Side effects of chronic systemic glucocorticoid therapy: what dermatologists should know<sup/>

In dermatologists' clinical practice, the use of systemic glucocorticoids is recurrent for the management of different comorbidities that require chronic immunosuppression. The prescription of this medication requires caution and basic clinical knowledge due to the several adverse effects inherent to the treatment. However, different doubts may arise or inappropriate conduct may be adopted due to the lack of objective and specific guidelines for the screening, prophylaxis and management of complications from chronic corticosteroid therapy. Considering this problem, the authors carried out a narrative review of the literature to gather up-to-date data on adverse effects secondary to the chronic use of systemic glucocorticoids. The broad approach to this topic made it possible to review the pathophysiology and risk factors for these complications, as well as to develop updated orientation that can be used as a learning tool and quick reference for dermatologists during their clinical practice with glucocorticoids.

Keywords
Glucocorticoids; Drug-related side effects and adverse reactions; Drug monitoring; Risk factors

Authorship

Lucas Campos Prudente Tavares ^** Corresponding author. E-mail: lucasptavares@gmail.com (L.C. Tavares).

Design and planning of the study

drafting and editing of the manuscript

collection

analysis and interpretation of data.

Department of Tropical Medicine and Dermatology, Hospital das Clínicas da Universidade Federal de Goiás, Goiânia, Goiás, BrazilHospital das Clínicas da Universidade Federal de GoiásBrazilGoiânia, Goiás, BrazilDepartment of Tropical Medicine and Dermatology, Hospital das Clínicas da Universidade Federal de Goiás, Goiânia, Goiás, Brazil

https://orcid.org/0000-0002-6002-8027

Lívia de Vasconcelos Nasser Caetano

Design and planning of the study

drafting and editing of the manuscript

collection

analysis and interpretation of data

critical review of the manuscript

approval of the final version of the manuscript.

https://orcid.org/0000-0002-7880-1022

Mayra Ianhez

Critical review of the manuscript

approval of the final version of the manuscript.

https://orcid.org/0000-0003-3604-3128

* Corresponding author. E-mail: lucasptavares@gmail.com (L.C. Tavares).

Conflicts of interest

None declared.

☆
Study conducted at the Department of Tropical Medicine and Dermatology, Hospital das Clínicas da Universidade Federal de Goiás, Goiânia, Goiás, Brazil.

SCIMAGO INSTITUTIONS RANKINGS

Tables

Tables (4)

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Table 1
Main risk factors, prophylaxis and monitoring for glucocorticoid-induced diabetes mellitus.

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Table 2
Recommendations for glucocorticoid tapering according to the daily dose of prednisone.

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Table 3
Main risk factors, prophylaxis and monitoring for glucocorticoid-induced osteoporosis.

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Table 4
Recommendations for infections screening, prophylaxis and vaccination in chronic systemic corticosteroid therapy.

Table 1 Main risk factors, prophylaxis and monitoring for glucocorticoid-induced diabetes mellitus.

Main risk factors	Obesity, advanced age, genetic predisposition, chronic inflammation, smoking, high blood pressure, high levels of glycated hemoglobin.
Prophylactic measures:	• Healthy diet and physical activity.
Prophylactic measures:	• Metformin can be helpful.
Monitoring:	• Glycated hemoglobin at the start of treatment.
	• Laboratory screening at least every 6 months.
	• Assessment of signs and symptoms of DM.
	• Capillary blood glucose in the afternoon at least 2 to 3 times a week.
	• Joint follow-up with an endocrinologist if necessary.

DM: diabetes mellitus.

Table 2 Recommendations for glucocorticoid tapering according to the daily dose of prednisone.

≥ 40 mg/day:	Weekly reduction of 5‒10 mg in the daily dose until reaching 20 mg/day.
20‒40 mg/day:	Weekly reduction of 5 mg in the daily dose until reaching 20 mg/day.
10‒20 mg/day:	Weekly reduction of 1‒2.5 mg in the daily dose until reaching 10 mg/day.
5‒10 mg /day:	Weekly reduction of 1 mg in the daily dose until reaching 5 mg/day.
≤ 5 mg/day:	Withdrawal only with adrenal function recovery documented by laboratory test in the morning, after 24 hours without the use of corticosteroids.^a a Prete et al.13 In the absence of the test, weekly reduction of 1 mg in the daily dose until complete withdrawal.^b b Caplan et al.7
Recommendations:	• Individualize tapering according to patient's characteristics and disease.
	• Instruct the patient about adrenal insufficiency symptoms.
	• If symptoms of adrenal insufficiency occur, interrupt tapering for 2‒4 weeks. Consider support from an endocrinologist.

^a
Prete et al.¹³13 Prete A, Bancos I. Glucocorticoid induced adrenal insufficiency. BMJ. 2021;374:n1380.
^b
Caplan et al.⁷7 Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG. Prevention and management of glucocorticoid-induced side effects: a comprehensive review: gastrointestinal and endocrinologic side effects. J Am Acad Dermatol. 2017;76:11-6.

Table 3 Main risk factors, prophylaxis and monitoring for glucocorticoid-induced osteoporosis.

Main risk factors:	Dose/duration of treatment, advanced age, female gender, low BMI, low BMD, previous fractures, falls, smoking, alcohol abuse, family history of osteoporosis and hypovitaminosis D.
Prophylactic measures:	• Healthy diet, physical activity with weights, reduce alcohol consumption.
	• Daily intake of calcium (1,000‒1,200 mg/day) and vitamin D (600‒800 IU/day) for all patients.
	• Associate bisphosphonates in specific cases.^a
	• Assess fracture risk (FRAX).
Monitoring:	• Assess serum 25-OH-vitamin D, creatinine and calcium levels annually.
	• Annual bone densitometry.
	• Always inquire about joint pain.
	• Consider support from an osteoporosis specialist.

• Adults ≥ 40 years (men and women with no childbearing potential): moderate to high fracture risk.

• Adults < 40 years old (men and women with no childbearing potential): previous fracture due to osteoporosis; on glucocorticoids at a dose ≥ 7.5 mg/day of prednisone for ≥ 6 months and with a Z score < -3 or bone loss ≥ 10%/year.

BMI: Body Mass Index; BMD: Bone Mineral Density; FRAX: Fracture Risk Assessment Tool.

Table 4 Recommendations for infections screening, prophylaxis and vaccination in chronic systemic corticosteroid therapy.

Pre-treatment screening:	• Serological tests: Anti-HIV, HBsAg, Anti-HBc, Anti-HCV.
Pre-treatment screening:	• Consider TB test (Mantoux or IGRA test) if population at risk.^a
Prophylactic measures:	• PCP: consider prophylaxis if there are other risk factors (hematological malignancy, interstitial lung disease, use of another immunosuppressive drug). Drug options: trimethoprim-sulfamethoxazole 800/160 mg/day (every day or 3 times/week) or dapsone 100 mg/day or atovaquone (1500 mg/day).
Prophylactic measures:	• Strongyloidiasis: consider prophylaxis if the patient is from an endemic area. Drug options: ivermectin 200 mcg/kg/day for 2 days or albendazole 400 mg/day for 3 days.
Vaccination:	• Confirm that the patient is up to date with the following vaccines: H. influenza B, hepatitis A and B, influenza, HPV, N. meningitides, measles, mumps, rubella, tetanus and S. pneumoniae. If not, vaccinate 2‒4 weeks before treatment.
	• Varicella zoster: vaccinate patients >50 years, 2‒4 weeks before treatment.
	• Vaccinate against influenza annually.
	• Avoid vaccines with live agents.

TB: Tuberculosis; IGRA: Interferon Gamma Release Assay; PCP: Pneumocystosis Pneumonia; HPV: human papillomavirus.

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E-mail: revista@sbd.org.br

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