PROCEEDINGS PRACTICAL APPLICATIONS: CASE STUDY REVIEWS* Bernard A. Cohen, MD, FAAP

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1 PRACTICAL APPLICATIONS: CASE STUDY REVIEWS* Bernard A. Cohen, MD, FAAP A HEALTHY 4-WEEK-OLD INFANT WITH ACNE A 4-week-old infant was brought to the pediatrician s office by his parents following the appearance of a widespread papular-pustular rash affecting his head and neck (Figure 1). The lesions first began to appear soon after birth. The infant was otherwise healthy, and a complete physical examination and review of systems were normal. Watchful waiting, with reassurance of the parents, was selected as an appropriate management strategy for this patient. The lesions resolved spontaneously over the course of the following 4 weeks. Many newborns exhibit rash that is characterized by varying combinations of neonatal acne, seborrheic dermatitis, milia, miliaria, tinea versicolor, or sebaceous hyperplasia. Neonatal acne commonly develops within 2 to 3 weeks of birth, and may include inflammatory lesions (ie, papules, pustules and, in some cases, cysts) and noninflammatory lesions (ie, open and closed comedones). Acne in newborns and infants occurs as a consequence of increased sebaceous gland activity during the first few months of life, which may be caused by elevated endogenous adrenal activity in girls, and by endogenous adrenal and testicular activity in boys. In 1 *Based on proceedings from a satellite symposium held during the American Academy of Pediatrics Annual Meeting on October 28, 2007, in San Francisco, California. Director of Pediatric Dermatology, Johns Hopkins Children s Center, Professor, Dermatology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. Address correspondence to: Bernard A. Cohen, MD, FAAP, Professor, Dermatology and Pediatrics, Johns Hopkins University School of Medicine, East Baltimore Campus, 208 Brady Pediatric Dermatology, 600 North Wolfe Street, Baltimore, MD bcohen2@jhmi.edu. study, investigators performed clinical examinations and lesion counts in 22 infants (18 boys, 4 girls) with acne. 1 The mean age at the onset of lesions was approximately 3 weeks. Most of the patients exhibited papules and pustules, and some also exhibited open or closed comedones. Only 5 of the patients had comedonal acne only. A positive family history of severe acne was noted for only 3 of the patients. Skin biopsies were performed for 2 of the patients, revealing enlarged sebaceous follicles, sebaceous glands, and keratin plugging that were identical in appearance to the types of histological changes that are observed in preadolescent, adolescent, and adult acne. Six of the children were evaluated for the presence of Pityrosporum ovale, a fungal species that is associated with tinea versicolor, folliculitis (usually in immunocompromised individuals, but also occasionally in patients with intact immune function), and with a condition that has been referred to as benign cephalic pustulosis in the newborn (described in more detail later in this article). All of the P ovale smears were negative. On the basis of these findings, the investigators concluded that neonatal acne reflects transient sebaceous gland overactivity that is similar to that observed in older patients with acne, which probably occurs in response to endogenous androgens. These investigators also found that topical therapy helped to relieve acne symptoms for some patients. However, even without treatment, the acne had resolved in most patients within 1 to 3 months. Watchful waiting, with reassurance and education of the parents, are the principal treatments for neonatal acne. A low-risk topical preparation (eg, a topical antibiotic or topical benzoyl peroxide) is a reasonable option for some patients, especially if acne has persisted for more than 3 months. A short course of topical therapy may also help to reassure the parents. The most significant risk is skin irritation. Oral antibiotics may be prescribed for an otherwise healthy infant who is at high risk of scarring due to inflammatory acne. In Johns Hopkins Advanced Studies in Medicine 113

2 Figure 1.A Healthy 4-Week-Old Infant with Acne rare cases, neonatal acne may be caused by an inborn error of adrenal metabolism, and will be accompanied by other signs of hyperandrogenism. In a child with severe acne and normal growth parameters, assessment of bone age is a good screening study to exclude endocrinologic disorders. 2 During the past 10 to 15 years, several investigators have described a condition that has been referred to as neonatal cephalic pustulosis. It has been estimated that neonatal cephalic pustulosis may affect as many as 20% of newborns. 3 Neonatal cephalic pustulosis resembles acne in some respects, although differences in the clinical presentation between the 2 disorders have been noted. The lesions associated with neonatal cephalic pustulosis tend to be relatively uniform, with a widespread distribution that involves the cheeks, eyelids, and forehead. In some cases, the lesions may also extend to the scalp, neck, and the upper chest. As with neonatal acne, neonatal cephalic pustulosis tends to resolve after approximately 1 to 3 months, although it may persist for up to 12 months when there is involvement of the scalp. Several studies have linked neonatal cephalic pustulosis to skin colonization by the yeast genus Malassezia during the first few days after birth. In 1 study, the investigators cultured skin samples from 102 consecutive neonates with neonatal cephalic pustulosis. 4 At birth, 11 neonates and 36 mothers tested positive for Malassezia. At 3 weeks of age, 29 of 56 neonates (52%) and 18 of the mothers (32%) tested positive for Malassezia species. In addition, the investigators found a significant correlation between pustulosis and increased likelihood of Malassezia colonization among the affected infants. It has been hypothesized that these acneiform lesions may be caused by an inflammatory reaction that results from follicular occlusion by these lipophilic yeast species. 5 However, it is unclear whether infants with neonatal cephalic pustulosis represent a subset of patients with acne or whether this is actually a distinct condition. A HEALTHY ADOLESCENT MALE WITH SKIN OF COLOR This patient is a healthy 14-year-old black male with mixed comedonal and inflammatory acne (Figure 2). He had been using a nonprescription acne cleaner and scrub without improvement. He received a prescription for adapalene 0.1% cream, and was instructed to apply it every other night at bedtime. He was also given a benzoyl peroxide 5% wash to use before showering. The patient received instruction about skin care, including the use of nonirritating and noncomedogenic products. He was reminded not to expect clearing of his lesions within the first few days, and that treatment for several weeks would be required before his acne would improve sig- EVIDENCE-BASED PRACTICE RECOMMENDATION I. Practice Recommendation: Acne management guidelines developed by the American Academy of Dermatology recommend laboratory endocrinologic evaluation for children with acne who have signs of androgen excess (eg, body odor, axillary or pubic hair, and clitoromegaly). Determination of bone age using a hand film is a specific screening method for androgen excess that may be used before hormonal testing in prepubertal children. Name of AAFP-Approved Source: American Academy of Dermatology: Guidelines of Care for Acne Vulgaris Management. Specific Web Site of Supporting Evidence from Approved Source: _docs/clinicalresearch_acne%20vulgaris.pdf. Strength of Evidence: An expert consensus panel convened by the American Academy of Dermatology noted that there is little evidence to support routine endocrinologic evaluation for patients with acne, as most patients exhibit hormone concentrations within the normal range. The panel recommended hormonal testing for patients with other signs of hyperandrogenism. Determination of bone age was identified as an effective screening tool for selecting candidates for hormonal testing in prepubertal children. 114 Vol. 8, No. 4 March 2008

3 PROCEEDINGS Figure 2. Acne in a Healthy 14-Year-Old Boy with Darkly Pigmented Skin nificantly. At a follow-up examination 4 weeks later, his acne had begun to improve and he had not experienced significant skin irritation. His adapalene treatment was increased to once daily at bedtime. Patients of color who have acne are at substantial risk of postinflammatory hyperpigmentation and keloidal scarring.6,7 In many cases, it is the hyperpigmentation, and not the acne, that is the patient s primary complaint. Early and aggressive management is especially important in patients with darkly pigmented skin to prevent postinflammatory hyperpigmentation and scarring. Several studies have demonstrated that topical retinoids improve acne symptoms and hyperpigmentation in patients of color. The effects of tazarotene cream for the treatment of postinflammatory hyperpigmentation were examined in a double-blind, vehicle-controlled study of patients of color with acne.8 A total of 74 patients with darker skin (Fitzpatrick skin types III VI), mild-to-moderate acne, and postinflammatory hyperpigmentation were randomized to receive tazarotene 0.1% cream or vehicle for up to 18 weeks. Tazarotene treat- Johns Hopkins Advanced Studies in Medicine ment significantly improved overall disease activity, area of hyperpigmentation, and intensity of hyperpigmentation. On a pigmentation intensity scale of 0 (no hyperpigmentation) to 5 (severe, prominent, and dense hyperpigmentation), tazarotene was associated with a mean improvement of 1.1 grades from baseline versus 0.5 grades with vehicle (P =.04). The results obtained from a representative patient at baseline and after 6 and 18 weeks of treatment are shown in Figure 3, demonstrating marked improvement with tazarotene. In a second study, Taylor et al examined the efficacy of a topical retinoid, in combination with topical benzoyl peroxide and clindamycin, in a racially diverse group of patients from a community setting.9 All patients were treated with a topical gel of clindamycin 1% and benzoyl peroxide 5%, and were randomized to additional therapy with 1 of 3 different topical retinoids tretinoin microsphere 0.04%, tretinoin microsphere 0.1%, or adapalene gel 0.1%. Patients in all 3 treatment groups exhibited significant decreases from baseline in acne severity, including counts of both noninflammatory and inflammatory lesions. In patients of color, all 3 retinoids also improved postinflammatory hyperpigmentation. The effectiveness of retinoid treatment must be balanced against the risk of skin irritation, as severe irritation may exacerbate hyperpigmentation. The risk of irritation is reduced by instructing the patient to apply the topical retinoid 2 to 3 days a week for the Figure 3. Effects of Tazarotene on Acne and Hyperpigmentation in a Patient with Darkly Pigmented Skin From left to right, the images show acne lesions and hyperpigmentation at baseline and after 6 weeks and 18 weeks of treatment. Reprinted with permission from Grimes and Callender. Cutis. 2006;77:

4 Figure 4. A Healthy 10-Year-Old Girl with an Asymptomatic Eruption for 3 Months, Unresponsive to Nonprescription Hydrocortisone first few weeks, increasing to daily treatment after the patient s skin has adapted to the retinoid. A 10-YEAR-OLD GIRL WITH PERIORIFICIAL DERMATITIS A healthy 10-year-old girl was referred to a dermatologist for evaluation of an asymptomatic facial eruption that had developed 3 months previously (Figure 4). Her primary care physician had attempted to treat the eruption using an over-the-counter hydrocortisone product, without noticeable improvement. She was diagnosed with periorificial dermatitis, with a typical clinical presentation that included the presence of uniform red papules without comedones or lichenificiation around the mouth, sparing of the vermillion, and involvement of the cheek within the nasolabial folds. She was treated with oral erythromycin 200 mg per day. She did not improve after 1 month of oral erythromycin, but the lesions resolved after a second month of treatment, and the antibiotic was discontinued. She exhibited a brief, mild exacerbation of dermatitis following the discontinuation of antibiotic therapy. Periorificial dermatitis is a childhood variant of rosacea that typically presents as an acneiform eruption around the mouth, nose, or eyes, and that is often accompanied by pruritus or burning. 10 Few studies have examined the characteristics of periorificial dermatitis in pediatric patients. Nguyen and Eichenfield performed a retrospective chart review, with telephone follow-up, of 79 patients with periorificial dermatitis between the ages of 6 months and 18 years. 10 The average time between symptom onset and diagnosis was 8 months. Perioral lesions were noted for 70% of the patients, periocular lesions for 25%, perinasal lesions for 43%, and perivulvar lesions for 1%. Most of the patients (72%) had previously been treated with topical or intranasal steroids. Topical metronidazole cream was effective for many patients, with resolution of symptoms occurring after an average of 7 weeks. Although intranasal, topical, or oral steroids have been implicated in many patients, most of our patients denied a history of exposure to topical or systemic steroids. A biopsy is not necessary for the diagnosis of this condition. Topical metronidazole and other topical antibiotics may improve symptoms. However, patients with perioral dermatitis often exhibit significant skin irritation and may be unable to tolerate topical therapy. Oral erythromycin is an effective EVIDENCE-BASED PRACTICE RECOMMENDATION II. Practice Recommendation: Acne in patients of color is associated with a high risk of scarring and postinflammatory hyperpigmentation. Topical retinoids are effective for the treatment of acne and postinflammatory hyperpigmentation in these patients. Name of AAFP-Approved Source: Jacyk WK. Adapalene in the treatment of African patients. J Eur Acad Dermatol Venereol. 2001;15(suppl 3): Specific Web Site of Supporting Evidence from Approved Source: entrez?db=pubmed&cmd=showdetailview&termto Search= &ordinalpos=10&itool=Entrez System2.PEntrez.Pubmed.Pubmed_ResultsPanel. Pubmed_RVDocSum. Strength of Evidence: Individuals with darkly pigmented skin are at high risk of acne scarring and hyperpigmentation, yet few clinical studies have specifically assessed acne treatment in these patients. A recent study examined the effects of topical adapalene 0.1% gel in 65 black South African patients with acne. Topical retinoid treatment reduced the number of hyperpigmented macules and the density of hyperpigmentation in approximately 66% of the patients. 116 Vol. 8, No. 4 March 2008

5 alternative for prepubertal children, who are less likely to develop gastritis than older patients. REFERENCES 1. Katsambas AD, Katoulis AC, Stavropoulos P. Acne neonatorum: a study of 22 cases. Int J Dermatol. 1999;38: Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol. 2007;56: Cantatore-Francis JL, Glick SA. Childhood acne: evaluation and management. Dermatol Ther. 2006;19: Bernier V, Weill FX, Hirigoyen V, et al. Skin colonization by Malassezia species in neonates: a prospective study and relationship with neonatal cephalic pustulosis. Arch Dermatol. 2002;138: Bergman JN, Eichenfield LF. Neonatal acne and cephalic pustulosis: is Malassezia the whole story? Arch Dermatol. 2002;138: Callender VD. Considerations for treating acne in ethnic skin. Cutis. 2005;76: Taylor SC. Cosmetic problems in skin of color. Skin Pharmacol Appl Skin Physiol. 1999;12: Grimes P, Callender V. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis. 2006;77: Taylor SC. Maximizing combination therapy in ethnic skin. Paper presented at 31st Hawaii Dermatology Seminar; March 3-9, 2007; Maui, Hawaii. 10. Nguyen V, Eichenfield LF. Periorificial dermatitis in children and adolescents. J Am Acad Dermatol. 2006;55: Johns Hopkins Advanced Studies in Medicine 117