The treatment of acne

Transcription

1 The treatment of acne Lindsay Shaw Cameron Kennedy Abstract Acne is common but not trivial. It affects up to 85% of adolescents to some extent. Less commonly, it occurs in infancy. The pathophysiology centres on occluded pilosebaceous follicles and is multifactorial. An underlying pathological cause is rare, and investigations are not usually indicated. The psychosocial impact of acne may be significant and it can affect employment opportunities. Quality of life indices indicate that its impact can be as high as diseases such as diabetes mellitus. Although treatment is often effective. it is slow to work and there are frequent minor side-effects; this may affect compliance. Early treatment may prevent scarring, and this is particularly important in severe nodulo-cystic acne. We will review the topical and oral treatments suitable for use in children and discuss how to tailor treatment depending on the severity of the acne and the types of lesion present. Keywords acne; child; infant; therapeutics Pathophysiology There is no proven dietary factor of any importance in acne. Personal hygiene is of little relevance, and excessive cleaning of the skin may exacerbate symptoms. The development of acne is influenced by genetic factors. 1 Sebum is a greasy material produced by pilosebaceous glands, which are mainly distributed over the face, chest and back. Its production is largely under the control of circulating androgens, which peak in both sexes in early infancy and again at puberty. Androgen levels are usually normal, but androgen metabolism at the receptor sites in the skin varies from one individual to another, genetic factors playing a part in this. 2,3 In acne, an increased secretion of sebum is accompanied by thickening of the epidermis at the outlet to the pilosebaceous follicle. This creates an obstruction to flow, and a comedo develops. Colonisation of the follicle with Propionibacterium acnes and the host inflammatory response to this plays a pivotal role in the development of the typical inflammatory papulopustular lesions. 4 Acne in young children Sebaceous gland hyperplasia is common in the neonatal period. Less often, the formation of true comedones occurs. This probably relates to physiologically elevated androgen levels. Papulopustular lesions, mainly distributed on the face, are not uncommon, and there is sometimes an overlap with a condition described as neonatal cephalic pustulosis, in which there is an overgrowth of normal skin yeasts. 5 Whatever the aetiology, so-called neonatal acne tends to be mild and self- limiting. True infantile acne usually starts beyond 6 months of age and can persist for some years if untreated (Figure 1). Boys are affected 4 5 times more frequently than girls. Physiologically elevated levels of androgens of both adrenal and testicular origin may act in susceptible individuals to produce acne lesions. Affected individuals may also be at increased risk of developing acne in adolesence. 6 Clinically, the condition is similar to acne at other ages and may be severe, including nodulo-cystic acne requiring treatment with isotretinoin. 7 Early-onset or prepubertal acne may occur in association with premature adrenarche. This is associated with an elevation of adrenal androgens and is physiological. The pathological endocrine causes of acne most frequently identified are late-onset congenital adrenal hyperplasia and, in older girls, polycystic ovary syndrome. More rare causes are androgen-producing tumours of the adrenal gland, gonads and ectopic sites. Most infantile and adolescent acne is not related to a hormone problem, and investigations should be limited to situations in which: there are other pointers towards hyperandrogenism, such as clitoromegaly, pubic hair development, rapid growth or hirsutism; acne occurs outside the normal physiological age peaks. Bone age, plasma free testosterone, 17-hydroxyprogesterone and urinary adrenal steroid metabolites are the most useful baseline tests in younger age groups. When there is a strong index of suspicion, dynamic adrenal tests may be required to identify partial deficiency of enzymes resulting in adrenal hyperplasia. 8 In older girls, follicle-stimulating hormone, luteinising hormone and sex hormone-binding globulin levels will help to identify polycystic ovary syndrome. Acne occurring outside expected age groups with other signs of normal pubertal development needs to be investigated as for precocious puberty. Lindsay Shaw BSc MBChB MRCP MRCPCH is Dermatology Specialist Registrar in the Department of Dermatology, Bristol Royal Infirmary, Bristol, UK. Cameron Kennedy MA MB BChir FRCP is Consultant Paediatric Dermatologist at Bristol Royal Hospital for Children, and Consultant Dermatologist and Clinical Senior Lecturer in the Department of Dermatology, Bristol Royal Infirmary, Bristol, UK. Figure 1 Infantile acne. PAEDIATRICS AND CHILD HEALTH 17: Elsevier Ltd. All rights reserved.

2 Treating different types of lesion The comedo is the primary pathological lesion. Open comedones ( blackheads ) (Figure 2) and closed comedones ( whiteheads ) can be treated with topical agents that have a direct effect on the keratinisation process and promote shedding of the outer layers of the epidermis. Topical retinoids are the first choice. Treatments aimed at comedolysis should be applied to all acne-prone skin rather than just to individual spots. Macrocomedones are large closed comedones that respond poorly to conventional treatment. Gentle cautery is required for these. Papules and pustules occur because of a host inflammatory response to the comedo colonised with P. acnes. They need to be treated with anti-inflammatory and antibiotic agents. Acne nodules or cysts are deep pustules rather than true cysts (Figure 3). They represent a very brisk inflammatory reaction that is likely to scar. When these are present, early aggressive treatment, i.e. with systemic retinoid, is indicated. Long-established individual lesions may respond to steroid injection. True epidermoid cysts occasionally occur, arising from the remnants of disrupted pilosebaceous follicles. These may require excision. Scars (Figure 4) may be atrophic or hypertrophic and are often associated with skin colour change. The colour change may continue to resolve up to a year or so after the active acne has resolved. Deep atrophic ice-pick scars are particularly disfiguring, and individual lesions are sometimes excised. More Figure 3 Severe inflammatory acne lesions and early scarring. superficial scarring may respond to dermabrasion or ablative laser treatment, but the results are at best modest and not without risk. 9 Keloid scars are difficult to deal with. They occur most often at certain sites such as the chest, upper back and jaw line and are more common in dark skin. Steroid injections and silicone-based dressings are sometimes used. Structured approach to the treatment of acne Table 1 summarises the structured approach to acne management. Topical treatments Topical treatments aimed at preventing the formation of new comedones take several months to show maximal benefit. Figure 2 Open comedones or blackheads inside the ear. Retinoids: are vitamin A derivatives. They act directly on the keratinocytes in the epidermis and are effective in the treatment of comedones. 10 Tretinoin (Retin-A) and isotretinoin (Isotrex) are commonly used examples. The major side-effects are dryness, redness and irritation of the skin. The key to successful treatment is to slowly build up to the maximally tolerated frequency of application and use a non-comedogenic moisturiser. Despite this, some patients, especially those who are atopic, find this treatment uncomfortable. Modified/slowrelease formulations and a third-generation retinoid adapalene (Differin) may be less irritant. 11 Cream formulations tend to PAEDIATRICS AND CHILD HEALTH 17: Elsevier Ltd. All rights reserved.

3 Benzoyl peroxide: this is the staple ingredient of many overthe-counter preparations and is available in strengths ranging from 2.5% to 10%. It has comedolytic activity and is good at treating inflammatory acne through both direct antibacterial and anti-inflammatory mechanisms. It may be at least as effective as oral tetracycline. 12 It often causes some dryness and irritation, which may be minimised by building up the concentration to the limit of tolerance. Benzoyl peroxide can also bleach clothes and hair. Despite this, it is a safe and proven therapy that is well tolerated by most. Azelaic acid (Skinoren): a naturally occurring dicarboxylic acid with modest antibacterial and comedolytic effects. 13 It may be tolerated when retinoids and benzoyl peroxide are not. It can cause hypopigmentation and this can be used to advantage in darker skins when post- inflammatory hyperpigmentation has become a cosmetic problem. Topical antibiotics: erythromycin and clindamycin are the most common. They are useful in inflamed lesions but there is a problem with increasing antibiotic resistance. 14 Use in combination with other topical agents is advised. Figure 4 An acne cyst or nodule. be less drying than gel. Photosensitivity can be a problem, and patients should be advised to apply the treatment in the evening. Topical retinoids have theoretical risks in pregnancy and should be avoided. Combination treatments: combinations of benzoyl peroxide and antibiotic or retinoid and antibiotic may work better and be no more irritant than the agents used alone. 12 This may be because the multifactorial pathophysiology of the underlying problem is addressed. There is also some evidence to suggest that using antibiotics in combination with non-antibiotic agents puts less selective pressure on the development of antibiotic-resistant strains of P. acnes. 15 There are many other topical treatments available containing zinc, sulphur, salicylic acid and nicotinamide to name but a few. These may have a part to play in individual patients when other treatments have not been tolerated. A structured approach to the treatment of acne Mild acne Moderate acme Severe acne Topical treatment indicated Start with a topical comedolytic (retinoid, benzoyl peroxide OR azelaic acid if others are not tolerated) If inflammatory lesions are a feature, add in anti-inflammatory (topical antibiotic, benzoyl peroxide) NON-RESPONDERS OR RELAPSE ON TREATMENT: Check compliance and manage side-effects Try alternative or combined topical treatments Consider treatment as for moderate acne if there is sufficient patient motivation Oral plus topical treatment indicated Topical comedolytic treatment Oral antibiotic (a tetracycline if over 12 years of age, erythromycin if younger) NON-RESPONDERS OR RELAPSE ON TREATMENT: Check compliance and manage side effects Try alternative or combined topical treatments Change oral antibiotic Think about gram negative folliculitis and consider oral trimethoprim treatment Consider Dianette in suitable girls Consider treatment as for severe acne if sufficient patient motivation Oral plus topical treatment indicated Topical comedolytic treatment Oral antibiotic (a tetracycline if over 12 years of age, erythromycin if younger) PLUS Dianette in suitable girls Isotretinoin if the above gives no significant improvement in 3 4 months. Have a low threshold for starting isotretinoin early with nodulo-cystic acne Table 1 PAEDIATRICS AND CHILD HEALTH 17: Elsevier Ltd. All rights reserved.

4 Oral treatments Oral antibiotics: tetracycline and oxytetracycline are the standard first-line antibiotics in those over 12 years of age, their drawback being that they have to be taken twice daily and not with food. Where these factors affect compliance, doxycycline or minocycline is preferable. Minocycline has the added advantage of inducing less P. acnes resistance, but it may occasionally cause the deposition of a bluish pigmentation in the skin. It has also been associated with a hypersensitivity reaction and an autoimmune hepatitis/lupus-type illness with at least two reported deaths. A recent Cochrane review found insufficient evidence to advocate its first-line use. 16 All the tetracyclines can be associated with photosensitivity, and patients should be cautious in terms of sun exposure. In younger children, tetracyclines are contraindicated because of dental staining Erythromycin (10 25 mg/kg twice daily) is the first choice, although P. acnes resistance is increasingly common and gastrointestinal side-effects are relatively frequent. Trimethoprim (2 4 mg/kg twice daily) is a reasonable alternative. 7 Maximal benefit from oral antibiotics is not seen for up to 6 months. A sudden relapse on oral antibiotics, particularly if the lesions are monomorphic pustules, may be due to the development of Gram-negative folliculitis. This should be treated with a course of oral trimethoprim. Dianette: this is a combination of cyproterone acetate (2 mg), an anti-androgenic progesterone, and ethinylestradiol (35 μg). It is no longer licensed for the sole purpose of oral contraception as it is associated with an increased risk of venous thromboembolism compared with the low-dose combined oral contraceptive pill. As for the standard oral contraceptive pill, Dianette requires GP supervision to monitor blood pressure, etc., and a careful personal and family history should be taken to exclude an increased risk of thromboembolism. It is a useful addition to treatment in girls who have failed to respond to oral antibiotic plus topical treatment. Isotretinoin (Roaccutane): this oral retinoid is the gold standard acne treatment and is exceptionally effective. It reduces sebum production, affects follicular epithelial differentiation and has anti-inflammatory effects. It is very expensive and has significant side-effects. It is only licensed for use under the supervision of a consultant dermatologist. Courses typically last 4 5 months at a dose of mg/kg, but modification of this may be necessary depending on the response and side-effects, which are common. 17 Skin and mucous membrane dryness occurs in almost all who are treated. Other minor side-effects such as muscle aches and pains and tiredness are also common and may interfere with sporting activities. Skin lesions may worsen in the first week or two of treatment, and patients should be warned about this. More serious side-effects, including hepatitis and hyperlipidaemia, are a genuine concern, and blood monitoring is required for this. Suicidal depression is reported but the significance of this in an already vulnerable group is unclear. Isotretinoin is a potent teratogen, and sexually active females need adequate contraception both during and a month either side of treatment. Other treatment modalities including laser treatment and photodynamic therapy are being actively researched. These are not widely available, and further evidence on efficacy and safety is needed. Unusual patterns of acne Exogenous acne triggers can result in unusual clinical patterns. Monomorphic papular lesions can result from follicular occlusion by exogenous greases and emollients, and this is particularly seen in Afro-Caribbean infants as a so-called pomade acne. Lesions are sometimes restricted to sites of friction from clothing, etc., which is known as acne mechanica. Aromatic hydrocarbons with chlorine groups such as Agent Orange, which was used as a defoliant in the Vietnam war, cause acne in exposed sites such as the face and forearms. A monomorphic acneiform eruption may be caused by longterm systemic steroids. The illicit use of anabolic steroids may also be associated with acne, and this is worth considering when faced with an adolescent boy whose acne does not seem to respond well to treatment. Some genetically acquired conditions seem to predispose towards acne, and Apert s syndrome is an example in which severe acne affecting unusual sites such as the arms may be the result of a disordered end-organ response to androgens. Acne also occurs as part of the SAPHO syndrome (an acronym for synovitis, acne, pustulosis, hyperosteosis and osteitis). In children, this usually presents as a sterile recurrent multifocal osteomyelitis that tends to resolve without long-term problems. References 1 evans DM, Kirk KM, Nyholt DR, et al. Teenage acne is influenced by genetic factors. Br J Dermatol 2005; 152: Shaw JC. Acne: effect of hormones on pathogenesis and management. Am J Clin Dermatol 2002; 3: Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology 2003; 206: Cunliffe WJ. Acne. In: Harper J, Oranje AP, Prose N, eds. Textbook of pediatric dermatology. Oxford: Blackwell Sciences, 2000, p Bernier V, Weill FX, Hirigoyen V, et al. Skin colonization by Malassezia species in neonates. Arch Dermatol 2002; 138: Chew EW, Bingham A, Burrows D. Incidence of acne vulgaris in patients with infantile acne. Clin Exp Dermatol 1990; 15: Cunliffe WJ, Baron SE, Coulson IH. A clinical and therapeutic study of 29 patients with infantile acne. Br J Dermatol 2001; 145: de Raeve L, De Schapper J, Smitz J. Prepubertal acne: a cutaneous marker of androgen excess? J Am Acad Dermatol 1995; 32: Hirsch RJ, Lewis AB. Treatment of acne scarring. Semin Cutan Med Surg 2001; 20: Shalita A. The integral role of topical and oral retinoids in the early treatment of acne. J Eur Acad Dermatol Venereol 2001; 15: Cunliffe WJ, Caputo R, Dreno B, et al. Efficacy and safety comparison of adapalene (CD271) gel and tretinoin gel in the topical treatment of acne vulgaris. A European multicentre trial. J Dermatolog Treat 1997; 8: ozolins M, Eady EA, Avery AJ, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne PAEDIATRICS AND CHILD HEALTH 17: Elsevier Ltd. All rights reserved.

5 vulgaris in the community: randomised controlled trial. Lancet 2004; 364: gollnick H, Schramm M. Topical drug treatment in acne. Dermatology 1998; 196: Coates P, Vyakrnam S, Eady EA, et al. Prevalence of antibioticresistant proprionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study. Br J Dermatol 2002; 146: eady EA, Farmery MR, Ross JI, et al. Effects of benzoyl peroxide and erythromycin alone and in combination against antibiotic-sensitive and resistant skin bacteria from acne patients. Br J Dermatol 1994; 131: garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2003; 1: CD mclane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol 2001; 45: S Practice points acne is usually treatable effective treatment depends on establishing the type of acne lesions present treatments work slowly, and educating patients about this is important for compliance. treatments frequently have minor side-effects, and patients and parents need to understand how to manage these in order to persevere with treatment oral isotretinoin is an effective treatment for acne. Its sideeffects limit its use to severe nodulo-cystic acne, and less severe acne when other treatments have failed the treatment of scarring is not good, and the most useful strategy is prevention by early treatment of active lesions PAEDIATRICS AND CHILD HEALTH 17: Elsevier Ltd. All rights reserved.