KatCarney

Dermatology Times
Sept, 2000

Interactions, resistance often foil acne Tx.

Author/s: Cheryl Guttman

Nashville, Tenn. -- Dermatologists should be on the lookout for drug interactions, antibiotic resistance, and other comorbid conditions as causes of treatment failure in acne patients, plus keep in mind that medical management rather than treatment discontinuation may be the appropriate intervention for some acne drug-induced adverse events, Mark Lebwohl, M.D., said at Academy '00.

Dr. Lebwohl presented a diverse group of therapeutic pearls for management of the acne vulgaris patient.

To highlight the importance of seeking a complete drug history, Dr. Lebwohl described a patient receiving tetracycline 500 mg/day, who presented with moderately severe acne, had failed topical acne treatment, and was concomitantly taking lithium for manic depression. "The first lesson from this case is there is a long list of drugs that can cause acne," said the professor and chairman, department of dermatology, Mt. Sinai School of Medicine, New York.

Dr. Lebwohl introduced a mnemonic -- PIMPLES (Phenytoin, Isoniazid or Iodides, Moisturizers, Phenobarbital, Lithium, Ethionamide, Steroids) -- that he has developed to represent a partial list of some of the most commonly used acnegenic medications. He also pointed out that there is a drug interaction between lithium and tetracycline, wherein tetracycline increases the serum lithium concentration and thereby exacerbates its acne-inducing potential.

In addition, he used this case to comment on the increasing problem of Propionibacterium acnes resistance to tetracycline. Although the microorganisms are also likely to be cross-resistant to doxycycline, in general, they remain susceptible to minocycline.

Adverse effects of minocycline

Dr. Lebwohl discussed a number of adverse events that have been associated with minocycline, including a recent flurry of cases of minocycline-induced lupus and hepatitis along with staining of soft tissues and teeth. However, he stated that these drawbacks of minocycline have been greatly overrated and should not be a deterrent to its use in acne patients.

Minocycline-induced lupus generally develops with long-term exposure, although it can occur early. In a paper that reviewed 57 cases, the affected patients had a mean age of about 22 years and the exposure time averaged 19 months, but ranged from three days to six years. The lupus resolves upon minocycline discontinuation.

The soft tissue staining that can occur with minocycline appears as a blue discoloration of the skin or as blue rings around the teeth. The results of an animal study suggest that cotherapy with vitamin C, an antioxidant, may resolve and prevent this oxidation-induced reaction. Dr. Lebwohl reported that he has successfully used this approach to treat a patient with minocycline-related discoloration, and with continued use of vitamin C, the blue staining did not recur when minocycline was resumed.

Negative retinoid effects

Concomitant treatment with vitamin E may have a role in preventing isotretinoin-induced cheilitis, although its efficacy remains to be proved definitively.




"There are a few reports in the oncology literature evaluating prophylaxis of retinoid-induced mucocutaneous side effects with vitamin E, and it has been reported that vitamin E 800 IU per day greatly mitigates these adverse events in patients treated with isotretinoin doses up to 100 mg/day. Nevertheless, in clinical trials, it has been difficult to demonstrate any dramatic benefit from that intervention," Dr. Lebwohl said.

Isotretinoin may also cause marked elevations in serum lipids, but that is not a reason to back away from treatment with the very effective drug. Instead, Dr. Lebwohl recommended instituting use of gemfibrozil (Lopid) or atorvastatin calcium (Lipitor), either of which can be very effective in controlling serum lipids in isotretinoin-treated patients.

Recognizing that isotretinoin is a dramatically effective drug for the vast majority of patients with severe acne, the presence of acne imitators is one point to consider in the evaluation of persons who fail isotretinoin treatment. Sinus tracts, syringomas, adenoma sebaceum, acne keloidalis nuchae, and pseudofolliculitis barbae may all be mistaken for acne and will not respond to isotretinoin.

PCOS most often to blame

Polycystic ovary syndrome (PCOS), however, is by far the most common cause of refractoriness to isotretinoin.

"In one study of 23 patients resistant to oral isotretinoin, 22 were found to be hyperandrogenic, and PCOS is the most common hyperandrogenic state," Dr. Lebwohl said.

The cardinal symptoms of PCOS include oligomenorrhea or amenorrhea, anovulation and infertility, acne, and hirsutism. These patients are likely to be obese, have insulin resistance, and are at risk for early-onset type 2 diabetes and cardiovascular disease. Because of those associated features, a diagnosis of PCOS is worth seeking in any woman with acne and other androgenic features as well as in women in whom isotretinoin has failed, even in the absence of clinical signs, Dr. Lebwohl said.

Using tazarotene wisely

Wrapping up his tips, Dr. Lebwohl reviewed short-contact tazarotene as a highly effective, well tolerated approach for using this topical retinoid. "Tazarotene can be very irritating when left on overnight according to the prescribing information. In the short-contact regimen, patients apply the medication beginning with one minute a day, and titrate the exposure as tolerated up to five minutes a day. This technique markedly reduces irritation while providing clear therapeutic benefit to most patients," he noted.

The technique of short-contact tazarotene treatment has been patented. Susan Bershad, M.D., and Dr. Lebwohl are the first and second names, respectively, on the patent.


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