大島久二, 牛窪真理,久田治美: 副腎皮質ステロイド. Medicina,医学書院, 2013; 50(3): 494-498.
大島久二, 牛窪真理, 遠藤隆太, 松本弘俊, 秋谷久美子, 田中郁子: ステロイド. 日本内科学会雑誌 2011; 100(10): 2881-2887.
大島久二, 秋谷久美子, 田中郁子: ステロイドの種類と選び方. 山本一彦,鈴木洋司編. ステロイドの使い分け. 羊土社, 2010; 20-22.
Kawai S, Ichikawa Y, Homma M.
Differences in metabolic properties among cortisol, prednisolone, and dexamethasone in liver and renal diseases: accelerated metabolism of dexamethasone in renal failure.
J Clin Endocrinol Metab. 1985 May;60(5):848-54. doi: 10.1210/jcem-60-5-848.
Abstract/Text
Since previous reports concerning the altered metabolism of various glucocorticoids in liver or renal diseases were inconsistent, this study was undertaken to reexamine the metabolism of cortisol, prednisolone, and dexamethasone in patients with these diseases. One milligram each of these glucocorticoids was given iv simultaneously to patients with chronic liver disease, patients with chronic renal failure, and normal subjects after 1 mg betamethasone was administered on the previous night to suppress endogenous cortisol secretion. Plasma steroid levels in periodically collected blood samples were assayed by respective RIA after separation by paper chromatography. Prolongation of the t1/2 of cortisol was found in both patients with liver disease and those with renal failure, and prolonged t1/2 and reduced MCR of prednisolone were found in renal failure but not in liver disease. In contrast, while prolonged t1/2 and reduced MCR of dexamethasone were found in liver disease, shortened t1/2 and increased MCR were found in renal failure. These results suggest that different glucocorticoids are metabolized differently in patients with liver disease and those with renal failure, and that these differences may be important when these agents are used for therapeutic purposes or for study of hypothalamic-pituitary-adrenocortical function in patients with liver and renal diseases.
大島久二, 秋谷久美子, 田中郁子: ステロイドの種類と選び方. 山本一彦,鈴木洋司編. ステロイドの使い分け. 羊土社, 2010; 23-29.
大島久二, 秋谷久美子, 牛窪真理, 松本弘俊, 田中郁子, 玉置繁憲: ステロイドの使い方と副作用. カレントテラピー 2010; 28(10): 642-948.
大島久二, 田中郁子, 牛窪真理, 秋谷久美子: 副作用―いかに対応すべきか. 山本一彦編. 改訂版ステロイド薬の選び方・使い方ハンドブック. 羊土社, 2011; 35-44.
Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW.
Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data.
Ann Rheum Dis. 2006 Mar;65(3):285-93. doi: 10.1136/ard.2005.038638. Epub 2005 Aug 17.
Abstract/Text
Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.
McDonough AK, Curtis JR, Saag KG.
The epidemiology of glucocorticoid-associated adverse events.
Curr Opin Rheumatol. 2008 Mar;20(2):131-7. doi: 10.1097/BOR.0b013e3282f51031.
Abstract/Text
PURPOSE OF REVIEW: The introduction of glucocorticoid therapy by Dr Philip Hench in the 1950s revolutionized the treatment of rheumatic and inflammatory disease. These preparations remain an important component of therapy for a variety of diseases. As with any potent medication, however, they are not without side effects. Analysis of physician understanding and practice suggest that appreciation for the frequency and significant morbidity associated with glucocorticoids is poor. The purpose of this review is to provide an update on the most recent literature regarding glucocorticoid use and associated adverse events.
RECENT FINDINGS: Recent studies suggest that adverse events such as weight gain, skin thinning, sleep disturbance and neuropsychiatric disorders may occur in patients taking glucocorticoids. Adverse events may occur even in low-dose therapy and appear to be dose and duration dependent. Glucocorticoid-induced osteoporosis is a potentially preventable complication but physician adherence to preventive guidelines is poor. New data reinforce the understanding that glucocorticoids significantly increase the risk of infection. There are strong data-driven concerns about the increased susceptibility of children and possibly even neonates to glucocorticoid-associated adverse events.
SUMMARY: Glucocorticoid therapy, while important in the treatment of a variety of serious inflammatory diseases, causes significant morbidity among long term users.
Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B, Kohler JA, Furst DE.
Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events.
Am J Med. 1994 Feb;96(2):115-23. doi: 10.1016/0002-9343(94)90131-7.
Abstract/Text
PURPOSE: The purpose of this study was to better define the toxicity of low dose (less than or equal to 15 mg/d prednisone or equivalent) long-term (greater than 1 year) corticosteroids in the treatment of rheumatoid arthritis (RA).
PATIENTS AND METHODS: We examined an historical cohort of 112 RA patients on low dose (6.1 +/- 3.1 mg/d, mean +/- SD) long-term (6.2 +/- 4.6 years) prednisone (CS) and compared them to 112 matched RA patients not using prednisone (CO). CS were matched one-to-one with CO for sex (75% women), age (+/- 5 yrs), race (98% white), and duration of disease (+/- 5 yrs). Subjects were determined by review of unselected medical records from three distinct rheumatology practice settings. For CS, charts were abstracted from the date of prednisone start for predefined adverse events (AEs).
RESULTS: Ninety-two (92) AEs were noted in CS versus 31 in CO and included: fracture (CS:21 versus CO:8), serious infections (CS:14 versus CO:4), gastrointestinal (GI) bleed or ulcer (CS:11 versus CO:4), and cataracts (CS:17 versus CO:5). At time of first AE, CS prednisone average dose was 7.0 +/- 2.6 mg with a duration of 4.9 +/- 3.9 years. Stepwise multiple logistic regression analysis was used to create a model which included all clinically relevant variables and all parameters significantly different at the cohort inception. Prednisone average dose of greater than 10 to less than or equal to 15 mg/d correlated most strongly with the development of an AE (Odds Ratio (OR) = 32.3, 95% Confidence Interval (CI) 4.6, 220). Average prednisone 5 to 10 mg (OR = 4.5, 95% CI 2.1, 9.6), RA nodules (OR = 3.9, 95% CI 1.9, 8.0), and bony erosions (OR = 2.4, 95% CI 1.2, 4.7) also entered the final model. Kaplan Meier survival curves for the development of the first AE showed a dose-response relationship between prednisone and AE occurrence, independent of rheumatoid nodules. Subset analyses utilized a nested case control design for the development of three serious AEs: fractures, serious infections, and GI events. These analyses revealed possible relationships between prednisone use and the development of each specific AE (prednisone use OR: fracture 3.9, 95% CI 0.8, 18.1; infection 8.0, 95% CI 1.0, 64.0; and GI event 3.3, 95% CI 0.9, 12.1).
CONCLUSIONS: Although disease severity is an important confounding factor, low dose long-term prednisone use equal to or greater than 5 mg/d is correlated with the development of specific adverse events in a dose-dependent fashion.
Duru N, van der Goes MC, Jacobs JW, Andrews T, Boers M, Buttgereit F, Caeyers N, Cutolo M, Halliday S, Da Silva JA, Kirwan JR, Ray D, Rovensky J, Severijns G, Westhovens R, Bijlsma JW.
EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.
Ann Rheum Dis. 2013 Dec;72(12):1905-13. doi: 10.1136/annrheumdis-2013-203249. Epub 2013 Jul 19.
Abstract/Text
To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.
Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG.
American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis.
Arthritis Care Res (Hoboken). 2010 Nov;62(11):1515-26. doi: 10.1002/acr.20295. Epub 2010 Jul 26.
Abstract/Text
一般社団法人日本骨代謝学会 グルココルチコイド誘発性骨粗鬆症の管理と治療のガイドライン作成委員会（委員長 田中良哉） 編：グルココルチコイド誘発性骨粗鬆症の管理と治療のガイドライン2023．南山堂、2023.
Suzuki Y, Nawata H, Soen S, Fujiwara S, Nakayama H, Tanaka I, Ozono K, Sagawa A, Takayanagi R, Tanaka H, Miki T, Masunari N, Tanaka Y. Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research: 2014 update. J Bone Miner Metab. Springer-Verlag Tokyo; 2014;32(4):337–350.
顎骨壊死検討委員会：薬剤関連顎骨壊死の病態と管理：顎骨壊死検討委員会ポジションペーパー2023．https://www.jsoms.or.jp/medical/pdf/work/guideline_202307.pdf.
Humphrey MB, Russell L, Danila MI, Fink HA, Guyatt G, Cannon M, Caplan L, Gore S, Grossman J, Hansen KE, Lane NE, Ma NS, Magrey M, McAlindon T, Robinson AB, Saha S, Womack C, Abdulhadi B, Charles JF, Cheah JTL, Chou S, Goyal I, Haseltine K, Jackson L, Mirza R, Moledina I, Punni E, Rinden T, Turgunbaev M, Wysham K, Turner AS, Uhl S.
2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.
Arthritis Rheumatol. 2023 Dec;75(12):2088-2102. doi: 10.1002/art.42646. Epub 2023 Oct 16.
Abstract/Text
OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily.
METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included.
CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.
© 2023 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S, Sylvestre MP.
Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis.
Ann Rheum Dis. 2012 Jul;71(7):1128-33. doi: 10.1136/annrheumdis-2011-200702. Epub 2012 Jan 12.
Abstract/Text
OBJECTIVES: To explore the relationship of serious infection risk with current and prior oral glucocorticoid (GC) therapy in elderly patients with rheumatoid arthritis (RA).
METHODS: A case-control analysis matched 1947 serious infection cases to five controls, selected from 16207 RA patients aged ≥ 65 between 1985-2003 in Quebec, Canada. Adjusted odds ratios for infection associated with different GC patterns were estimated using conventional models and a weighted cumulative dose (WCD) model.
RESULTS: The WCD model predicted risks better than conventional models. Current and recent GC doses had highest impact on current risk. Doses taken up to 2.5 years ago were also associated with increased risk, albeit to a lesser extent. A current user of 5mg prednisolone had a 30%, 46% or 100% increased risk of serious infection when used continuously for the last 3 months, 6 months or 3 years, respectively, compared to a non-user. The risk associated with 5mg prednisolone taken for the last 3 years was similar to that associated with 30 mg taken for the last month. Discontinuing a two-year course of 10mg prednisolone six months ago halved the risk compared to ongoing use.
CONCLUSIONS: GC therapy is associated with infection risk in older patients with RA. The WCD model provided more accurate risk estimates than conventional models. Current and recent doses have greatest impact on infection risk, but the cumulative impact of doses taken in the last 2-3 years still affects risk. Knowing how risk depends on pattern of GC use will contribute to an improved benefit/harm assessment.
Dixon WG, Suissa S, Hudson M.
The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: systematic review and meta-analyses.
Arthritis Res Ther. 2011 Aug 31;13(4):R139. doi: 10.1186/ar3453. Epub 2011 Aug 31.
Abstract/Text
INTRODUCTION: Infection is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). The objective of this study was to perform a systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy on the risk of infection in patients with RA.
METHODS: A systematic review was conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials database to January 2010 to identify studies among populations of patients with RA that reported a comparison of infection incidence between patients treated with GC therapy and patients not exposed to GC therapy.
RESULTS: In total, 21 randomised controlled trials (RCTs) and 42 observational studies were included. In the RCTs, GC therapy was not associated with a risk of infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of events in the RCTs meant that a clinically important increased or decreased risk could not be ruled out. The observational studies generated a RR of 1.67 (1.49, 1.87), although significant heterogeneity was present. The increased risk (and heterogeneity) persisted when analyses were stratified by varying definitions of exposure, outcome, and adjustment for confounders. A positive dose-response effect was seen.
CONCLUSIONS: Whereas observational studies suggested an increased risk of infection with GC therapy, RCTs suggested no increased risk. Inconsistent reporting of safety outcomes in the RCTs, as well as marked heterogeneity, probable residual confounding, and publication bias in the observational studies, limits the opportunity for a definitive conclusion. Clinicians should remain vigilant for infection in patients with RA treated with GC therapy.
坪内博仁，熊田博光，清澤研道ら：免疫抑制・化学療法により発症するB型肝炎対策―厚生労働省「難治性の肝・胆道疾患に対する調査研究」班 劇症肝炎分科会および「肝硬変を含めたウイルス肝疾患の治療の標準化に関する研究」班合同報告―．肝臓 2009；50:38-42.
岡田純, 角家明文, ラナ美代子, 石川章, 飯国弥生, 近藤啓文：膠原病患者のカリニ肺炎予防に対するSulfamethoxazole-Trimethoprim (ST) 合剤の有効性．感染症学雑誌 1999;73(11):1123-1129．.
山口牧子、梅田幸寛、園田智明ら；ニューモシスチス肺炎予防のためのスルファメトキサゾール・トリメトプリム投与量の検討．日本呼吸器学会雑誌 2017;6(2):53-57.
