.5, 9) mg. People still taking glucocorticoids were more likely to be older (72.5 vs 70.2 years, P = 0.035), live alone (31.8 vs 15.0%, P = 0.01) and have self-managed their glucocorticoid dose (39.1 vs 11.0%, P < 0.0001). They were also more likely to belong to a pain–stiffness trajectory class with sustained symptoms.ConclusionsPMR is not always a time-limited condition. Few patient characteristics are associated with prolonged treatment early in the disease course, but those who are older and who have sustained symptoms might be at greater risk. Although accurate prediction is not yet possible, clinicians should monitor people with PMR carefully to manage symptoms and reduce the cumulative glucocorticoid dose.

P291 Long-term use of glucocorticoids for polymyalgia rheumatica: follow-up of the PMR cohort study

Abstract Background/Aims Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition in older adults, characterised by pain and stiffness in the shoulder and hip girdles. The mainstay of treatment is oral glucocorticoids (GCs). Classically, treatment is tapered to a stop over two years, but there is growing evidence this does not happen in practice. International guidelines recommend early referral to specialist services for patients at risk of prolonged treatment. However, they do not specify who these patients are. This study considers the factors at, and shortly after, diagnosis that might be associated with prolonged glucocorticoid treatment, and therefore who may benefit from early specialist review. Methods 652 people with incident PMR were recruited from English general practice between 2012 and 2014. They completed up to seven questionnaires over two years and a further long-term follow-up questionnaire (LTFUQ) 4.5-6.5 years after diagnosis. The first seven questionnaires have previously been used to allocate people to pain-stiffness trajectory classes. In the LTFUQ, participants reported current symptoms and other general health and lifestyle characteristics, as well as whether they were still taking GCs and whether they self-managed their GC use. Characteristics of those having successfully stopped GCs were compared to those still taking them. Results A median 5.16 years after diagnosis, 179 people responded to the LTFUQ. Of these, 67 (40.1%) were still on GCs with a mean daily dose of 5mg (1.5, 9). Those still taking GCs were more likely to be older (72.5 vs 70.2 years, p = 0.035), to live alone (31.8% v 15.0%, p = 0.01), and to report having self-managed their GCs (39.1% versus 11.0%, p &amp;lt; 0.0001). They were also more likely to have reported sustained pain-stiffness symptoms in the first two years, as defined by their trajectory class in earlier work (trajectory class [n{%} still treated]; partial recovery, sustained moderate symptoms [23 {34.3%}]; recovery before worsening [17 {25.4%}]; rapid and sustained recovery [15 {22.4%}]; Slow and continuous recovery [11 {16.34%}]). Conclusion PMR is not always the typically-described, time-limited condition. There are few patient characteristics that are associated with prolonged treatment early in the disease course, but those who are older and have sustained or recurrent pain and stiffness over two years appear to be at greater risk of remaining on GCs. Whilst accurate prediction of long-term treatment need is not possible from our data, people with sustained symptoms may benefit from specialist review to ensure diagnostic accuracy and consider need for additional therapies to reduce their GC burden. Disclosure S. Muller: None. S.L. Hider: None. B. Singh Sokhal: None. S.A. Lawton: None. T. Helliwell: None. C.D. Mallen: None.

Glucocorticoid-induced hyperglycaemia and diabetes: Call for action.

Glucocorticoid-induced hyperglycaemia and diabetes: Call for action.

Efficacy of Glucocorticoids and Glucocorticoid-Induced Hyperglycaemia in Renal Disease: A Meta-Analysis of Randomized Controlled Trials.

Background Glucocorticoids are the most effective anti-inflammatory and immunosuppressive drugs used to treat patients with renal disease. This study pooled the current evidence of the efficacy of Glucocorticoids and Glucocorticoid-induced hyperglycaemia in renal disease. Methods We conducted a systematic literature search on PubMed, Cochrane Central, and Web of Science for relevant randomized controlled trials (RCTs) up to September 1, 2021. The meta-analysis, sensitivity analysis and bias analysis were performed using Review Manager 5. 3. Results In this study, seven RCTs with 797 patients were included in our analysis. The analysis revealed that glucocorticoids had a certain alleviating effect on the reduction of renal function. (risk ratio [RR] 0.49 95% confidence interval [Cl] 0. 28 to 0.85, p =0.01) and reduction of proteinuria (weight mean difference [WMD] -0.43; 95% CI -0.57 to-0.28) when compared with the control group. Patients receiving glucocorticoids therapy did not have an increased risk of developing new-onset diabetes mellitus or impaired glucose tolerance. (RR 3.76 95% CI 0.54 to 26.10, p =0.18). For other safety outcomes, glucocorticoids therapy did not increase risk of respiratory infections (RR 1.63, 95% CI 0. 69to3. 89, p =0.27) and Gastrointestinal SAEs is relatively controversial (RR 1.10, 95% CI 0.32 to 3.79, p =0.88). Discussion. In conclusion, current clinical evidence indicates that glucocorticoids is efficacious and safe to renal disease compared with control. Further research comparing long-term glucocorticoids use is needed.

Delayed Diagnosis of a Tibial Stress Fracture Associated with Glucocorticoid and Methotrexate Therapy in a Patient with Rheumatoid Arthritis: A Case Report

The risk of stress fractures is associated with rheumatoid arthritis (RA), which can aggravate bone loss. We report the case of a patient who was on long-term medication for RA presenting with lower extremity pain on the left and swelling without trauma. Magnetic resonance imaging and plain radiographs at the previous hospital showed no signs of fracture, but radiographs performed later, revealed a stress fracture of the left distal tibia. The stress fracture may have occurred due to multiple reasons such as long-term use of methotrexate and glucocorticoids, active RA, postmenopausal state, and immobility. Suspicion of a stress fracture should not be ruled out especially in RA patients with persistent pain, even if the radiographical findings are normal. Additional imaging and follow-ups are essential. The patient’s pain was relieved with Korean medicine treatments, which suggests their potential application for stress fractures in RA patients.

Therapeutic effect of platelet-rich plasma on glucocorticoid-induced rat bone marrow mesenchymal stem cells in vitro

BackgroundGlucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro.MethodsIn this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins.ResultsWe observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro.ConclusionOur vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.

SMAD4 transcriptionally activates GCN5 to inhibit apoptosis and promote osteogenic differentiation in dexamethasone-induced human bone marrow mesenchymal stem cells

BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is a serious complication caused by long-term or excessive use of glucocorticoids (GCs). General control non-derepressible 5 (GCN5) has been reported to be lowly expressed in bone tissue. Therefore, this paper attempts to investigate the role of GCN5 in SONFH and identify the potential regulatory mechanism. Experimental designFollowing human bone mesenchymal stem cells (hBMSCs) being stimulated with dexamethasone (Dex), GCN5 expression was detected using RT-qPCR and western blotting. Then, GCN5 was overexpressed and cell viability was assessed by cell counting kit and lactate dehydrogenase kit. Cell apoptosis was determined with terminal deoxynucleotidyl transferase dUTPnickendlabeling (TUNEL) and the expression of apoptosis-related proteins was evaluated using western blotting. Alkaline phosphatase (ALP) staining and alizarin red staining were adopted for the analysis of osteogenic differentiation. Additionally, the relationship between small mothers against decapentaplegic protein 4 (SMAD4) and GCN5 was predicted by hTFtarget website and verified by luciferase reporter- and chromatin immunoprecipitation (ChIP) assays. Subsequently, SMAD4 was silenced to determine cell viability, apoptosis and osteogenic differentiation in Dex-induced hBMSCs with GCN5 upregulation. ResultsGCN5 expressed lower in hBMSCs exposed to Dex. GCN5 overexpression elevated cell viability, attenuated apoptosis and promoted osteogenic differentiation of hBMSCs. Additionally, SMAD4 transcriptionally activated GCN5 and upregulated GCN5 expression. While SMAD4 knockdown reversed the protective effects of GCN5 overexpression on Dex-induced cell viability loss, apoptosis increase and osteogenic differentiation inhibition in hBMSCs. ConclusionsSMAD4 transcriptionally activated GCN5 to inhibit apoptosis and promote osteogenic differentiation in Dex-induced hBMSCs.

Treatment of Sarcoidosis in US Rheumatology Practices: Data From the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) Registry.

Sarcoidosis is often treated with glucocorticoids, although the use of biologics is growing. Prescribing patterns for biologics for patients with sarcoidosis in US rheumatology practices have never been examined. Given that there are no steroid-sparing US Food and Drug Administration-approved therapies for sarcoidosis, we sought to characterize the real-world treatment of sarcoidosis and to assess practice-level variation in prescribing patterns. We conducted an observational study of patients with sarcoidosis using data from the Rheumatology Informatics System for Effectiveness (RISE) registry (2014-2018). The RISE registry represents an estimated 32% of the US clinical rheumatology workforce. Adult patients with ≥2 codes for sarcoidosis ≥30 days apart were included. We examined sarcoidosis-specific medication use at any time during the study period. Data were analyzed at the practice level. A total of 3,276 patients with sarcoidosis from 184 practices were included. Of those patients, 75.1% were women, with a mean age of 59.0 ± 12.5 years; 48.3% were White and 27.6% were Black. Overall, 59.3% of patients were prescribed glucocorticoids, and 24.7% received prolonged glucocorticoid therapy (≥10 mg/day for ≥90 days). In all, 12.1% received a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD), most commonly tumor necrosis factor inhibitors. There was wide practice-level variation among 31 practices with ≥30 patients with sarcoidosis; biologic use ranged from 15.6% to 69.2%. Infliximab represented the most common biologic prescribed. In a large sample of US rheumatology practices, 12.1% of patients with sarcoidosis received biologics or tsDMARDs. We found high variability in biologic use across practices. The significant use of long-term glucocorticoids suggests unmet therapeutic needs in this patient population.

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome

Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core–shell structure was designed. Metal–organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.Graphical

Utilization of glucocorticoids among White and Black patients with systemic lupus erythematosus: Observations from the enrollment visit of a prospective registry.

Black patients with systemic lupus erythematosus (SLE) face higher rates of morbidity and mortality compared to White patients. Long-term glucocorticoid use has been associated with worse health outcomes among patients with SLE. We sought to quantify chronic glucocorticoid use among Black and White patients with SLE within a prospective registry. Using enrollment data from a registry at a large academic institution, we compared glucocorticoid use among Black and White patients with SLE. Multivariable logistic regression of race and glucocorticoid use was performed, adjusting for covariates exhibiting a bivariate association with glucocorticoids at significance level p < 0.10. 114 White participants (mean age 45; standard deviation (SD) 15) and 59 Black participants (mean age 42; SD 14) were analyzed. White participants had mean SLEDAI-2K score of 3.7 (SD 5.2). Black participants had mean SLEDAI-2K scores of 6.3 (SD 6.0). Among Black participants, 43 (72%) utilized glucocorticoids compared to White participants 39 (34%) (unadjusted odds ratio (OR) 5.17; 95% confidence interval (CI) 2.59-10.33). We did not observe differences between unadjusted hydroxychloroquine (OR 0.69; 95% CI 0.28-1.65) or conventional disease-modifying anti-rheumatic drug (cDMARD) (OR 1.07; 95% CI 0.57-2.01) utilization among Black and White participants. SLEDAI-2K, disability, recent hospitalization, and past or present hydroxychloroquine or cDMARD use were included in a logistic regression model. Adjusting for covariates, Black participants were more likely to be on glucocorticoids (adjusted OR 5.69; 95% CI 2.17-14.96); p = 0.0004). Adjusting for disease activity and other medications, Black patients had more exposure to chronic glucocorticoids than White patients in the Cleveland Clinic SLE registry. These patients may face increased glucocorticoid-related morbidity, which could contribute significantly to long-term health outcomes and utilization of health care resources. Future research in larger, more diverse registries should be conducted to further characterize patterns of glucocorticoid use.

Tacrolimus Plus High-Dose Dexamethasone Versus High-Dose Dexamethasone Alone As First-Line Treatment for Adult Immune Thrombocytopenia: The Phase 2, Open Label, Randomized Trial (TARGET 020)

▪IntroductionImmune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission.MethodsThis open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts <30×10 9/L, or < 50×10 9/L and significant bleeding symptoms (World Health Organization bleeding scale ≥ 2). Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral tacrolimus (initial 0.03 mg/kg/day and maintain blood concentration at 3-5 ng/mL for 12 weeks) plus high-dose dexamethasone (HD-DXM) or HD-DXM monotherapy for 12 weeks. DXM (40 mg) was administered orally daily for 4 consecutive days to both study arms. The 4-day course of DXM was repeated on days 11-14 in patients who lacked response by day 10. The primary endpoint was 6-month sustained response (SR), defined as platelet count maintained >50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080).ResultsTotal 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups.ConclusionsLow-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:It includes information or discussion of off-label drug use of tacrilimus.

Variability in Glucocorticoid Prescribing for Rheumatoid Arthritis and the Influence of Provider Preference on Long-Term Use of Glucocorticoids.

Glucocorticoids are recommended for short-term use in rheumatoid arthritis (RA), but many patients continue receiving long-term therapy. We evaluated the variability in glucocorticoid prescribing across rheumatologists to inform interventions to limit long-term glucocorticoid use to the lowest dose necessary. Two cohorts were created using Medicare data from 2006 to 2015. Using cohort 1 (RA patients receiving disease-modifying antirheumatic drugs [DMARDs]), we calculated each rheumatologist's "provider preference" for glucocorticoids (frequency of use compared to other providers), using the ratio of observed to expected number of patients receiving glucocorticoids to account for case mix. In cohort 2 (RA patients receiving stable DMARD therapy), we evaluated whether provider preference for glucocorticoids could independently predict use of ≥5 mg/day of glucocorticoids 6-9 months after initiation of DMARD therapy. Using cohort 1 (1,272,644 yearly observations; 385,597 patients), we calculated provider preference among 6,875 rheumatologists (28,936 yearly observations). Provider preference was highly variable, with physicians at the lowest and upper quartiles prescribing glucocorticoids 33% less often to 31% more often (25th and 75th percentiles, respectively) than expected. In cohort 2 (155,539 patients receiving stable DMARD therapy), provider preference was strongly associated with glucocorticoid use ≥5 mg/day at 6-9 months, with a predicted probability of use of 22% (95% confidence interval [95% CI] 21.7-22.7) versus 11% (95% CI 10.2-10.9) for a patient seeing a provider in the highest versus lowest quintile of preference. Glucocorticoid prescribing for RA varies greatly among rheumatologists, and provider preference is one of the strongest predictors of a patient's long-term glucocorticoid use. These findings raise quality of care concerns and highlight the need for stronger evidence to guide RA treatment.

Long-term use of glucocorticoid exacerbates bone lesions in postmenopausal women with rheumatoid arthritis

Glucocorticoid-induced osteoporosis is osteoporosis arising due to long-term use of glucocorticoids. Despite decades of intense research, the effects of long-term use of glucocorticoids in humans on bone cells and bone structural changes remain unclear. We performed post-mortem histomorphometric analysis of bone from two female patients with rheumatoid arthritis aged 64 and 85years. Our two patients had been treated with glucocorticoids for 19 and 14 years, respectively. In Case 1, all markers of cancellous bone volume were markedly decreased compared with the age-matched reference range. Connectivity of cancellous bone trabecula was absent. Only a few island bones were noted. There was prominent thinning of the cortical bone and extension of the bone marrow cavity into the cortical bone with prominent cortical porosis. Cortical nodes between the endocortical surface and the trabecula disappeared due to endocortical resorption. Stoppage of lamellar structure was observed because the bone resorption by osteoclasts surpassed bone formation by osteoblasts. Empty lacunae characterised by disappearance of osteocytes were visible. In Case 2, all volume markers of cancellous bone were decreased to the same extent as Case 1. However, cortical porosis was more prominent than Case 1. These two cases suggest that use of glucocorticoid therapy >10years can induce severe osteoporosis in elderly rheumatoid arthritis women with higher disease activity and that the disappearance of cancellous bone is the common characteristic. The 85-year-old woman was characterised by cortical porosis.

The impact of testosterone therapy on quality of life in adolescents with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood. It is associated with progressive muscle function decline and premature death. Long-term oral glucocorticoid use slows muscle weakness but is associated with several side effects including delayed puberty. This study assessed the impact of a 2-year incremental intramuscular testosterone regimen on quality of life (QoL) in a cohort of 15 adolescents with DMD. The Pediatric Quality of Life Inventory (PedsQL) Neuromuscular module was used to assess QoL and was completed by parent-child dyads. Semi-structured interviews were carried out to understand patient views on testosterone therapy. QoL scores increased in 10 of the 15 participants during treatment, with a mean total PedsQL score of 74.6 pre-treatment v 80.2 post treatment (p = 0.04). This was supported by comments in the semi-structured interviews. Parent-reported PedsQL scores were lower than their child's post treatment (p = 0.007). Testosterone therapy for pubertal induction was associated with an improvement in QoL and the observed physical changes during puberty played an important role. Low self-esteem was also a prevailing theme. This data supports the inclusion of testosterone therapy for pubertal induction as a Standard of Care.

Дискусійні питання визначення порога втручання при глюкокортикоїдіндукованому остеопорозі: кого лікувати?

Глюкокортикоїдіндукований остеопороз є найпоширенішою причиною вторинного остеопорозу. Після початку перорального прийому глюкокортикоїдів протягом декількох місяців відзначається швидка втрата кісткової маси й зростання ризику переломів. Важливість глюкокортикоїдіндукованого остеопорозу як проблеми охорони здоров’я асоційована з частим застосуванням глюкокортикоїдів пацієнтами з різними хронічними захворюваннями та високим рівнем остеопорозу, виявленого в цих груп пацієнтів. Розвиток глюкокортикоїдіндукованого остеопорозу обумовлений пригніченням процесу утворення кістки, що супроводжується раннім, але короткочасним збільшенням резорбції кістки. Серед численних механізмів, що лежать в основі порушення кісткового метаболізму при тривалому прийомі глюкокортикоїдів, необхідно відзначити збільшення співвідношення RANKL/OPG, підвищення експресії склеростину, активацію PPARγR2, а також гіпогонадизм, порушення всмоктування кальцію в кишечнику й зниження вироблення інсуліноподібного фактора росту 1. Незважаючи на доступні й ефективні профілактичні заходи, багато пацієнтів, які починають або отримують глюкокортикоїдну терапію, недостатнім чином оцінені в плані стану кісткової тканини й ризику переломів. Установлено порогові значення добових доз глюкокортикоїдів (≥ 2,5 мг/добу) і тривалість їх прийому (≥ 3 місяців), при яких пацієнти повинні бути обов’язково піддані оцінці ризику переломів і необхідності проведення лікування антиостеопоротичними препаратами. Національні керівництва з менеджменту глюкокортикоїдіндукованого остеопорозу пропонують різні підходи до визначення порогу втручань, базуючись на використанні різних критеріїв. Алгоритм FRAX® розраховує 10-річну ймовірність переломів за клінічними факторами ризику з тестуванням мінеральної щільності кістки або без нього і калібрується для регіональної частоти переломів і смертності. Незважаючи на обмеження, цей інструмент є найдієвішим у визначенні порога втручань. У рекомендаціях ACR — 2017 вказується, що початковий абсолютний ризик переломів слід оцінювати з використанням алгоритму FRAX® з урахуванням доз глюкокортикоїдів і тестування мінеральної щільності кістки якомога швидше (до 6 місяців від початку прийому глюкокортикоїдів).

Труднощі й помилки ведення пацієнта з подагрою

У статті обговорюються питання найбільш частих помилок і труднощів у ранній верифікації діагнозу подагри і подальшій курації пацієнтів. Відомо, що діагноз «подагра» встановлюється в перший рік захворювання лише в 1/4 випадків, у середньому ж проходить 7–8 років до встановлення правильного діагнозу. Тільки в одному з 4–5 випадків подагра правильно верифікується на ранніх стадіях. Причиною пізньої діагностики є особливості перебігу подагри з періодами відсутності симптомів (інтермітуюча подагра), діагностичні помилки при першому зверненні пацієнта, раннє проведення рентгенологічного дослідження без виявлення типових ознак захворювання, відсутність пункції суглоба й верифікації кристалів сечової кислоти в синовіальній рідині. Ще однією причиною діагностичної помилки є визначення рівня сечової кислоти в сироватці крові під час гострого нападу. Несвоє­часна діагностика подагри призводить до низки подальших діагностичних і тактичних помилок. Насамперед це стосується призначення нестероїдних протизапальних препаратів і глюкокортикоїдів без правильно встановленого діагнозу. Сучасні рекомендації щодо ведення пацієнтів з подагрою акцентують, що застосування глюкокортикоїдів при подагрі можливо тільки короткими курсами, їх тривале вживання неприпустиме в зв’язку з високим ризиком розвитку побічних ефектів у даного контингенту хворих, які часто мають супутні захворювання. Ще однією тактичною помилкою є призначення уратзнижуючих препаратів у періоді гострого артриту без титрації дози й проведення протизапальної терапії. У статті наведений клінічний випадок пізньої діагностики подагри, нераціонального лікування із тривалим застосуванням глюкокортикоїдів, відсутністю прийому уратзнижуючих препаратів, що призвело до серйозних побічних ефектів — розвитку цукрового діабету та артеріальної гіпертензії. Проводиться детальний розбір допущених клінічних помилок, а також надані рекомендації з раціональної тактики в даному випадку.

Ревматическая полимиалгия в клинических рекомендациях 2018–2020 годов. Часть I. Группы риска, адъювантная терапия

В начале Декады здорового старения стал доступен ряд клинических рекомендаций по ведению ревматических болезней у пожилых. Цель публикации — характеристика и обсуждение руководства по ревматической полимиалгии Итальянского общества ревматологов (2020) и рекомендаций по применению позитронно-эмиссионной томографии/компьютерной томографии при васкулитах крупных сосудов и ревматической полимиалгии Европейской ассоциации ядерной медицины, Общества ядерной медицины и молекулярной визуализации и Американского общества ядерной кардиологии (2018). Материалы и методы. Содержание, первоисточники и методология разработки руководств изучены с помощью методов информационного анализа и сопоставлены с рекомендациями 2018–2020 гг. по ревматической полимиалгии и гигантоклеточному артерииту Европейской антиревматической лиги, Американской коллегии ревматологов, Немецкого, Австрийского, Швейцарского, Британского обществ ревматологов, Европейской федерации головной боли и их первоисточниками. Установлен приоритет консенсусного подхода в разработке современных руководств по ревматической полимиалгии. Особенность методологии создания итальянских рекомендаций состоит в сужении поиска прототипов до двух баз данных доказательной медицины и «серой» литературы и в отборе для адаптации трех руководств, включая разработку обществ ядерной медицины. Актуализированы вопросы ведения пациентов в первичном звене (предложен алгоритм), совместного принятия клинических решений, настороженности в отношении гигантоклеточного артериита. Доказательствами поддержаны лишь начальные дозы глюкокортикоидов как терапии первой линии; допускается альтернирующий режим их снижения. Обоснована неэффективность гидроксихлорохина, не обсуждается прием азатиоприна и средств альтернативной медицины. Следует установить факторы риска развития васкулита, рецидивов, длительного приема глюкокортикоидов и их побочных эффектов. Впервые для выявления васкулита рекомендовано применение позитронно-эмиссионной томографии/компьютерной томографии. Самой доказанной, сильной, согласованной является рекомендация по адъювантной терапии метотрексатом и отказу от биологических препаратов, наименее согласованной — позиция по направлению к ревматологу. Выводы. Решение такой актуальной проблемы здравоохранения, как повышение качества медицинской помощи при ревматической полимиалгии, предполагает усовершенствование медицинских стандартов по большинству клинически важных вопросов, выявление пациентов высокого риска, направление их к ревматологам и офтальмологам и рассмотрение преимуществ лечения метотрексатом.

Rehabilitation in a case of severe osteoporosis with prevalent fractures in a patient known with multiple sclerosis and prolonged glucocorticoid therapy

Introduction. Osteoporosis has a major influence on the quality of life because of its impact on bone strength. Osteoporosis and fractures are frequent in patients with multiple sclerosis, decreased mobility being an important risk factor in these patients. Objectives. This paper presents a case of severe osteoporosis in a patient with multiple sclerosis, to emphasize a correlation between this two pathologies. Material and Methods. We present the case of a female Caucasian patient, aged 65 years, known with progressive multiple sclerosis, on long-term use of glucocorticoids, and severe osteoporosis, who is investigated for mechanical pain and functional deficiency in the lumbar spine and the right hip, motor deficit, predominantly on right limbs and walking disorders. The patient was diagnosed with severe osteoporosis treated with raloxifene and bisphosphonates, with multiple vertebral fractures and vitamin D deficiency. During hospitalization the patient followed myorelaxant therapy and an individualized rehabilitation program. Results and discussion. During follow-up, there was a significant increase followed by a recent decrease in bone mass density in the lumbar spine and hip. The patient was recommended a loading dose of cholecalciferol for three months and initiation of teriparatide therapy after restoring 25-hydroxy vitamin D levels. Conclusion. In patients with multiple sclerosis,screening and early management of osteoporosis and osteopenia are essential. Keywords: multiple sclerosis, glucocorticoid therapy, osteoporosis,

Resolution of the Expert Council «The role of type I interferon inhibitor in the treatment of patients with systemic lupus erythematosus»

On April 28, 2021, a meeting of the Council of Experts was held with the participation of the leading experts in the field of rheumatic diseases, approaches to the treatment of patients with systemic lupus erythematosus (SLE) were discussed. The issues of medical care for patients with SLE and their routing, key points of Russian and international clinical guidelines for the management of patients with SLE, as well as the role of interferon (IFN) type I in the pathogenesis of the disease were discussed. It is noted that the management of patients with SLE requires a multidisciplinary approach. The basis of therapy is the use of glucocorticoids (GC), immunosuppressive drugs and their combinations. But long-term use of GC in patients with SLE leads to severe complications. Early prescription of biological disease-modifying antirheumatic drugs (bDMARDs) allows to achieve the greatest effect and prevent the development of irreversible organ damage associated with SLE. Currently data from three clinical trials on the efficacy and safety of the type I IFN inhibitor anifrolumab are available. During the discussion, experts defined the clinical profile of a patient with SLE, for whom administration of bDMARD therapy is indicated. According to experts, the use of a type I IFN inhibitor in routine clinical practice can improve disease outcomes in both short and long term.

Can large doses of glucocorticoids lead to Perthes? a case report and review of the literature

BackgroundPerthes disease (Legg-Calvé-Perthes, LCP) is a self-limited and non-systemic disease occurring in the femoral heads of children, which is mainly manifested as an ischemic necrosis of the femoral head epiphysis, leading to subchondral ossification injury of the femoral head.Case presentationHere we report a case of 11-year-old child with long-term use of high-dose glucocorticoids. With MRI examination finding the epiphyseal necrosis of right humeral head, femur and tibia, and X-ray examination finding bilateral femoral head necrosis, the child was diagnosed as Perthes disease based on his clinical and imaging data.ConclusionsLong-term and high-dose glucocorticoids may be one of the causes of Perthes disease.