adolescent acne: a review of aetiology and management

Cltrrcwr Parr/iulrit:v ( 1999) 9, I 6 0 I999 IHarcourt Bract & Co. Ltd

Symposium: Dermatology

Childhood/adolescent acne: a review of aetiology and management

S. M. Clark, W. J. Cunliffe, A. D. Katsambas

INTRODUCTION

ductal corneocytes.’ Ductal hyperproliferation is multifactorial;‘,’ it is modulated by androgens, the irritant effect of certain sebaceous lipids and ductal cytokines in particular interleukin la. The skin surface is colonized by Propionibacterium acnes (f? ucnes), Staphylococcus epidertnidis and Malassesia furfur. P acnes is a major stimulus for acne inflammation. Selective antibiotic studies have shown a relationship between a reduction in skin surface !? acnes and clinical benefit.5 This evidence is further supported by the correlation of P acnes resistance and a clinical failure to that particular antibiotic.6 The presence of seborrhoea encourages colonization with P acnes and ductal colonization is a likely pre-requisite for acne inflammation. Changes in the ductal micro-environment influence the function of ductal P acnes and so influence colonization and the production of inflammatory mediators.’ which diffuse into the dermis triggering initially a lymphocyte mediated inflammatory reaction. Subsequently, polymorphs are recruited, the duct may rupture, and a macrophage-giant cell reaction may occur.s Fibrogenie cytokines may be down-regulated or up-regulated to produce atrophic or hypertrophic scarring. One of the several enigmas which exist in our understanding of acne is why acne resolves.

The purpose of this paper is to review the aetiology, clinical features, and therapy of acne as it may present to pacdiatricians.

AETIOLOGY

OF ACNE

Acne is an endocrine disease and probably one of the most frequently seen in late childhood and adolescence. However, by far the majority of acne subjects have no evidence of systemic hormonal disease. In acne the sebaceous glands are larger than in controls and, consequently, produce more sebum. the quantity of which is related to disease severity. The pilosebaceous units are primarily controlled by androgens’ and clinical observation, principally the localization of acne lesions, suggests that in most patients the seborrhoea represents an end-organ hyper-response of the glands to normal levels of circulating androgens. Many patients can have acne for 15-20 years and yet only have acne at limited sites. Using a special sebum absorbent tape, differences in individual sebaceous gland function suggests that some glands may be more acne prone than others. Microscopic hypercornification (a microcomedone) of the pilosebaceous duct frequently precedes development of the clinical lesions. Ductal hypercornification is due to the retention of hyperproliferating

CLINICAL

FEATURES

Acne vulgaris Peak incidence in girls is from 14-16 years and in boys from 15-19 years. In 93%, the disease becomes quiescent in the mid-twenties. The sites of involvement are the face, neck, and upper trunk. Virtually all youngsters will develop some acne lesions, usually of no clinical or personal consequence, the so-called

Dr S. M. Clark. Professor W. J. Cunliffe. Dcpartmcnl or Dermatology. Leeds General Infirmary. Great George Street, Leeds LSI 3EX. UK, Professor A.D. Katsambas. Department of Dermatology, University of Athens. ‘A‘ Sygros Hospital, Athens, G rcccc. Correspondence

and requests for ofTprinls

LO: WJC.

I

2

Current

Paediacrics

-.Fig. I

Demonstrates

non-inflamed

and inflamed

lesions.

‘physiological acne’.9Six percent of youngsters up to 15 years old will develop clinical acne which merits medical intervention. Blackheads and/or seborrhoea usually develop before the inflamed lesions.” With increasing seborrhoea, the youngster is aware of the need to wash the skin and hair more regularly. Twenty per cent of female patients may notice acne some months or even a few years before the menarche but the acne frequently develops at the same time as breast development and sexualhair. Thirty per cent of young females are aware of premenstrual inflammatory flare. Examination of late childhood skin will reveal that the acne is often localized for some years to a particular part of the face, particularly the forehead and upper cheeks. Eventually, the acne may involve the whole face, neck and upper trunk. By 1.5years, 25% will have developed truncal acne. Acne lesions are classifiedas non-inflamed, inflamed or scars(Fig. 1). Non-inflamed lesions (cornedones) are either microcomedones, blackheads or whiteheads. In blackheads (open cornedones), the external orifice is easily seen; the pigmentation is due to melanin, Blackheads do not usually progress to inflamed lesions unless picked. Whiteheads (closed cornedones), are small l-3 mm diameter skin coloured white macules or papules; their orifice is rarely visible. These are more difficult to seebut it is important to recognize them as they are the forerunners of inflamed lesions.Inflamed lesionsare small and red (papules) or pussy (pustules) spots. Larger inflamed lesions (nodules) occur in the more severecases. Scarring does occur in youngsters and though often associatedwith nodular acne subjects with less severeacne may scar.The scarsmay show loss of collagen (atrophic or ice-pick scars) or excesscollagen (hypertrophic or keloid scars)(Fig. 2). TREATMENT OF ACNE It is essentialto examine the patient with a good light (such as a Brighton 1001 cold fluorescent light) in order to assessthe acne severity and lesion type, The

Fig. 2

Kcloid scars in a 14.year-old

child.

patient should be reviewed 2-3 times monthly and therapy changed if progress is deemed unsatisfactory or if side-effectsare a problem. Progresswill be difficult to assessunlessthe physician quantifies the acne by using a global grading scalel’or by counting inflamed lesions.Global grading and the counting of inflamed lesions is with practise a simple technique. Non-inflamed lesions should be noted but not counted as they are difficult to quantify. GENERAL ADVICE Explain to your patient and the family that acne is a condition which will last for many years and that responseto therapy is slow. There is often little or no improvement in the first 4 weeksbut at 2 months there should be a 20% improvement and 80% improvement by 6 months. Acne is not infectious and not related to lack of hygiene and also not caused by food. TOPICAL THERAPY Figure 3 is an algorithm for treating acne. Mild acne usually requires topical therapy, often twice daily. Lesion type dictates choice of topical therapy (Table 1). a) Retinoids such as Retin A (all-trans-retinoic acid), Isotretinoin and Adapalene,” act by reducing

Table 1

Commonly

used topical

therapy

Anticomedonal

Anti-inflammatory

Adapalene Azelaic Acid Isotretinoin Tretinom

Adapalene Azelaic Acid Benzoyl Peroxide Topical antibiotics erythromycin clindamycin tetracycline Combined therapies Benzamycin Isotrexin Zineryt

Childhood/adolescent acne 3

EARLY ASSESSMENT

AND COUNSELLING +

Mild/Moderate A Inflammatory(90%)

Moderate

Comedonal(

1 Topical therapy -benzoyl peroxide, antrbiotrcs, combined therapies

10%)

4 Topical therapy retinoids, antibiotics, combined therapies

eg 4% erylhromycml 1.2% 21°Cacetate

-antibiotics at correct dose or oestrooenl cyproterone&etate

e.g wylhromycm 500mg W oxytetra cline 500m bd mnccyc ane 1OOmg1ally doxvcvclme lOOma dailv

,,

1 Assess after 2-3 months

2% eryt&nycln/ 0 5% lretlnoln /

\J

J+ Good response I

Assess after 2-3months

Inadequateresponse (check compliance)

I

Continue therapy, review regularly every 2-3 months

Fig. 3

An algorithm

7

and ” ‘ relevant topical therapy

3% ery&mycm 5% bnzoyl peroxide

Good response

Severe acne, significant scarring or psychological problems, irrespective of acne grade

1 Oral therapy

I

Consider alternative topical thera y or treat as mo 8 erate acne

for treating

Inadequate response (check compliance

Stop oral antibiotics after 6 months, continue topical therapy

+

Relapse

1 Review

I I Start/continue oral and/or therapy, referral to derma

r

Jpical ‘logist

acne.

comedone formation, and loosening the comedo plug. It is the topical treatment of choice for patients with many comedones. Retin A tends to cause more irritation and redness than benzoyl peroxide and other retinoids. b) Benzoyl peroxide is predominantly an antimicrobial agent, available in a variety of strengths from 25IO%, and in a variety of bases.” c) Topical antibiotics include erythromycin, tetracycline and clindamycin.‘” These are useful but, to minimize the risk of increased (I? acnes) bacterial resistance, should not be used as first line topical agents. Combined therapies, i.e. benzoyl peroxide and erythromycin minimize the risk of resistance. Most topical agents dry the skin, and can cause mild erythema and scaling, (a primary irritant dermatitis) but rarely is this troublesome. If this occurs, treatment should be temporarily discontinued and emollients applied. Do emphasize to your patient that topical therapy will be required for many years and that it should be applied not only to the spots but to the whole of the affected areas. Topical therapy is used in conjunction with oral therapy and as maintenance therapy when oral therapy is discontinued.

ORAL

ANTIBIOTICS

Moderate and severeacne requires both oral and topical therapy. 9 The choice of oral therapy is, in most instances, an oral antibiotic. Tetracyclines, such as oxytetracycline 500 mg bd, should be the first choice provided that the deciduous teeth have fully erupted. Other tetracyclines include doxycycline and minocycline (100 mg/day). We warn patients of the low risk (
l

Do not use dissimilar oral and topical antimicrobials Do minimize the duration of oral antibiotics to 6 month courses

4

l

Current

Paedialrics

Douse, where possible, topical benzoyl peroxide as the first choice for topical therapy in predominantly inflammatory acne.

PSYCHOLOGICAL

SUPPORT

The physician has also to take into account the psychological effect of the disease. Acne can produce much anxiety, depression and social maladjustment.‘J In our clinic, we regularly use a questionnaire which is aimed at assessingthe social and psychological impact of the disease. If the patient scores highly even though he or she has physically mild acne then the patient must be given both topical and oral therapy. The questionnaire is also helpful in assessingprogress.

TREATMENTS

Side-etTccts

of isotretinoin

Very Common (>9O’Y”)

Occasional <20%

Rare < I%

Skin/mucous membranes

Cheilitis Dry skin

Systemic

Tcratogcnic

Nose bleeds conjunctivitis sun sensitivity headache arthralgia myalgia

Pseudo pyogenic granuloma malaise. benign inlra cranial hwr tension mood swings depression

Laboratory

usually insignificant transienl rises in LFTs & lipids

FOR SEVERE ACNE

Seventy five per cent of young patients treated with such therapies will respond to their and the physician’s satisfaction. Referral to a dermatologist is necessaryin about 20% of subjects. Some dermatologists have links with a microbiologist to grow P acnes; this will provide information on the choice of alternative antibiotics. The dermatologist may consider mega-dose antibiotics (i.e. minocycline 200 mg/day, trimethoprim 600 mg/day) oral Isotretinoin, Dianette and occasionally short courses of oral steroids. Oral Isotretinoin, (Roaccutane), can be used in young acne subjects but is only prescribable by a dermatologist.” It is superbly effective as it suppresses all four aetiological factors; for example there is a 90% reduction in sebum excretion by 4 weeks. An initial flare of acne, is not infrequent in the first 6 weeks of therapy. Virtually all patients respond and after a 4-6 month course only in 30% does the disease relapse (Figs 4 & 5). Oral Isotretinoin is associated with many mucocutaneous and some systemic side-effects (Table 2).” It is very teratogenic. Pregnancy must be avoided before, during, and for 6 weeks following therapy. Even females below the age of 10 years must have a negative pregnancy test prior to therapy. Short courses (34 weeks) of oral steroids (0.5-1.0 mg/Kg) are required for severenodular and other rare forms of inflammatory acne and acne fulminans, when they are usually administered in conjunction with isotretinoin. TREATMENT

Table 2

OF SCARS

Keloid scars may respond to intralesional triamcinolone or gentle cryotherapy (15-20 seconds). Dermabrasion should be avoided in the young. Even in adults the results are often disappointing. Much more promising for atrophic scars is laserbrasion.

THE ROLE OF THE PAEDIATRICIAN TREATING ACNE

IN

The paediatrician, like the General Practitioner, can be the first physician to recognize clinical acne and so is in an advantageous position to institute therapy. The patient may not be seeing the paediatrician because of the acne. Although definitive data is lacking clinical experience suggests that early treatment does minimize disease progression and definitely reduces scarring.

UNUSUAL CLINICAL PAEDIATRIC PRESENTATIONS OF ACNE Neonatal and infantile acne The sebaceous glands of neonates produce considerable sebum in the first few weeks of life due to the effect of maternal androgens. Many infants have tiny whitish yellow papules over the nose, forehead, and cheeks as a result of the sebaceous hyperplasia. These are clinically insignificant and settle after 3 months of age as the glands atrophy. Acne very occasionally develops in neonates or in the first 18 months of life and may persist until the age of 4 years old.‘” Males are most frequently affected and the face is virtually always involved (Fig. 6). Such infants are otherwise in excellent health and only in the presence of other features of androgenicity are endocrine investigations warranted. Therapy is dependent on acne severity. Mild cases should be treated with benzoyl peroxide if inflammatory, a topical retinoid if comedonal, and both if the acne is of mixed pattern. Moderate cases necessitate 6 months of oral erythromycin 125 mg bd, not tetracyclines since this will discolour teeth. If the response is poor, referral to a dermatologist is necessary. Juvenile acne may predispose to acne later in life.

Childhood/adolescent

Fig. 4

A 13-year-old

boy with troublesome

Fig. 6

A 6-month-old

child with neonatal

facial acne

acne.

Drug induced acne Oral and topical corticosteroids arc the most common iatrogenic cause.19 The incidence of acne in patients on antiepileptic medications usually phenytoin is possibly increased. Less commonly, isoniazid and rifampicin have been reported to induce acne. Dactinomycin used intravenously to treat paediatric cancers has precipitated acne. Pomade acne Topically applied hair pomades frequently used by the Afro-Caribbeans to de-frizz their hair produces a monomorphic low grade inflammatory comedonal acne (Fig. 7).2” Black skinned youngsters, like their older counterparts, easily develop persistent post inflammatory hyperpigmentation. Cosmetic acne Some cosmetics may be comedogenic.” Treatment of both cosmetic and pomade acne necessitates with-

acne

5

Fig. 5 The effect of oral isotretinoin in improving acne. (Fig. 4, Pre-therapy, Fig. 5 shows the effect of 3 months therapy).

Fig. 7

A

patient with pomade acne.

drawal of the offending agents and topical retinoids. Some youngsters may wish to wear make up (preferably oil Tree) for psychological reasons. Acne excoriCe Some anxious youngsters may excessively scratch their spots producing the clinical picture of acne excorike. The need not to scratch must be discussed with such patients who tend not to well tolerate topical therapy. Acne fulminans Acne fuhninans is a rare severe ulcerative form of acne with an acute onset and systemic symptoms, which most commonly affects adolescent boys’* In addition, the patient may also present with fever, weight loss, arthralgia, myalgia, and erythema nodosum. The aetiology is uncertain but an increased response to intradermal F! acnes antigen favours an abnormal immunological response to Pacnes antigens. These

6

Current

Paediatrics

patients require urgent dermatological review and hospitalization. Treatment involves oral prednisoione, (0.5-l .O mg/kg/day), which should be continued for a minimum of 4 weeks at which stage with oral isotretinoin 0.5-I .Omg/kg/day is added.” Hyperandrogenism

Hyperandrogenism must be considered in any girl with premature or excessivedevelopment of pubic hair or acne, menstrual irregularity (particularly if it be oligo or amenorrhoea) or obesity. The most common cause of hyperandrogenism presenting in a teenage girl is polycystic ovary syndrome. However, the differential diagnosis includes ‘exaggerated adrenarche,’ late-onset congenital adrenal hyperplasia, virilizing tumours, Cushing’s syndrome, hyperprolactinemia and acromegaly. In our clinic we only investigate about I:100 acne youngsters for a suspected systemic endocrine problem - but rarely find an abnormality.

4. 5. 6. 7. 8. 9. IO. II. 12.

13. 14.

Apert’s syndrome 15.

(acrocephalosyndactyly) is an end-organ hyperresponse of the epiphysis and sebaceous glands to androgens.” This produces early epiphyseal fusion resulting in short stature, short and fused digits, and acrocephaly. Inheritance is mainly sporadic but it can be transmitted as an autosomal dominant. The acne of Apert’s syndrome is not easy to treat and often necessitates a dermatological referral, for oral isotretinoin.” REFERENCES

1. Pochi PE, Strauss JS. Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol 1974: 62: 191~201. 2. Pierard GE, Pierard-Franchimont C. Gotlin V. Digital image analysis of microcomedones. Dermatology 1995; 190: 99 103. 3. Thiboutot DM, Knaggs H, Gilliland K ct al. Activity or type I Sa-reductase is greater in the follicular inliainfundibulum

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