https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
45
ADVERSE EFFECTS OF GLUCOCORTICOID THERAPY IN
RHEUMATOID ARTHRITIS
Khamrayev Khamza Khamidullayevich
Khamraev Botirjon
Samarkand State Medical University Department of Internal Medicine
Abstract: Glucocorticoids are widely used in the management of rheumatoid
arthritis (RA) due to their potent anti-inflammatory and immunosuppressive
properties. While these agents offer significant symptomatic relief and are often
used as bridging therapy alongside disease-modifying antirheumatic drugs
(DMARDs), their long-term use is associated with a broad spectrum of adverse
effects. This article reviews the most common complications linked to
glucocorticoid therapy in RA patients, including osteoporosis, adrenal
suppression, metabolic disturbances, cardiovascular risks, ocular disorders,
gastrointestinal effects, neuropsychiatric symptoms, and increased susceptibility to
infections. Recognizing and managing these complications is essential to optimize
patient outcomes and minimize treatment-related risks. The article emphasizes the
importance of individualized therapy, dose minimization strategies, and preventive
measures to reduce the burden of glucocorticoid-induced side effects.
Keywords: glucocorticoids, rheumatoid arthritis, side effects, osteoporosis,
immunosuppression, corticosteroid therapy
Introduction
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease
characterized by persistent synovial inflammation, progressive joint destruction,
and varying degrees of extra-articular involvement. Glucocorticoids (GCs) have
played a pivotal role in the management of RA for several decades due to their
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
46
rapid and effective anti-inflammatory and immunosuppressive actions. They are
commonly used as adjunctive therapy, particularly in early stages of disease or
during acute exacerbations, often in combination with disease-modifying
antirheumatic drugs (DMARDs).
Despite their therapeutic efficacy, glucocorticoid use is accompanied by a
wide array of adverse effects, especially when administered in high doses or for
prolonged periods. These complications can affect multiple organ systems and
significantly impact patients’ overall health and quality of life. Common adverse
effects include osteoporosis, Cushingoid features, adrenal suppression, glucose
intolerance or steroid-induced diabetes, hypertension, increased infection risk,
cataracts, and neuropsychiatric disorders.
Given the clinical importance of these complications, a thorough
understanding of the risk profile associated with glucocorticoid therapy is essential
for clinicians managing RA patients. This article aims to provide a comprehensive
overview of the potential side effects of glucocorticoids in the treatment of RA and
to highlight strategies for minimizing their impact through careful monitoring,
dosage optimization, and preventive measures.
Materials and Methods
This article is a narrative review based on a comprehensive analysis of
scientific literature related to the adverse effects of glucocorticoid therapy in
rheumatoid arthritis. A systematic search was conducted using online medical
databases including
PubMed
,
Scopus
, and
Google Scholar
, focusing on articles
published between
2010 and 2024
. The keywords used in the search included
"glucocorticoids,"
"rheumatoid
arthritis,"
"adverse
effects,"
"steroid
complications," "corticosteroid therapy,"
and
"systemic side effects."
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
47
Only peer-reviewed articles, clinical guidelines, randomized controlled trials,
systematic reviews, and meta-analyses written in English were included. Studies
specifically addressing the complications and systemic side effects of
glucocorticoid therapy in RA patients were selected for detailed review.
Relevant data were extracted and categorized based on the organ systems
affected by glucocorticoid use, such as musculoskeletal, cardiovascular, endocrine,
gastrointestinal, ocular, neurological, and immunological systems. The findings
were synthesized to provide an organized overview of the clinical implications of
glucocorticoid-associated adverse effects in RA management.
Results
The analysis of the selected literature revealed that glucocorticoid therapy in
rheumatoid arthritis patients is consistently associated with a broad range of
systemic adverse effects. These complications vary in frequency and severity
depending on the dosage, duration of therapy, and individual patient susceptibility.
The most frequently reported adverse effects include:
•
Musculoskeletal
_
Complications:
Long-term glucocorticoid use was strongly linked to decreased bone mineral
density, leading to osteoporosis and increased risk of vertebral and non-
vertebral fractures. Several studies reported a 2–3-fold increase in fracture
risk among chronic GC users.
•
Endocrine
_
and
_
Metabolic
_
Effects:
Adrenal suppression and iatrogenic Cushing’s syndrome were observed in
patients receiving prolonged GC therapy. Steroid-induced hyperglycemia
and new-onset diabetes mellitus were also commonly reported, especially in
high-risk individuals.
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
48
•
Cardiovascular
_
Effects:
Elevated blood pressure, dyslipidemia, and increased risk of atherosclerosis
were noted in multiple studies. These changes contribute to a higher
incidence of cardiovascular events in long-term GC users.
•
Ocular
_
Complications:
Cataracts (particularly posterior subcapsular type) and steroid-induced
glaucoma were among the most prevalent eye-related complications
documented in RA patients receiving GC therapy.
•
Gastrointestinal
_
Effects:
Gastric mucosal damage, peptic ulcers, and gastrointestinal bleeding were
identified as significant risks, especially when glucocorticoids were
combined with nonsteroidal anti-inflammatory drugs (NSAIDs).
•
Neuropsychiatric
_
Effects:
Mood disturbances such as anxiety, irritability, insomnia, and, in some cases,
psychosis were associated with both short- and long-term GC use.
•
Immunosuppression
_
and
_
Infection
_
Risk:
Several
studies
emphasized
the
immunosuppressive
effect
of
glucocorticoids, which increased the susceptibility to opportunistic
infections including tuberculosis, fungal infections, and bacterial
pneumonia.
Overall, the findings underscore the importance of carefully balancing the
therapeutic benefits of glucocorticoids with their potential systemic toxicity.
Preventive strategies such as dose tapering, supplementation (e.g., calcium and
vitamin D), and regular monitoring are strongly recommended to mitigate these
risks.
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
49
Discussion
Glucocorticoids remain an essential component in the treatment of rheumatoid
arthritis (RA), particularly for achieving rapid control of inflammation and
providing symptomatic relief. However, their therapeutic benefits are
counterbalanced by a wide array of systemic adverse effects that can significantly
compromise patient safety and quality of life, especially with long-term or high-
dose use.
The findings of this review highlight that glucocorticoid-induced
complications are multi-systemic in nature, affecting the musculoskeletal,
endocrine, cardiovascular, gastrointestinal, ocular, neuropsychiatric, and immune
systems. Among the most clinically significant effects,
osteoporosis
and
subsequent fractures are consistently reported across multiple studies. This
underscores the importance of bone health monitoring and the need for preventive
measures such as calcium, vitamin D supplementation, and bisphosphonate therapy
in patients receiving prolonged glucocorticoid treatment.
Endocrine disturbances
, including adrenal suppression and steroid-induced
diabetes, represent another critical challenge. These complications often go
unnoticed until clinical manifestations appear, emphasizing the need for regular
metabolic assessments in patients on glucocorticoid therapy. Similarly,
cardiovascular risks
, such as hypertension and atherosclerosis, further elevate the
long-term morbidity in RA patients and necessitate a multidisciplinary
management approach.
Moreover,
ocular side effects
, such as cataracts and glaucoma, may develop
insidiously and lead to irreversible visual impairment if not promptly diagnosed.
Routine ophthalmologic evaluations are thus recommended for patients on long-
term therapy.
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
50
Neuropsychiatric symptoms
, although less frequently emphasized, can
significantly affect patient well-being and adherence to therapy. Mood changes,
anxiety, insomnia, and even psychosis may require psychiatric evaluation and dose
adjustments.
Importantly, the
increased susceptibility to infections
, resulting from the
immunosuppressive nature of glucocorticoids, poses a serious concern, especially
in elderly or comorbid patients. Vigilance for latent infections such as tuberculosis
and appropriate prophylactic strategies are vital in these cases.
Despite these risks, glucocorticoids continue to play a key role in RA
management. Therefore, a
risk-benefit approach
is crucial when initiating
therapy. The use of the
lowest effective dose for the shortest duration possible
,
along with
regular monitoring
,
preventive strategies
, and
individualized
treatment plans
, can help minimize the incidence and severity of glucocorticoid-
induced adverse effects.
Conclusion
Glucocorticoids play a pivotal role in the management of rheumatoid arthritis
due to their rapid anti-inflammatory and immunosuppressive effects. However,
their long-term use is associated with a wide spectrum of adverse effects that can
affect multiple organ systems and contribute to significant morbidity. This review
highlights the most commonly encountered complications, including osteoporosis,
endocrine and metabolic disturbances, cardiovascular risks, ocular disorders,
gastrointestinal
issues,
neuropsychiatric
manifestations,
and
increased
susceptibility to infections.
To optimize the therapeutic benefits while minimizing the associated risks,
clinicians must adopt a balanced, patient-centered approach. This includes using
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
51
the lowest effective dose for the shortest duration possible, implementing
preventive strategies such as bone protection and infection prophylaxis, and closely
monitoring patients for early signs of systemic toxicity.
Ultimately, awareness and proactive management of glucocorticoid-related
adverse effects are essential for improving patient outcomes and ensuring safer
long-term treatment in individuals with rheumatoid arthritis.
References:
1.
Van der Goes, M. C., Jacobs, J. W. G., & Bijlsma, J. W. J. (2014).
Glucocorticoids in the treatment of rheumatoid arthritis.
Arthritis Research &
Therapy, 16
(Suppl 2), S1. https://doi.org/10.1186/ar4686
2.
Buttgereit, F., Boers, M., Burmester, G. R., Saag, K. G., Bijlsma, J. W. J., &
Kirwan, J. R. (2020). Glucocorticoids in rheumatoid arthritis: current status and
future studies.
RMD Open, 6
(2), e001347. https://doi.org/10.1136/rmdopen-2020-
001347
3.
Strehl, C., Bijlsma, J. W. J., de Wit, M., & Buttgereit, F. (2017).
Glucocorticoid-induced osteoporosis: mechanisms, management, and prevention.
Nature
Reviews
Rheumatology,
13
(5),
231–240.
https://doi.org/10.1038/nrrheum.2017.26
4.
Caplan, L., Wolfe, F., Russell, A. S., Michaud, K., Katz, J., & Cannon, G.
W. (2017). Risk of serious infection in older adults with rheumatoid arthritis taking
glucocorticoids.
Arthritis
&
Rheumatology,
69
(6),
1135–1144.
https://doi.org/10.1002/art.40032
5.
Kirwan, J. R., Bijlsma, J. W. J., Boers, M., & Shea, B. (2007). The effect of
glucocorticoids on radiological progression in rheumatoid arthritis: A meta-
analysis.
Rheumatology,
46
(4),
610–614.
https://doi.org/10.1093/rheumatology/kel345
https://scientific-jl.com/luch/
Часть-40_ Том-2_ Март-2025
52
6.
Fardet, L., Petersen, I., & Nazareth, I. (2007). Corticosteroid-induced
adverse events in adults: Frequency, screening and prevention.
Drug Safety,
30
(10), 861–881. https://doi.org/10.2165/00002018-200730100-00006
7.
Dixon, W. G., Watson, K. D., Lunt, M., Hyrich, K. L., Silman, A. J., &
Symmons, D. P. M. (2007). Influence of glucocorticoid therapy on mortality in
patients with rheumatoid arthritis.
Arthritis & Rheumatism, 56
(3), 820–830.
https://doi.org/10.1002/art.22416
8.
Curtis, J. R., Westfall, A. O., Allison, J., Freeman, A., Kovac, S. H., & Saag,
K. G. (2006). Population-based assessment of adverse events associated with long-
term glucocorticoid use in rheumatoid arthritis.
Arthritis Care & Research, 55
(3),
420–426. https://doi.org/10.1002/art.21983
9.
Schäcke, H., Döcke, W. D., & Asadullah, K. (2002). Mechanisms involved
in the side effects of glucocorticoids.
Pharmacology & Therapeutics, 96
(1), 23–
43. https://doi.org/10.1016/S0163-7258(02)00297-8
10.
Moutsopoulos, N. M., Katsifis, G. E., & Moutsopoulos, H. M. (2019).
Adverse effects of corticosteroids in autoimmune diseases: Balancing the benefits
and risks.
Autoimmunity Reviews, 18
(7), 673–679.
