8/18/2019 Pde 12238

1/6

Acne Vulgaris in Preadolescent Children:Recommendations for Evaluation

Alanna F. Bree, M.D.,* and Elaine C. Siegfried, M.D.†,‡

*Baylor College of Medicine, Houston, Texas, †Cardinal Glennon Children’s Hospital, St. Louis, Missouri, ‡Saint

Louis University School of Medicine, St. Louis, Missouri 

Abstract:   Acne vulgaris in infants and children often triggers exten-sive laboratory evaluation out of concern about associated endocrinop-

athy. Clinical parameters to help guide evaluation of these children havenot been defined. This was a retrospective chart review of 24 preadoles-

cent patients with acne and a review of related medical literature. Two age-

related subsets were identified: 12 patients who developed acne before

the age of 15 months, 75% male, with comedonal and inflammatory

lesions; and 12 patients who developed acne between the ages of 2 and

7 years, 75% female, with primarily comedonal lesions. Laboratory

evaluation in 13 of the patients was unremarkable. Bone age was

advanced in 1 of the 11 children imaged. Premature adrenarche was

diagnosed in four patients; all four had additional clinical signs of puberty

and growth parameters   >90th percentile. None required additional treat-

ment. Our cohort of preadolescent children presenting with acne included

an equal number of patients in two distinct subsets: infantile and

childhood-onset acne. Literature review identified a rare third subsetpresenting with acne, signs of advanced puberty, and associated endo-

crinopathy. There was no evidence of endocrinopathy in our patients with

infantile acne. Two-thirds of our patients with childhood-onset acne had

no additional clinical signs of puberty and no evidence of endocrinopathy.

A focused history and physical examination is sufficient to evaluate the

majority of infants and children with acne. Hand X-ray for bone age is a

useful screening test. Further evaluation and endocrinology referral are

warranted in preadolescents with acne and advanced bone age or

additional clinical evidence of early puberty.

Acne vulgaris affects up to 95% of teenagers and

young adults (1) but can begin in infancy and earlychildhood.   Acne neonatorum   was first reported in

1913, followed by a review on the subject of infantile

acne in 1945 (2). A comprehensive search of themedical literature for relevant data on this acne subset

Address correspondence to Elaine C. Siegfried, M.D., 1465South Grand Blvd, Saint Louis, MO 63104, or e-mail: esiegfri@slu.edu.

This work was presented in poster format at the 29th AnnualMeeting of the Society for Pediatric Dermatology, Seattle,Washington, June 19, 2003.

DOI: 10.1111/pde.12238

© 2013 Wiley Periodicals, Inc.   27

Pediatric Dermatology Vol. 31 No. 1 27–32, 2014

8/18/2019 Pde 12238

2/6

yielded fewer than 25 papers, largely descriptive. The

most recent classification of pediatric acne based on

expert consensus includes five subgroups defined

largely according to age of onset: neonatal, infantile,

midchildhood, preadolescent, and adolescent (3).

Neonatal acne has been defined as onset in infants

younger than 6 weeks old. In most cases, neonatal

acne is not typically true acne vulgaris but a transient

acneiform eruption, with the most common of these

being neonatal cephalic pustulosis, which is thought

to be caused by colonization of   Malassezia   (4). An

important concern for older infants and children with

infantile or midchildhood acne vulgaris is that it may

be a presenting sign of a treatable endocrinopathy

(3,5,6). Timely diagnosis and treatment of androgen

excess can prevent sequelae, including accelerated

bone maturation, which may result in short adult

stature. Recognition of this entity may also lead to

detection of rare, but life-threatening, androgen-secreting tumors, although a classification system

based simply on age of onset does not help distinguish

children with androgen excess.

The goal of this study was to establish an approach

to the evaluation of infants and children presenting

with acne based on a retrospective analysis of a cohort

of preadolescent patients seen over 5 years at an

academic dermatology clinic as well as a critical

review of the literature.

MATERIALS AND METHODS

We performed a retrospective chart review of 24

infants and children with a diagnosis of acne vulgaris

evaluated over a 5-year period at Saint Louis Uni-

versity. Subjects were chosen from patients evaluated

during that period who were ages 0 to 14 years old

who developed acne at the age of 7 years or younger

and who had a full history and physical examination

documenting pertinent positive and negative findings.

For included subjects, a complete medical history had

been obtained, including age of acne onset and

duration of disease, type of treatment, growth, devel-

opmental milestones, menarche, breast development,

and presence of body odor and axillary or pubic hair.

Pertinent physical examination parameters included

height, weight, types and location of acne, and signs of 

puberty (body odor, axillary and pubic hair, breast

buds, genital development). Diagnostic testing, per-

formed on 13 of the 24 subjects, which was not based

on uniform clinical characteristics, may have included

dehydroepiandrosterone sulfate, free and total testos-

terone, urine 17-ketosteroids, cortisol, 17-hydroxy-

progesterone, androstenedione, estradiol, and in some

cases cosyntropin stimulation test, dexamethasone

suppression test, and hand X-ray for bone age.

RESULTS

Twenty-four patients (12 female, 50%) were included

in the analysis. All were Caucasian. The age of acne

onset ranged from 1 week to 7 years. Further anal-

ysis of the type and distribution of lesions identified

two separate, age-related subsets. The first subset

consisted of 12 patients (50%) with an onset of acne

between 1 week and 14 months of age, 75% of whom

were male. Their lesions were predominantly mixed

comedonal and inflammatory, and in all 12 (100%),

lesions were limited to the cheeks (Fig. 1A). The

second subset consisted of 12 patients (50%) whoseacne began between 2 and 7 years of age, 75% of 

whom were female (75%). The majority of their

lesions were comedonal and were distributed on the

forehead, nose, and cheeks (Fig. 1B). Weight in those

that had been weighed was greater than the 75th

percentile in 89% of the first group and 67% of the

second group, and height in those measured was

A   B

Figure 1.   (A) A 9-month-old boy with comedonal and inflammatory lesions on the cheeks, typical of infantile acne. ( B) A3-year-old boy with primarily comedonal acne on the midface, typical of midchildhood onset. (Photo courtesy of AndreaZaenglein.)

28 Pediatric Dermatology Vol. 31 No. 1 January/February 2014

8/18/2019 Pde 12238

3/6

greater than the 75th percentile in 42% of the first

group and 67% of the second group (Table 1). None

of the patients in the first group and six in the second

group (50%) exhibited pubarche, body odor, thelar-

che, or menarche. Blood work was performed in 7

(29%) patients and bone age was determined in 11

(46%). The only abnormal diagnostic test identified

in this cohort was bone age, with one patient in the

second subset (8%) having advanced bone age. There

were no identified cases of congenital adrenal hyper-

plasia, androgen-secreting tumor, or central preco-

cious puberty in the 13 patients who had a diagnostic

evaluation, and these conditions were not suspected

in the remaining 11 because they did not have other

signs of advanced puberty. There were no diagnosed

endocrinopathies in the first group, but four female

subjects in the second group had premature adren-

arche. All four of these girls (100%) had other

clinical signs of advanced puberty; four had growthparameters above the 90th percentile, two had body

odor, three had breast development, three had pubic

hair, and one was postmenarchal. One was also noted

to have acanthosis nigricans.

DISCUSSION

The most recent classification of pediatric acne is an

age-based, descriptive, five-group categorization: neo-

natal, infantile, midchildhood, preadolescent, and

adolescent (3). The existing classification systems are

based on collective expert opinion or long-standingobservations that have been propagated in the litera-

ture (3,6). Therefore they fail to distinguish which

children with early onset acne are truly at risk of 

treatable forms of virilizing endocrinopathy and there-

fore should undergo a more extensive examination.

Puberty, with a mean onset of 10.2 years in

Caucasian girls and 9.6 years in African American

girls (5), is characterized by a variable combination of 

several signs: adrenarche, pubarche, gonadarche,

thelarche, and menarche. Adrenarche represents mat-

uration of the adrenal gland, characterized by adrenal

androgen production and increases in return of the

zona reticularis and acquisition of the enzymes that

facilitate synthesis of androgens from cholesterol.

This increase in androgen production is measured

by an increase in the serum levels of dehydroepiand-

rosterone and dehydroepiandrosterone sulfate (7).

TABLE 1.   Clinical Characteristics of the Preadolescent Study Patients with Acne

SubjectAge of onset Sex

Lesiontype

Additional signs of advanced puberty

Height Weight

Endocrinologic evaluation and examinationPercentile

1 2 mos Male C, I None ND   >95 No2 2 wks Female I None ND 80 No3 6.5 yrs Female C Body odor, thelarche ND ND No4 5 yrs Female C Axillary hair, body odor   >95   >95 Normal laboratory results, advanced bone age,

premature adrenarche5 1 mo Male C, I None 55 80 Normal laboratory results and bone age6 3 mos Male C, I None 90   >95 No7 6 yrs Male C None ND ND No8 2 mos Male I None 75 80 No9 10 mos Female I None ND ND No

10 7 yrs Female C, I None ND ND No11 13 mos Male I, N None ND ND Normal bone age12 6 yrs Female C, I None 45 55 Normal bone age13 1 yr Female I, N None ND ND No14 14 mos Male C, I, N None 10   >95 Normal laboratory results15 7 yrs Male I None 90 50 Normal bone age

16 2 wks Male C, I None 10 80 Normal bone age17 29 mos Female I None 70 90 Normal laboratory results18 6 yrs Female C Body odor, pubarche,

thelarche95 90 Normal la bor atory re sult s and b one age ,

premature adrenarche19 2 mos Male C None 10   95 95 Normal la bor atory re sult s and b one age ,

premature adrenarche24 6 yrs Female C, I Axillary hair, pubarche,

thelarche, menarche90   >95 Normal laboratory results and bone age,

premature adrenarche

C, comedonal; I, inflammatory (papules and pustules); N, nodules; ND, not determined.

Bree and Siegfried: Preadolescent Acne Vulgaris 29

8/18/2019 Pde 12238

4/6

Pubarche is defined according to the appearance of 

pubic hair, which is causally related to adrenarche,

and clinically may mark true pubertal maturation (8).

Premature pubarche is defined by the presence of 

pubic hair before the age of 8 years in girls and before

the age of 9 years in boys (7,9). Gonadarche is the

activation of the hypothalamic – pituitary – gonadal

axis, which manifests as thelarche in girls and testic-

ular enlargement in boys (9). Thelarche is demon-

strated by the presence of palpable breast tissue below

the areola. The average age of onset is 9 to 10 years

(range 8 – 13 yrs) (9). Finally, menarche is defined as

the first menses, with the average onset of 12.5 years

in Caucasians (range 10 – 16 yrs), and 12.0 years in

African Americans (5,9).

Adrenal androgens play an important role in the

pathogenesis of acne vulgaris, but the precise nature

of this role has been elusive (10,11). The most

common identifiable androgenic abnormality associ-ated with acne vulgaris is a marginal, but statistically

significant, increase in adrenal androgens, usually

within a normal defined range (12,13). Studies suggest

that rising levels of ovarian androgens at adrenarche

may be responsible for early onset acne in girls (14),

whereas adrenal and testicular androgens trigger acne

in pubertal boys (15,16).

Any of the signs of puberty can occur prematurely

as an isolated abnormality. The diagnosis of preco-

cious puberty, precocious pseudopuberty, and pre-

mature adrenarche can be controversial because

clinical signs may not be associated with measurablestandard biochemical markers, and published defini-

tions differ, with many not including acne as a sign of 

these conditions (17). Low birthweight has been

implicated as a risk factor for premature adrenarche,

but others have not confirmed this correlation,

although there is some evidence that low birthweight

is associated with higher androgen levels in childhood

(17). Other associations with premature adrenarche

include impaired insulin sensitivity, possible dyslipi-

demia, and proinflammatory shift of the adipokine

profile that is commonly seen in polycystic ovarian

syndrome (17).

There is also debate regarding the long-term risksand follow-up of children with isolated signs of 

advanced puberty (7,9,10,14,18), but recent literature

supports following patients with signs of early onset

androgen excess, including those with premature

adrenarche, because they appear to have a risk of 

metabolic syndrome (17). This spectrum of disorders,

including polycystic ovarian syndrome and metabolic

syndrome (or syndrome X) (10,12), has been best

characterized in adults, but premature adrenarche

may be the first sign of these conditions in childhood

(17). Although it is important to recognize this

phenotype, current treatment recommendations are

not based on laboratory abnormalities or pharmaco-

therapy, but focus on a healthy diet and regular

exercise whereas in girls with a history of low birth

weight and precocious pubarche, early metformin

therapy seemed to prevent or delay the development

of hirsutism, androgen excess, and oligomenorrhea

(19).

One report of two toddlers and two case series

including 45 infants and toddlers with acne found no

evidence of androgen excess or other clinical signs of 

virilization (20 – 22). Isolated case reports such as

that of a 23-month-old boy with infantile acne and

an occult adrenocortical tumor have offset these

reassuring numbers, although this patient also had

several other signs of androgen excess, including

large hands, large phallus, and facial, axillary, andpubic hair (23). Another case series focused on 25

girls diagnosed with virilization who all had multiple

signs of androgen excess, including seven with acne

(24). Three of the seven were diagnosed with isolated

adrenarche. Two had congenital adrenal hyper-

plasia and two had virilizing tumors, and all four

of these girls with associated endocrinopathy had

above average height and advanced bone age in

addition to multiple virilizing signs. A report of 

fifteen 5- to 10-year-old children who presented with

acne before age 8 years emphasized the importance

of hormonal evaluation (7). Extensive laboratoryevaluation confirmed congenital adrenal hyperplasia

in two girls, but both of these girls also had

pubarche and advanced bone age. All of the children

with acne but without pubic hair had normal

endocrine evaluation.

Our study identified two subsets of patients with

preadolescent acne vulgaris based on clinical charac-

teristics. The first subset, which closely correlates to

the recent classification of infantile acne (3), is

characterized by onset of acne before 18 months of 

age, male predominance, mixed comedonal and

inflammatory lesions involving only the cheeks, and

no other clinical signs of androgen excess. There wereno children identified with underlying endocrinopathy

in the infantile group. The second subset, which

closely correlates to the recent classification of mid-

childhood acne (3), is characterized by onset after

18 months of age, female predominance, and a high

proportion of comedones located on the forehead,

cheeks, and chin; half of the patients in this subset had

additional signs and symptoms of puberty. There were

four cases of premature adrenarche in this childhood

30 Pediatric Dermatology Vol. 31 No. 1 January/February 2014

8/18/2019 Pde 12238

5/6

group, but all had growth parameters greater than the

90th percentile and additional signs of advanced

puberty (Table 2).

Therefore most cases of preadolescent acne, similar

to children with premature pubarche (25), are not

associated with virilizing endocrinopathies. They may

instead represent a functional hyperandrogenism that

could be the earliest sign of polycystic ovarian

syndrome or a metabolic syndrome phenotype. In

these cases, the children are not at risk for advanced

gonadarche or compromised final height (9,24), but are

at risk of more severe or prolonged acne in adolescence

or adulthood (18). Infants and children with patho-

logic forms of acne always have other clinical signs of 

androgen excess — most often accelerated height veloc-

ity, body odor, pubic hair, and enlarged genitalia.

Deadly adrenocortical tumors are rare, accounting for

only 0.02% of pediatric neoplasms (23).

We feel that a bias toward publishing isolated,

memorable cases has overemphasized the risk of 

TABLE 2.   Subsets of Acne Vulgaris in Preadolescent Children

Factor Infantile onset Childhood onset Endocrinopathy associated

Onset Before 18 mos old After 18 mos old Any ageSex predominance Male Female NonePrimary lesion type Mixed comedones and

inflammatory lesions

Comedones All types

Distribution Cheeks only Forehead, nose, cheeks Face, chest, backAverage height, percentile   75 Typically advancedAverage body mass index, kg/m2 >20 15 Typically highAssociated clinical findings None May have advanced signs of puberty Always has advanced signs of pubertyPossible pathophysiology Testicular and adrenal

androgen secretionAccelerated adrenarche — a

possible early sign of polycysticovarian syndrome

Underlying endocrine abnormality

History: Physical Exam: Growth Curve:

- age of onset - axillary hair - height

- body odor - breast development - weight

- axillary/pubic hair - g enital development - B MI

- breast development - escutcheon

- menarche

Any HistoryAND/OR

Physical Examparameter

Refer to Pediatric

Endocrinology

Any Growth Curveparameter

Assess bone age

Refer to PediatricEndocrinology

No further work-up needed;

connue follow-up for new signsof early puberty

History, Physical Exam

AND Growth Curves

No further work-up needed;

connue follow-up for new signsof early puberty

abnormal

WNL

WNL≥ 2 SD above the norm

Figure 2.   Evaluation algorithm for a preadolescent child presenting with early onset acne vulgaris. BMI, body mass index;WNL, within normal limits; SD, standard deviation.

Bree and Siegfried: Preadolescent Acne Vulgaris 31

8/18/2019 Pde 12238

6/6

endocrinopathy in children with acne vulgaris. These

cases have led some authors to recommend extensive

laboratory evaluation and endocrine consultation for

all children with midchildhood and prepubertal acne

(6,26), but our study and review of the literature

indicates a low risk of true endocrinopathy in infants

and children with acne vulgaris who have no other

signs of androgen excess. Concern about preventable

sequelae of precocious puberty is often dispropor-

tionate to the risk in children with early onset acne. In

these cases, additional investigative examination is

often superfluous and provokes needless parental

angst.

Based on our data and review of prior reports in

the literature, we recommend a focused history and

physical examination, which should include a growth

curve, for all children age 7 years and younger with

acne (Fig. 2). A left hand and wrist X-ray for bone

age is a sufficient initial screening test for those withhigh growth parameters. If there is evidence of 

advanced bone age, or if there are any additional

symptoms or signs of advanced puberty, pediatric

endocrinology referral is recommended because this

is the subset of children who seem to be at risk of 

possible underlying endocrinopathy. The develop-

ment of acne in childhood, along with premature

adrenarche, may be the initial sign of polycystic

ovarian syndrome or metabolic syndrome (2,3,12,

17,27), so anticipatory guidance and follow-up is

indicated in all cases of acne vulgaris in preadoles-

cent children.

REFERENCES

1. Cordain L, Lindeberg S, Hurtado M et al. Acnevulgaris: a disease of Western civilization. ArchDermatol 2002;138:1584 – 1590.

2. Aitken R. Acne vulgaris in infants. Br J Dermatol1999;54:272.

3. Eichenfield LF, Krakowski AC, Piggott C et al. Evi-denced-based recommendations for the diagnosis andtreatment of pediatric acne. Pediatrics 2013;131:S163 – S186.

4. Bernier V, Weill FX, Hirigoyen V et al. Skin coloniza-

tion by Malassezia species in neonates: a prospectivestudy and relationship with neonatal cephalic pustulo-sis. Arch Dermatol 2002;138:215 – 218.

5. Biro FM, Huang B, Crawford PB et al. Pubertalcorrelates in black and white girls. J Pediatr2006;148:234 – 240.

6. Antoniou C, Dessinioti C, Stratigos AJ et al. Clinicaland therapeutic approach to childhood acne: an update.Pediatr Dermatol 2009;26:373 – 380.

7. De Raeve L, De Schepper J, Smitz J. Prepubertal acne: acutaneous marker of androgen excess? J Am AcadDermatol 1995;32:181 – 184.

8. Biro FM, Huang B, Daniels SR et al. Pubarche as wellas thelarche may be a marker for the onset of puberty.J Pediatr Adolesc Gynecol 2008;21:323 – 328.

9. Iba~nez L, Dimartino-Nardi J, Potau N et al. Prematureadrenarche — normal variant or forerunner of adultdisease? Endocr Rev 2000;21:671 – 696.

10. Kousta E. Premature adrenarche leads to polycysticovary syndrome? Long-term consequences. Ann N YAcad Sci 2006;1092:148 – 157.

11. Strickland J, Hornberger L. Female pubertal growthand development. J Pediatr Adolesc Gynecol2005;18:363 – 366.

12. Dimartino-Nardi J. Pre- and postpuberal findings inpremature adrenarche. J Pediatr Endocrinol Metab2000;13:1265 – 1269.

13. Rosenfield RL, Lucky AW. Acne, hirsutism, andalopecia in adolescent girls. Clinical expressions of androgen excess. Endocrinol Metab Clin North Am1993;22:507 – 532.

14. Lucky AW, Biro FM, Huster GA et al. Acne vulgaris inpremenarchal girls. An early sign of puberty associatedwith rising levels of dehydroepiandrosterone. ArchDermatol 1994;130:308 – 314.

15. Herane MI, Ando I. Acne in infancy and acne genetics.Dermatology 2003;206:24 – 28.

16. Tabata N, Terui T, Watanabe M et al. Infantile acneassociated with a high plasma testosterone level in a21-month-old boy. J Am Acad Dermatol 1995;33:676 – 678.

17. Idkowiak J, Lavery GG, Dhir V et al. Prematureadrenarche: novel lessons from early onset androgenexcess. Eur J Endocr 2011;165:189 – 207.

18. Lucky AW, Biro FM, Huster GA et al. Acne vulgaris inearly adolescent boys. Correlations with pubertalmaturation and age. Arch Dermatol 1991;127:210 – 216.

19. Ibanez L, Lopez-Bermejo A, Diaz M et al. Earlymetformin therapy (age 8 – 12 years) in girls with preco-cious pubarche to reduce hirsutism, androgen excess,and oligomenorrhea in adolescence. J Clin EndocrinolMetab 2001;96:E1262 – E1267.

20. Mengesha Y. Toddler-age nodulocystic acne. J Pediatr1999;134:644 – 648.

21. Cunliffe WJ, Baron SE, Coulson IH. A clinical andtherapeutic study of 29 patients with infantile acne. BrJ Dermatol 2001;145:463 – 466.

22. Hello M, Prey S, Leaute-Labreze C et al. Infantile acne:a retrospective study of 16 cases. Pediatr Dermatol2008;25:434 – 438.

23. Mann MW, Ellis SS, Mallory SB. Infantile acne as theinitial sign of an adrenocortical tumor. J Am AcadDermatol 2007;56:S15 – S18.

24. Street ME, Weber A, Camacho-H€ubner C et al. Girlswith virilisation in childhood: a diagnostic protocol for

investigation. J Clin Pathol 1997;50:379 – 383.25. Ibanez L, Diaz R, Lopez-Bermejo A et al. Clinical

spectrum of premature pubarche: links to metabolicsyndrome and ovarian hyperandrogenism. Rev EndocrMetab Disord 2009;10:63 – 76.

26. Marcoux D, McCuaig CC, Powell J. Prepubertal acne:clinical presentation, evaluation and treatment. J CutanMed Surg 1998;2:S2 – S6.

27. Saenger P, Dimartino-Nardi J. Premature adrenarche.J Endocrinol Invest 2001;24:724 – 733.

32 Pediatric Dermatology Vol. 31 No. 1 January/February 2014