What are systemic corticosteroids?
Corticosteroids taken by mouth or given by intramuscular injection are often called systemic steroids. They are synthetic derivatives of the natural steroid, cortisol, produced by the adrenal glands, and have profound anti-inflammatory effects.
Systemic (cortico)steroids are also called glucocorticoids or cortisones. They include prednisone, prednisolone, methylprednisolone, beclomethasone, betamethasone, dexamethasone, hydrocortisone and triamcinolone. Fludrocortisone is predominantly a mineralocorticoid and its anti-inflammatory effects are minimal.
Prednisone and prednisolone are equivalent, and are the most commonly prescribed oral corticosteroids for inflammatory skin diseases. Oral prednisone is the most commonly prescribed systemic steroid in New Zealand.
What is prednisone used for in dermatology?
Prednisone is used for a few days (short-term) to indefinitely (long-term) in a wide variety of skin conditions including:
Systemic steroids are best avoided in patients with psoriasis.
How do systemic steroids work?
Systemic steroids work in the same way as natural cortisol. Natural cortisol has important effects in the body, including regulation of:
- Protein, carbohydrate, lipid and nucleic acid metabolism
- Inflammation and immune response
- Distribution and excretion of water and solutes
- Secretion of adrenocorticotrophic hormone (ACTH) from the pituitary gland.
How do systemic steroids differ?
Systemic steroids differ in dose, mineralocorticoid potency, half-life (duration of action) and how effectively they suppress the hyphothalamic-pituitary-adrenal (HPA) axis (suppression leads to reduced production of natural cortisol).
|Daily dose causing HPA axis suppression (mg)||25??0||20??0||7.5||7.5||1??.5|
* Comparison of systemic corticosteroids ??Vancouver Coastal Health Formulary tool. Accessed 12 July 2014.
What is the usual dose of prednisone?
Generally, a higher dose of prednisone, such as 40??0 mg daily, is prescribed at first, to gain control of the skin condition. In 2?? weeks, the dose is reduced.
Prednisone is best taken as a single dose in the morning, which is thought to reduce steroid-induced suppression of the pituitary-adrenal axis compared to evening dosing.
The maintenance dose should be kept as low as possible to minimise adverse effects.
Steroid dose is commonly characterised as:
- Low dose, eg < 10mg/day of prednisone
- Medium dose, eg 10??0 mg/day of prednisone
- High dose, eg > 20mg/day of prednisone, sometimes more than 100 mg/day
Treatment for less than one month is considered short-term treatment. Corticosteroids for a few days or weeks are relatively safe when prescribed for acute dermatitis. Treatment continuing for more than 3 months is regarded as long term, and results in the majority of undesirable side effects.
What are the side effects and risks of short-term systemic steroids?
Side effects are rarely serious if systemic steroids have been prescribed for one month or less. The following problems may arise, particularly when higher doses are taken:
- Sleep disturbance
- Increased appetite
- Weight gain
- Psychological effects, including increased or decreased energy
Rare and potentially serious side effects of a short course of corticosteroids include: severe infection, mania, psychosis, delirium, depression with suicidal intent, heart failure, peptic ulceration, diabetes and avascular necrosis of the hip. The risk increases with increasing dose.
What are the side effects and risks of long-term systemic steroids?
Nearly everyone on systemic steroids for more than a month suffers from some adverse effects, depending on daily dose and how long they have been on systemic steroids. The main concerns are infections, hypertension, diabetes, osteoporosis, avascular necrosis, myopathy, cataracts, and glaucoma. The list that follows is incomplete.
Cutaneous adverse effects
Cutaneous adverse effects from long-term systemic steroids may include:
- Bacterial infections: cellulitis, wound infection
- Fungal infections: tinea, candida, pityriasis versicolor
- Viral infections: herpes zoster
- Skin thinning, purpura, fragility, telangiectasia and slow wound healing, especially in sun-damaged areas
- Stretch marks (striae) under the arms and in the groin
- Steroid acne
- Hypertrichosis and hair loss
Effects on body fat
- Redistribution of body fat: moon face, buffalo hump, truncal obesity
- Weight gain: increased appetite and food intake
Effects on the eye
- Posterior subcapsular cataracts; children are more susceptible than adults
- Eyelid oedema and exophthalmos
- Central serous chorioretinopathy
- Ischaemic heart disease
- Stroke and transient ischaemic attack (TIA)
The effects of systemic steroids on atherosclerotic vascular disease may be due to complex metabolic changes, including:
- Peripheral insulin resistance and hyperinsulinaemia
- Dyspepsia, gastritis, peptic ulceration and perforation of the gut, especially in patients also taking non-steroidal anti-inflammatory drugs
- Acute pancreatitis
- Fatty liver
- Fluid balance
- Sodium and fluid retention cause leg swelling and weight increase
- Potassium loss causes general weakness
- Irregular menstruation
- Lowered fertility in men and women
- Possible fetal growth retardation in women taking prolonged courses of steroids during pregnancy
- Breast feeding can usually continue but infant should be monitored for adrenal suppression if mother on > 40 mg prednisone daily
- Bone fracture
- Osteonecrosis, especially hip
- Myopathy affecting shoulders and thighs
- Tendon rupture
- Growth restriction in children
Osteoporosis is particularly common in smokers, postmenopausal women, the elderly, underweight or immobile, and patients with diabetes or lung problems. Osteoporosis may result in fractures of the spine, ribs or hip joint with minimal trauma. These occur after the first year in 10??0% of patients treated with more than 7.5 mg prednisone daily. It is estimated that up to 50% of patients on long-term prednisone will develop bone fractures. Vertebral fractures are more common in patients on steroids, even in those with normal bone density.
- Psychological effects: mood changes, increased energy, excitement, euphoria, agitation
- Less often: hypomania, psychosis, delirium, memory loss, depression, anxiety, personality change
- Insomnia and sleep disturbance
- Shakiness and tremor
- Transient or persistent diabetes in previously non-diabetic patients
- Higher blood sugar levels in patients with diabetes mellitus
- Cushing syndrome
- Raised neutrophil and total white cell count are usual on prednisone
- Impaired innate and acquired immunity
- Increased susceptibility to tuberculosis
- Increased severity of measles, varicella
- Reduced efficacy and increased risk of vaccines
Live vaccines such as polio or MMR (measles, mumps, rubella) should not be given to patients taking ??20 mg prednisone daily. It is safe and advisable to have other routine immunisations, such as annual influenza vaccination.
Risks during intercurrent illness or surgery
Significant intercurrent illness, trauma, or surgical procedure requires a temporary increase in corticosteroid dose, or if already stopped, a temporary re-introduction of corticosteroid treatment for up to twelve months after the steroids are stopped.
Patients who have taken ??0 mg prednisone daily within 3 months of surgery requiring a general anaesthetic are advised to tell their anaesthetist so that intraoperative intravenous hydrocortisone can be added.
Effects of reducing the dose of systemic steroids
No tapering is necessary if a course of prednisone has been for less than one to two weeks. Steroids should be withdrawn slowly after longer courses, to avoid acute adrenal insufficiency, particularly if the medication has been taken for several months or longer.
Side effects from reducing prednisone may include:
- Muscle and joint aches
- Weight loss
- Painful itchy skin nodules
Hypopituitary-pituitary-adrenal (HPA) axis suppression can persist for months or years after steroids are stopped.
Monitoring during steroid treatment
Regular monitoring during treatment with systemic steroids may include:
- Blood pressure
- Body weight
- Blood sugar
Patients on prednisone should be advised to avoid non-steroidal anti-inflammatory drugs and licorice.
Prevention of osteoporosis
Bone density scans should be considered for patients that have taken or are expected to take 7.5 mg or more of prednisone each day for three months or longer. Baseline fracture risk can be estimated from T-scores.
Current recommendations are:
- Bisphosphonate therapy (alendronate, etidronate, zolidronic acid) for individuals with femoral T-scores <-2.5. It reduces fracture risk by half.
- Smoking cessation
- Balanced diet, aiming for healthy body weight
- Minimal alcohol
- Regular weight-bearing exercise
- Consider risk of falling and its mitigation
Calcium, vitamin D and oestrogen are no longer recommended for prophylaxis of osteoporosis, as adverse events outweigh benefit.