Alan R. Shalita

New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group.

The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment-such as lasers and light therapy-and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

Isotretinoin therapy for acne: Results of a multicenter dose-response study

One hundred fifty patients with treatment-resistant nodulocystic acne were entered into a double-blind clinical study. Three different dosing levels (0.1, 0.5, 1.0 mg/kg/day) were used in equal-sized groups. In addition to the clinical response, the clinical side effects, the laboratory abnormalities, and the duration of the induced remissions were evaluated with each dose of the drug. There was a highly significant clinical response to treatment with all three dosages of isotretinoin. There was no significant difference in the clinical response between dosages. However, 42% of the patients who received 0.1 mg/kg/day of isotretinoin required retreatment with the drug. This finding, coupled with only minor differences in the clinical side effects and the laboratory abnormalities, indicates that higher dose levels of isotretinoin are indicated for treatment of nodulocystic acne.

Finasteride in the treatment of men with frontal male pattern hair loss

BACKGROUND Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne

Background: The androgen receptor (AR) is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic. Expansion of CAG repeats in the AR has clinical implications for human disease. Objective: Androgens influence androgenetic alopecia (AGA), hirsutism, and acne; the polymorphisms in CAG repeat length may affect the clinical course of patients with these cutaneous disorders. The purpose of this study is to test for an association between these disorders and CAG repeat length. Methods: We analyzed normal lymphocyte genomic DNA from a total of 48 men and 60 women. The CAG repeat region of the AR was amplified by polymerase drain reaction (PCR) and the products were sized on polyacrylamide gels. Results: In normal men and women controls, a range of 12 to 29 trinucleotide repeats was found, with men having 22 ± 4 (M ± SD), women 21 ± 3. Men with AGA had 19 ± 3, whereas women with AGA had 17 ± 3. Men with acne had 21 ± 3, whereas women had 20 ± 3; men with AGA and acne had 18 ± 4; and women with hirsutism had 16 ± 3. Women with a combination of at least two disorders also had 16 ± 3 trinucleotide repeats. Conclusion: Shorter CAG-repeat lengths may be associated with the development of androgen-mediated skin disorders in men and women. These data suggest that CAG-repeat length in AR may affect androgen mediated gene expression in hair follicles and sebaceous glands in men and women with these androgenic skin disorders.

Isotretinoin treatment of acne and related disorders: An update

In the one year since isotretinoin has been available in the United States for the treatment of severe, recalcitrant, nodulocystic acne, there has been extensive clinical verification of the reports of its dramatic efficacy in the treatment of this troublesome disease. Proper selection of patients, as well as treatment with adequate doses of drug for 3 to 5 months, will most often result in significant clinical improvement or total clearing. Although dosages of less than 1 mg/kg/day may produce a nearly equivalent degree of improvement with somewhat fewer or less severe side effects, the recommended daily dose remains 1 mg/kg/day because lower dosages are associated with more frequent relapses. In severe cases, the daily dosage may be increased to 2 mg/kg/day. Teratogenicity, elevation of serum triglycerides, liver function abnormalities, pancreatitis, and pseudotumor cerebri may all be associated with isotretinoin therapy and require close monitoring of the patient.

TRIVIAL OR TERRIBLE? THE PSYCHOSOCIAL IMPACT OF PSORIASIS

Background. Psoriasis remains a chronic disease with lesions that are often extensive and disfiguring. While the potential for psychosocial morbidity and impairment are recognized, the literature remains equivocal with regard to the prevalence and degree of this impairment.

Diet and acne

Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne. This article critically reviews the literature and discusses how dermatologists might address diet when counseling patients with acne. Dermatologists can no longer dismiss the association between diet and acne. Compelling evidence exists that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne, and the roles of omega-3 fatty acids, antioxidants, zinc, vitamin A, and dietary fiber remain to be elucidated. This study was limited by the lack of randomized controlled trials in the literature. We hope that this review will encourage others to explore the effects of diet on acne.

A double-blind study of the effectiveness of a 3% erythromycin and 5% benzoyl peroxide combination in the treatment of acne vulgaris

One hundred sixty-five subjects completed a 10-week, double-blind controlled study comparing the following: (1) a combination of 3% erythromycin and 5% benzoyl peroxide in a gel, (2) 5% benzoyl peroxide gel, (3) 3% erythromycin gel, and (4) the gel vehicle. The benzoyl peroxide gel and the erythromycin gel were superior to the control gel; however, the combination product was more effective than any of the others. This was true for both pustular and papular lesions, but the most dramatic effect was on combined inflammatory lesions, i.e., papules and pustules.

Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy

Summary Antibiotic resistance of the resident cutaneous bacterial flora is a well recognized consequence of systemic antibiotic therapy. In this study, we followed the development of antibiotic resistance of coagulase‐negative staphylococci (CNS), the most numerous aerobic bacteria found on the skin surface, during treatment with three topical antimicrobial agents used to treat acne vulgaris. Groups of 20 subjects received either topical erythromycin, benzoyl peroxide or a combination of the two for 16 weeks. After 12 weeks of treatment with erythromycin, the aerobic flora was dominated by S. epidermidis which was completely resistant to erythromycin. In addition there was an increase in resistance to clindamycin and tetracycline. Treatment with benzoyl peroxide and the combination of erythromycin and benzoyl peroxide resulted in a significant reduction in the number of aerobic bacteria without any change in the resistance pattern to erythromycin or other antibiotics.

Clinical applications of non-antimicrobial tetracyclines in dermatology.

There are many proposed non-antimicrobial actions of tetracyclines. Pathways affected by these medications are often overexpressed in various dermatologic conditions. Matrix metalloproteinases (MMPs) are enzymes best known for breaking down connective tissue proteins and are upregulated in conditions involving dermal destruction. Inhibition of MMPs by tetracyclines has been emphasized as one major non-antimicrobial action. Other effects of tetracyclines that are important in dermatology include inflammatory cytokine regulation, inhibition of leukocyte chemotaxis and activation, and anti-oxidation. Dermatologists have utilized the non-antimicrobial benefits of using tetracycline, through their success in treating disorders that do not have a primary infectious etiology such as rosacea. Even in acne, there is believed to be overactive inflammation to a normally commensal organism which is inhibited by tetracyclines. These medications have also been reported as successful in cases of less common skin conditions, such as pyoderma gangrenosum and bullous pemphigoid, both of which involve inflammation and dermal destruction which are inhibited by tetracyclines. The pathologic mechanisms of several dermatologic conditions are reviewed, followed by evidence of how tetracyclines and chemically modified tetracyclines (CMTs; structurally altered tetracyclines to remove antimicrobial properties while retaining non-antimicrobial properties) affect these pathways. Clinical testing of sub-antimicrobial doxycycline, in both 20mg twice daily and 40 mg once daily (controlled release; 30 mg immediate release, 10mg delayed release) forms, in rosacea and acne is reviewed as evidence that non-antimicrobial actions are valuable for treatment. Chemically modified tetracycline-3 (CMT-3) for Kaposis sarcoma is highlighted as the only clinical evidence available for CMTs in dermatology. Certain evidence of success using antimicrobial tetracyclines in inflammatory conditions of the skin is reviewed as well, because they are likely working through non-antimicrobial properties. Finally, dermatologic side effects of non-antimicrobial tetracyclines are assessed.