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Acne, Pediatric

Basics

Description

- Age of onset: Early or late onset of acne may indicate androgen excess. - Medications and supplement use (including some OCPs, progestin implants, depot medroxyprogesterone, steroids (topical, inhaled, or oral), anticonvulsants, lithium, isoniazid, nicotine products) may worsen acne. - Menstrual history: Premenstrual flares may occur due to androgenic effects of progesterone. - Androgen excess (history of or current) - Prepubertal: early-onset acne or body odor, increased linear growth, axillary or pubic hair, genital maturation, or clitoromegaly - Postpubertal: alopecia, hirsutism, truncal obesity, acanthosis nigricans, irregular menses, increased muscle mass

- Sulfur/sulfacetamide: - Mild antibacterial and keratolytic properties - Very well-tolerated - Distinctive odor

- Prescription topical medications - Topical antibiotics (erythromycin, clindamycin): - Reduce P. acnes concentration and inflammatory mediators - Available in combination products to increase compliance, but these products are often more expensive - Combine with BP to decrease antibiotic resistance. - Combine with retinoids to help yield faster results. - Side effects: well-tolerated but may include drying or irritation

- Topical retinoids: - Prevent formation of microcomedones, clear existing microcomedones, anti-inflammatory - Available in 3 forms - Adapalene - Available as cream, gel, lotion. Also as a combination product with BP - Pregnancy class C (see Appendix 4; Table 10) - Photostable - Better tolerability than tretinoin

- Topical dapsone: - Synthetic sulfone has antimicrobial and anti-inflammatory effects. - Available in 5% gel, twice daily application recommended - Most effective against inflammatory acne lesions - Safe in patients with G6PD deficiency and with sulfonamide allergy - Enhanced efficacy when combined with retinoids - Side effects: erythema and dryness - Caution: When used with BP, a temporary orange staining of skin can occur.

- Oral antibiotics: reduce P. acnes concentration and inflammatory mediators - Tetracyclines (doxycycline, minocycline, tetracycline): pregnancy class D. Must be >8 years of age due to staining of tooth enamel - Doxycycline and minocycline are preferred due to 1-2 —/day dosing and greater follicular penetration. - Dosing: 50-100 mg daily or b.id.

- Sulfa (trimethoprim-sulfamethoxazole): - Dosing: 160-800 mg PO b.i.d. - Used judiciously, refractory cases - Systemic side effects: severe cutaneous reactions (SJS, toxic epidermal necrolysis, drug hypersensitivity reaction, fixed drug eruption), bone marrow suppression - Check baseline CBC and periodically thereafter.

- Need baseline and monthly labs (see "Lab/Imaging"¯) - Side effects: - Common: dry skin, dry eyes, cheilitis, myalgias - Teratogen - 2 forms of birth control need to be used while on medication. - FDA-mandated registry (iPledge: see https://www.ipledgeprogram.com/). Prescribed only by registered users

- Limited empiric studies on CAM and acne. - RCTs of the following showed that they were not as effective as 5% BP but resulted in less skin irritation: - Tea tree oil: a mixture of terpenes and alcohols with antibiotic and antifungal properties; 5% solution may be effective in treating comedonal and inflammatory acne; may be associated with male gynecomastia - Gluconolactone 14% solution may be effective on comedonal and inflammatory acne.

Acne vulgaris is one of the most common skin conditions in children and adolescents. It is a disorder of pilosebaceous units (PSUs). PSUs are found predominantly on the face, chest, back, and upper arms. Acne presents as comedonal or inflammatory lesions and can cause depressed scars and hyperpigmentation. Presentation, treatment, and associated systemic manifestations differ by age of presentation, pubertal status, and severity of disease.

  • Classification of acne by age:Neonatal (birth to 6 weeks): affects up to 20% of neonates. Also known as neonatal cephalic pustulosis. Presents with a papulopustular eruption predominantly on face. Thought to be due to Malassezia colonization. No treatment necessary. For severe cases can use ketoconazole cream 2%.Infantile acne (6 weeks to 1 year): presents with comedonal and inflammatory lesions on face. Some evidence that it may predispose to severe adolescent acne. Often, no underlying endocrine abnormality. Self-limited but in severe cases can use topical acne treatmentsMidchildhood acne (1-6 years): uncommon. Presents with comedonal and inflammatory lesions on face. Suspect an underlying endocrinopathy.Preadolescent (7-11 years): presents with predominantly comedonal lesions in "T-zone,"¯ central face. Can be first sign of onset of pubertyAdolescent (12-19 years): very common presentation, affects 85% of adolescents

Risk Factors

Genetics

Familial patterns exist, but no inheritance pattern has been demonstrated.

General Prevention

  • Effective and early treatment limits scarring, postinflammatory pigment alteration, and minimizes psychosocial impact.
  • Use of noncomedogenic moisturizers and sunscreens

Pathophysiology

  • Pathogenesis of acne is multifactorial and involves 4 different components:Increased sebum production: stimulated by an increase in androgen levels. The adrenal gland is active during the 1st year of life and then reawakens in preadolescent time period. Production peaks in teens and decreases in the 20s.Alteration in follicular growth and differentiation leading to the creation of a microcomedone, a precursor of inflammatory and comedonal acne lesionsFollicular colonization with Propionibacterium acnes, an anaerobic, gram-positive diphtheroid bacteria. P. acnes produces free fatty acids (FFAs) leading to inflammation.Inflammation and immune response through the innate immune system

Etiology

  • Androgen excess (physiologic vs. pathologic)
  • Medication-induced (corticosteroids, anticonvulsants, lithium, etc.)
  • Occlusion (from topical- or oil-based products)
  • Friction from athletic helmets, shoulder pads, chin straps, or bra straps may worsen acne.

Commonly Associated Conditions

  • Polycystic ovarian syndrome (PCOS)
  • SAPHO syndrome: synovitis, acne, pustulosis, hyperostosis, and osteitis
  • Adrenal or gonadal/ovarian tumors
  • Late-onset congenital adrenal hyperplasia

Diagnosis

History

  • Age of onset: Early or late onset of acne may indicate androgen excess.
  • Medications and supplement use (including some OCPs, progestin implants, depot medroxyprogesterone, steroids (topical, inhaled, or oral), anticonvulsants, lithium, isoniazid, nicotine products) may worsen acne.
  • Menstrual history: Premenstrual flares may occur due to androgenic effects of progesterone.
  • Androgen excess (history of or current)Prepubertal: early-onset acne or body odor, increased linear growth, axillary or pubic hair, genital maturation, or clitoromegalyPostpubertal: alopecia, hirsutism, truncal obesity, acanthosis nigricans, irregular menses, increased muscle mass
  • Previous treatments tried and reason failed (cost, adherence, tolerability, ease of use).

Alert

Psychological impact: Ask patients about self-esteem, depression, and suicidal ideations.

Physical Exam

  • SkinDistribution of lesionsType of acne lesions: comedonal (open: blackhead, due to oxidation of lipids and not dirt; closed: whitehead), inflammatory (erythematous papule, pustule, nodule, pseudocyst)Scarring and hyperpigmentation
  • Global assessment of acne severity (number, size, extent, and scarring)
  • Note signs of androgen excess (see "History"¯).
  • Height, weight, growth curve
  • Blood pressure

Diagnostic Tests & Interpretation

Lab/Imaging

  • Consider for patients with signs of androgen excess, midchildhood acne, or acne unresponsive to traditional therapy.Serologic testing (LH, FSH, testosterone total and free, DHEA-S, androstenedione prolactin, 17-hydroxyprogesterone)Bone ageReferral to pediatric endocrinologyImaging for adrenal or gonadal tumor
  • Lab monitoring while using isotretinoin should include baseline and monthly complete blood count, fasting lipid panel (triglycerides and cholesterol), transaminases, and pregnancy test for females. Prior to starting females need two negative pregnancy tests 1 month apart.

Differential Diagnosis

  • Adenoma sebaceum (facial angiofibromas)
  • Keratosis pilaris
  • Flat warts
  • Molluscum contagiosum
  • Periorificial dermatitis
  • Milia
  • Miliaria
  • Syringomas
  • Demodex folliculitis
  • Malassezia (Pityrosporum) folliculitis
  • Gram-negative folliculitis
  • Staphylococcal folliculitis
  • Chloracne (exposure to chlorinated aromatic hydrocarbons)
  • Papular sarcoidosis

Treatment

  • Choose regimen based on previous therapies, cost, vehicle selection, regimen complexity, active scarring, and psychosocial impact.
  • Vehicle selection:Creams and lotions less drying than gels and solutionsCreams better for sensitive skin/eczemaGels and solutions may be better for oily skin or for make-up application.
  • Manage patient expectations.
  • Treatment may take 2-3 months to be effective.
  • Acne may initially flare prior to improving.
  • Counsel about medication side effects.

General Approach

Categorized by acne severity and age of patient.

  • Mild acne: comedonal, inflammatory, or mixedInitial:Topical monotherapy:Benzoyl peroxide (BP)Topical retinoidTopical combination therapy:BP + antibioticRetinoid +BPRetinoid + BP + antibioticInadequate response:Assess adherence.Add BP or retinoid if not already prescribed.Change:Topical retinoid concentration, type, or formulationChange topical combination therapy.
  • Moderate acne: comedonal, inflammatory, or mixedInitial:Topical combination therapy:Retinoid + BPRetinoid + BP + antibioticOral antibiotic + topical retinoid + BPInadequate response:Assess adherence.Change topical retinoid concentration, type, or formulation.Add or change oral antibiotic.Females: Consider hormonal therapy.Consider oral isotretinoin.Consider dermatology referral.
  • Severe acne: inflammatory, mixed, and/or nodular lesions. Extensive involvement often with significant scarringInitial:Oral antibiotic + topical retinoid + BP ± topical antibioticConsider dermatology referral.Inadequate response:Assess adherence.Change topical retinoid concentration, type, or formulation.Change oral antibioticFemales: consider hormonal therapyConsider oral isotretinoinScars warrant aggressive treatment targeting inflammation

Medication (Drugs)

  • Topical agents/over the counterGentle cleansers:Use gentle soap free, pH-balanced cleansers are recommended for everyday washing.Benzoyl peroxide (BP):Bactericidal, mild comedolytic, and anti-inflammatory properties.Limits antibiotic resistance and provides increased efficacy in combination with retinoids.Available as lotion, cream, wash, and gel in 2.5-10%Increased concentration does not increase efficacy but can cause more irritation.5% concentration generally effective. Can start with lower concentration or decrease number of days of use if too irritatingSide effects: drying, erythema, burning, peeling, stinging, and rarely contact dermatitisCautions: can cause bleaching of hair, clothing, and linen; increased risk of photosensitivity. Rare but serious and potentially life-threatening allergic reactions or severe irritation have been reported.Salicylic acid (SA):Promotes comedolysis with drying and peelingNot as effective as BPSulfur/sulfacetamide:Mild antibacterial and keratolytic propertiesVery well-toleratedDistinctive odor
  • Prescription topical medicationsTopical antibiotics (erythromycin, clindamycin):Reduce P. acnes concentration and inflammatory mediatorsAvailable in combination products to increase compliance, but these products are often more expensiveCombine with BP to decrease antibiotic resistance.Combine with retinoids to help yield faster results.Side effects: well-tolerated but may include drying or irritationTopical retinoids:Prevent formation of microcomedones, clear existing microcomedones, anti-inflammatoryAvailable in 3 formsAdapaleneAvailable as cream, gel, lotion. Also as a combination product with BPPregnancy class C (see Appendix 4; Table 10)PhotostableBetter tolerability than tretinoinTretinoinAvailable as cream, gel, microsphere gel of various strengthsPregnancy class C (see Appendix 4; Table 10)Apply to dry skin.Can be very irritating and dryingStart with 0.025%, low strength only a few times a week, and titrate up.Inactivated by sunlight, use at nighttime.TazaroteneAvailable in cream and gelPregnancy class X; contraindicated in pregnancyApply to dry skin.More irritating than other retinoidsInactivated by sunlight, use at nighttime.1st-line therapy for most patientsSide effects: erythema, dryness, irritation, initially acne flares, and photosensitivity (advise use of daily noncomedogenic sunscreen with SPF 30+ and facial moisturizer applied beforetazarotene).Apply at night, as medication is inactivated by sunlight.Apply pea-sized amount to entire face.Start with lowest strength three times a week, and increase frequency slowly to every night as tolerated. Some patients may not tolerate medication every night. Increase concentration of medication if patient still with oily skin or getting new acne lesions.Azelaic acid:Comedolytic and antibacterial; decreases hyperpigmentation15% gel or 20% cream, applied twice daily.Pregnancy class B (see Appendix 4; Table 10)Side effects include itching, burning, tingling, stinging, and erythema.Consider for patients with comedonal acne who cannot use retinoids.Topical dapsone:Synthetic sulfone has antimicrobial and anti-inflammatory effects.Available in 5% gel, twice daily application recommendedMost effective against inflammatory acne lesionsSafe in patients with G6PD deficiency and with sulfonamide allergyEnhanced efficacy when combined with retinoidsSide effects: erythema and drynessCaution: When used with BP, a temporary orange staining of skin can occur.
  • Oral antibiotics: reduce P. acnes concentration and inflammatory mediatorsTetracyclines (doxycycline, minocycline, tetracycline): pregnancy class D. Must be >8 years of age due to staining of tooth enamelDoxycycline and minocycline are preferred due to 1-2 —/day dosing and greater follicular penetration.Dosing: 50-100 mg daily or b.id.Tetracycline is cheap but has least efficacy.Increasing antibiotic resistance. Limit treatment length and do not use as monotherapy. Use with BP or topical retinoid.Taper or switch to topical retinoid monotherapy after 12 weeks and when patient is no longer getting new acne lesions.Systemic side effects and cautions:Doxycycline: GI upset, vaginal candidiasis, pill esophagitis, photosensitivity (phototoxicity), benign intracranial hypertension. Take with food and large glass of water, stay upright 1 hour after taking medication, photoprotection, can use enteric-coated form.Minocycline: acute vestibular reaction (vertigo, dizziness), vaginal candidiasis, hyperpigmentation, drug hypersensitivity reaction 2-8 weeks after starting medication, lupuslike syndrome, Stevens-Johnson syndrome (SJS), benign intracranial hypertensionSulfa (trimethoprim-sulfamethoxazole):Dosing: 160-800 mg PO b.i.d.Used judiciously, refractory casesSystemic side effects: severe cutaneous reactions (SJS, toxic epidermal necrolysis, drug hypersensitivity reaction, fixed drug eruption), bone marrow suppressionCheck baseline CBC and periodically thereafter.Cephalosporins (cephalexin, cefadroxil):Dosing: 500 mg PO b.i.d.Well-toleratedSystemic side effects: GI upsetPenicillins (amoxicillin):Well-toleratedSystemic side effects: GI upsetMacrolides (erythromycin, azithromycin)High prevalence of P. acnes resistance to erythromycinSystemic side effects: erythromycin: GI upset, drug-drug interaction
  • Oral retinoids (isotretinoin): decreases sebum production, is anti-inflammatory, and reduces P. acnes.Used as monotherapyUsed for recalcitrant acne or with significant scarring, given side effectsDosing:Start with 0.5 mg/kg/day for first 4 weeks and then advance to 1 mg/kg/day.Goal cumulative treatment course is 120-150 mg/kg.For patients with severely inflamed acne, start at lower dose to prevent initial acne flares or pretreat with oral corticosteroids.Need baseline and monthly labs (see "Lab/Imaging"¯)Side effects:Common: dry skin, dry eyes, cheilitis, myalgiasTeratogen2 forms of birth control need to be used while on medication.FDA-mandated registry (iPledge: see https://www.ipledgeprogram.com/). Prescribed only by registered usersDepression and suicide have been reported in patients on isotretinoin (causality not established, but counsel about this risk).IBD: conflicting data. Association may exist, but rare, and there are many confounding factors.Bone effects: conflicting data regarding increased risk of fractures and demineralization. Hyperostoses and premature epiphyseal closure are rare and uncommon side effects.Rare, sporadic reports of serious skin infections including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis
  • Hormonal therapy: 2nd-line therapy for women. Usually used in combination with other acne treatmentsOCPs (for women): Suppress ovarian androgen production.Can be used as an adjunct for females with moderate to severe acne not responding to topical retinoids3 OCPs are FDA-approved for acne:Ethinyl estradiol (35 mcg) and norgestimate (≥15 years of age)Ethinyl estradiol (20-30-35 mcg) and norethindrone (≥15 years of age)Ethinyl estradiol (30 mcg) and drospirenone (3 mg) (≥14 years of age)Screen for personal tobacco use and family history of thromboembolic event.Use caution in girls who smoke tobacco.May need 3-6 months to see improvementSide effects include nausea, breast tenderness, headache, weight gain, breakthrough menstrual bleeding, myocardial infarction, ischemic stroke, and DVTs.Controversial effect on bone density and growth. Recommendation to start at least 1 year after onset of menstruation
  • Spironolactone (for women): Blocks androgen receptor in sebaceous glandGive 50-150 mg daily.Off-label use can be used in combination with OCP.Teratogenic effect must be on oral contraceptive.

Alert

Avoid vigorous cleansing of the skin or harsh facial astringents and toners that may irritate the skin.

Alert

BP inactivates tretinoin when used together. Apply BP in the morning and tretinoin at night.

Alert

Do not use antibiotics as monotherapy due to slow onset of action and development of antibiotic resistance. Use with BP.

Alert

Do not use tetracycline antibiotics with oral retinoids due to risk of pseudotumor cerebri.

Complementary & Alternative Therapies

  • Limited empiric studies on CAM and acne.
  • RCTs of the following showed that they were not as effective as 5% BP but resulted in less skin irritation:Tea tree oil: a mixture of terpenes and alcohols with antibiotic and antifungal properties; 5% solution may be effective in treating comedonal and inflammatory acne; may be associated with male gynecomastiaGluconolactone 14% solution may be effective on comedonal and inflammatory acne.

Ongoing Care

Patient Education

  • http://www.aad.org/dermatology-a-to-z/diseases-and-treatments/a-d/acne
  • http://www.nlm.nih.gov/medlineplus/acne.html (handout in Spanish also available)

Complications

  • Scarring may be permanent.
  • Hyperpigmentation: occurs more in dark-skinned individuals. Self resolves but may take months to years
  • Self-esteem: Acne severity correlated to social variables including embarrassment and lack of enjoyment in social activities among teenagers.
  • Patients with mild to moderate acne showed clinical depression and >5% suicidal ideation. Depression scores improve in correlation with response to acne treatment.

Additional Reading

  • Eichenfield LF, Krakowski AC, Piggott C, et al. Evidence-based recommendations for the diagnosis and treatment of pediatric acne. Pediatrics. 2013;131(Suppl 3):163-186. [View Abstract]
  • Friedlander SF, Eichenfield LF, Fowler JF Jr, et al. Acne epidemiology and pathophysiology. Semin Cutan Med Surg. 2010;29(2)(Suppl 1):2-4. [View Abstract]
  • Sawni A, Singh A. Complementary, holistic, and integrative medicine: acne. Pediatr Rev. 2013;34(2):91-93. [View Abstract]
  • U.S. Food and Drug Administration. Over-the-counter topical acne products: drug safety communication-rare but serious hypersensitivity reactions. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm402722.htm. Accessed February 5, 2015.
  • Yan AC, Baldwin HE, Eichenfield LF, et al. Approach to pediatric acne treatment: an update. Semin Cutan Med Surg. 2011;30(3)(Suppl):S16-S21. [View Abstract]

Codes

ICD09

  • 706.1 Other acne
  • 704.8 Other specified diseases of hair and hair follicles

ICD10

  • L70.9 Acne, unspecified
  • L70.4 Infantile acne
  • L70.0 Acne vulgaris
  • L73.8 Other specified follicular disorders

SNOMED

  • 11381005 Acne (disorder)
  • 49706007 Neonatal acne (disorder)
  • 88616000 Acne vulgaris (disorder)
  • 402922003 Propionibacterium acnes folliculitis (disorder)

FAQ

  • Q: Can I modify my diet to improve my acne?
  • A: No. Specific dietary modifications are recommended, but there has been limited data that low glycemic diets may be correlated with improvement in acne.
  • Q: Does poor hygiene cause acne?
  • A: No. Use of harsh astringents, exfoliating scrubs, and vigorous scrubbing can worsen acne by causing more inflammation and scarring. They also can be more irritating and drying, decreasing tolerability of acne treatments. Recommend use of a gentle, soap free, pH-balanced cleanser for daily use in addition to noncomedogenic moisturizers and sunscreen in conjunction with acne treatments.
  • Q: Do cosmetics worsen acne?
  • A: Recommend use of oil free, noncomedogenic make-up, which have been proven not to delay treatment response or worsen acne severity.