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Management and Treatment with Systemic Glucocorticoids

Active Imageby Victoria Werth, M.D.,
Assistant Professor Dermatology
University of Pennsylvania
Chief Dermatology Section
Philadelphia Veterans Administration Hospital
Philadelphia, PA

 Systemically administered glucocorticoids are potent immunosuppressive and anti-inflamatory drugs that play an important role in treating many dermatologic disorders, including the different types of pemphigus. Unfortunately, their potency also results in numerous side effects, many of which can be minimized by attention to a few details.

About 10 mg of cortisol is secreted daily by the adrenal cortex with peak cortisol levels occurring early in the morning.

Prednisone is a glucocorticoid steroid used to treat pemphigus. It is usually administered to pemphigus sufferers orally, but can also be administered intralesional, intramuscular, and intravenously. The route depends on the type and severity of the disease. Prednisone given once in the morning or every other day, will minimize side effects. Occasionally, split daily doses are needed early in an illness to achieve better therapeutic effect, but conversion to daily or every-other-day regimens should occur as soon as possible. Early conversion to every-other-day regimens is best to control long-term side effects, but may not be possible because it minimizes hypothalamic-pituitary-adrenal (HPA) axis suppression. With cases using prednisone longer than two to three weeks, the drug must be tapered down.

Conversion to every other day is then based on how difficult it is to control the disease process. One approach is to keep the steroid dose constant on one day and reduce the attentive day by 5-mg of prednisone on the alternate day. Steroids must be tapered at a slower rate at the lower doses. When to discontinue maintenance therapy on alternate days is controversial. Some feel that if the patient feels well, then the prednisone can be reduced by 1 mg/week to zero on the alternate days.

Patients who are on long-term glucocorticoids or are within one year of terminating glucocorticoids should wear a bracelet or carry a card indicating they are on glucocorticoids. Any stress such as trauma, surgery, diarrhea or a fever over 101 degrees F (38.3 degrees C) can precipitate acute adrenal insufficiency related to an inadequate stress response. During stress situations, it is necessary to give high doses of glucocorticoids, generally 25 to 70 mg/day of prednisone or 100 to 300 mg/day of cortisol in divided doses. Patients must be educated about the need for stress coverage.

An ACTH stimulation test will assess adrenal reserves after maintenance glucocorticoids are terminated. If the response is normal, then it is usually reasonable to assume that the patient is not adrenally suppressed and that supplementation for stress is not needed. In general, pemphigus vulgaris often requires an initial dose 100 to 200 mg of prednisone or equivalent by mouth if there is widespread involvement and 60 to 100 mg/day if more focal disease exists. If patients do not respond rapidly, the dose should be increased 50% every four to seven days to bring the disease process under control. Slower increases in dosing often leads to a need for even higher doses ultimately and slower control of the disease.

Complications of glucocorticoids

Glucocorticoids cause numerous side effects. Acute side effects include psychiatric disorders, insomnia, fluid and salt retention, and diabetes. Most side effects increase with higher dose and longer duration of use. These effects are minimized with every-other-day dosing, although this dose schedule does not appear to impede development of cataracts or osteoporosis.

A great deal is known about many of the side effects and knowledge about risk factors and pathogenesis can help in prevention and treatment of these problems.

Cataracts are common in patients treated with glucocorticoids. Glaucoma occurs in a significant number of patients and thus all glucocortcoid-treated patients should have their intraocular pressure monitored.

There is some indication that there is an increased incidence of peptic ulcers. There may be a slight increase, with a greater likelihood occurring with prolonged use of high-dose glucocorticoids, other ulcerogenic drugs (aspirin, nonsteroidal anti-inflammatory agents), and severe underlying disease.

Exacerbate hypertension, hyperglycemia and hyperlipidemias, all of which have been considered risk factors for atherosclerosis. Glucocorticoids have been shown to induce lipid abnormalities, including high total and low-density lipoprotein cholesterol levels.

Patients with overt or subclinical diabetes can have increased serum glucose due to increased gluconeogenesis and decreased uptake of glucose peripherally. Such patients may require institutional or increased amounts of insulin. Patients with hyperglycemia requiring insulin or oral antihyperglycemics do better with daily rather than every-other-day dosing glucocorticoids. The hyerglycemia usually improves after stopping glucocorticoids.

The thinning of skin after menopause may be prevented or reversed with estrogen replacement, but its role in glucocorticoids-treated patients is unclear.

The effects of glucocorticoids on host defense is controversial. At low to moderate doses, there is no increased risk of infection, except where TB may have been present. Infection, bacterial, viral, fungal and parasitic can occur with doses of prednisone above 50 mg/day. Some related to the under-lying disease process. Glucocorticoids decrease the inflammatory response to infection and thus it is possible to miss infections. Any fever or other sign of infection must be taken seriously and evaluated.

Methods of minimizing or preventing side effects

Careful evaluation of the patient before and during treatment is important. Patients should be seen at least monthly while on high doses of prednisone, depending on the underlying disease process.

A diet low in calories, fat and sodium and high in potassium and calcium is best.

Alcohol, coffee and nicotine aggravate osteoporosis and peptic ulcers and should be minimized. Exercise is beneficial. Calcium and vitamin D can decrease, but not prevent glucocorticoid-induced osteoporosis. Estrogen treatment can be helpful in postmenopausal women on prednisone in preventing bone loss. Newer medication such as bisphosphonate and calcitonin can prevent bone loss or increase bone density in patients on steroids.

Patients with a family history of heart disease should be followed carefully. All patients should have monthly evaluation of blood pressure and serum glucose and periodic analysis of serum lipids. Any abnormalities should be treated with diet and appropriate medication.

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