Newer therapies offer options in acne treatment

SAN FRANCISCO — New insights into the presentation and biology of acne and the introduction of novel therapies have expanded physicians’ ability to treat children with this condition, explained a speaker here at the 2010 American Academy of Pediatrics National Conference and Exhibition.

Albert C. Yan, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania School of Medicine, said that acne can occur at all ages and treatment approaches should vary according to the individual patient.

He noted neonatal acne presents as benign, monomorphic eruptions of papules and pustules on the cheeks, forehead and scalp of infants aged younger than 6 months. Persuasive evidence, implicates Malassezia in the development of this condition. Although treatment with antifungals is effective, the condition can resolve on its own within a few weeks, Yan said.

Infantile or toddler acne is also a serious problem in those typically aged older than 6 months. Comedones, papules and inflammatory lesions carry the potential for permanent scarring. Recent studies indicate that infantile acne is rare, but the disease course may last more than 1 year in most cases, and the potential for residual scarring warrants appropriate therapeutic intervention.

Topical treatments are appropriate for infantile acne, as are oral antibiotics, such as erythromycin derivatives or trimethoprim. Additionally, isotretinoin in low doses may be beneficial in some cases. Studies also demonstrate a correlation between acne at this early age and the appearance of more severe acne during preadolescence and adolescence, explained Yan.

Adolescent acne

Although acne is common among adolescents and young adults, treatment can be tricky in this population. Yan noted that providing simple explanations of the background and pathophysiology of the disease can be helpful in improving compliance by helping adolescents understand why certain therapies are appropriate and keeping them motivated to use them.

Physicians should also stress the need for patience and the fact that acne can only be controlled, not cured, at least until patients outgrow the condition. Highlighting treatment adherence is important and anticipating and explaining possible adverse events associated with certain treatments may improve patients’ willingness to follow a treatment regimen, Yan said.

Benzoyl peroxide is an attractive treatment option because it is inexpensive, effective and can minimize the development of antibiotic-resistant strains of Propionibacterium, Yan said. Cleansers usually work best for chest and back areas, while both cleansers and leave-on products are reasonable options for the face. Patients should be warned, however, about the medication’s potential for bleaching fabric.

Yan said patients also respond well to topical retinoids and pointed out that physicians can recommend milder agents for patients with sensitive skin and minimize irritation by utilizing a short-contact approach (leaving the agent on for about 30 to 60 minutes and then washing it off) until patients are able to tolerate overnight applications more consistently.

Other acceptable therapies include oral antibiotics. Yan said he favors the use of doxycycline and minocycline over erythromycin and tetracycline due to current resistance patterns among P. acnes. These can be particularly useful for patients with more significant inflammatory acne, although physicians should consider resistance issues before prescribing.

Oral contraceptives can be a useful agent to improve acne in girls and women. Yan noted, however, that the treatment is slower-acting, with studies showing about 83% efficacy after 3 months. Currently, Ortho-Tricyclen, Estrostep and Yaz have FDA-approval for treatment of acne, but prescribing other oral contraceptives (off-label) will usually have similar benefits, Yan said.

Studies traditionally preclude diet as a factor in acne development, but early pilot studies suggest that a low glycemic index diet may have a beneficial effect on acne. The subject, however, remains controversial and further data are required.

Novel therapies

Research does back the efficacy of other novel treatment approaches to acne, according to Yan. Photodynamic therapy, for example, exhibits potential and is still being studied to determine which form of the treatment is most beneficial.

New vehicles, such as microsphere technologies and hydrogel formulations, may boost efficacy while minimizing irritation, according to Yan. Further, foams and emollient-based treatments might ease use by increasing spreadability. Yan also noted that having a wider variety of treatments allows patients to select a form that may be more comfortable and easier to use and thereby improve compliance.

Additionally, while not a completely new molecule, dapsone for topical treatment of acne is a novel addition to the acne armamentarium, said Yan. It is available in a 5% concentration solvent microparticulate gel. Physicians should note, however that using the product at the same time as other products, such as topical benzoyl peroxide, retinoids and sulfacetamides may produce a temporary yellow-orange reside that can be wiped off.

Alternate dosing regimens for systemic therapy may also provide efficacy, according to Yan, with off-label subantimicrobial dosing of doxycycline appearing to reduce comedones and inflammatory lesions by using 20 mg po BID dosing and 40 mg po once daily dosing.

Surgical modalities may improve acne scarring. Fractional laser resurfacing is particularly interesting, said Yan, because it is less traumatic than traditional resurfacing techniques and allows for more rapid post-laser healing.

Yan also said a number of other agents that target other acne pathogenetic pathways are being evaluated by investigators that may have future clinical utility, including those that target 5-alpha-reductase type 1-inhibitors, leukotrienes, prostaglandins, interleukins 6 and 8, peroxisome proliferators-activated receptors (PPARs) and toll-like receptors (P. acnes and bacterial peptidoglycans). — by Melissa Foster

For more information:

• Yan AC. Acne update. F2045. Presented at: 2010 AAP National Conference and Exhibition; Oct. 2-5, 2010; San Francisco.

Acne vulgaris is seen in 80 to 95% of adolescents, though as Dr. Yan points out, can be seen in infants and younger children as well. The Malassezia-associated pustular eruption seen in neonates is not really acneiform, and has been termed "neonatal cephalic pustulosis" to differentiate from the rarer comedonal and inflammatory acne seen in infants ans children. Acne is increasingly common in 8 to 11 year olds, often preceding other signs of puberty. While it may be important to stress that patience can be helpful in allowing acne medicines the time to work, physicians should recognize when acne is moderate to severe with scarring risks, and not delay or withhold treatment in hopes of the patient "outgrowing it." By recognizing significant acne early, one or more of the many interventions discussed by Dr. Yan can be intitated to control or minimize acne's physical and psychological effects.

– Lawrence F. Eichenfield, MD
Infectious Diseases in Children Editorial Board

Dr. Yan's presentation reminds us that acne can affect any age group and signifies different risks at different ages. Neonatal acne, which occurs shortly after birth, is generally transient, may be related to the presence of Malazessia yeasts, and usually poses little concern or long term risk. In contrast, infantile acne, which generally develops after 6 mos of age, often has a prolonged course and may lead to scarring and higher risk for severe acne later in life. Clinicians should take an appropriately aggressive therapeutic stance with infantile acne, utilizing topical agents such as benzoyl peroxide, antibiotics and retinoids as necessary to prevent scarring. Unfortunately, young skin may be less tolerant of these agents given the relative lack of sebum in this age group. Oral antibiotics may be required, and rarely even systemic isotretinoin therapy may be necessary. However, health care providers must keep in mind that tetracyclines, which are the most commonly used oral antibiotics in adolescence, are contraindicated in children less than 8 years of age due to their detrimental effects on developing teeth.

Acne in slightly older children (e.g. onset from 1 to 6 years of age) may signify an underlying hormonal abnormality, and such children need a thorough evaluation to rule out excess androgen production from a pathological state. Classic mild comedonal acne can be observed in children as young as 7 years of age, and if no clinical signs of hyperandrogenism are present, hormonal work up is not required.

The classic teaching that acne is the direct result of infection with P. acnes has been supplanted with more complex models invoking the importance of hormonal sensitivity and host response to P. acnes as key factors. Oral contraceptive pills are useful in many women, and spironalactone, an androgen receptor antagonist, can also be used as effective hormonal therapy in females. Inhibitors of enzymes which convert weaker androgens to more potent forms may also eventually prove beneficial. Investigators are currently interested in the benefits of agents which control host immune response to infectious agents such as toll-like receptors and modification of inflammatory mediators including leukotrienes, prostaglandins and interleukins. Future therapies may well focus on these agents.

For the present, practitioners continue to rely on drugs which inhibit P. acnes growth. These include oral doxycycline, minocycline, and trimethoprim-sulfamethoxazole. Patients must be aware of drug side effect and the slow onset of activity. Bacterial resistance remains a concern, and the use of topical benzoyl peroxide agents, either in leave-on or wash formulations, helps discourage the development of resistance. Topical retinoids are particularly useful in encouraging normal epithelial cell keratinization, and decreasing comedone formation. Patient care must always be individualized, factoring in safety patient tolerance and comliance.

– Sheila Fallon Friedlander, MD
Infectious Diseases in Children Editorial Board

Follow the PediatricSuperSite.com on Twitter.