The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Dose-related patterns of glucocorticoid-induced side effects
Abstract
Objective To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. Methods Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. Results The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). Conclusion The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.
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“A dose-related pattern was found for clinical features such as cushingoid phenotype, skin thinning, ecchymosis, and sleep disturbances.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [35]
In the citing paper
“Although other adverse effects manifested above a certain threshold of daily glucocorticoid dosage (eg, epistaxis and weight gain with daily prednisone equivalent dose of > 5.0-7.5 mg), whereas depression and high blood pressure were especially prevalent with > 7.5 mg/d (35).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [35]
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Xia, W., Deng, J., Zhuang, L., Xu, F., Jin, Y., Zhou, H., Zhang, T., Liu, Z., Zhang, H., Zeng, C., et al. (2024) · Clinical Kidney Journal · doi:10.1093/ckj/sfae148 · Cited by 10
“Kidney relapse is common in patients with lupus podocy-topathy and a proportion of patients may experience repeated kidney relapses, resulting in an increased risk of adverse reactions from exposure to high doses of glucocorticoids and other immunosuppressants [27 ].”
BackgroundInsufficient data on glucocorticoid use in RA trials
Alten, R. H.-E. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.70 · Cited by 10
Efficacy, safety and mechanism of action of modified-release prednisone in rheumatoid arthritis
Clarke, L. L., & Kirwan, J. (2012) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x12441274 · Cited by 10
“Others have, however, found significantly increased adverse events even at low doses [Huscher et al. 2009].”
BackgroundAvis d’experts pour le traitement des uvéites non infectieuses
Diwo, E., Sève, P., Trad, S., Bielefeld, P., Sène, D., Abad, S., Brézin, A. P., Quartier, P., Koné‐Paut, I., Weber, M., et al. (2018) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2018.03.001 · Cited by 10
New concepts to reduce glucocorticoid toxicity
Alten, R., & Weinbrecht-Mischkewitz, M. (2018) · Joint Bone Spine · doi:10.1016/j.jbspin.2018.11.006 · Cited by 10
Cell‐Mediated Assembly of Phototherapeutics
Smith, W. J., Oien, N. P., Hughes, R. M., Marvin, C. M., Rodgers, Z. L., Lee, J., & Lawrence, D. S. (2014) · Angewandte Chemie · doi:10.1002/ange.201406216 · Cited by 10
Bridgewater, S., Shepherd, M. A., Dawson, J., Richards, P., Silverthorne, C. A., Ndosi, M. E., Almeida, C., Black, R. J., Cheah, J. T. L., Dures, E. K., et al. (2023) · Rheumatology · doi:10.1093/rheumatology/kead081 · Cited by 11
“GCs are key in the management of life-and organ-threatening rheumatic diseases [5, 7], but they have wide-ranging dose-and duration-dependent adverse effects [8] which are of great concern to patients and clinicians [9–13].”
BackgroundThe current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review
Davies, E., Chetwynd, A. J., McDowell, G., Rao, A., & Oni, L. (2024) · Journal of Nephrology · doi:10.1007/s40620-024-01923-w · Cited by 11
“Immunosuppressive regimens in GN are often dependent on glucocorticoids, which are increasingly highlighted as having significant long-term effects, including increasing the risk of cardiovascular events [69, 70].”
BackgroundResponsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus
Saboo, B., Joshi, S., Gupta, A. S., Maheshwari, A., Saboo, B., Makkar, B. M., Bantwal, G., Kesavadev, J., Murthy, L. S., TIWASKAR, M. H., et al. (2024) · Journal of the Association of Physicians of India · doi:10.59556/japi.72.0573 · Cited by 9
“41 .”
Suay, G., García‐Cañaveras, J. C., Aparisi, F., Garcia, J., Juan, Ó., & Lahoz, A. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217317 · Cited by 10
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“Although Corticosteroids are crucial in treating ophthalmic diseases, long-term or high-dose use can lead to side effects such as increased intraocular pressure, cataract formation, corneal ulcers, and secondary infections (Huscher et al., 2009; Roberti et al., 2020).”
Advances and challenges in immunosuppressive antibody drug conjugates
Yaseen, A. A., & Tumey, L. N. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117576 · Cited by 9
Caporali, R. F., Cavagna, L., & Montecucco, C. (2009) · European Journal of Pain Supplements · doi:10.1016/j.eujps.2009.07.009 · Cited by 9
Rheumatoid arthritis and nutritional profile: A study in Brazilian females
Doubek, J. G. C., Kahlow, B. S., Nisihara, R., & Skare, T. L. (2022) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.14394 · Cited by 9
Glucocorticoid therapy for gastrointestinal diseases
Triadafilopoulos, G. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2014.904852 · Cited by 9
“The risk of both cataracts and glaucoma is dose-related [72,73].”
BackgroundEfficacy of iguratimod vs. salazosulfapyridine as the first-line csDMARD for rheumatoid arthritis
Nozaki, Y., Inoue, A., Kinoshita, K., Funauchi, M., & Matsumura, I. (2019) · Modern Rheumatology · doi:10.1080/14397595.2019.1572267 · Cited by 9
“AEs were defined as any adverse reaction resulting in any of the following outcomes: a life-threatening condition or death, a significant or permanent disability, a malignancy, hospitalization or prolongation of hospitalization, or a congenital abnormality.”
BackgroundInfluentialGlucocorticoids in acute pancreatitis: a propensity score matching analysis
Wang, M., Jiang, Z., & Liang, H. (2021) · BMC Gastroenterology · doi:10.1186/s12876-021-01907-1 · Cited by 9
“GCs are versatile and may lead to some adverse effects, such as hyperglycaemia, secondary infections, osteoporosis, wound healing difficulty, and gastrointestinal bleeding [6].”
BackgroundRituximab in the Treatment of Refractory Noninfectious Scleritis
Cao, J. H., Oray, M., & Foster, C. S. (2016) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2016.03.037 · Cited by 9
Evolving Concepts in Treat-to-Target Strategies for Systemic Lupus Erythematosus
Nikolopoulos, D., Lourenço, M. H., Depascale, R., Triantafyllias, K., & Parodis, I. (2024) · Mediterranean Journal of Rheumatology · doi:10.31138/mjr.290424.eci · Cited by 9
Alomari, M., Chadalavada, P. N., Afraz, S., AlGhadir-AlKhalaileh, M., Suarez, Z. K., Swartz, A., Rashid, M., Khazaaleh, S., Cohen, B. L., Rahman, A. U., et al. (2024) · Crohn s & Colitis 360 · doi:10.1093/crocol/otae025 · Cited by 8
“23,24 Management of patients hospitalized for ASUC is challenging, 25 and the response to steroids is assessed daily during the first 3 to 5 days.”
BackgroundD’Auria, E., Bova, S. M., Dallapiccola, A. R., Santis, R. D., Leone, A., Calcaterra, V., Mannarino, S., Garbin, M., Olivotto, S., Zirpoli, S., et al. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05706-0 · Cited by 8
“Of all the factors influencing the adverse effects of systemic glucocorticoids, dose and duration of therapy are the most important independent and well-documented risk factors [25].”
BackgroundHutto, S. K., Balaban, D. T., Rohm, Z., Lackey, E., Samudralwar, R. D., Sammak, S. E., Nakirikanti, A., Oyerinde, E., Bou, G., Herman, M., et al. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13209-7 · Cited by 8
“This target dose of prednisone was previously shown to be achievable, in addition to noting the relative risk for adverse effects with varying daily doses [19, 20].”
Irish, G. L., & Jesudason, S. (2019) · Obstetric Medicine · doi:10.1177/1753495x18816923 · Cited by 8
“The increasing prevalence of diabetes and obesity highlights the need for treatment protocols with steroid minimisation.(11,12) Tacrolimus monotherapy has been used with success and safely in non-pregnant patients with IMN.”
BackgroundDexamethasone release pattern via a three-dimensional system for effective bone regeneration
Channey, H. S., Holkar, K., Kale, V. P., & Ingavle, G. C. (2023) · Biomedical Materials · doi:10.1088/1748-605x/acdb1e · Cited by 8
“The side effects depend upon the current and accumulated dosages [61, 62].”
Rheumatoid Arthritis Has Won the Battle but Not the War: How Many Joints Will We Save Tomorrow?
Oberemok, V. V., Andreeva, O., Laikova, K. V., Alieva, E. E., & Temirova, Z. Z. (2023) · Medicina · doi:10.3390/medicina59101853 · Cited by 11
“…inhibits the production of inflammatory mediators, such as a variety of MMPs, tumor necrosis factor-alpha (TNF-α ), interleukin (IL)-8, IL-1, NO, via diminishing the activation of MAPK signaling pathways protein kinase B (Akt) and NF-κ B [117,118] and leads to a decrease in prostaglandin synthesis…”
BackgroundGlucocorticoid-Induced Osteoporosis (GIOP)
Jha, S. S. (2023) · Indian Journal of Orthopaedics · doi:10.1007/s43465-023-01037-8 · Cited by 8
Tsujimae, M., Masuda, A., Takagi, M., Kato, T., Nakano, R., Fujita, K., Hirata, Y., Kakuyama, S., Furumatsu, K., Nakagawa, T., et al. (2024) · Pancreatology · doi:10.1016/j.pan.2024.01.006 · Cited by 8
Metadata
- Authors
- Huscher, D., Thiele, K., Gromnica-Ihle, E., Hein, G., Demary, W., Dreher, R., Zink, A., & Buttgereit, F.
- Affiliations
- German Rheumatism Research Centre (DE)
- Jena University Hospital (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Huscher, D
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 68
- Issue
- 7
- Pages
- 1119-1124
- ISSN
- 0003-4967 (ISSN-L)
- OpenAlex
- W2167459187
- Cited by
- 604
- References
- 35
- Citations by year
- 2026: 43 · 2025: 55 · 2024: 67 · 2023: 55 · 2022: 47 · 2021: 41 · 2020: 49 · 2019: 38 · 2018: 27 · 2017: 28 · 2016: 32 · 2015: 21 · 2014: 26 · 2013: 28 · 2012: 19
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- glucocorticoid adverse effects, dose-response relationship, rheumatoid arthritis, prednisone-equivalent dose, glaucoma, cataract, depression, hypertension, weight gain, bruising, lower limb edema, fungal infection, sleep disorders, risk-benefit ratio, threshold dose
- MeSH terms
- Arthritis, Rheumatoid, Data Collection, Dose-Response Relationship, Drug, Female, Glucocorticoids, Humans, Male, Middle Aged, Risk Factors, Time Factors
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