Puberty: Physiology and Abnormalities, 1st ed. 2016

14. Pubertal Acne

Devinder Mohan Thappa  and Munisamy Malathi 

(1)

Department of Dermatology and Sexually Transmitted Diseases, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, Pondicherry, 605006, India

Devinder Mohan Thappa (Corresponding author)

Email: dmthappa@gmail.com

Munisamy Malathi

Email: mmalthi.dr@live.com

Keywords

AcneAndrogensChildrenComedonesPubertal

Introduction

Acne, often the first sign of puberty in boys and girls, occurs due to increased sebum production resulting from hormonal surges. Nowadays, the onset of acne in children has been found to oc cur earlier than has been described in the past as evidenced by the declining age of children seeking treatment for acne over time indicating that puberty is occurring earlier [12]. The appearance of mild acne at the pubertal age group is generally not of concern as it represents what may be called the “adrenal awakening.” However, hyperandrogenism and other dermatologic conditions need to be considered in the differential diagnosis when they occur with increased severity warranting detailed evaluation [3]. In addition to the challenging differentiation of the eruptions, treatment also requires special consideration among children of this age group owing to contraindications to the use of certain treatments.

Epidemiology

The epidemiology and demographic profile of acne has changed considerably over the past two decades, to affect children as young as 7 years of age conforming to the documented evidence of e arlier onset of puberty [24]. It has been observed that acne was three times higher in pubertal girls and five times higher in pubertal boys when compared with prepubertal children in whom the prevalence of acne was already high [4]. In recent cross-sectional study involving school children from Lithuania, it was observed that 42 % of those aged 7–9 years and 76 % of those aged 10–12 years had acne indicating an earlier age at onset [4]. Among premenarchal girls, the prevalence of acne ranges between 61 and 71.3 %, and the prevalence and severity of acne increase with advancing pubertal maturation in boys and girls [5].

Gender and ethnic differences exist in the prevalence of pubertal acne. Acne was found to be more prevalent in girls at younger age with increased prevalence among boys as they reached puberty [6]. Also, a decreasing trend in the age at onset of acne has been observed among white children with no significant changing trend among black children with acne owing to the fact that the onset of puberty is earlier in black individuals and sebum production increases during puberty [7]. Thus the prevalence of pubertal acne is higher among black girls. But as most studies till date have focused on Caucasian and black skin types, there are no such studies in Asian or Hispanic patients for comparison [7].

A family history of acne among first-degree relatives especially mothers has been shown to have the strongest impact on prevalence, age at onset, severity, and treatment success of acne in children. Other risk factors include dietary factors with high glycemic load and dairy products and higher body mass index which may be associated with hyperandrogenism which in turn affects sebum production and follicular keratinization resulting in acne [4].

Etiology and Pathogenesis

Pubertal acne occurs prior to true p uberty which is due to maturation of gonads mediated by the hypothalamo-pituitary axis. Prior to puberty, during the period of adrenarche which occurs at the age of 6–7 years in girls and 7–8 years in boys, the adrenal glands secrete increased levels of androgens—dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS)—resulting in reactivation of sebaceous glands. Since DHEAS closely correlates with the initiation of acne, it is known as the “acne hormone” and its levels have been found to correlate with sebum production [5]. However, DHEAS is a weak androgen and is further converted to testosterone, and part of testosterone is converted by 5-alpha reductase to dihydrotestosterone (DHT), which is a more potent androgen, which acts on the skin, penis, prostate, and other tissues. In addition, the skin being an intracrine organ can locally convert DHEA to testosterone and DHT which act on the androgen receptors found in the basal layer of sebaceous glands and follicular keratinocytes, thereby augmenting the androgen-mediated signaling in acne prone skin [8].

During this period, the gonadal androgen secretion is minimal, and ovarian androgen excess should raise the possibility of polycystic ovarian syndrome or rarely ovarian tumors. Low birth weight has been implicated as a risk factor for premature adrenarche, and low birth weight has been associated with higher androgen levels in childhood. Other associations with premature adrenarche include impaired insulin sensitivity, dyslipidemia, and proinflammatory shift of the adipokine profile commonly seen in polycystic ovarian syndrome [5]. The onset of menarche was found to be earlier in girls with severe acne associated with high levels of serum DHEAS. In addition, a high number of comedones , early development of comedones, and high–normal levels of DHEAS, free and total testosterone was found to be predictive for the severity of late inflammatory acne, or persistent acne [5].

The clinical course of acne was found to correspond less closely to plasma androgen levels than it does to growth hormone (GH) and insulin-like growth factor 1 (IGF-1). During puberty, there is an increase in the pulsatile pituitary secretion of GH resulting in a physiological state of transient insulin resistance. GH induces the synthesis and secretion of IGF-1, and all three factors—GH, insulin, and IGF-1—stimulate sebocyte growth and differentiation [8]. IGF-1 enhances the sensitivity of the adrenal gland to ACTH thereby inducing adrenal androgen biosynthesis and product ion of DHEAS, which results in an increase in sebum production and the development of comedonal acne [8].

Thus acne is considered as an androgen-dependent multifactorial disease originating from the pilosebaceous unit that usually starts at puberty when growth hormone (GH), transient insulin resistance, plasma insulin-like growth factor-1 (IGF-1), and androgen plasma levels are elevated [8].

Whatever may be the initiating factor in pubertal acne, the pathogenesis of acne involves a complex interplay of four main factors [910] (Fig. 14.1).

A334826_1_En_14_Fig1_HTML.gif

Fig. 14.1

Pathogenesis of a cne

·               Excess sebum production: Sebum production which is considered the prerequisite for the formation of microcomedone occurs at the onset of puberty due to activation of the sebaceous glands by androgens .

·               Disturbed keratinization within the follicle: Hypercornification of the pilosebaceous duct due to the retention of hyperproliferating ductal corneocytes is modulated by androgens . This along with the irritant effect of certain sebaceous lipids and ductal cytokines leads to microcomedone formation. Sebum and keratinocyte debris accumulate in the microcomedone, resulting in macrocomedones, which clinically manifest as closed or open comedones .

·               Colonization of the pilosebaceous duct by the oxygen-tolerant, anaerobic bacterium Propionibacterium acnes (P. acnes): Presence of seborrhoea at puberty results in marked increase in ductal colonization of facial skin by P. acnes which is likely the prerequisite for acne inflammation.

·               Release of inflammatory mediators into the skinP. acnes stimulates the release of inflammatory mediators into the surrounding perifollicular dermis which act as chemoattractants to immunocompetent cells resulting in the development of inflammatory acne lesions.

Clinical Features

Acne can be clinically categorized based on the predominant morph ology as follows:

1.     (a)

2.     (b)

3.     (c)

The microcomedone resulting from hyperactive sebaceous glands and altered follicular growth and differentiation is the clinically unapparent precursor of both comedonal and inflammatory lesions. Comedones occur due to increased cell division and cohesiveness of cells lining the follicular lum en. Abnormal accumulation of these cells mixed with sebum partially obstructs the follicular opening forming the closed comedone or whitehead. In case of larger follicular opening, increased keratin and sebum buildup with oxidization results in open comedone or blackhead. Inflammatory papules and pustules occur as a result of inflammation mediated by follicular colonization with P. acnes. Nodular acne, characterized by large inflammatory nodules or pseudocysts, is often accompanied by scarring and sinus tracts [511].

The severity of acne can be graded as mild, moderate, or severe (Table 14.1) based on the number and type of lesions and the depth and extent of skin involved [11]. There are many methods of measuring the severity of acne vulgaris which include simple grading based on clinical examination, lesion counting, and those that require complicated instruments such as photography, fluorescent photography, polarized light photography, video microscopy, and measurement of sebum production. The two commonly used measures are grading and lesion counting. Grading is a subjective method, which involves determining the severity of acne, based on observing the dominant lesions, evaluating the presence or absence of inflammation, and estimating the extent of involvement. Lesion counting involves recording the number of each type of acne lesion and determining the overall severity. However, no universal standard exists for grading acne severity till date [12].

Table 14.1

Evidence-based recommendations by the American Acne and Rosacea Society for the treatment of pubertal acne

Grade of acne

Clinical presentation

Initial treatment

Inadequate response

Special remarks

Mild

Predominantly comedonal or mixed comedonal and mild inflammatory disease

Over-the-counter products such as benzoyl peroxide (BP) as a single agent, topical retinoids, or combinations of topical retinoids, antibiotics, and BP as individual agents or fixed-dose combinations

Check adherence

Topical antibiotic monotherapy is not recommended

A topical retinoid or BP may be added to monotherapy with either agent

If topical antibiotic treatment is to be prolonged more than a few weeks, topical BP should be added to optimize efficacy and reduce antibiotic resistance

Concentration, type, and/or formulation of the topical retinoid may be changed, or the topical combination therapy can be changed to topical dapsone

Comparative studies of dapsone versus other topicals are lacking in pediatric patients

Moderate

Predominantly inflammatory or mixed comedonal and marked inflammatory lesions

Topical combinations including a retinoid and BP and/or antibiotics, or with combinations that include topical dapsone or with oral antibiotics in addition to a topical retinoid and BP and/or topical antibiotics

Check adherence

Tetracycline derivatives (tetracycline, doxycycline, and minocycline) should not be used in children <8 years of age

Type, strength, or formulation of the retinoid, BP, or BP-antibiotic component of the topical regimen

Second-generation tetracyclines (doxycycline, minocycline) are preferred to tetracycline in children > 8 years of age because of ease of use, fewer problems with absorption with food, and less-frequent dosing

Referral to a dermatologist or pediatric dermatologist

Monitor for potential adverse events

Discontinue (or taper) within 1–2 months once new inflammatory acne lesions stop

For children <8 years of age and in those with tetracycline allergies, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole should be used

Severe

Extensive inflammatory or mixed and nodular lesions

Oral antibiotics and topical retinoids with BP, with or without topical antibiotics, with consideration of hormonal therapy in pubertal females, oral isotretinoin, and dermatologist referral

Check adherence

Prompt initiation of appropriate treatment to prevent scarring

Change the oral antibiotic agent or the class of antibiotic

Isotretinoin is recommended for severe, scarring, and/or refractory acne in adolescents and may be used in younger patients.

For female patients, combination oral contraceptive (OC) therapy should be considered. Both males and females unresponsive to topical and oral therapies will benefit from oral isotretinoin

Extensive counseling regarding the avoidance of pregnancy as well as careful monitoring of potential side effects and toxicities

Withhold OC for acne unassociated with endocrinologic pathology until 1 year after onset of menstruation

In congenital adrenal hyperplasia, low-dose glucocorticoids are used to suppress the adrenal production of androgens

Based on data from [11]

The prevalence and severity of acne increases with pubertal maturation, and hence comedonal acne predominates in preteens with the onset of facial sebum production, with increasing inflammatory acne developing during the teen years with the colonization by P. acnes [6].

Acne in preadolescent children occurs as a result of normal adrenarche and testicular/ovarian maturation and may precede any other sign of pubertal maturation. In fact the comedonal type of acne can be the first sign of pubertal maturation in girls, even preceding pubic hair and areolar development. With the trend toward earlier age of onset of adrenarche and menarche, there appears to be a downward shift in the age at which acne first appears [5].

Pubertal acne usually presents with comedones with or without inflammatory lesions predominantly affecting the central area of the face, involving the mid-forehead, nose, and chin (“T-zone”) (Fig. 14.2). Comedones of the ear (concha) can be an early presentation. Inflammatory acne lesions may involve the face, chest, and back. However, in the case of severe acne with nodules and cysts, the lesions might involve the arms, abdomen, buttocks, and scalp in addition to the face, chest, and back [8].

A334826_1_En_14_Fig2_HTML.gif

Fig. 14.2

Pubertal acne affects “T”-zone of the face

Since acne may be the first physical sign of pubertal maturation in some girls, the presence of severe acne in prepubertal girls that is unresponsive to treatment and if associated with other signs of excess androgens should raise a suspicion of possible endocrine disorders such as premature adrenarche, polycystic ovarian syndrome, congenital adrenal hyperplasia, or true precocious puberty [611].

In the largest population-based study on pubertal acne involving 6200 Caucasian boys, the interrelations between the presence of acne and several variables associated with somatic growth, pubertal maturation, and environmental conditions (altitude and regions of residence) were studied [13]. They observed that 12–15-year-old boys with acne were taller and heavier than the ones without acne, and they also had increased penile length and circumference as well as larger testicular volumes. However, there were no differences in the somatometric and pubertal characteristics of 17–19-year-old boys with and without acne. Overall, the prevalence of acne among Caucasian boys was 7.74 %. There was no difference in the acne prevalence between the rural and urban inhabitants, but they made an interesting observation that the risk for acne development was significantly higher in adolescent boys living at the altitude under 200 m compared to those living at 500 m or more.

Differential Diagnosis

Pubertal and prepubertal acne needs to be differentiated fro m childhood granulomatous periorificial dermatitis (characterized by discrete yellow brown papules, lack of pustules, less prominent erythema in the perinasal, periorbital, and perioral areas of the face, and noncaseating granulomatous infiltrate on histologic examination occurs in prepubertal children with history of prior topical corticosteroid application), lupus miliaris disseminatus faciei (presents as firm, yellowish brown or red, 1–3 mm monomorphous smooth-surfaced papules on the face especially eyelids histologically showing caseating epithelioid cell granulomas), childhood granulomatous rosacea (persistent facial erythema of convexities of the face with papular eruption; histologically papules show perifollicular granulomatous response), and acne secondary to hyperandrogenism, Cushing’s syndrome , congenital adrenal hyperplasia, gonadal/adrenal tumors, and precocious puberty (adolescent females present with severe, persistent, or recalcitrant form of acne in the setting of other signs of androgen excess like menstrual irregularity and hirsutism or virilizing features like deepening voice, increased muscle mass, and androgenetic alopecia) [511].

Evaluation

Adrenal androgens play an important role in the pathogenesis of acne with the most common identifiable androgenic abnormality associated being a marginal increase in adrenal androgen levels usually within a normal defined range. It has been shown that increasing levels of ovarian androgens and adrenal and testicular androgens at adrenarche may be responsible for early onset of acne at puberty in girls and boys, respectively. Early onset acne before obvious signs of puberty is usually a clinical sign of a normal or accelerated biological adrenarche but may also be the first sign of an underlying hormonal abnormality. Any of the signs of puberty can occur prematurely as an isolated abnormality, and the diagnosis of precocious puberty, precocious pseudopuberty, and premature adrenarche can be controversial because clinical signs may not correlate with measurable standard biochemical markers. However, long-term follow-up of these children with signs of early onset androgen excess, including those with premature adrenarche, appeared to have a risk of metabolic syndrome, thus warranting the need for identification and follow-up of this phenotype of children with stress on lifestyle modifications. Thus most cases of preadolescent acne represent a functional hyperandrogenism that could be the earliest sign of polycystic ovarian syndrome or a metabolic syndrome phenotype and are not associated with virilizing endocrinopathies. But, they are at risk for more severe or prolonged acne in adolescence or adulthood [514].

Concern about preventable sequelae of precocious puberty is often disproportionate to the risk in children with early onset acne in the absence of other signs. Hence extensive investigations often provoke needless parental anxiety. A left-hand and wrist X-ray for bone age would be a sufficient initial screening test for those with high growth parameters [1].

Hence a focused history and physical examination are sufficient to evaluate the majority of children with acne. Further work-up is generally unnecessary unless there are signs of excess androgen. However, hormonal evaluation is recommended in children with prepubertal acne with associated advanced bone maturation and early pubarche [11114].

Treatment

The therapeutic objective in acne is to target the age-appropriate pathogenetic factors which include reduction of sebum production, prevention of microcomedone formation, suppression of P. acnes, and reduction of inflammation to prevent scarring. Reduction in existing microcomedones and preventi on of the formation of new ones are central to the management of all acne lesions [311]. As regards to pubertal acne, the approach should be to use the least aggressive regimen that is effective while avoiding regimens that encourage the development of bacterial resistance. Though it is unknown whether treatment of pubertal acne can alter P. acnes colonization and therefore subsequent inflammatory acne, appropriate treatment in this population is important as early development of comedonal acne is one of the best predictors of later, more severe disease, thereby necessitating early intervention to prevent unwanted sequelae [715].

Educating the child and parents about reasonable expectations and treatment-related side effects can maximize both compliance and efficacy.

Management issues in pubertal acne are of special concern for the following reasons [11]:

1.     (a)

2.     (b)

3.     (c)

4.     (d)

5.     (e)

6.     (f)

7.     (g)

8.     (h)

To address these issues, the first detailed, evidence-based clinical guidelines for the management of pediatric acne has been recommended by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics [11].

As per their recommendations, treatment of uncomplicated preadolescent or pubertal acne (7–12 years of age) is comparable to that of acne in older age groups, and work-up is generally unnecessary unless there are signs of androgen excess, PCOS, or other systemic abnormalities. Nevertheless, it is important to elicit the child’s level of concern regarding his or her acne in this age group as it may not always be concordant with parental concern. The consensus recommendations for the various grades of acne are summarized in Table 14.1 [11].

The general measures to be followed include:

1.     (a)

2.     (b)

3.     (c)

4.     (d)

5.     (e)

6.     (f)

7.     (g)

Quality of Life

The pubertal years are a time of significant physical, psychological, and social change. Self-esteem plays a major role in this transition, both psychologically and socially. Acne is perceived to ha ve important negative influence on the self-esteem resulting in long-term personal and social consequences. The documented negative psychosocial effects of acne on self-esteem are significant more so in this age group as they are concerned with their physical appearance and place great importance on the opinions of their peers in this regard. Also, the level of distress may not correlate directly with acne severity; hence effective and early treatment is essential to prevent sequelae and to limit the long-term physical and psychological impact of acne [17].

Prognosis

Acne in children may be a sign of more severe acne with early comedonal prepubertal acne being predictive for severe comedonal acne or a long-term disease later in life. However, in most case s, acne decreases in a few years after the adolescence, while in up to 20 % it can persist beyond the age of 25, with higher prevalence among females [4].

Conclusion

Acne which commonly accompanies normal adrenarche and gonadal maturation is becoming a more common diagnosis in younger, preadolescent children relating to a trend toward children reaching puberty at an earlier age. A focused history and physical examination are sufficient to evaluate majority of these children with the exception of few who have severe acne associated with signs of hyperandrogenism requiring an endocrinological work-up. Treatment of uncomplicated pubertal acne is comparable to that of acne in older age groups except that most of the available treatments are considered off label for this age group thereby necessitating the need for future studies to optimize treatment outcomes in this population.

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