Dermatology

Neonatal Acne (Acne - neonatal and infantile)

Neonatal Acne ICD-9-CM 706.1

Infantile Acne

Are You Confident of the Diagnosis?

Acne vulgaris is a condition so ubiquitous in adolescents that it could almost be considered a normal skin variant, rather than a disorder of the pilosebaceous unit. The most well-known clinical features, papules and pustules limited to the face, can also develop in young children, a phenotype colloquially referred to as “baby acne.” The most well-accepted nomenclature for this group of conditions defines two groups: “acne neonatorum,” first reported in 1913, and “infantile acne,” reported three decades later. These two categories have been distinguished mainly by age of onset, distribution of lesions, and presence of or absence of comedones. More recently, additional information has allowed further characterization of distinct subsets.

  • Neonatal Acne

The term, “neonatal acne” (historically “acne neonatorum”) has been used to refer to a short list of pathogenically unrelated but clinically similar conditions that all feature benign, self-limited facial papules present at birth or apparent during the first few weeks of life (Figure 1, Table I). Of the conditions listed, true comedonal acne is less common than sebaceous hyperplasia, erythema toxicum, or miliaria. Both sebaceous hyperplasia (Figure 2) and neonatal comedonal acne have been attributed to transiently elevated androgens, of either maternal origin and placentally transferred, or neonatal adrenal or testicular androgens. Both of these conditions resolve spontaneously with waning androgen levels during the first few months of life.

Figure 1.

These polymorphous facial papules and pustules have been colloquially referred to as baby acne." Some of the papules are undoubtedly sebaceous hyperplasia; others are milia and neonatal cephalic pustulosis.

Figure 2.

Enlarged sebaceous glands most prominent on the nose are characteristic of sebaceous hyperplasia.

Neonatal cephalic pustulosis (NCP) is a distinct subset of neonatal acne first described in 1991. NCP features fine papules and pustules but absence of comedones (Figure 3). Lesions may be sparse or densely distributed, and located primarily on the cheeks, brows and forehead, often extending into the scalp. Prospective studies have reported the incidence of NCP at 10-50%, and clinical reviews estimated a similar incidence for neonatal acne. Because the clinical features that distinguish these conditions are often subtle, the overlap in estimated incidence is not surprising.

Figure 3.

Monomorphous pink papules and scattered fine pustules on the cheeks and chin in a 2-week-old infant are characteristic of neonatal cephalic pustulosis.

The cause of NCP was initially attributed to Malassezia spp after investigators detected pustule-associated organisms and noted response to topically applied ketoconazole. However, this yeast species colonizes normal epidermis, including facial skin from infants with and without NCP, so the etiology of NCP remains controversial. Like neonatal comedonal acne, NCP also resolves without treatment within several weeks to months, but in annoying or severe cases a topical anti-pityrosporum medication may be prescribed. Ketoconazole or ciclopiroxolamine shampoos may be used as a scalp and face wash, with instructions to avoid eye contact. The same active ingredients can also be used with caution in a cream vehicle because topical antifungal creams can cause an iatrogenic irritant, or less often, allergic contact dermatitis.

The differential diagnosis is much longer than the Table I list for widespread papules and pustules not limited to the face but also involving trunk or extremities. This list includes conditions important to recognize and treat in a timely fashion (Figure 4). All the disorders listed in Table I are benign and regress spontaneously, except Candida or Staphylococcus aureus pustulosis. A directed history and examination for corroborating evidence should raise suspicion for these infections and prompt further evaluation and treatment. Relevant history includes perinatal exposure to antibiotics and maternal history of vaginal yeast infections.

Figure 4.

The differential diagnosis of papules and pustules not localized to the face includes scabies, as seen in this infant.

Skin lesions are typically monomorphous perifollicular pustules not limited to the face (Figure 5, Figure 6, Figure 7). Candida often involves palms and soles, periungual areas, and occasionally proximal nail plates. (Figure 8, Figure 9, Figure 10) The diagnoses can be supported by skin scraping for smear and culture. Otherwise healthy and well-appearing term infants with few lesions may be treated topically.

Figure 5.

These scattered inflammatory papules and pustules on the back are Staphylococcus aureus folliculitis.

Figure 6.

These facial papules are more subtle, but similar to some of the papules illustrated in Figure 1. However, this childs truncal involvement (see Figure 5) expands the differential diagnosis.

Figure 7.

Corticosteroid acne affecting this 6-year-old heart transplant patient features monomorphous facial pustules and cushingoid facies.

Figures 8A and B

The signs of neonatal cutaneous candidiasis often include pustules on the palms and soles.

Figure 9.

These facial papules are more subtle, but similar to some of the papules illustrated in Figure 8A and B. However, this child's palmoplantar involvement (see Figures 7 and 8) expands the differential diagnosis to include other entities such as scabies and infantile acropustulosis.

The most well-tolerated topical choices to treat Candida pustulosis are nystatin ointment or ciclopiroxolamine cream or shampoo. Premature or ill-appearing infants with widespread lesions need more aggressive evaluation for systemic infection and timely administration of a systemic antifungal treatment. Staphylococcal pustulosis limited to the face may be treated with mupirocin ointment. Because mupirocin-resistant S. aureus is emerging, persistent or recurrent lesions should be sampled for bacterial culture and antibiotic sensitivities. Alternative topical antibiotics include retapamulin and bacitracin, but efficacy against resistant S. aureus and use in infants has been less well-studied. Creams and ointments containing neomycin carry a high risk of allergic sensitization and should be avoided.

Therapeutic use of very dilute household bleach (5% sodium hypochlorite) is an increasingly popular alternative to antibiotics. Sodium hypochlorite is a broad spectrum disinfectant that works by denaturing protein, skirting the issue of antimicrobial resistance. It has been widely used for decades to disinfect swimming pools and drinking water. Addition of household bleach (5% sodium hypochlorite) to the bath water has been shown to be safe and effective in controlling S. aureus colonization in children with atopic dermatitis, another condition exacerbated by S. aureus. For infants, the estimated dose of bleach is 1 tablespoon to a baby bathtub or sink.

No safe or effective treatments have been identified to hasten resolution of any of the other problems listed in Table I. So, the most important aspect of treatment is to encourage bland skin care and actively discourage use of complex topical products that could trigger a secondary contact dermatitis.

Table I.

Differential diagnosis of neonatal facial papules
Comedones
Benign cephalic pustulosis
Sebaceous hyperplasia
Erythema toxicum neonatorum
Miliaria
Neonatal pustular melanosis
Candidal pustulosis
Staphylococcal pustulosis
  • Infantile Acne

The historic term, “infantile acne” has been used to describe true comedonal and inflammatory acne vulgaris that generally begins after the neonatal period, usually between 4 months and 5 years of age. A more accurate term for this condition is “early-onset acne vulgaris.” Similar to adolescent acne, the severity of this condition can range from mild and comedonal, to severe and nodulocystic, with scarring (Figure 10).

Figure 10.

In addition to the appearance, chronicity and potential for scarring, an important but often over-emphasized issue for older infants and children with early onset acne vulgaris is the risk of associated endocrinopathy. Androgens undeniably play a role in the pathogenesis of isolated acne in infants and children, and timely diagnosis of androgen excess diseases can prevent sequelae, including accelerated bone maturation with ultimate short stature. Only rarely is a life-threatening androgen-secreting tumor responsible. Treatable forms of endocrinopathy are rare in children presenting with acne but without other evidence of androgen excess. In the majority of patients, a directed history and physical examination are sufficient to rule out underlying disease.

Lesions of early onset acne vulgaris are identical to those of adolescent acne, but the distribution is more limited. It often occurs in children with a strong family history of acne. Scarring may be more related to a familial tendency towards scarring than the degree of nodulocystic involvement (Figure 11 and Figure 12). The course of this condition is variable, lasting months to years. Although it usually improves in childhood, it may be a predictor of more severe adolescent acne.

Figure 11.

Early onset acne may leave scars.

Figure 12.

Scarring may be more related to a familial tendency towards scarring than the degree of nodulocystic involvement. This is the mother of the child in Figure 11.

The existing classification system for early-onset acne fails to differentiate the small subset of children at risk for treatable forms of endocrinopathy. A retrospective analysis of our patients with early onset acne identified two age-based cohorts that could logically be referred to as “infantile” and “prepubertal” acne (Table II). The infantile group included slightly less than half who all developed acne before the age of 18 months. In this subset, two thirds were male with weights above the seventy-fifth percentile in 50%, while height was above the seventy-fifth percentile in only 14%, reflecting an average body mass index in the obese range, more than 20 kg/meter squared. Their lesions were predominantly inflammatory, and limited to the cheeks (Figure 13). None of the patients in this group exhibited signs of virilization.

Table II.

Benign subsets of early-onset acne vulgaris
Infantile Prepubertal
Onset Prior to 18 months After age 2
Gender predominance Male Female
Primary lesion type Inflammatory lesions Comedones
Distribution Cheeks only Forehead, cheeks, back
Average height < 50% tile >75% tile
Average BMI >20 15
Possible pathophysiology Testicular and adrenal androgen secretion Accelerated adrenarcheA possible sign of early PCOS

Figure 13A.

Infantile acne features a predominance of inflammatory lesions limited to the cheeks and notably sparing other sites.

Figure 13B.

The prepubertal acne group comprised slightly more than half of the patients, who all developed acne after age 2. In this cohort, three quarters were girls with primarily comedonal acne involving the forehead, nose, cheeks and less often, the upper back. Both weight and height were above the seventy-fifth percentile in over two thirds of these patients with an average body mass index in the healthy range at 15 kg/m2. Four girls in the prepubertal group, had early signs of puberty, including accelerated height velocity, body odor or pubic hair. The only abnormal diagnostic test was an accelerated bone age in two of them. All four were diagnosed with isolated premature adrenarche, characterized by adrenal androgen production and increases in dehydroepiandrosterone (DHEA) and DHEA-S.

Premature adrenarche may be a presenting sign of the incompletely understood spectrum of disorders variably known as polycystic ovarian syndrome (PCOS), metabolic syndrome or “Syndrome X.” While it is important to recognize this phenotype, current treatment recommendations are not based on laboratory abnormalities but focus on a healthy diet and regular exercise.

The risk of virilizing endocrinopathy in a child with acne vulgaris has been overemphasized by a bias towards publishing isolated, memorable cases. These cases have led some authors to recommend extensive laboratory evaluation and endocrine consultation for children with early onset acne. However, a literature review indicates a very low risk of true precocious puberty in infants and children with acne vulgaris but no other signs of virilization. In these cases, additional laboratory evaluation and subspecialty referral is superfluous and provokes needless parental angst.

Adequate screening evaluation of children with acne vulgaris requires only a directed history and physical examination. The history should include age of acne onset, duration of disease, growth parameters, and age of onset for any early signs of virilization, such as body odor, axillary or pubic hair. The physical examination should include height, weight, types and location of acne, and signs of puberty, (body odor, axillary and pubic hair, breast buds, enlarged phallus, testis or clitoris). Laboratory evaluation is only indicated for patients with other signs of virilization. Hand film for bone age is a simple, practical initial screen. Anticipatory guidance and long-term follow-up is indicated in all cases.

Early-onset acne is also a feature of a few rare genetic diseases (Table III). Treatment is the same for children with acne who have one of these syndromes. A short list of medications includes drugs that have been observed to trigger acne in neonates and children (Table IV). In these cases, optimal treatment is discontinuation of the drug. When this is not possible, standard treatment may help control the acne.

Table III.

Nonandrogenic syndromes associated with early-onset acne
Chronic granulomatous disease
Apert syndrome
Patau syndrome (trisomy 13)
Fetal hydantoin syndrome
PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne)
SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis)
Borrone dermatocardioskeletal syndrome

Table IV.

Drugs associated with early-onset acne (including maternal-fetal exposure)
Azathioprine
Cyclosporine
Corticosteroids
Lithium carbonate
Phenytoin
Phenobarbital
Isoniazid
Vitamins B2, B6, B12

Who is at Risk for Developing this Disease?

Neonates who have been exposed to transiently elevated androgens, including androgens of maternal origin and placentally transferred, or neonatal adrenal, or testicular androgens.

Infantile acne often occurs in children with a strong family history of acne. Scarring may be more related to a familial tendency towards scarring than to the degree of nodulocystic involvement

What is the Cause of Neonatal Acne?

  • Etiology

  • Pathophysiology

Neonatal acne has been attributed to transiently elevated androgens, of either maternal origin and placentally transferred, or neonatal adrenal or testicular androgens.

In infantile acne, androgens undeniably play a role in the pathogenesis of the disorder, but their role may be over-emphasized. Although the timely diagnosis of androgen excess diseases can prevent sequelae, including accelerated bone maturation with ultimate short stature, only rarely is a life-threatening androgen-secreting tumor responsible. Other treatable forms of endocrinopathy are rare in children presenting with acne but without other evidence of androgen excess.

Systemic Implications and Complications

Although the possibility of an excess androgen state must be considered, the risk of virilizing endocrinopathy in a child with acne vulgaris has been overemphasized by a bias towards publishing isolated, memorable cases. These cases have led some authors to recommend extensive laboratory evaluation and endocrine consultation for children with early onset acne. However, a literature review indicates a very low risk of true precocious puberty in infants and children with acne vulgaris but no other signs of virilization. In these cases, additional laboratory evaluation and subspecialty referral is superfluous and provokes needless parental angst.

Adequate screening evaluation of children with acne vulgaris requires only a directed history and physical examination. The history should include age of acne onset, duration of disease, growth parameters, and age of onset for any early signs of virilization, such as body odor, axillary or pubic hair. The physical examination should include height, weight, types and location of acne, and signs of puberty, (body odor, axillary and pubic hair, breast buds, enlarged phallus, testis, or clitoris). Laboratory evaluation is only indicated for patients with other signs of virilization. Hand film for bone age is a simple, practical initial screen. Anticipatory guidance and long-term follow-up is indicated in all cases.

Treatment Options

Topical therapy

-benzoyl peroxide

-salicylic acid

-retinoids (tretinoin, adapalene, tazarotene)

-antibiotics (erythromycin, clindamycin)

-others (azaleic acid, niacinamide, sodium sulfacetamide, dapsone)

Systemic agents

-antibiotics (erythromycin as the first choice, ampicillin, trimethoprim-sufamethoxisole)

-isotretinoin

Optimal Therapeutic Approach for this Disease

Therapeutic choices for children with early-onset acne vulgaris are similar to medications used for adolescents, with a few exceptions. Initial treatment is with topical monotherapy using once daily salicylic acid 2% or a retinoid (tretinoin 0.05%, adapalene 0.1%, tazarotene 0.1%). Combination therapy may be used in more severe or persistent cases by adding once daily benzoyl peroxide and erythromycin or clindamycin. Use products with lower concentrations formulated in vehicles with low potential for irritation. There are no data on the use of azeleic acid and niacinamide, and greater potential risks in this age group from other active ingredients such as sodium sulfacetamide and dapsone.

For infants and children with more severe disease, second line therapy is with an oral antibiotic, but choices are more limited than for adolescents. Use of tetracyclines is contraindicated in children under age 8. Of the other antibiotics widely used for acne, erythromycin has the best safety profile in children. The dose is 10-15mg/kg/dose, given 3 times a day. However, nausea, abdominal pain and diarrhea are common side effects and generic preparations are increasingly hard to find. Other macrolides, (azithromycin and clarithromycin), and penicillins are more well-tolerated, but not well studied for this indication. In addition, the newer macrolides have a greater spectrum of antimicrobial activity.

Trimethoprim/sulfamethoxazole has also been used to treat acne, but carries the rare but serious risks for agranulocytosis and Stevens-Johnson syndrome. Long-term use of any antibiotic is associated with alterations in skin, oropharynx, and gut bacterial colonization and may carry a higher risk of microbial resistance. The implications of this treatment in young children are unclear.

Isotretinoin is an option for children with scarring disease (Figure 14 and Figure 15). Like the majority of medications that have earned a USFDA indication for acne vulgaris, isotretinoin is not approved for use in children. Nevertheless, there is broad experience using isotretinoin in children for thetreatment of early onset acne, severe forms of ichthyosis, and neuroblastoma.

Figure 14.

This infant had severe nodulocystic acne that required treatment with isotretinoin.

Figure 15.

The infant pictured in Figure 14 at age 7, 5 years after completing 150mg/kg isotretinoin. He had residual scarring but no active acne.

The dose for acne is 0.2-1.5mg/kg/day. The medication is formulated as a liquid in a soft gelatin capsule. The smallest sizes are 10 and 20 mg. The capsule is easily swallowed, but can be pierced and chewed. However, drug stability and bioavailability may be compromised by out-of-capsule administration. To optimize dosing for children who cannot swallow whole capsules, instruct caregivers to open the capsule in dim light. Bioavaility is enhanced when the drug is taken twice daily with food. The capsule contents can be mixed with a soft food or spread on a slice of bread topped with jam. A 5mg dose is possible by cutting a frozen 10mg capsule and administering it in a strongly flavored sweet food such as a caramel.

Although pregnancy is not an issue,PLEDGE restrictions apply in treating prepubertal children. The FDA is aware that additional information is needed on the pharmacokinetic effects of route of administration, and that a stable formulation suitable for young children and safe for handling by women of child-bearing potential would be optimal.

Patient Management

Although an associated endocrinopathy is unlikely, one should obtain a history that includes age of acne onset, duration of disease, growth parameters, and age of onset for any early signs of virilization, such as body odor, axillary or pubic hair. The physical examination should include height, weight, types and location of acne, and signs of puberty, (body odor, axillary and pubic hair, breast buds, enlarged phallus, testis, or clitoris). Laboratory evaluation is indicated only for patients with other signs of virilization. Hand film for bone age is a simple, practical initial screen. Anticipatory guidance and long-term follow-up is indicated in all cases.

Regarding treatment itself, a combination of topical and systemic agents may be necessary depending on the severity of the presentation, degree of inflammation, and risk of scarring. Explain to the parents that the foremost goal of treatment is to minimize the risk of scarring; the condition is likely to improve, and the treatments tapered or discontinued based on the patient's progress.

In more severe cases, there may be an increased risk for more severe acne in adolescence. Treatment should begin early in adolescence if acne develops.

Unusual Clinical Scenarios to Consider in Patient Management

There are rare genetic syndromes associated early onset acne, which are not dependent on androgens. These include:

-chronic granulomatous disease

-Apert syndrome

-Patau syndrome (trisomy 13)

-fetal hydantoin syndrome

-PAPA syndrome -SAPHO

-Borrone dermatocardioskeletal syndrome (a severe progressive disorder characterized by thick skin, acneconglobata, "coarse" face, osteolysis, gingival hypertrophy,brachydactyly, camptodactyly, and mitral valve prolapse)

Drugs may also be associated with early-onset acne; in some cases, this may be due maternal fetal exposure. These drugs include:

-azathioprine

-cyclosporine

-corticosteroids

-lithium carbonate

-phenytoin

-phenobarbital

-isoniazid

-vitamins B2, B6, B12

What is the Evidence?

Aitken, R. "Acne vulgaris in infants". Br J Dermatol. vol. 54. 1999. pp. 272.

(This is a review article summarizing well-accepted nomenclature of the twentieth century.)

Ayhan, M, Sancak, B, Karaduman, A, Arikan, S, Sahin, S. "Colonization of neonate skin by Malassezia species: relationship with neonatal cephalic pustulosis". J Am Acad Dermatol. vol. 57. 2007. pp. 1012-8.

(A prospective study of Malassezia colonization on skin from 104 neonates that found no correlation with neonatal cephalic pustulosis.)

Hello, M, Prey, S, Léauté-Labrèze, C, Khammari, A, Dreno, B, Stalder, JF, Barbarot, S. "Infantile acne: a retrospective study of 16 cases". Pediatr Dermatol. vol. 25. 2008. pp. 434-8.

(This is a retrospective review of children under age 2. None had associated endocrinopathy. Two thirds had a family history of severe adolescent acne. The average duration of disease was 22 months. Two were treated with isotretinoin. More than half had residual scars.)

De Raeve, L, De Schepper, J, Smitz, J. "Prepubertal acne: a cutaneous marker of androgen excess". J Am Acad Dermatol. vol. 32. 1995. pp. 181-4.

(A 15-case series of children with early onset acne. Two with pubic hair and advanced bone age had 21 hydroxylase deficiency.)

Kousta, E. "Premature adrenarche leads to polycystic ovary syndrome? Long-term consequences". Ann N Y Acad Sci. vol. 1092. 2006. pp. 148-57.

(This is a review article summarizing premature adrenarche and proposing that this condition may be a forerunner of PCOS and the metabolic syndrome.)

Strahan, JE, Burch, JM. "Cyclosporine-induced infantile nodulocystic acne". Arch Dermatol. vol. 145. 2009. pp. 797-9.

(This is a case report and literature review featuring of a 9-month-old heart transplant patient with cyclosporine-induced nodulocystic acne. Work-up for endocrinopathy was negative. Cyclosporine was discontinued and he was successfully treated with isotretinoin.)

Antoniou, C, Dessinioti, C, Stratigos, AJ, Katsambas, AD. "Clinical and therapeutic approach to childhood acne: an update". Pediatr Dermatol. vol. 26. 2009. pp. 373-80.

(This is a review on the subject of early onset acne, including the use of isotretinoin.)

Barnes, CJ, Eichenfield, LF, Lee, J, Cunningham, BB. "A practical approach for the use of oral isotretinoin for infantile acne". Pediatr Dermatol. vol. 22. 2005. pp. 166-9.

(A report of 2 cases of severe infantile acne without associated endocrinopathy, both were treated with isotretinoin, that includes a review of the literature and practical tips for administering isotretinoin to infants.)

Kuiri-Hänninen, T, Haanpää, M, Turpeinen, U, Hämäläinen, E, Dunkel, L, Sankilampi, U. "Transient postnatal secretion of androgen hormones is associated with acne and sebaceous gland hypertrophy in early infancy". J Clin Endocrinol Metab. vol. 98. 2013. pp. 199-206.

Bree, AF, Siegfried, EC. "Acne vulgaris in preadolescent children: recommendations for evaluation". Pediatr Dermatol.. vol. 31. 2014. pp. 27-32.

(This retrospective analysis of patients with preadolescent acne identified two age-based cohorts: a predominately male infantile group who developed acne before age 18 months and had no signs of virilisation; and a predominately female prepubertal group who developed acne after age 2. A minority of girls in this group had early signs of puberty associated with isolated premature adrenarche.)

Eichenfield, LF, Krakowski, AC, Piggott, C, Del Rosso, J. "American Acne and Rosacea Society.Evidence-based recommendations for the diagnosis and treatment of pediatric acne". Pediatrics.. vol. 131 Suppl 3. 2013. pp. S163-86.

(2013 consensus panel recommendations for diagnosis and treatment of acne in children.)

Miller, IM, Echeverría, B, Torrelo, A, Jemec, GB. "Infantile acne treated with oral isotretinoin". Pediatr Dermatol.. vol. 30. 2013. pp. 513-8 .

(A retrospective case series of infants with severe acne successfully treated with isotretinoin.)
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