Systemic steroids, commonly referred to as corticosteroids, are synthetic derivatives of cortisol, a natural steroid produced by the adrenal glands. These medications, whether taken orally or administered via intramuscular injection, have profound anti-inflammatory effects, making them invaluable in the treatment of various inflammatory conditions. Systemic steroids are also known as glucocorticoids or cortisones and include medications such as prednisone, prednisolone, methylprednisolone, beclomethasone, betamethasone, dexamethasone, hydrocortisone, and triamcinolone.
Among these, prednisone and prednisolone are considered equivalent and are the most commonly prescribed oral corticosteroids for inflammatory skin diseases. It is important to note that fludrocortisone, although also a steroid, is predominantly a mineralocorticoid with minimal anti-inflammatory effects.
Prednisone is widely used in dermatology for both short-term and long-term treatment of a variety of skin conditions. These include eczema or dermatitis, autoimmune bullous diseases, lupus erythematosus, sarcoidosis, and vasculitis. However, systemic steroids like prednisone are generally avoided in patients with psoriasis due to the potential for exacerbation of the condition.
Systemic steroids mimic the action of natural cortisol in the body. Cortisol plays a crucial role in regulating various bodily functions, including the metabolism of proteins, carbohydrates, lipids, and nucleic acids, as well as modulating inflammation and immune responses. It also influences the distribution and excretion of water and solutes and regulates the secretion of adrenocorticotrophic hormone (ACTH) from the pituitary gland.
Systemic steroids differ in several ways, including their dosage, mineralocorticoid potency, half-life (duration of action), and their effectiveness in suppressing the hypothalamic-pituitary-adrenal (HPA) axis. Suppression of the HPA axis leads to reduced production of natural cortisol, which can have significant implications for the patient.
The dosage of prednisone usually starts at a higher level, such as 40–60 mg daily, to quickly gain control over the skin condition. After about 2–4 weeks, the dosage is typically reduced. Prednisone is best taken as a single dose in the morning, as this is thought to minimize the suppression of the pituitary-adrenal axis, which can occur with evening dosing. To reduce the risk of adverse effects, the maintenance dose should be kept as low as possible. Prednisone dosages are generally characterized as low (less than 10 mg/day), medium (10–20 mg/day), or high (more than 20 mg/day, sometimes exceeding 100 mg/day).
When prescribed for less than one month, systemic steroids are considered relatively safe, particularly for treating acute dermatitis. However, even in the short term, side effects can occur, especially at higher doses. Common short-term side effects include sleep disturbances, increased appetite, weight gain, elevated postprandial blood sugar levels, and psychological effects, such as increased or decreased energy. Although rare, serious side effects from a short course of corticosteroids can include severe infections, psychological disturbances (such as mania, psychosis, or depression), heart failure, peptic ulcers, diabetes mellitus, and avascular necrosis of the hip. The risk of these serious side effects increases with higher doses.
Long-term use of systemic steroids, typically defined as treatment lasting more than three months, is associated with a wide range of adverse effects. Nearly everyone on long-term steroid therapy experiences some side effects, which vary depending on the daily dose and duration of treatment. Major concerns include an increased risk of infections, hypertension, diabetes, osteoporosis, avascular necrosis, myopathy, cataracts, and glaucoma. Cutaneous side effects from long-term systemic steroids may include bacterial infections (such as cellulitis), fungal infections (such as tinea or candida), viral infections (such as herpes zoster), skin thinning, purpura, fragility, slow wound healing, stretch marks, steroid acne, and hair changes.
Systemic steroids can also cause significant changes in body fat distribution, leading to conditions such as moon face, buffalo hump, and truncal obesity, as well as weight gain due to increased appetite. Ocular effects can include glaucoma, posterior subcapsular cataracts (with children being more susceptible than adults), eyelid oedema, exophthalmos, and central serous chorioretinopathy. Vascular diseases, such as hypertension, ischemic heart disease, stroke, and transient ischemic attack (TIA), may also arise due to the complex metabolic changes induced by systemic steroids, including hyperlipidemia and insulin resistance.
In the gastrointestinal tract, systemic steroids can cause dyspepsia, gastritis, peptic ulceration, and even gut perforation, particularly in patients also taking non-steroidal anti-inflammatory drugs (NSAIDs). Other gastrointestinal issues include acute pancreatitis and fatty liver. Fluid balance can be disrupted, leading to sodium and fluid retention, leg swelling, weight gain, and potassium loss, which may cause general weakness.
The reproductive system is also affected by long-term steroid use, with potential issues including irregular menstruation, hirsutism, lowered fertility in both men and women and possible fetal growth retardation in women taking prolonged courses of steroids during pregnancy. Although breastfeeding can usually continue, infants of mothers taking more than 40 mg of prednisone daily should be monitored for adrenal suppression.
Musculoskeletal side effects include an increased risk of bone fractures, osteoporosis, osteonecrosis (especially of the hip), myopathy affecting the shoulders and thighs, tendon rupture, and growth restriction in children. Osteoporosis is particularly common in smokers, postmenopausal women, the elderly, underweight or immobile individuals, and patients with diabetes or lung problems. Vertebral fractures are more common in patients on long-term steroids, even in those with normal bone density.
The nervous system can be impacted as well, with psychological effects ranging from mood changes, increased energy, excitement, and euphoria, to more severe conditions such as hypomania, psychosis, delirium, memory loss, depression, and anxiety. Insomnia, tremors, headaches, and other neurological symptoms may also occur.
Systemic steroids can also have significant metabolic effects, including transient or persistent diabetes in previously non-diabetic patients and higher blood sugar levels in those with diabetes mellitus. Cushing syndrome, characterized by symptoms such as weight gain, moon face, and skin changes, is another potential outcome of long-term steroid use.
The immune response is also altered by systemic steroids, leading to an increased susceptibility to infections such as tuberculosis and more severe cases of measles and varicella. The efficacy of vaccines is reduced, and the risk associated with live vaccines, such as polio or MMR, is heightened for patients taking 20 mg or more of prednisone daily. However, other routine immunizations, such as the annual influenza vaccine, are both safe and recommended.
Significant intercurrent illness, trauma, or surgical procedures may necessitate a temporary increase in corticosteroid dosage or the reintroduction of corticosteroid treatment for up to twelve months after the steroids have been discontinued. Patients who have taken 10 mg or more of prednisone daily within three months of surgery requiring general anaesthesia should inform their anaesthetist, as intraoperative intravenous hydrocortisone may be needed.
When discontinuing prednisone, no tapering is necessary if the course has lasted less than one to two weeks. However, for longer courses, steroids should be withdrawn gradually to avoid acute adrenal insufficiency, particularly if the medication has been taken for several months or longer. Side effects from reducing prednisone may include fever, hypotension, tiredness, headaches, muscle and joint aches, weight loss, depression, rhinitis, conjunctivitis, and painful itchy skin nodules. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis can persist for months or even years after steroids are stopped.
Regular monitoring during treatment with systemic steroids is essential and may include checks on blood pressure, body weight, and blood sugar levels. Patients on prednisone should be advised to avoid non-steroidal anti-inflammatory drugs (NSAIDs) and licorice, as these can exacerbate steroid-related side effects.
For patients who have taken or are expected to take 7.5 mg or more of prednisone daily for three months or longer, bone density scans should be considered. Baseline fracture risk can be estimated from T-scores, and current recommendations for reducing fracture risk include bisphosphonate therapy for individuals with femoral T-scores below -2.5. This treatment has been shown to reduce fracture risk by half. Additionally, lifestyle modifications such as smoking cessation, maintaining a balanced diet aimed at healthy body weight, minimizing alcohol intake, and engaging in regular weight-bearing exercise are important preventive measures. The risk of falling and ways to mitigate it should also be considered. However, calcium, vitamin D, and estrogen are no longer recommended for the prevention of osteoporosis, as the potential adverse events outweigh the benefits.
In conclusion, systemic steroids play a crucial role in the management of various inflammatory skin conditions. However, their use must be carefully monitored and managed due to the potential for significant side effects, particularly with long-term use. By understanding the risks and following recommended guidelines for monitoring and prevention, patients and healthcare providers can work together to minimize adverse effects and ensure the safe and effective use of these powerful medications.
