Acne: A Review of Diagnosis and Treatment – Oral Therapies

9 Mar
2010

Antibiotics

Oral antibiotics are effective in the treatment of acne, particularly when acne is related to inflammation or P. acnes infection. As previously stated, the antibiotics are useful for moderate and severe grades of inflammatory acne because of their anti-inflammatory properties.

Tetracyclines. Tetracyclines are commonly used to treat acne. Some authors think that more lipophilic antibiotics and antibiotics with less P. acnes resistance, are more effective than tetracycline. Others claim that there is no clear proof that generic minocycline is superior to tetracycline. Because tetracyclines stain the teeth, they should not be used in children.

A new development in the role of oral antibiotics for acne treatment is the use of submicrobial doses. These doses have only anti-inflammatory rather than antibiotic activity, and they have been shown to be equivalent to higher antimicrobial doses.

Erythromycin. Oral erythromycin has been a mainstay of anti-acne treatment. P. acnes resistance to erythromycin has greatly reduced its utility in acne therapy.

Azithromycin

It has been suggested as an effective acne treatment, and it might be more useful than erythromycin because of its longer half-life, greater anti-inflammatory activity, wider coverage of gram-negative organisms, and fewer gastrointestinal adverse effects. Irreversible deafness has been reported after the use of low-dose azithromycin in healthy patients, but the handful of cases suggests that this side effect is rare.

Sulfa agents. Generic Trimethoprim/sulfamethoxazole (Canadian Bactrim), given as a double-strength tablet twice a day, can be effective; it often works when other antibiotics fail. It is useful in treating gram-negative folliculitis, a mimic of acne that does not respond to tetracycline or macrolides but does respond to isotretinoin and trimethoprim/sulfamethoxazole.

The most common adverse side effect is a maculopapular eruption; rare side effects include Stevens-Johnson syndrome, hepatitis, and toxic epidermal necrolysis.

The combination of methotrexate plus trimethoprim/ sulfamethoxazole can be fatal. If patients are taking methotrexate for psoriasis or rheumatoid arthritis or if they intend to use methotrexate as an abortifacient and they seek treatment of acne, these drugs should not be prescribed together. For many dermatologists, these possible adverse effects make trimethoprim/sulfamethoxazole a third-line therapy for acne.

Oral Contraceptives

Oral contraceptives are effective in women for acne that is related to androgen excess or that waxes and wanes with their menstrual periods. These agents increase sex hormone-binding globulin; this decreases circulating free testosterone, thereby abating acne in some cases. Combination birth control tablets have shown efficacy in the treatment of acne vul-garis. Which may also be used in the treatment of acne vulgaris, binds the androgen receptor and reduces androgen production.

Oral Retinoids (Isotretinoin)

Isotretinoin (Generic Accutane), a systemic retinoid, is the single most effective agent for the treatment of acne of all types. It normalizes epidermal differentiation and inhibits sebum excretion permanently by 70%. Isotretinoin also works as an antiinflammatory agent. However, it is not a panacea; one study found that 7.2% of patients with acne did not respond to isotretinoin therapy.

Some dermatologists find that dispensing enough iso-tretinoin to achieve a cumulative dose of 120 to 150 mg/kg is the optimal way to use this agent for acne; they prefer that kg be given in a divided dose twice a day for five months or that therapy be initiated at a dose of 0.5 mg/kg per day for four weeks and increased as tolerated until a dose of 1 mg/kg daily is achieved. Other experts advocate the low-dose regimens of isotretinoin involving six months of treatment with 20 mg/day, noting that such dosing has a low incidence of severe side effects and is less expensive than higher-dose regimens.

As a rule, a single course of isotretinoin at a cumulative dose of 120 to 150 mg/kg should cure acne in two-thirds of patients. A side effect from the continued use of isotretinoin, however, is a condition known as diffuse idiopathic skeletal hyperostosis (DISH). For this reason, some physicians order a radiographical skeletal baseline examination if repeated courses of isotretinoin are considered. Patients should be warned of the rare possibility of the occurrence of DISH before therapy is begun.

Isotretinoin is a teratogen, and fertile women must be informed of this fact. In the U.S., isotretinoin may be distributed only if patients, physicians, and pharmacists participate in the iPledge program. Before pharmacists may distribute the product, patients must enroll in this program and a negative pregnancy test in fertile women must be confirmed.

Isotretinoin does not seem to have a negative effect on mood. Some reports suggest that it increases the incidence of depression, but larger studies have not borne this out. Children exposed to high doses of isotretinoin are at risk for premature epiphyseal closure, whereas adults maintaining long-term therapy have an increased tendency to develop hyperostosis and other changes in bones. In any case, physicians must counsel women regarding contraception, and two negative pregnancy test results are required before therapy can be initiated. These test results must be confirmed monthly.

For all patients, a baseline laboratory examination should also include assessments of cholesterol, triglyceride, and hepatic transaminase levels as well as a complete blood count. Although an increase of isotretinoin has been shown to raise triglyceride levels in well-documented cases, its adverse effects on the liver are less well defined and certainly less common.

In cases of acne fulminans, canadian isotretinoin can worsen acne initially. Coadministration with corticosteroids at the beginning of therapy can be useful in severe cases to prevent the initial flaring of acne.

Nutritional Supplements

Vitamins and minerals have been used to treat acne. Pharmacological doses of nicotinamide tablets (e.g., Nicomide, DUSA/Sirius), 1.5 g/day, given in divided doses two or three times a day, have been used often in combination with zinc, copper, and folic acid. Oral and topical zinc have also been advocated, but strong evidence of its effect needs to be established.

Other Treatments

For variations of acne, other therapies can be attempted.

Triamcinolone. Cysts of acne respond within a day after injections with triamcinolone acetonide (Kenalog, Apothecon) at a concentration of 2 to 3 mg/mL, although atrophy can result temporarily. Recently, lasers and light sources have been advocated, but controlled studies are lacking and such treatments are expensive.

Psychotropic medications. Acne excoriee is characterized by excessive scratching or picking of normal skin or skin with minor surface irregularities. It is most common in young women who pick at scattered acne papules, which are turned into scars. The compulsion is best treated with antidepressants or antipsychotic medications combined with isotretinoin. Medications that can be used include the selective serotonin re-uptake inhibitors (SSRIs) as first-line psychiatric agents (e.g., Zoloft, Paxil, or Prozac). If the obsessive-compulsive disability is severe, low-dose risperidone (Risperdal, Janssen) 2 mg or olanzapine (Zyprexa, Eli Lilly) 2.5 mg can be helpful. It may be advisable for patients to seek out psychological assistance or counseling in these cases.

Surgery. Acne surgery involves the extraction of comedones. Open comedones are pores that contain keratin plugs with black tops (blackheads). Closed comedones are pores containing keratin plugs with white tops that may be more firmly embedded than open comedones (whiteheads). Comedones are not usually inflamed, but they can be.

How Long Should Therapy Continue?

Acne naturally waxes and wanes, and the use of therapy can be instituted and discontinued as needed. After the inflammation is controlled with oral antibiotics, acne can often be controlled with topical retinoids and benzoyl peroxide canadian for long periods. Long-term therapy with minocycline beyond six months carries an increased risk of pigmentary deposition. Many acne patients continue with an antibiotic for more than a year without adverse effects.

Isotretinoin can “cure” acne in many cases, although up to 20% to 25% of patients need to be re-treated for optimal re-sults. Topical retinoids have anti-aging effects on the skin; thus, long-term therapy, if tolerated, can be seen as desirable.

Role of the Pharmacist

Pharmacists play an important role in acne treatment. They must be aware of the side effects of acne medications and the potential interactions of acne medications with other agents, in particular methotrexate and sulfamethoxazole/trimetho-prim. Pharmacists are active participants in the iPledge program and must use an online database to disburse iso-tretinoin.

Many patients with acne never see a physician, and they often seek advice from a pharmacist about therapy. In an Australian study by Yeatman et al., 70% of the 315 consumers interviewed were purchasing OTC products, and 50% purchased prescription items. Of the OTC products, 42% were originally recommended by the pharmacy staff members and 18% were recommended by doctors. More than one-third of consumers buying OTC products described symptoms to the pharmacy staff, and in about 50% of cases, they spoke to the pharmacy assistant. Pharmacists must be aware of different OTC preparations, including, salicylic acid, sulfur, and sodium sulfacetamide, all of which are available in concentrations of 2% or more.

Conclusion

Acne continues to be one of the most common diseases in the U.S. Treatments have greatly improved the quality of life for patients. In particular, isotretinoin has been useful in severe cases. However, the new iPledge program has limited the ease of prescribing medications. Submicrobial doses, topical dapsone, and adapalene 0.3% cream are promising new modalities.

Acne is a disease with substantial morbidity that can be ameliorated with treatment and that requires the partnership of the patient, physician, and pharmacist to achieve its greatest effectiveness.

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