Feature: Staying a Step Ahead - By Michael S. Krivda, Contributing editor Tips for sidestepping acne treatment failures. D espite the very good drugs available to treat acne, for 10% to 15% of patients, treatment fails. According to Andreas Katsambas, professor and chairman of the department of dermatology at the University of Athens in Greece, there are a number of reasons for this, some having to do with the physician, some with the treatment and some with the patient. The Role of Dermatologists According to Dr. Katsambas, who spoke on this topic at last year’s Annual American Academy of Dermatology meeting, many dermatologists experience difficulty treating acne because they rely too much on older, less effective treatments, they don’t spend enough time explaining treatments to their patients, they give false expectations or they simply use the wrong dosage for medications, either creating side effects or no effect at all if they give too little. There are many dermatologists who still insist on diet restrictions, forbidding patients to eat things like chocolate or sweets. Some use unnecessary methods like ultraviolet light, massage, etc. Dermatologists must do more to keep up with the latest developments. Often the least effective dermatologist in treating acne is the well-trained, experienced, but busy, dermatologist. “This doctor often does not make enough time to talk to patients and undervalues patients’ questions,” says Dr. Katsambas. “He pays little attention to minimal acne, rejects cosmetics and is overly reliant on new drugs and methods.” Some dermatologists try to impress patients, saying things like, “Give me 2 weeks and I will clear up your acne.” This creates unrealistic expectations for the patient, which can impact treatment. There are also some dermatologists who are often too concerned about and who exaggerate side effects, instead of simply and properly explaining them. Fearing side effects, a dermatologist may use too low a dose, making the treatment ineffective. Take Time to Talk Prior to acne treatment, time must be spent with the patient to fully explain the disease, the typical course of treatment, the possible side effects and the need for patience. This is critical for compliance, especially in young patients. You must be willing to listen to and answer all of a patient’s questions, no matter how trivial you think the questions are. “You must also explain the daily routine of cleansing, moisturizing, applying cosmetics and so on,” says Dr. Katsambas. “You must dispel the myths about acne.” You should also explain the potential benefits of sun exposure, which can lead to a 60% to 70% improvement, especially in body acne. However, you must point out that there is a risk that sun exposure can make acne worse in some patients. Dr. Katsambas says it’s important to pay attention to minimal acne. Sometimes a few spots are very important to the patient. The aggressiveness of the treatment should be based not only on the severity of the acne, but also on the psychological impact of the disease. Do not reject cosmetics because in many cases cosmetics are essential for the successful treatment of acne in that they maximize compliance. Topical cosmetics, especially non-comedogenic and non-greasy make-up, can be effectively used to cover irritant dermatitis or flare ups after treatment with retinoids. There are also many prescription products available to treat acne patients. “There are wonderful new medications that can really benefit many patients. A dermatologist must keep abreast of all the new treatments, but must not over rely on new drugs and methods,” explains Dr. Katsambas. “Don’t be over-influenced by recent studies, or prescribe drugs simply to impress the patient.” Effective Doses According to Dr. Katsambas, tetracycline and erythromycin should be given at 1 gram per day for 4 to 6 months. Instruct patients to take tetracycline and erythromycin at least a half an hour before a meal. Also, patients taking tetracycline should avoid the sun. Minocycline (Dynacin, Minocin) and doxycycline (Monodox, Vibramycin, Adoxa) should be given at 100 mg per day for 4 to 6 months. Administer isotretinoin (Accutane, Amnesteem, Claravis, Sotret) for 4 to 8 months, at a minimum cumulative dose not less than 120 mg per kilogram of weight, or there will be a high possibility of relapse. If relapse occurs, repeat treatment with a proper dose. Combining tetracycline and isotretinoin can cause headaches and dizziness (pseudotumor cerebri). Topicals must be applied to the entire area and not just on acne spots. Otherwise, treatment will fail. Also, topical retinoids work best on dry skin. Warn patients that benzoyl peroxide will bleach clothing. Poor Response to Antibiotics In 1991, a study showed that only 35% of patients had strains of acne resistant to at least one or more of the anti-acne antibiotics. Six years later, the level of resistance had nearly doubled to 64%. One of the reasons may be the extensive use of topical formulations of erythromycin (A/T/S, Benzamycin, Emgel, Erycette, Erygel) and clindamycin (Benzaclin, Cleocin T, Clindets, Duac). “Dermatologists should avoid all formulations containing topical antibiotics if the failure of the treatment is due to resistant acne. If this is the case, then switch to either minocycline or isotretinoin.” A very high sebum excretion rate dilutes the antibiotic lowering the concentration of the antibiotic in the pilosebaceous unit causing a poor response. Double the dose of the antibiotic to 200 mg per day of minocycline or 200 mg a day of doxycycline. Consider switching to isotretinoin or, in women, consider administering estrogens and antiandrogens that minimize the sebum excretion rate. In all cases, you must extend treatment well beyond what constitutes a normal course of treatment, because ending treatment too soon will cause a relapse. Gram-negative folliculitis is a rare phenomenon that typically occurs in patients doing well with antibiotic treatment who suddenly deteriorate and develop pustules. Dr. Katsambas says to treat with ampicillin or isotretinoin at 1 mg/kg. Also, a recent study in the Journal of the American Medical Association showed evidence of link between antibiotics and an increased risk of breast cancer. Researchers concluded that the more antibiotics the women in the study used, the higher their risk for breast cancer. The study showed that women who took antibiotics for more than 500 days or who had more than 25 prescriptions over an average of 17 years had more than twice the risk of breast cancer as women who had not taken any antibiotics. The risk was smaller for women who took antibiotics for fewer days. Problems with Isotretinoin Some patients don’t respond to isotretinoin and some do well initially but relapse quickly. For patients with many microcomedones and microcysts, isotretinoin is much less effective. For these patients, excise or cauterize the microcomedones and microcysts under topical anesthesia — then resume isotretinoin. According to Dr. Katsambas, the most important reason for failure of isotretinoin treatment in women is endocrine problems, women suffering with polycystic ovarian syndrome or late onset of adrenal hyperplasia. If acne returns in these patients, test for hyperandrogenism, especially in female acne patients with irregular menses, hirsutism, sicca syndrome, seborrhea, acne, hirsutism or thinning hair. To manage this, Dr. Katsambas recommends oral estrogens alone or in combination with anti-androgens given with, or just after, isotretinoin treatment. For teenage patients who relapse after isotretinoin, repeat the treatment. You can repeat treatment with isotretinoin as many as four times without any problem. Almost every patient suffers some level of the common side effects of isotretinoin, including dermatitis and dry or cracked lips. Patients should use an emollient and lip balm and in severe cases, hydrocortisone cream for a very short period of time. Sometimes, Staphylococcus aureus boils occur, which can be treated with erythromycin. Severe joint and muscle pain can also occur with isotretinoin. If this occurs, lower the dose or discontinue isotretinoin, depending upon the severity of the pain. A rare but real side effect of isotretinoin is mild depression. Isotretinoin-induced depression occurs almost immediately after starting the drug. If the depression is a result of the medication and not incidental to the general state of mind of the patient, then discontinue isotretinoin immediately and have the patient seek psychiatric treatment. Topical Treatment Side Effects A poor response to topical treatments can be caused by non-compliance due to the slow rate of improvement or because the patient couldn’t tolerate the side effects. When treating with a common topical treatment, such as tretinoin cream (Avita, Renova, Retin-A), or benzoyl peroxide, there will typically be an irritant dermatitis or aggravation of the acne in the first month, followed by a 10% to 15% improvement per month resulting in an 80% to 100% improvement in 6 months. “The best approach is to inform the patient prior to starting treatment about the possibility of a temporary worsening of the acne,” says Dr. Katsambas. “If you realize that the patient is not prepared to accept an initial flare, it may be better not to start treatment, because he or she will stop the treatment.” If the contact dermatitis is severe, use topical retinoids on alternate evenings, and every morning, with moisturizers, and occasionally, hydrocortisone cream in the morning for no more than 20 days. Or, use a less irritating topical retinoid like adapalene (Differin) and isotretinoin gel. Adapalene gel 0.1% may be equally effective and better tolerated than tretinoin cream or isotretinoin gel for treating acne. If dealing with an extreme acne flare, a single cortisone injection will reduce the symptoms. Problems with Minocycline Minocycline can cause benign intracranial hypertension, causing dizziness and headache (pseudotumor cerebri). If this should occur, lower the dose or to switch to doxycycline. Minocycline can also cause hyper-pigmentation, which, though rare, can last for many months or even years. You can see minocycline brown patches or even darkening of the nails. If this occurs, discontinue minocycline immediately because there is no treatment. Minocycline has also been associated with a rare occurrence of lupus-like symptoms. Acne Variants and Cystic Acne A poor response can occur in patients with acne variants and cystic acne, like pyoderma faciale, acne fulminans or cystic acne. Pyoderma faciale occurs in women 25 to 40 years of age who suddenly develop devastating acne-like symptoms. Dr. Katsambas recommends isotretinoin 1 mg per day. For acne fulminans, which occurs primarily in men and appears suddenly as severe acne primarily on the trunk often with fever and polyarthropathy, treat with erythromycin, isotretinoin and prednisone at 40 mg a day. Cystic acne can respond poorly to treatment, especially with whiteheads behind the ear or inflamed cysts. You must extract these whiteheads with light cautery under topical anesthesia. If the patient has cysts, administer isotretinoin 1 mg per day and intralesional therapy with steroids. For older cysts (more than 3 weeks), you should remove with liquid nitrogen. Patient-Related Problems Sometimes a poor response to treatment is directly related to the state of mind of the patient. You can have cases of acne excoriee — acne caused by the patient. It is most common in women, and occurs when they scratch. “Do not use topical treatment, because that only gets the patient involved with the face again, making the problem worse,” says Dr. Katsambas. “Psychological treatment is essential. If you must treat the acne, use only a systemic treatment, or even isotretinoin.” Patients who are overly concerned about their appearance are difficult to treat. For some of these patients, no treatment outcome is satisfactory. For these patients, set realistic expectations and use an aggressive systemic treatment, such as isotretinoin, even for minimal acne. Making Treatment Work Despite the problems that can occur, a proper response can almost always result in improvement for the patient. With the wide variety of treatment options, a little patience and a willingness to try other methods if one fails can go a long way toward achieving a satisfactory result. “All acne cases can be adequately controlled if the relationship between the doctor and the patient has been built on trust and confidence,” says Dr. Katsambas. “It is up to us as dermatologists to create that confidence and trust and make sure that we are doing everything that we can to help all of our patients, not just those who respond to standard treatments.” Skin & Aging - ISSN: 1096-0120 - Volume 12 - Issue 8_2004 - August 2004 - Pages: 50 - 52