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Ethnic skin: Kids are not just little people
Ethnic Skin: Kids Are Not Just Little People Lisa Y. Shen MD, Brandi Kenner-Bell MD, Janelle Ricketts MD, Roopal V. Kundu MD PII: DOI: Reference:
S0738-081X(16)30180-8 doi: 10.1016/j.clindermatol.2016.07.003 CID 7076
To appear in:
Clinics in Dermatology
Please cite this article as: Shen Lisa Y., Kenner-Bell Brandi, Ricketts Janelle, Kundu Roopal V., Ethnic Skin: Kids Are Not Just Little People, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.07.003
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Lisa Y Shen, MD1
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Ethnic Skin : Kids Are Not Just Little People
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Brandi Kenner-Bell, MD 1, 2
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Janelle Ricketts, MD3
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Roopal V. Kundu, MD1
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,
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Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
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Department of Dermatology, University of Connecticut Health Science Center, Farmington, CT
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Corresponding Author:
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Roopal V. Kundu, MD Northwestern University Feinberg School of Medicine Department of Dermatology 676 N St. Clair Street, Suite 1600 Chicago, IL 60611 Phone: 312- 926-4926 Fax: 312-695-0664 Email: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT: There are numerous skin conditions that occur commonly in children with ethnic skin, including
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vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae,
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pseudofolliculitis barbae, and keloids. Though these conditions occur in both children and adults, children may have different patterns of clinical presentation and response to therapy. In caring
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for such patients, important treatment considerations include side effects of systemic medications
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and tolerability of invasive procedures. Quality of life is an important measure and should not be
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compromised by either the skin disease or its treatment.
ACCEPTED MANUSCRIPT Numerous skin conditions are common in the pediatric patient population with Fitzpatrick III-VI skin types, including vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis
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nuchae, pseudofolliculitis barbae, and keloids. Many of these conditions also occur in adults, but
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special considerations are made in the treatment of children in terms of side effects of systemic medications and tolerability of invasive procedures.
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How does the clinical presentation of vitiligo differ in children and adults?
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Vitiligo is an acquired disorder of cutaneous depigmentation affecting approximately 1% of the world population.1, 2 (Figure 1) It is especially relevant to the pediatric population, as the
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condition manifests before age 20 in about half of affected individuals, with a mean age of onset
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of childhood vitiligo ranging between 4 and 8 years.3-7
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There are several notable differences between childhood-onset and adult-onset vitiligo, including a higher incidence of segmental vitiligo,3, 4, 8 (Figure 2) and a slower rate of progression among
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children.9, 10 Another epidemiologic finding unique to the pediatric population includes a
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possible higher prevalence in girls,3 5, 7, 11 but this was not observed in two Chinese and Korean populations in which the boys and girls were affected with equal frequency.6, 12 Though the majority of cases occur sporadically, there is a greater likelihood of having a positive family history of vitiligo reported in children.3, 5, 13
Is laboratory testing warranted in patients with vitiligo? In the evaluation of suspected vitiligo, a thorough history and physical exam including examination with a Wood’s lamp is typically sufficient in establishing the diagnosis. Skin biopsies are rarely performed especially in the pediatric population, though biopsies of lesional
ACCEPTED MANUSCRIPT and normal skin may be warranted if the diagnosis is in question or infectious, postinflammatory,
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or neoplastic mimickers should be considered. (Table 1)
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Screening for associated autoimmune conditions should be considered in both adults and children, especially in the context of a positive family history. Autoimmune conditions reported
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to be associated with vitiligo include autoimmune thyroiditis, insulin-dependent diabetes mellitus,
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pernicious anemia, alopecia areata, and systemic lupus erythematosus.4, 14 (Table 2) Consequently, various experts have proposed screening labs to include a complete blood count,
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fasting blood glucose, thyroid stimulating hormone, thyroid autoantibodies, antiparietal cell antibodies, and antinuclear antibodies. 15-17 A recent retrospective study of 79 children with
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nonsegmental vitiligo found a prevalence of thyroid lab abnormalities (TSH or thyroid
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autoantibodies) to be 25%, with subclinical hypothyroidism being the most frequent diagnosis.18 At our institutions, the authors typically only check thyroid studies (thyroid stimulating hormone
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with reflexive thyroxine and anti-thyroid antibodies) if no other clinically significant findings
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exist, given the low prevalence of other autoimmune diseases. In one study, 13 of 121 pediatric patients demonstrated thyroid parameter alterations; however none of the patients with segmental vitiligo had thyroid alterations, suggesting that this subset of patients may not require screening labs.19 Another group found a similar protective association of segmental vitiligo and lack of thyroid alterations.20
How does the age of the patient affect the treatment of vitiligo? The therapeutic options for childhood vitiligo are much the same as those for adults, though age is an important consideration in deciding whether to treat and which treatment modality to select.
ACCEPTED MANUSCRIPT In general, children seem to have a better response to treatment than adults.12, 15, 21, 22 With increasing age and development of interpersonal relationships at school, the condition may have
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significant psychosocial implications which further drive motivation to treat. In counseling
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young patients and their parents, it is important to establish realistic expectations for treatment outcomes. Parents should be advised that most patients will not achieve 100% repigmentation
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and that a response of 50-75% repigmentation is the goal, with acral sites, lesions with
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leukotrichia (Figure 3), and segmental distributions of vitiligo being most refractory to medical therapies.23, 24 For all patients, the use of broad spectrum sunscreens should be encouraged to
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prevent sunburn of the depigmented areas and more prominent contrast between pigmented and nonpigmented skin. Cosmetic camouflage is another useful tool to improve the appearance of
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unevenly pigmented skin with resulting improvement in quality of life.25 Patients ages 8-16 may
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also benefit from the Camp Discovery program, a week long camp experience sponsored by the
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conditions.
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American Academy of Dermatology, where they may meet other children with similar skin
Topical corticosteroids are among the most commonly utilized therapies with response rates ranging from 41% to 64%.12, 15, 26, 27 High potency corticosteroids (ie clobetasol proprionate) have been reported to demonstrate better response in darker skinned patients;28 however, the duration of therapy may be limited by side effects including epidermal atrophy, telangiectasia, hypertrichosis, and corticosteroid-induced acne, 26, 27, 29. The use of topical corticosteroids is limited to focal areas of vitiligo with affected body surface area less than 20%. Some clinicians cycling class I corticosteroids with class V steroids for 6-8 week cycles or hybrid 2-day/5-day therapy to minimize risk of local side effects.30 Others have observed that high- versus
ACCEPTED MANUSCRIPT moderate-potency corticosteroids had no statistically significant difference in either response rates or occurrence of local side effects,27. Topical tretinoin 0.025% or 0.05% in addition to
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topical corticosteroids was reported to be more effective than topical corticosteroids with vehicle
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in 55% of patients, without adverse effects noted in either group.31 Topical calcipotriene has also been proposed as a useful adjunct to topical corticosteroids with 10 out of 12 pediatric
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patients achieving a mean of 95% repigmentation, 4 of whom previously did not respond to over
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3 months of topical corticosteroid alone.32 Systemic corticosteroids are not advised, as the risks of systemic side effects in children outweigh the benefits. In adults with worsening vitiligo, use
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of either systemic corticosteroids or minocycline may help to halt spread of the disease.33 A randomized controlled study conducted in 50 subjects with actively spreading vitiligo showed
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oral pulse dexamethasone 2.5 mg twice weekly versus minocycline 100 mg daily for 6 months,
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were similarly effective in significantly reducing vitiligo disease activity scores.33
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Topical calcineurin inhibitors (tacrolimus 0.03% or 0.1%, pimecrolimus 0.1%) are another
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therapeutic option in patients over the age of 2 years. Of note, only tacrolimus 0.03% ointment is approved for children 2 to 15 years of age. A double-blind, randomized controlled trial in childhood vitiligo patients compared the effects of twice daily application of clobetasol propionate 0.05% ointment versus tacrolimus 0.1% ointment on similar lesions located on opposite sides of the body with no statistically significant difference in response rates between the two treatments.29 Other studies with tacrolimus have similarly demonstrated good results (>75% repigmentation in 59%),34 with best results in pediatric patients with segmental involvement of the head and neck lesions as well as darker Fitzpatrick skin types. 35, 36 Pimecrolimus 1% cream has also been evaluated as an effective treatment for childhood
ACCEPTED MANUSCRIPT segmental vitiligo.37 Given the lack of side effects when compared to topical corticosteroids, we recommend that topical calcineurin inhibitors be considered as maintenance topical therapy to
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avoid long term exposures to topical corticosteroids.
Narrowband ultraviolet B light (NBUVB) phototherapy (ranging from 311 to 313nm) is one of
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the most effective therapies when large areas of the body are affected or if first line topical
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therapies are ineffective. NBUVB is much more effective in patients under the age of 20 as compared to older adults;38 however there must be proper selection of pediatric patients who are
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able to tolerate being in a phototherapy unit. Depending on the maturity and motivation of the child, patients as young as 5 years old have been able to undergo phototherapy treatment.39, 40
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Response rates (>75% repigmentation) after 1 year of therapy range from 44-75%.39-42
308 nm excimer laser is a focal therapy that works in a similar fashion to NBUVB. Though
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there are few studies done in children, one group demonstrated >50% repigmentation in 50% of
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treated lesions of childhood vitiligo and 75% repigmentation in 12.5% of treated lesions.43 Another study treated 49 patients ages 6-14 with excimer laser twice weekly in conjunction with unilateral application of topical 1% pimecrolimus cream twice daily resulting in greater improvement within the lesions treated with the combination treatment.44
In contrast, photochemotherapy with UVA (PUVA) generally is not recommended for children under 12 years of age,45 as it has not been shown to be as effective in children as compared to adults.4 The potential adverse effects of PUVA, including nausea, photosensitivity, cataract formation, and dyspigmentation, also limit its use in adults. Several studies comparing PUVA
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efficacy than PUVA in the treatment of vitiligo.46, 47
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Surgical therapies are available for older children who do not respond to medical treatments, particularly in subtypes of vitiligo that have poor response rates including segmental and acral
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vitiligo. Prerequisites for surgical therapy include stability of the affected area of skin
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recommended for at least 6-12 months and lack of previous Koebner reactions. Two main categories of procedures include tissue grafting (ie. suction blisters, split thickness skin grafts,
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punch grafts) and cellular grafting in which melanocytes are isolated and expanded from a thin skin sample and transplanted onto abraded/denuded areas of vitiligo. Suction blister grafting was
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performed in 15 recalcitrant patches of stable vitiligo in 10 children (ages 11-19 years) and noted
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that 8 of the 10 children attained more than 75% pigmentation.48 Others performed autologous noncultured cellular grafting in 25 children and reported 62% and 75% with excellent
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repigmentation (defined as 95%-100% improvement) in the segmental and focal vitiligo groups,
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respectively.8 Still another group reported that transplantation of autologous cultured pure melanocytes works as well in children and adolescents as it does in adults.49
Depigmentation therapies are generally not recommended in children, because the child would face a lifetime of sun avoidance from an early age. In adults, depigmentation can be accomplished in patients with widespread involvement. A psychologic evaluation prior to treatment is recommended to address the potential psychosocial ramifications of changing skin color.
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Which age groups are affected by progressive macular hypomelanosis? Progressive macular hypomelanosis is a condition first described by Guillet et al which presents
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as asymptomatic ill-defined hypopigmented macules favoring the trunk.50 (Figure 4) It commonly occurs in adolescents and young adults and frequently occurs in darker skin types
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(Fitzpatrick skin types III-IV).51 The diagnosis is supported by the presence of red follicular fluorescence within the hypopigmented skin upon Wood’s lamp examination, and
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Propionibacterium acnes has been isolated within lesional skin.52-54 It is reasonable that a first-
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line approach to treatment in children includes topical benzoyl peroxide and clindamycin.55 If topicals alone are not effective, natural sunlight exposure or phototherapy (narrow band UVB
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preferred over UVA) may be considered as a more effective adjunct. 56-59 In older children and young adults, oral tetracyclines have been reported as an effective treatment though patients
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should be cautioned against concomitant use of phototherapy or heavy sun exposure given the
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risk of photosensitivity.54, 60-62
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What accounts for pityriasis alba commonly affecting children but not adults? Pityriasis alba is an entity that commonly manifests as discrete minimally scaly, hypopigmented patches on the head, neck, and proximal extremities of darkly pigmented children. (Figure 5) It has been frequently associated with atopic dermatitis, xerosis, and sun exposure.63-65 It is rarely seen in post-pubertal adolescents and young adults due to the proposed protective effect of sebum.66 The first line of treatment (and prevention of further episodes) involves rigorous sun protection and dry skin care with liberal use of emollients.63, 66 Medical therapies include mild nonhalogenated topical corticosteroids (hydrocortisone acetate 1% or desonide 0.05%) and topical calcineurin inhibitors (tacrolimus 0.1% or pimecrolimus 1%).67-69
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What factors contribute to the development of acne keloidalis nuchae (synonyms: folliculitis
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keloidalis, folliculitis nuchae)?
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Acne keloidalis nuchae (AKN) is a progressive scarring folliculitis and perifolliculitis, resulting in fibrotic papules and nodules usually affecting the nape of the neck and occipital scalp.70
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(Figure 6) It is most frequently seen in African-American postpubertal boys and men and is
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thought to be caused by a combination of factors including skin penetration of closely shaven hairs with resulting inflammation and/or mechanical irritation from shirt collars or helmets.71 In
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a study of African school children, the prevalence of AKN was highest in older high school boys who have frequent haircuts (<4 week intervals).72 Acne mechanica (consisting of inflammatory
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papules, pustules, cysts, and nodules in areas of friction) has been proposed as a precursor to
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AKN in adolescents, as demonstrated by the higher prevalence of nuchal acne mechanica (and absence of AKN) in high school football players as opposed to a higher prevalence of AKN in
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older collegiate and professional football players.73 This suggests that early intervention is
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warranted in an effort to prevent disease progression and future keloids. The first priority in treatment is education to avoid mechanical irritation of the skin and close haircuts with clippers or razors. Potent corticosteroids (class I and II) in addition to topical antimicrobials(clindamycin, chlorhexadine) are the mainstays of topical treatments.70, 74 Topical retinoids may also be used as an adjunct. Treatment for more advanced or refractory disease may include intralesional triamcinolone injections (ranging from 5mg/cc to 40mg/cc), systemic antibiotics, laser hair reduction, and surgical excision;70, 75, 76 however, the ability of adolescents to withstand these more invasive procedures may be a concern.
ACCEPTED MANUSCRIPT What is the optimal therapeutic approach to pseudofolliculitis barbae? Pseudofolliculitis barbae is an inflammatory condition of the hair follicles commonly occurring
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on the face and neck of men with curly, coarse hair. It is thought to be a result of traumatic hair
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removal practices, such as shaving and plucking, with subsequent inflammation due to the cut hairs curling in on themselves causing a foreign body-like reaction. 71, 77 It can affect women, if
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they are using hair removal techniques on the face, axillae, and suprapubic areas.74 In women
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with this condition, the clinician should ask about menstrual history, presence of hirsutism, and possible hormonal abnormalities as indicated.77 Although somewhat controversial, our group
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suggests adjustment of hair removal practices may include avoiding shaving entirely, not holding the skin taut while shaving, or using single blade razors or electric clippers/shavers to avoid too
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close of a shave. Topical therapy includes use of a mild- to medium-potency topical
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corticosteroid after shaving in combination with benzoyl peroxide or clindamycin.74, 78 A topical retinoid may be used nightly, as well. In women, topical eflornithine cream to slow the growth
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of hair in the affected sites alone or in combination with electrolysis or laser hair removal may be
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effective in reducing the inflammatory papules.79
How does age impact the development of keloids and their management? Keloids are progressive overgrowths of scar tissue developing months to years after trauma and are notoriously difficult to treat. In children ,they most commonly occur on the ear lobes after ear piercing. (Figure 7) Keloids are more likely to develop when the ears are pierced after age 11, and we recommend ear piercing before the age of seven, particularlyin children with the darker skin types more predisposed to keloids.80 There is also weak evidence for the use of silicone gel sheeting in prevention of keloids.81 First-line therapy includes intralesional steroid
ACCEPTED MANUSCRIPT injection (triamcinolone 10 to 40mg/cc).74, 82 Though surgery is generally not recommended, keloids on the ear lobes do seem to respond to surgical excision in combination to intralesional
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triamcinolone injection.83 For larger keloids, in reliable and compliant adults who have been
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recalcitrant to intralesional steroid injections, treatment options may include surgical excision
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followed by radiation therapy, as well as topical or intralesional chemotherapy.84, 85
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CONCLUSIONS
Children with ethnic skin are more susceptible to or more affected by certain skin conditions
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such as vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae, pseudofolliculitis barbae, and keloids. Additionally, our young patients require unique treatment
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considerations with safety and treatment tolerability as main priorities. Care should be taken to
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offer therapies that are safe and effective without being an excessive burden to the patient and parents. Ultimately, the goals of treatment should include improving quality of life and self-
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confidence at a critical time when children and adolescents are establishing their identities and
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forming interpersonal relationships.
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Santos JB, Almeida OL, Silva LM, et al. Efficacy of topical combination of benzoyl peroxide 5% and clindamycin 1% for the treatment of progressive macular hypomelanosis: a randomized, doubleblind, placebo-controlled trial. An Bras Dermatol. 2011;86:50-54. Montero LC, Belinchon I, Toledo F, et al. Progressive macular hypomelanosis, excellent response with narrow-band ultraviolet B phototherapy. Photodermatol Photoimmunol Photomed. 2011;27:162-163. Sim JH, Lee DJ, Lee JS, et al. Comparison of the clinical efficacy of NBUVB and NBUVB with benzoyl peroxide/clindamycin in progressive macular hypomelanosis. J Eur Acad Dermatol Venereol. 2011;25:1318-1323. Kim MB, Kim GW, Cho HH, et al. Narrowband UVB treatment of progressive macular hypomelanosis. J Am Acad Dermatol. 2012;66:598-605. Perman M, Sheth P, Lucky AW. Progressive macular hypomelanosis in a 16-year old. Pediatr Dermatol. 2008;25:63-65. Tierney EP, Hamzavi I. Progressive macular hypomelanosis arising in a young African American woman in association with pregnancy and a toxic nodular goiter. J Drugs Dermatol. 2010;9:393-397. Cavalcanti SM, Querino MC, Magalhaes V, et al. The use of lymecycline and benzoyl peroxide for the treatment of progressive macular hypomelanosis: a prospective study. An Bras Dermatol. 2011;86:813-814. Wells BT, Whyte HJ, Kierland RR. Pityriasis alba: a ten-year survey and review of the literature. Arch Dermatol. 1960;82:183-189. Darnell TF. Relationship of pityriasis alba to eczema. South Med J. 1962;55:183-184. Blessmann Weber M, Sponchiado de Avila LG, Albaneze R, et al. Pityriasis alba: a study of pathogenic factors. J Eur Acad Dermatol Venereol. 2002;16:463-468. O'Farrell NM. Pityriasis alba. AMA Arch Derm. 1956;73:376-377. Rigopoulos D, Gregoriou S, Charissi C, et al. Tacrolimus ointment 0.1% in pityriasis alba: an open-label, randomized, placebo-controlled study. Br J Dermatol. 2006;155:152-155. Fujita WH, McCormick CL, Parneix-Spake A. An exploratory study to evaluate the efficacy of pimecrolimus cream 1% for the treatment of pityriasis alba. Int J Dermatol. 2007;46:700-705. Jadotte YT, Janniger CK. Pityriasis alba revisited: perspectives on an enigmatic disorder of childhood. Cutis. 2011;87:66-72. Quarles FN, Brody H, Badreshia S, et al. Acne keloidalis nuchae. Dermatol Ther. 2007;20:128-132. Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae. Dermatol Clin. 2003;21:645-653. Khumalo NP, Jessop S, Gumedze F, et al. Hairdressing is associated with scalp disease in African schoolchildren. Br J Dermatol. 2007;157:106-110. Knable AL, Jr., Hanke CW, Gonin R. Prevalence of acne keloidalis nuchae in football players. J Am Acad Dermatol. 1997;37:570-574. Kundu RV, Patterson S. Dermatologic conditions in skin of color: part II. Disorders occurring predominately in skin of color. Am Fam Physician. 2013;87:859-865.
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Esmat SM, Abdel Hay RM, Abu Zeid OM, et al. The efficacy of laser-assisted hair removal in the treatment of acne keloidalis nuchae; a pilot study. Eur J Dermatol. 2012;22:645-650. Bajaj V, Langtry JA. Surgical excision of acne keloidalis nuchae with secondary intention healing. Clin Exp Dermatol. 2008;33:53-55. Quarles FN, Brody H, Johnson BA, et al. Pseudofolliculitis barbae. Dermatol Ther. 2007;20:133-136. Cook-Bolden FE, Barba A, Halder R, et al. Twice-daily applications of benzoyl peroxide 5%/clindamycin 1% gel versus vehicle in the treatment of pseudofolliculitis barbae. Cutis. 2004;73:18-24. Xia Y, Cho S, Howard RS, et al. Topical eflornithine hydrochloride improves the effectiveness of standard laser hair removal for treating pseudofolliculitis barbae: a randomized, double-blinded, placebo-controlled trial. J Am Acad Dermatol. 2012;67:694-699. Lane JE, Waller JL, Davis LS. Relationship between age of ear piercing and keloid formation. Pediatrics. 2005;115:1312-1314. O'Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2013;9:CD003826. Hochman B, Locali RF, Matsuoka PK, et al. Intralesional triamcinolone acetonide for keloid treatment: a systematic review. Aesthetic Plast Surg. 2008;32:705-709. Hamrick M, Boswell W, Carney D. Successful treatment of earlobe keloids in the pediatric population. J Pediatr Surg. 2009;44:286-288. Ledon JA, Savas J, Franca K, et al. Intralesional treatment for keloids and hypertrophic scars: a review. Dermatol Surg. 2013;39:1745-1757. Yan D, Zhao B, Yang H, et al. A combination of nonoperative treatment modalities used for treatment of keloids. Dermatol Ther. 2014;27:48-51.
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ACCEPTED MANUSCRIPT Figure 1. Well circumscribed depigmented patches on the leg consistent with vitiligo. Figure 2. Segmental vitiligo on the face of a child.
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Figure 3. Leukotrichia or poliosis overlying vitiligo patches on the scalp.
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Figure 4. Progressive macular hypomelanosis presenting as ill-defined hypopigmented macules on the back.
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Figure 5. Pityriasis alba on the cheek of an atopic patient. (Courtesy of Anthony Mancini, MD)
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Figure 6. Acne keloidalis nuchae manifesting as follicularly based fibrotic papules and nodules on the occipital scalp and nape of the neck.
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Figure 7. A keloid developing on the ear lobe after piercing.
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Inflammatory/neoplastic
Tinea versicolor (Malassezia sp) Leprosy (Mycobacterium leprae) Progressive macular hypomelanosis (Propionibacterium acnes) Pityriasis lichenoides chronica Hypopigmented cutaneous T cell lymphoma Sarcoidosis Pityriasis alba Post inflammatory hypopigmentation Chemical induced leukoderma Nevus depigmentosus Hypomelanosis of Ito Piebaldism Ash leaf spots/confetti macules associated with tuberous sclerosus
Postinflammatory
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Physical exposures Congenital / genetic
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Addison’s disease Alopecia areata Autoimmune thyroiditis Diabetes mellitus (Type I) Inflammatory bowel disease Pernicious anemia Systemic lupus erythematosus
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Table 2. Autoimmune conditions associated with vitiligo
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S0738-081X(16)30180-8 doi: 10.1016/j.clindermatol.2016.07.003 CID 7076
To appear in:
Clinics in Dermatology
Please cite this article as: Shen Lisa Y., Kenner-Bell Brandi, Ricketts Janelle, Kundu Roopal V., Ethnic Skin: Kids Are Not Just Little People, Clinics in Dermatology (2016), doi: 10.1016/j.clindermatol.2016.07.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Lisa Y Shen, MD1
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Ethnic Skin : Kids Are Not Just Little People
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Brandi Kenner-Bell, MD 1, 2
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Janelle Ricketts, MD3
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Roopal V. Kundu, MD1
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,
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Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
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Department of Dermatology, University of Connecticut Health Science Center, Farmington, CT
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Corresponding Author:
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Roopal V. Kundu, MD Northwestern University Feinberg School of Medicine Department of Dermatology 676 N St. Clair Street, Suite 1600 Chicago, IL 60611 Phone: 312- 926-4926 Fax: 312-695-0664 Email: [email protected]
ACCEPTED MANUSCRIPT ABSTRACT: There are numerous skin conditions that occur commonly in children with ethnic skin, including
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vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae,
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pseudofolliculitis barbae, and keloids. Though these conditions occur in both children and adults, children may have different patterns of clinical presentation and response to therapy. In caring
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for such patients, important treatment considerations include side effects of systemic medications
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and tolerability of invasive procedures. Quality of life is an important measure and should not be
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compromised by either the skin disease or its treatment.
ACCEPTED MANUSCRIPT Numerous skin conditions are common in the pediatric patient population with Fitzpatrick III-VI skin types, including vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis
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nuchae, pseudofolliculitis barbae, and keloids. Many of these conditions also occur in adults, but
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special considerations are made in the treatment of children in terms of side effects of systemic medications and tolerability of invasive procedures.
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How does the clinical presentation of vitiligo differ in children and adults?
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Vitiligo is an acquired disorder of cutaneous depigmentation affecting approximately 1% of the world population.1, 2 (Figure 1) It is especially relevant to the pediatric population, as the
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condition manifests before age 20 in about half of affected individuals, with a mean age of onset
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of childhood vitiligo ranging between 4 and 8 years.3-7
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There are several notable differences between childhood-onset and adult-onset vitiligo, including a higher incidence of segmental vitiligo,3, 4, 8 (Figure 2) and a slower rate of progression among
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children.9, 10 Another epidemiologic finding unique to the pediatric population includes a
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possible higher prevalence in girls,3 5, 7, 11 but this was not observed in two Chinese and Korean populations in which the boys and girls were affected with equal frequency.6, 12 Though the majority of cases occur sporadically, there is a greater likelihood of having a positive family history of vitiligo reported in children.3, 5, 13
Is laboratory testing warranted in patients with vitiligo? In the evaluation of suspected vitiligo, a thorough history and physical exam including examination with a Wood’s lamp is typically sufficient in establishing the diagnosis. Skin biopsies are rarely performed especially in the pediatric population, though biopsies of lesional
ACCEPTED MANUSCRIPT and normal skin may be warranted if the diagnosis is in question or infectious, postinflammatory,
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or neoplastic mimickers should be considered. (Table 1)
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Screening for associated autoimmune conditions should be considered in both adults and children, especially in the context of a positive family history. Autoimmune conditions reported
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to be associated with vitiligo include autoimmune thyroiditis, insulin-dependent diabetes mellitus,
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pernicious anemia, alopecia areata, and systemic lupus erythematosus.4, 14 (Table 2) Consequently, various experts have proposed screening labs to include a complete blood count,
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fasting blood glucose, thyroid stimulating hormone, thyroid autoantibodies, antiparietal cell antibodies, and antinuclear antibodies. 15-17 A recent retrospective study of 79 children with
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nonsegmental vitiligo found a prevalence of thyroid lab abnormalities (TSH or thyroid
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autoantibodies) to be 25%, with subclinical hypothyroidism being the most frequent diagnosis.18 At our institutions, the authors typically only check thyroid studies (thyroid stimulating hormone
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with reflexive thyroxine and anti-thyroid antibodies) if no other clinically significant findings
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exist, given the low prevalence of other autoimmune diseases. In one study, 13 of 121 pediatric patients demonstrated thyroid parameter alterations; however none of the patients with segmental vitiligo had thyroid alterations, suggesting that this subset of patients may not require screening labs.19 Another group found a similar protective association of segmental vitiligo and lack of thyroid alterations.20
How does the age of the patient affect the treatment of vitiligo? The therapeutic options for childhood vitiligo are much the same as those for adults, though age is an important consideration in deciding whether to treat and which treatment modality to select.
ACCEPTED MANUSCRIPT In general, children seem to have a better response to treatment than adults.12, 15, 21, 22 With increasing age and development of interpersonal relationships at school, the condition may have
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significant psychosocial implications which further drive motivation to treat. In counseling
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young patients and their parents, it is important to establish realistic expectations for treatment outcomes. Parents should be advised that most patients will not achieve 100% repigmentation
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and that a response of 50-75% repigmentation is the goal, with acral sites, lesions with
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leukotrichia (Figure 3), and segmental distributions of vitiligo being most refractory to medical therapies.23, 24 For all patients, the use of broad spectrum sunscreens should be encouraged to
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prevent sunburn of the depigmented areas and more prominent contrast between pigmented and nonpigmented skin. Cosmetic camouflage is another useful tool to improve the appearance of
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unevenly pigmented skin with resulting improvement in quality of life.25 Patients ages 8-16 may
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also benefit from the Camp Discovery program, a week long camp experience sponsored by the
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conditions.
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American Academy of Dermatology, where they may meet other children with similar skin
Topical corticosteroids are among the most commonly utilized therapies with response rates ranging from 41% to 64%.12, 15, 26, 27 High potency corticosteroids (ie clobetasol proprionate) have been reported to demonstrate better response in darker skinned patients;28 however, the duration of therapy may be limited by side effects including epidermal atrophy, telangiectasia, hypertrichosis, and corticosteroid-induced acne, 26, 27, 29. The use of topical corticosteroids is limited to focal areas of vitiligo with affected body surface area less than 20%. Some clinicians cycling class I corticosteroids with class V steroids for 6-8 week cycles or hybrid 2-day/5-day therapy to minimize risk of local side effects.30 Others have observed that high- versus
ACCEPTED MANUSCRIPT moderate-potency corticosteroids had no statistically significant difference in either response rates or occurrence of local side effects,27. Topical tretinoin 0.025% or 0.05% in addition to
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topical corticosteroids was reported to be more effective than topical corticosteroids with vehicle
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in 55% of patients, without adverse effects noted in either group.31 Topical calcipotriene has also been proposed as a useful adjunct to topical corticosteroids with 10 out of 12 pediatric
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patients achieving a mean of 95% repigmentation, 4 of whom previously did not respond to over
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3 months of topical corticosteroid alone.32 Systemic corticosteroids are not advised, as the risks of systemic side effects in children outweigh the benefits. In adults with worsening vitiligo, use
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of either systemic corticosteroids or minocycline may help to halt spread of the disease.33 A randomized controlled study conducted in 50 subjects with actively spreading vitiligo showed
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oral pulse dexamethasone 2.5 mg twice weekly versus minocycline 100 mg daily for 6 months,
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were similarly effective in significantly reducing vitiligo disease activity scores.33
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Topical calcineurin inhibitors (tacrolimus 0.03% or 0.1%, pimecrolimus 0.1%) are another
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therapeutic option in patients over the age of 2 years. Of note, only tacrolimus 0.03% ointment is approved for children 2 to 15 years of age. A double-blind, randomized controlled trial in childhood vitiligo patients compared the effects of twice daily application of clobetasol propionate 0.05% ointment versus tacrolimus 0.1% ointment on similar lesions located on opposite sides of the body with no statistically significant difference in response rates between the two treatments.29 Other studies with tacrolimus have similarly demonstrated good results (>75% repigmentation in 59%),34 with best results in pediatric patients with segmental involvement of the head and neck lesions as well as darker Fitzpatrick skin types. 35, 36 Pimecrolimus 1% cream has also been evaluated as an effective treatment for childhood
ACCEPTED MANUSCRIPT segmental vitiligo.37 Given the lack of side effects when compared to topical corticosteroids, we recommend that topical calcineurin inhibitors be considered as maintenance topical therapy to
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avoid long term exposures to topical corticosteroids.
Narrowband ultraviolet B light (NBUVB) phototherapy (ranging from 311 to 313nm) is one of
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the most effective therapies when large areas of the body are affected or if first line topical
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therapies are ineffective. NBUVB is much more effective in patients under the age of 20 as compared to older adults;38 however there must be proper selection of pediatric patients who are
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able to tolerate being in a phototherapy unit. Depending on the maturity and motivation of the child, patients as young as 5 years old have been able to undergo phototherapy treatment.39, 40
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Response rates (>75% repigmentation) after 1 year of therapy range from 44-75%.39-42
308 nm excimer laser is a focal therapy that works in a similar fashion to NBUVB. Though
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there are few studies done in children, one group demonstrated >50% repigmentation in 50% of
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treated lesions of childhood vitiligo and 75% repigmentation in 12.5% of treated lesions.43 Another study treated 49 patients ages 6-14 with excimer laser twice weekly in conjunction with unilateral application of topical 1% pimecrolimus cream twice daily resulting in greater improvement within the lesions treated with the combination treatment.44
In contrast, photochemotherapy with UVA (PUVA) generally is not recommended for children under 12 years of age,45 as it has not been shown to be as effective in children as compared to adults.4 The potential adverse effects of PUVA, including nausea, photosensitivity, cataract formation, and dyspigmentation, also limit its use in adults. Several studies comparing PUVA
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efficacy than PUVA in the treatment of vitiligo.46, 47
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Surgical therapies are available for older children who do not respond to medical treatments, particularly in subtypes of vitiligo that have poor response rates including segmental and acral
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vitiligo. Prerequisites for surgical therapy include stability of the affected area of skin
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recommended for at least 6-12 months and lack of previous Koebner reactions. Two main categories of procedures include tissue grafting (ie. suction blisters, split thickness skin grafts,
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punch grafts) and cellular grafting in which melanocytes are isolated and expanded from a thin skin sample and transplanted onto abraded/denuded areas of vitiligo. Suction blister grafting was
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performed in 15 recalcitrant patches of stable vitiligo in 10 children (ages 11-19 years) and noted
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that 8 of the 10 children attained more than 75% pigmentation.48 Others performed autologous noncultured cellular grafting in 25 children and reported 62% and 75% with excellent
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repigmentation (defined as 95%-100% improvement) in the segmental and focal vitiligo groups,
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respectively.8 Still another group reported that transplantation of autologous cultured pure melanocytes works as well in children and adolescents as it does in adults.49
Depigmentation therapies are generally not recommended in children, because the child would face a lifetime of sun avoidance from an early age. In adults, depigmentation can be accomplished in patients with widespread involvement. A psychologic evaluation prior to treatment is recommended to address the potential psychosocial ramifications of changing skin color.
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Which age groups are affected by progressive macular hypomelanosis? Progressive macular hypomelanosis is a condition first described by Guillet et al which presents
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as asymptomatic ill-defined hypopigmented macules favoring the trunk.50 (Figure 4) It commonly occurs in adolescents and young adults and frequently occurs in darker skin types
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(Fitzpatrick skin types III-IV).51 The diagnosis is supported by the presence of red follicular fluorescence within the hypopigmented skin upon Wood’s lamp examination, and
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Propionibacterium acnes has been isolated within lesional skin.52-54 It is reasonable that a first-
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line approach to treatment in children includes topical benzoyl peroxide and clindamycin.55 If topicals alone are not effective, natural sunlight exposure or phototherapy (narrow band UVB
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preferred over UVA) may be considered as a more effective adjunct. 56-59 In older children and young adults, oral tetracyclines have been reported as an effective treatment though patients
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should be cautioned against concomitant use of phototherapy or heavy sun exposure given the
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risk of photosensitivity.54, 60-62
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What accounts for pityriasis alba commonly affecting children but not adults? Pityriasis alba is an entity that commonly manifests as discrete minimally scaly, hypopigmented patches on the head, neck, and proximal extremities of darkly pigmented children. (Figure 5) It has been frequently associated with atopic dermatitis, xerosis, and sun exposure.63-65 It is rarely seen in post-pubertal adolescents and young adults due to the proposed protective effect of sebum.66 The first line of treatment (and prevention of further episodes) involves rigorous sun protection and dry skin care with liberal use of emollients.63, 66 Medical therapies include mild nonhalogenated topical corticosteroids (hydrocortisone acetate 1% or desonide 0.05%) and topical calcineurin inhibitors (tacrolimus 0.1% or pimecrolimus 1%).67-69
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What factors contribute to the development of acne keloidalis nuchae (synonyms: folliculitis
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keloidalis, folliculitis nuchae)?
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Acne keloidalis nuchae (AKN) is a progressive scarring folliculitis and perifolliculitis, resulting in fibrotic papules and nodules usually affecting the nape of the neck and occipital scalp.70
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(Figure 6) It is most frequently seen in African-American postpubertal boys and men and is
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thought to be caused by a combination of factors including skin penetration of closely shaven hairs with resulting inflammation and/or mechanical irritation from shirt collars or helmets.71 In
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a study of African school children, the prevalence of AKN was highest in older high school boys who have frequent haircuts (<4 week intervals).72 Acne mechanica (consisting of inflammatory
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papules, pustules, cysts, and nodules in areas of friction) has been proposed as a precursor to
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AKN in adolescents, as demonstrated by the higher prevalence of nuchal acne mechanica (and absence of AKN) in high school football players as opposed to a higher prevalence of AKN in
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older collegiate and professional football players.73 This suggests that early intervention is
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warranted in an effort to prevent disease progression and future keloids. The first priority in treatment is education to avoid mechanical irritation of the skin and close haircuts with clippers or razors. Potent corticosteroids (class I and II) in addition to topical antimicrobials(clindamycin, chlorhexadine) are the mainstays of topical treatments.70, 74 Topical retinoids may also be used as an adjunct. Treatment for more advanced or refractory disease may include intralesional triamcinolone injections (ranging from 5mg/cc to 40mg/cc), systemic antibiotics, laser hair reduction, and surgical excision;70, 75, 76 however, the ability of adolescents to withstand these more invasive procedures may be a concern.
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on the face and neck of men with curly, coarse hair. It is thought to be a result of traumatic hair
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removal practices, such as shaving and plucking, with subsequent inflammation due to the cut hairs curling in on themselves causing a foreign body-like reaction. 71, 77 It can affect women, if
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they are using hair removal techniques on the face, axillae, and suprapubic areas.74 In women
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with this condition, the clinician should ask about menstrual history, presence of hirsutism, and possible hormonal abnormalities as indicated.77 Although somewhat controversial, our group
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suggests adjustment of hair removal practices may include avoiding shaving entirely, not holding the skin taut while shaving, or using single blade razors or electric clippers/shavers to avoid too
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close of a shave. Topical therapy includes use of a mild- to medium-potency topical
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corticosteroid after shaving in combination with benzoyl peroxide or clindamycin.74, 78 A topical retinoid may be used nightly, as well. In women, topical eflornithine cream to slow the growth
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of hair in the affected sites alone or in combination with electrolysis or laser hair removal may be
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effective in reducing the inflammatory papules.79
How does age impact the development of keloids and their management? Keloids are progressive overgrowths of scar tissue developing months to years after trauma and are notoriously difficult to treat. In children ,they most commonly occur on the ear lobes after ear piercing. (Figure 7) Keloids are more likely to develop when the ears are pierced after age 11, and we recommend ear piercing before the age of seven, particularlyin children with the darker skin types more predisposed to keloids.80 There is also weak evidence for the use of silicone gel sheeting in prevention of keloids.81 First-line therapy includes intralesional steroid
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triamcinolone injection.83 For larger keloids, in reliable and compliant adults who have been
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recalcitrant to intralesional steroid injections, treatment options may include surgical excision
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followed by radiation therapy, as well as topical or intralesional chemotherapy.84, 85
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CONCLUSIONS
Children with ethnic skin are more susceptible to or more affected by certain skin conditions
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such as vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae, pseudofolliculitis barbae, and keloids. Additionally, our young patients require unique treatment
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considerations with safety and treatment tolerability as main priorities. Care should be taken to
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offer therapies that are safe and effective without being an excessive burden to the patient and parents. Ultimately, the goals of treatment should include improving quality of life and self-
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confidence at a critical time when children and adolescents are establishing their identities and
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References Alikhan A, Felsten LM, Daly M, et al. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65:473-491. Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2010:CD003263. Agarwal S, Gupta S, Ojha A, et al. Childhood vitiligo: clinicoepidemiologic profile of 268 children from the Kumaun region of Uttarakhand, India. Pediatr Dermatol. 2013;30:348-353. Halder RM, Grimes PE, Cowan CA, et al. Childhood vitiligo. J Am Acad Dermatol. 1987;16:948-954. Handa S, Dogra S. Epidemiology of childhood vitiligo: a study of 625 patients from north India. Pediatr Dermatol. 2003;20:207-210. Hu Z, Liu JB, Ma SS, et al. Profile of childhood vitiligo in China: an analysis of 541 patients. Pediatr Dermatol. 2006;23:114-116. Jaisankar TJ, Baruah MC, Garg BR. Vitiligo in children. Int J Dermatol. 1992;31:621623. Mulekar SV, Al Eisa A, Delvi MB, et al. Childhood vitiligo: a long-term study of localized vitiligo treated by noncultured cellular grafting. Pediatr Dermatol. 2010;27:132-136.9. de Barros JC, Filho CD, Abreu LC, et al. A study of clinical profiles of vitiligo in different ages: an analysis of 669 outpatients. Int J Dermatol. doi: 10.1111/ijd.12055. [Epub 2013 Oct 18]. Nicolaidou E, Antoniou C, Miniati A, et al. Childhood- and later-onset vitiligo have diverse epidemiologic and clinical characteristics. J Am Acad Dermatol. 2012;66:954-958. Kyriakis KP, Palamaras I, Tsele E, et al. Case detection rates of vitiligo by gender and age. Int J Dermatol. 2009;48:328-329. Cho S, Kang HC, Hahm JH. Characteristics of vitiligo in Korean children. Pediatr Dermatol. 2000;17:189-193. Pajvani U, Ahmad N, Wiley A, et al. The relationship between family medical history and childhood vitiligo. J Am Acad Dermatol. 2006;55:238-244. Alkhateeb A, Fain PR, Thody A, et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res. 2003;16:208-214. Halder RM. Childhood vitiligo. Clin Dermatol. 1997;15:899-906. Silverberg NB. Update on childhood vitiligo. Curr Opin Pediatr. 2010;22:445-452. Kakourou T, Kanaka-Gantenbein C, Papadopoulou A, et al. Increased prevalence of chronic autoimmune (Hashimoto's) thyroiditis in children and adolescents with vitiligo. J Am Acad Dermatol. 2005;53:220-223. Afsar FS, Isleten F. Prevalence of thyroid function test abnormalities and thyroid autoantibodies in children with vitiligo. Indian J Endocrinol Metab. 2013;17:10961099.
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ACCEPTED MANUSCRIPT Figure 1. Well circumscribed depigmented patches on the leg consistent with vitiligo. Figure 2. Segmental vitiligo on the face of a child.
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Figure 3. Leukotrichia or poliosis overlying vitiligo patches on the scalp.
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Figure 4. Progressive macular hypomelanosis presenting as ill-defined hypopigmented macules on the back.
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Figure 5. Pityriasis alba on the cheek of an atopic patient. (Courtesy of Anthony Mancini, MD)
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Figure 6. Acne keloidalis nuchae manifesting as follicularly based fibrotic papules and nodules on the occipital scalp and nape of the neck.
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Figure 7. A keloid developing on the ear lobe after piercing.
ACCEPTED MANUSCRIPT Table 1. Mimickers of vitiligo Infectious
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Tinea versicolor (Malassezia sp) Leprosy (Mycobacterium leprae) Progressive macular hypomelanosis (Propionibacterium acnes) Pityriasis lichenoides chronica Hypopigmented cutaneous T cell lymphoma Sarcoidosis Pityriasis alba Post inflammatory hypopigmentation Chemical induced leukoderma Nevus depigmentosus Hypomelanosis of Ito Piebaldism Ash leaf spots/confetti macules associated with tuberous sclerosus
Postinflammatory
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Physical exposures Congenital / genetic
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Addison’s disease Alopecia areata Autoimmune thyroiditis Diabetes mellitus (Type I) Inflammatory bowel disease Pernicious anemia Systemic lupus erythematosus
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Table 2. Autoimmune conditions associated with vitiligo
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Figure 7