Glucocorticosteroids are a mainstay in the dermatologist's armamentarium. In fact, almost 90 percent of dermatologists responding to a survey of the San Francisco Dermatologic Society in 1974 indicated they used long-acting parenteral corticosteroids in their practice, mostly the acetonide salt of triamcinolone (TAC-A1). Despite the age of the survey, findings likely still reflect practice, as no reliable alternatives to glucocorticosteroids have emerged for the most common dermatologic indications.
TAC-A in the Clinic
Despite its popularity and its general safety and tolerability, triamcinolone acetonide is associated with potential shortcomings. TAC-A is a suspension and must be shaken vigorously prior to injection. "Clumping" renders the product less effective, and irreversible clumping will occur with freezing. Product information accompanying TAC-A is vague and fails to outline a specific approach to long-term therapy of any dermatologic disease.
Using an example of chronic hand eczema in an atopic individual, 40mg of TAC-A is administered deeply in gluteal muscle to avoid lipoatrophy at the injection site. If such a depression is created, it will take many months—up to 18—to return to normal. In some cases, the lipoatrophy never completely resolves. After initial treatment, the patient is then seen in two to three weeks. Clearing is expected and will last an almost predictable 18-21 days. Early signs of recurrence prompt another dose administration of 40mg. The patient is then seen in about a month. Remission lasts longer with each successive dose, and the intervals are gradually extended to six weeks then to three months. Of note, this treatment is only effective if patients follow the advice of their dermatologist: minimize hand-washing and moisturize each time their hands are wet, use mild soaps, cotton liners and rubber gloves with dish-washing, and avoid any specific irritants or allergents that would potentiate the hand eczema.
Note that if divided to represent the average daily dose of oral triamcinolone, these relatively small doses of TAC-A would be well under 2mg, lessening the risks of undesirable side effects. However, menstrual irregularities often occur in premenopausal women who are not on anovulatory drugs. This has been shown to be a result of suppression of cyclical gonadotrophins, leading to decreased estrogen and markedly low levels of progesterone.1
Endometrial biopsies from such women show proliferative changes, and spotting is believed to be due to low-estrogen shedding. These occurrences are unique to TAC-A. Other injectables, such as betamethasone, methylprednisolone and triamcinolone diacetate, do not have this effect and may be substituted but are less effective with much shorter durations of action.
Another predictable effect of TAC-A is suppression of the hypophyseal-pituitary-adrenal (HPA) axis. In studies of the axis in patients treated with very high doses of TAC-A, there remains some production of cortisol by the adrenals, and this is assumed to be the reason that no adverse effects, such as Addisonian crisis, have been observed in patients on long-term therapy. Still, suppression of the HPA axis persists for months after TAC-A is discontinued,2 and, therefore, the potential for Addisonian crisis exists.
Capillary fragility with purpura on the dorsal forearms is frequently observed in elderly patients and is accentuated in people with chronic sun damage or those taking aspirin or Coumadin. Posterior, subcapsular cataracts have been found in patients on very high doses of TAC-A on an experimental basis but do not occur in patients on the suggested doses of 40mg or less per month.2
Other infrequent events seen with suggested doses of TAC-A include hirsutism, acneiform eruptions, emotional lability (mood swings, insomnia, hyperirritability), and postmenopausal spotting. Increased blood sugar in diabetics is a potential problem that must be monitored. Suggested doses of TAC-A as outlined above have not been reported to have an effect on intraocular pressure, hypertension, avascular necrosis of the femoral head, gastric upset, purple striae, or fat redistribution (moon facies, buffalo hump, etc.). All of these problems have been observed, for example, with oral prednisone over long periods. This fact again demonstrates the uniqueness and safety of TAC-A in recommended doses.
Applications of TAC-A
Table 1 provides a listing of conditions for which TAC-A treatment has been found effective.3 A special note should be made regarding aquagenic pruritus. Complete control of this very annoying problem with periodic TAC-A (40mg every two to three months) has been obtained in 15 patients. No other corticosteroid has this profound effect, and antihistamines are of no value.4
Despite the utility of TAC-A, adjunctive treatment with other medications is commonly necessary. Examples include chloroquine with lupus erythematosus, antibiotics with inflammatory rosacea, acyclovir with herpes zoster, azathioprine with pemphigus, antihistamines with chronic urticaria, and acitretin with pityriasis rubra pilaris.
In short, intramuscular triamcinolone is a valuable medication for a number of dermatologic disorders. Used judiciously, it is safe, and serious side effects are rare and predictable; however, little is known about the drug's effect on bone mineral density (BMD).
Investigating Effects on BMD
Significant bone loss is a predictable event in patients on oral glucocorticoids and is most dramatic in the first three to six months of therapy.11,12 Baseline DXA scans and concurrent bisphosphonate treatment are recommended for patients in whom long-term oral glucocorticoid therapy is anticipated.
In order to assess the effects of TAC-A on BMD, data were collected from the medical records of 32 patients (18 women and 14 men), who were on long-term TAC-A for various dermatologic conditions (Table 2). The average length of treatment was 8.6 years per patient. The average daily dose of TAC-A was calculated at 0.5mg (total milligrams of TAC-A divided by the number of days of treatment). Bone mineral density was ascertained employing dual energy X-ray absorptiometry (DXA).
The average age of the 18 women at the time of DXA scans was over 65 years (range 53-81). Six had BMD T-scores in the osteoporosis range, and 10 were osteopenic. One patient (subject #30) had a minor osteoporotic fracture of the wrist. About half of postmenopausal women in the general population have a bone density T-score at the femoral neck between –1.0 and –2.55 (osteopenia). In the present study, 55 percent of the women were osteopenic. Osteoporosis would be expected in 35 percent of women in the general population over 65,6 about the same as that found in this study group (33 percent).
The average age of the 14 men at the time of DXA scans was over 67 years (range 50-90). Three had T-scores in the osteoporosis range, and three were osteopenic. Fourteen percent of men over 65 would be expected to have osteoporosis,6 as opposed to 21 percent in this study group.
Managing Bone Density Loss
BMD increases to about the mid-to-late 30s and then declines, especially in women, where the loss is more pronounced than in men. Bone loss is a natural occurrence in the elderly; in fact, routine DXA scans are recommended for all women over 65.7
Results of this retrospective analysis in a small group of patients suggest that long-term TAC-A does not significantly contribute to bone loss. No correlation was evident with bone loss and the amount of TAC-A administered or the length of treatment in this small series. Nonetheless, dermatologists are among the most frequent prescribers of chronic glucocorticoids, and insight into the pathogenesis and treatment of bone loss is therefore very valuable.
Treatment with bisphosphonates is recommended for patients with osteoporosis, along with supplemental calcium and vitamin D8. Weight-bearing exercise (including simple walking or golfing) is very beneficial. A little sun exposure significantly increases vitamin D levels. Alternative treatments for osteoporosis include hormone replacement therapy, recombinant parathyroid hormone9 and human monoclonal antibodies targeting osteoclasts.10 The need for treatment of osteopenia with bisphosphonates is controversial.5
Clinical Insights
In summary, it appears that routine BMD screening is not necessary in persons on long-term TAC-A, and concurrent bisphosphonates are not indicated as they are with long-term oral glucocorticoids. However, other risk factors, including increased age (>70 years), low body weight, weight loss, physical inactivity, previous osteoporotic fracture, and androgen deprivation therapy should alert the physician to the need for BMD testing.13 Addressing these issues in the patient history is essential.
Some clinicians may consider calcaneal ultrasonography an alternative to DVA scanning—it is inexpensive, readily available, and devoid of ionizing radiation. It is probably not sensitive enough to diagnose osteoporosis, however. It does have predictability for possible future low bone density fractures.13
Prospective studies would be useful for more meaningful conclusions. Hopefully these findings heighten awareness of the need for further investigation.
Dr. Carson has no relevant disclosures.
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