Evidence-based Pharmacy Practice (EBPP): ACNE VULGARIS

Transcription

1 EVIDENCE BASED PHARMACY PRACTICE Evidence Evidence-based Pharmacy Practice (EBPP): ACNE VULGARIS Ilse Truter Drug Utilization Research Unit (DURU), Department of Pharmacy, Nelson Mandela Metropolitan University Acne is a disorder of the pilosebaceous follicles causing comedones, papules and pustules on the face, chest and upper back. 1 It affects virtually all adolescents, to varying degrees of severity, and usually appears at the time of puberty. 1 Although it may sometimes be unsightly and can persist for several years, it is not usually serious and resolves in most patients by the age of 25 years. 2 However, it can have a significant psychological impact as it affects young people at a stage in their lives when they are especially sensitive about their appearance. 2 Diagnosis is usually straightforward and most patients presenting in a community pharmacy will generally be seeking appropriate advice on correct product selection rather than wanting someone to put a name on their rash. The majority of cases seen in the pharmacy setting will be mild and can be managed appropriately without referral. More persistent and severe cases need referral for more potent topical or systemic treatment. It is important to note that all forms of acne can cause scarring. 3 Definition of acne vulgaris Acne vulgaris (acne) is the formation of comedones, papules, pustules, nodules and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland). 4 Epidemiology of acne vulgaris Acne affects approximately 80% of people aged 11 to 30 years at some time, with about 60% of those sufficiently affected to seek treatment. 2 Acne lesions typically develop at the onset of puberty. Girls therefore tend to develop acne at an earlier age than boys. 1 The peak incidence for girls is between 14 and 17 years, compared with 15 to 19 years for boys. 1,2,5 There may be a familial tendency to acne and it is slightly more common in boys, who also experience more severe involvement. 1 Acne is more common in males than females during adolescence, but is more common in women than in men during adulthood. 6 In addition, white patients are more likely to experience moderate to severe acne, although black skin is prone to worse scarring. 1 Acne usually resolves within 10 years of onset, although up to five percent of women and one percent of men in their thirties can have mild persistent acne. 1,2,5 The incidence of acne appears to have fallen in recent years, however the reasons are unknown. 2 Aetiology/pathophysiology The pathogenesis of acne vulgaris is multifactorial. 6 The various pathogenic factors represent specific targets for treatment and it has been proven that treatment directed at different pathogenic factors achieves better results than treatment methods aimed at the same pathogenic factors. 7 A cascade of events takes place at puberty resulting in the formation of non-inflammatory and inflammatory lesions. Acne arises in the pilosebaceous units in the dermis, which consist of a hair follicle and associated sebaceous gland. In response to increased testosterone levels, the pilosebaceous gland produces sebum, a mixture of fats and waxes that protect the skin and hair by retarding water loss and forming a barrier against external agents. The hair follicle is lined with epithelial cells that become keratinised as they mature. During puberty the production of androgenic hormones increases in both genders and testosterone levels rise. If the sebaceous glands become oversensitive to testosterone, they produce excess oil and the skin becomes greasy (a hallmark of acne). At the same time, keratin in the follicular epithelial wall (the cells lining the follicle) undergoes change. Prior to puberty, dead cells are shed smoothly out of the ductal opening but at puberty this process is disrupted and in patients with acne these cells develop abnormal cohesion and partially block the opening in the epidermis and effectively reduce sebum outflow. Over time the opening of the duct becomes blocked, trapping oil in the hair follicle. Oil blocks the follicle openings in the epidermis and causes them to dilate beneath the skin surface. If the orifice of the follicular canal opens sufficiently, the keratinous material extrudes through it and an open comedone results. This is known as a blackhead as the keratinous material darkens in contact with the air. Because this material can escape, the comedone does not become inflamed. If the follicular orifice does not open sufficiently, a closed comedone (whitehead) results, within which inflammation can occur. Most acne sufferers have a combination of both open and closed comedones. 2 12

2 EVIDENCE BASED PHARMACY PRACTICE Bacteria, particularly Propionibacterium acnes (P acnes), cause the follicular wall of closed comedones to disrupt and collapse, spilling their contents into the surrounding tissue and provoking an inflammatory response. In addition, bacterial enzymes decompose triglycerides in the sebum to produce free fatty acids, which also cause inflammation. This process leads to the formation of papules around the follicular openings in the more common, milder form of acne and to cyst formation in the deeper layers of the skin in the more severe form. P acnes proliferate in the stagnant oil, stimulating cytokine production, which produces the local inflammation leading to the appearance of a spot. In response to the proliferation of bacteria, white blood cells infiltrate the area and kill the bacteria and in turn die leading to pus formation. The pustule eventually bursts on the skin surface, carrying the plug away. The whole process then starts again. The main pathogenic factors involved in acne can therefore be summarised as 7 : Production of androgens in the body. Excessive sebum production. Abnormal desquamation of the follicular epithelium in the duct of the sebaceous gland. Proliferation of P acnes. Inflammatory and immunological responses. Diagnosis of acne vulgaris Diagnosis is by examination. Differential diagnosis of acne is routine and should not be difficult. The pharmacist will, however, need to assess the severity of the acne. The lesions usually occur on the forehead, nose and chin. The periorbital area is usually spared. 2 Acne, therefore, affects the areas of the skin with the densest population of sebaceous glands. The scalp is rarely involved although it is richly supplied with sebaceous glands. 7 In severe cases, the whole face, upper chest and back may be affected. 2 Lesions at different developmental stages often coexist. Several rating scales have been developed with the aim of trying to grade the severity of the individual s condition. No method has yet gained universal acceptance and most dermatology texts simply grade the severity of acne as mild, moderate and severe (see Table 1). 1 More complicated grading systems rely heavily on the use of photographs or diagrams, and the clinical appearance of the patient is compared with a standard set of photographs and severity is then decided on according to correspondence with a particular photograph. 7 Another classification is merely to describe these three grades of acne 1,5 : Mild acne Patients with mild acne typically have predominantly open and closed comedones (blackheads and whiteheads) with a small number of active lesions normally confined to the face. Mild acne should not cause permanent scarring. Any or all of the following is present: small, tender, red papules; pustules; and blackheads and/or whiteheads. Mild acne is therefore characterised by the presence of a few to several papules and pustules, but no nodules. Mild Moderate Severe Severity Moderate acne Similar to mild acne, but more papules and pustules. Patients with moderate acne typically have a few to several nodules. Lesions are often painful and there is a real possibility of scarring. 5 Severe acne Similar to moderate acne but with nodular abscesses, leading to extensive scarring. Patients with severe acne have numerous or extensive lesions. Another classification of acne severity is to grade acne as follows 7 : Grade 1: Comedones only. Grade 2: Inflammatory papules present in addition to the comedones. Grade 3: Pustules present in addition to any of the above. Grade 4: Nodules, cysts, conglobate lesions or ulcers present in addition to any of the above. Acne can also be classified by the type of lesion comedonal, papulopustular, and nodulocystic (pustules and cysts are considered inflammatory acne) 3 : Comedonal acne Comedonal acne presents with a tendency to greasiness and the presence of enlarged pores, comedones and occasionally papule and pustule formation. There may be plenty of open or obstructed comedones, but with scant inflammatory changes. Comedonal acne may cause scarring, requiring systemic therapy. Inflammatory acne Table 1: Classification of acne severity 4 Definition < 20 comedones, or < 15 inflammatory lesions, or < 30 total lesions 20 to 100 comedones, or 15 to 50 inflammatory lesions, or 30 to 125 total lesions > 5 cysts, or total comedone count >100, or total inflammatory count >5 0, or > 125 total lesions Nodular cystic acne This type of acne may reflect any or all of the above features of acne, but also includes the presence of sub-epidermal cysts and nodules. Nodulocystic acne consists of pustular lesions larger than 0.5 cm. 9 Cystic acne can be painful. Finally, a distinction is also made between various acne types 10, for example acne conglobata, acne fulmicans, acne keloidalis nuchae and acneiform eruptions. 13

3 EVIDENCE BASED PHARMACY PRACTICE Evidence Conditions to eliminate Acne may be triggered or worsened by external factors such as mechanical obstruction (for example, helmets or shirt collars), occupational exposure or certain medicine (see below). 9 Cosmetics and emollients may occlude follicles and cause an acneiform eruption. 9 Topical corticosteroids may produce perioral dermatitis, a localised erythematous papular or pustular eruption. 9 Endocrine causes of acne include Cushing s disease or syndrome, polycystic ovarian syndrome, and congenital adrenal hyperplasia. 9 Clinical clues to possible hyperandrogenism in women include dysmenorrhoea, virilisation (for example, hirsutism, clitoromegaly and temporal balding), and severe acne. 9 Differential diagnosis typically includes perioral dermatitis, rosacea (in which no comedones are seen), corticosteroid-induced acne (which lack comedones and in which pustules are usually in the same stage of development) and acneiform drug eruptions. Rosacea Rosacea is an inflammatory condition of the skin follicles causing acne-like papules and pustules. It is uncertain what causes rosacea although successful treatment with antibiotics suggests that bacterial pathogens play a significant role in the disease. 1 It is normally seen in patients over 40 years of age. 1,5 It is characterised by recurrent flushing and blushing of the central face especially the nose and medial cheeks. 1 Crops of inflammatory papules and pustules are also a common feature, but comedones are not present in rosacea. Eye irritation and blepharitis are present in approximately 20% of patients. Medicines causing acne-like skin eruptions Although an unlikely cause, certain medicines can produce acne-like lesions. Examples of medicine that can trigger or exacerbate acne are given in Table 2. 1,5,9 Counselling approach to follow The overall aim in the management of acne is to clear skin lesions and to prevent scarring. The aim is also to improve the patient s quality of life by identifying, treating and/or eliminating the underlying cause, and to use pharmacological therapy when indicated. This should be accomplished without adverse effects or with clinically acceptable adverse effects. A list of symptom-specific questions to assist the pharmacist with the patient assessment history is given in Table 3 and will also help the pharmacist to determine if referral is needed. Appropriate patient counselling is of the utmost importance in acne. Patients must know how to use their medicine, common side effects, likely timescale for improvement and that treatment is long-term (and may be needed for months or years). Patient involvement in the choice of topical treatment is vital and products must be cosmetically acceptable to the patient to ensure compliance. In general, gels and solutions are good for oily skin but may sting sensitive or dry skin. 11 Creams are suitable for sensitive or dry skin but may make oily skin more greasy. 11 Lotions are thinner than creams and are useful for large or hairy areas. 11 Table 2: Medicines that can trigger or exacerbate acne 1,5,9 More commonly Anabolic steroids (for example, danazol and testosterone) Bromides Corticosteroids (for example, prednisone) Corticotropin Isoniazid Lithium Phenytoin Rifampicin Oral contraceptives (especially those with high progestogen levels) Less commonly Azathioprine Ciclosporin Disulfiram Phenobarbital Quinidine Tetracycline Vitamins B 1, B 6, B 12 and D 2 When to refer The following symptoms suggest the need for referral 1,2,5,11,12 : Moderate or severe acne. Development of severe complications (for example, deep pustules, severe cases of nodular acne and/or pigmentation). Suspected occupational causes. Mild acne, if there is no improvement after two months with over-the-counter (OTC) treatment or if treatment response is poor. Acne beginning or persisting outside the normal age range for the condition or late onset acne. Severe psychological stress. Suspected medicine-induced acne. Suspected rosacea. Unpleasant side effects from current acne therapy. Available treatment options for acne vulgaris The main aims of acne management are to 11,12 : Reduce the number of lesions and improve the skin condition; Eliminate pathogens; Reduce the impact of psychological stress; and Prevent scarring. A structured approach to the management of acne requires an understanding of the cause, the severity, the type of lesions present and the treatment options available. Therapy should be started at an early stage to prevent scarring. The choice of medicine depends on previous treatment, patient acceptability and the type of lesion (comedonal or inflammatory). Ideally, an effective anti-acne treatment should reduce the number of both types of lesions. Treatment options are directed at reducing sebum production, comedone formation, inflammation and infection. 4 Selection of treatment is generally based on severity. It is important to show understanding and empathy when counselling patients since acne is predominantly a condition that affects adolescents, a time when appearance is very important. 14

4 EVIDENCE BASED PHARMACY PRACTICE Table 3: Specific questions to ask the patient with acne when taking a dermatological history 1,5 Question Relevance Age of onset? Where did the problem first appear? Severity? Are there any other symptoms? Occupational history (relevant to adults only) General medical history Foreign travel Family and household contact history The patient s thoughts on the cause of the problem Temperature Distribution Lesion shape Recent trauma Acne is common in adolescence. Patients with acne-like lesions who are outside the normal age range may be affected by an adverse drug reaction or rosacea. Certain skin problems start in one particular location before spreading to other parts of the body, for example impetigo usually starts on the face before spreading to the limbs. Acne is typically confined to the face, chest and upper back. Moderate acne is not confined to the face, but also involves the back and chest. Lesions are often painful and there is a real possibility of scarring. Severe acne has all the characteristics of moderate acne plus the development of cysts. Lesions are often widespread and scarring is frequent. Many dermatological conditions exhibit itch and/or pain, for example: Mild itch is associated with psoriasis and medicine eruptions. Severe itch is associated with scabies, atopic and contact dermatitis. There is no itch associated with acne. In some occupations, workers are exposed to irritants and chemicals (for example, hairdressing) or to excessively hot and humid conditions causing sweating. Car mechanics, for example, are exposed to frequent or prolonged contact with grease and oils, which can cause acne-like lesions. Skin disoders may be the first sign of internal disease. For example, diabetes can manifest with pruritis and thyroid disease with hair loss and pruritis. Acne can be due to a hormonal imbalance. Tropical skin conditions can be contracted when abroad but lesions do not appear until the person has returned home. Some skin conditions (such as scabies) can infect those with whom the patient is in close contact. Ask for the patient s opinion. This may help with the diagnosis or shed light on anxieties. The backs of the fingers can be used to identify generalised warmth or coolness of the skin. Generalised warmth might indicate fever. Local warmth could indicate inflammation or cellulitis. The pattern of involvement of the skin may assist with diagnosis. Acne typically affects the face, chest and upper back, whereas psoriasis typically affects elbows, knees, scalp and the sacral area, adult seborrhoeic dermatitis affects the face and mid-chest. Are the lesions arciform (in an arc), linear, annular (in a ring) or clustered? Tinea corporis (ringworm) usually presents as an annular rash. Have the lesions developed on a site of trauma or injury. This is seen in, for example, psoriasis and warts. Non-pharmacological management The following non-pharmacological treatment advice can be given to patients with acne 2 : There is no evidence that poor hygiene causes acne, but cleansing the affected areas two to three times daily is recommended. An antibacterial soap or a mild cleanser to degrease the skin and to remove bacteria can be used, and can help to reduce the severity of the condition, although extra washing, the use of antibacterial soaps and scrubbing have, according to evidence, no added benefit. 4 Sweat should not be allowed to remain on the skin, but should be washed off as soon as possible. Patients should be advised to avoid hairstyles in which the hair is constantly touching the face, and to shampoo the hair regularly. Herbal and various alternative therapies have been used to treat acne. Although these products appear to be well tolerated, limited data exist regarding the safety and efficacy of these agents. 13,14 Pimples and blackheads should not be squeezed or pinched with the fingers. Comedone expressors (blackhead removers) can be used, with removal aided by exposing the skin to steam first. There is limited evidence regarding the benefit of physical modalities including glycolic acid peels and salicylic acid peels. 13,14 Natural sunlight is thought to be helpful in reducing acne, but overexposure should be avoided. 15

5 EVIDENCE BASED PHARMACY PRACTICE Evidence Patients should avoid greasy cosmetics and rather use water-based moisturisers. They should also avoid using hairspray. Dietary restriction (either specific foods or food classes) has not been demonstrated to be of benefit in the treatment of acne. 3,13,14 There is, for example, no evidence that fatty foods and chocolate cause acne, although no harm is done by testing if excluding them from the diet has a beneficial effect. A healthy, balanced diet with plenty of water, and regular exercise, is always good advice. Psychological approaches, hypnosis and biofeedback have also been used. 13,14 Pharmacological treatment The pharmacological treatment of acne can be divided into topical and systemic treatment. The different medicines used in the treatment of acne are illustrated in Figure 1. 4 Topical treatments Non-prescription topical treatment is usually the first line of treatment for mild to moderate acne. Topical OTC acne treatments typically contain benzoyl peroxide, azelaic acid, salicylic acid, sulphur or an antibacterial. The overall aim of topical therapy is to remove follicular plugs, allowing sebum to flow freely, and to minimise bacterial colonisation of the skin. Treatment must be used regularly for up to three months to produce benefits. 2 Approximately 60% of patients should see an improvement in their symptoms after eight to 12 weeks. 5 If symptoms fail to improve after this time period, referral is necessary. Four types of preparations are available 2 : Drugs that normalise pattern of follicular keratinisation Adapalene Isotretinoin Tazarotene Tretinoin Compacted cells, keratin and sebum Proliferation of Propionibacterium acnes Drugs with antibacterial effects Antibiotics (topical and oral) Benzoyl peroxide Isotretinoin (indirect effect) Figure 1: Medicines used in the treatment of acne 4 Obstruction of pilosebaceous duct by cohesive keratinocytes, sebum and hyperkerotosis Hair Keratolytics (also known as comedolytics in relation to acne, or peeling agents) promote shedding of the keratinised epithelial cells on the skin surface, although the compounds used may do this via different mechanisms. They prevent closure of the pilosebaceous orifice and the formation of follicular plugs and facilitate sebum flow. They also possess varying levels of antimicrobial activity, which contribute to their effectiveness. Examples include benzoyl peroxide, salicylic acid, sulphur and resorcinol. Antimicrobials. Two of the contributory factors to acne are increased sebum production and P acnes. Therefore, one approach to treatment is to remove excess sebum from the skin and reduce the bacterial count. Several products are formulated as astringent lotions and detergent-based washes containing antibacterial or antiseptic ingredients, and there are some antimicrobial creams. Examples of antimicrobial active ingredients include cetrimide, chlorhexidine, povidone-iodine, triclocarban and triclosan. Topical antibiotics should never be used as monotherapy, and should preferably be combined with topical nonantibiotic antimicrobials such as benzoyl peroxide. 7 Anti-inflammatory agents. An example includes topical nicotinamide. It appears to be effective. It may produce sideeffects of dryness, peeling and irritation similar to those of benzoyl peroxide. Abrasive products contain small, gritty particles in a skin wash, intended to remove follicular plugs mechanically. They typically contain aluminium oxide particles or polyethylene granules. 3 Abrasives are contraindicated in the presence of superficial capillaries (telangiectasia), and overenthusiastic use can cause irritation. Abrasive cleansers and vigorous scrubbing may worsen acne by provoking inflammation. There is little evidence for the use of abrasive preparations in acne. Drugs with anti-inflammatory effects Antibiotics (by preventing neutrophil chemotaxis) Corticosteroids (intralesional and oral) NSAIDs Rupture of follicular wall Inflammation Increased sebum production Drugs that inhibit sebaceous gland function Antiandrogens (e.g. spironolactone) Corticosteroids (oral, in very low doses) Oestrogens (oral contraceptives) Isotretinoin 16

6 EVIDENCE BASED PHARMACY PRACTICE Benzoyl peroxide Benzoyl peroxide is generally accepted as the first-line topical treatment for mild to moderate acne. 2 It exerts its main effect by having a mild but significant keratolytic effect (therefore acting in a comedolytic fashion), but it is also a broad-spectrum antimicrobial, acting in a non-antibiotic fashion. 7 It has potent antimicrobial effects but is sloweracting than systemic antibiotics. 7 It reduces the concentration of P acnes., has slight anti-inflammatory and mild anticomedogenic effects. Many studies have investigated the efficacy of benzoyl peroxide. No resistance has been reported to date. 7 It is applied once or twice daily to the entire affected area. 7 There is no evidence to suggest that 10% benzoyl peroxide is more effective than 5%. 5 Therefore, because of its potential to cause erythema and irritation, concentrations of 10% should probably be avoided. 5 Lower strengths should be used in persons with sensitive skin and in very young or anxious patients. 7 Higher concentrations and washes can be used on the chest, shoulders and back. 7 Benzoyl peroxide can be used alone in mild acne or in combination with topical retinoids in severe comedonal and early inflammatory acne. It may be used in combination with systemic antibiotics when prolonged or repeated courses of the latter are necessary. A variety of other agents (for example, miconazole and hydrocortisone) have been used in combination with benzoyl peroxide but none has proved to be significantly better than benzoyl peroxide alone. 5 Benzoyl peroxide can cause drying, burning and peeling on initial application. 1,5 If patients experience these side effects, they should stop using the product for a day or two before starting again. Patients should start on the lowest strength available, especially if they have a sensitive or fair skin. 1,5 Azelaic acid Azelaic acid is a suitable topical agent for mild to moderate acne due to its antimicrobial effect on P acnes and its influence on follicular hyperkeratosis. 3 It is usually applied twice daily. Its safety and efficacy have not been proven for use for more than six months. 3 Retinoids Topical retinoids target the microcomedo, which forms the earliest precursor of visible acne lesions. 7 They have multiple anti-acne actions, namely to inhibit/reduce the number of microcomedones, reduce mature comedones, reduce inflammatory lesions, promote normal desquamation of follicular epithelium, have an anti-inflammatory effect, enhance the penetration of other medicines and maintain remission by inhibiting microcomedones. 7 Different topical retinoids are available, namely tretinoin, adapalene, isotretinoin and tazarotene. 3,7 They have similar efficacy but share a common side effect namely initial irritation on application. 7 The topical retinoids should be applied to the whole affected area and not only on visible lesions. According to the Global Alliance recommendations, 7 the topical retinoids should be the primary form of treatment for most forms of acne vulgaris. They should be used early for best results, and antimicrobial therapy should be added for inflammatory lesions if present. 7 They are an essential part of maintenance therapy. Salicylic acid Salicylic acid is used in concentrations of up to two percent for acne. 2 It exerts a keratolytic effect by increasing the hydration of epithelial cells. It may also have some bacteriostatic activity and a direct anti-inflammatory effect on lesions. 2 It is believed to enhance penetration of other medicines into the skin, and is combined with sulphur in some preparations. 2 Salicylic acid is a mild irritant and similar precautions should be adopted as for benzoyl peroxide. Preparations are applied twice or three times a day. It is readily absorbed through the skin and excreted slowly. Salicylate poisoning can occur if preparations are applied frequently, in large amounts and over large areas. 2 Patients who are sensitive to aspirin should avoid these preparations. Sulphur and recorcinol Sulphur and resorcinol are claimed to possess keratolytic and antiseptic properties, but there is little evidence of their effectiveness. Sulphur may be used on its own or in combination preparations with other keratolytic agents, such as resorcinol, salicylic acid or benzoyl peroxide, or with calamine. 3 Both sulphur and resorcinol can cause skin irritation and sensitisation. These agents are now infrequently used. 2 Salicylic acid and sulphur have been used for many years on the basis of their keratolytic action but based on evidence they are probably best avoided. 5 Prescription treatment Prescription treatment includes the following 2 : Topical comedolytic, antibacterial and combined comedolytic/antimicrobial preparations. Oral antibiotics. Hormonal agents. Isotretinoin. Other medicines. Oral antibiotics Oral antibiotics are indicated for moderate to severe acne (Grades 2 to 4). 7 Examples are tetracyclines (especially doxycycline, lymecycline, minocycline, and the older firstgeneration tetracyclines such as oxytetracycline), erythromycin, clindamycin and co-trimoxazole. 7 Penicillins are not considered to be effective in the management of acne. Minocycline, doxycycline and lymecycline have similar efficacy and pharmacoeconomically there is very little difference between them. 7 The Standard Treatment Guidelines and Essential Drugs List for South Africa: Primary Health Care 12 recommends benzoyl peroxide 5% gel applied at night, as well as oral doxycycline 100 mg daily for three months, if there are many pustules. Oral antibiotics induce improvement within the first three or four months of treatment, with little improvement thereafter, 17

7 EVIDENCE BASED PHARMACY PRACTICE Evidence while antibiotic resistance usually becomes apparent after four months of treatment. 7 It is therefore suggested that courses of antibiotics for acne should be limited to a maximum of four months. 7 Oral antibiotics should therefore be prescribed for three months, and an additional month can be considered if total clearance has not been achieved. Compliance should be checked in patients who do not respond well. Oral antibiotics should be used in combination regimens and never as monotherapy. 7 Female patients must be counselled that some antimicrobials can impair the efficacy of oral contraceptives and that additional non-hormonal contraceptive measures may be required. 12 The Global Alliance recommends the following with respect to oral antibiotics for acne 7 : Oral cyclines should be considered first-line agents when treating moderate to severe acne. Lymecycline should be considered first. The optimal dosage is 300 mg to 600 mg per day. Doxycycline or minocycline can be prescribed as secondline agents. The optimal dosage for both active ingredients is 100 mg to 200 mg per day, respectively. First-generation tetracyclines such as oxytetracycline should be considered as third-line agents. Erythromycin can be used in children under 12 years old or during pregnancy. Co-trimoxazole can be considered in selected cases. Hormonal agents The mainstay of hormonal therapy for acne includes oral contraceptives, cyproterone acetate, drospirenone and spironolactone. 7 Hormonal therapy is useful in androgen-driven acne. They are an excellent choice for women who need oral contraception for gynaecological reasons. They should be used early for patients with moderate to severe acne who also have signs of androgen over-activity (Seborrhoea, Acne, Hirsutism, Androgenic alopecia (SAHA)). 7 They should also be used early in female patients with clinical signs of hyperandrogenism (endocrine evaluation dehydroepiandrosterone (DHEA), testosterone, luteinising hormone/folliclestimulating hormone (LH/FSH) ratio). 7 They can be considered in women with normal serum androgens with persistent inflammatory papules and nodules on the lower face, or with prominent acne flare at menstruation. 7 They are also useful in combination treatment and in women with late-onset acne. Isotretinoin Oral isotretinoin is the standard of care for severe acne. 7 It targets all the pathophysiological factors involved in acne. It may achieve dramatic results even in severe disease, and may be used in moderate and unresponsive disease. 7 Side effects are common but usually manageable. The rate of recurrence is variable, and retreatment may be needed. 7 Isotretinoin, a naturally occurring metabolite of vitamin A, inhibits sebaceous gland differentiation and proliferation, reduces sebaceous gland size, suppresses sebum production, and normalises follicular epithelial desquamation. Isotretinoin is indicated in severe nodular acne and acne unresponsive to other therapies. It is used at a dosage of 0.5 to 1 mg/kg per day with a cumulative dosage of 120 to 150 mg/kg over a four to six-month treatment period. 7,8 Coadministration with steroids at the onset of therapy may be useful in severe cases to prevent initial worsening. 6 Oral isotretinoin is highly effective at reducing sebum secretion and a 16 to 20 week course leads to remission in most patients. 11 There may be an indication for the so-called pulse-dosage regimen, where 0.5 mg/kg is taken daily on the first seven days of each month. 13 This usually reduces side effects, except for the teratogenic effect, and has proved to be highly effective for patients who relapsed after a previous full course of oral isotretinoin, as well as for older patients with chronic, indolent, resistant acne. 7 Oral isotretinoin should only be prescribed by a dermatologist or specialist because it may cause serious adverse effects. It is highly teratogenic (classified as Category X in pregnancy 3 and should be avoided) and women of childbearing age should use effective contraception for one month before starting treatment, during treatment and for at least one month after stopping isotretinoin. 3 A United States of America Food and Drug Administration-mandated registry (called ipledge) is in place for all individuals prescribing, dispensing and taking isotretinoin. 6 The aim of this registry is to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy. 6 Special investigations during therapy should include serum lipids and liver function (before and after one month of therapy, relative to risks), blood glucose, haematology and uric acid (as indicated). 3 Depression is a known complication of acne, and may be exacerbated by isotretinoin. 3 Psychological evaluation of acne patients is therefore an important aspect of acne management. Patients with nodulocystic acne are at greatest risk of scarring and should be referred for oral isotretinoin treatment. Also, patients with inflammatory acne with scarring, moderate to severe acne unresponsive to treatment, acne with severe psychological distress (dysmorphophobic patients), gramnegative folliculitis, and frequently relapsing acne where repeated or prolonged courses of systemic antibiotics are needed, should be referred for oral isotretinoin therapy. 7 Other medicines that may be used in acne treatment Intralesional corticosteroid injections are effective in the treatment of individual acne nodules. 13,14 For patients who may not have access to expensive treatments for severe inflammatory acne, a combination of co-trimoxazole and low dosage prednisone for a few weeks may give excellent results. 7 Another useful drug is dapsone, which at a dosage of 50 mg to 150 mg per day, can bring about complete clearance of nodular inflammatory acne. 7 The condition can be controlled with long-term maintenance treatment, with low dosage dapsone being relatively safe, provided that the patient has a normal glucose-6-phosphate dehydrogenase (G6PD) level and that full blood counts are done regularly to detect any resulting anaemia. 7 High-dose vitamin A used to 18

8 EVIDENCE BASED PHARMACY PRACTICE be a popular treatment for acne in the past, but evidence for its effectiveness is lacking and because of its potential for severe toxicity, its use in acne should be discouraged. 7 Treatment of scars Small scars can be treated with chemabrasion (which uses chemicals to peel away top layers of skin), laser resurfacing (which uses a carefully controlled laser to burn away scar tissue) or dermabrasion (which uses a whirling wire brush to skim off scar tissue) under the supervision of a trained professional. 4,15 Deeper, discrete scars can be excised. 4 Wide, shallow depressions can be treated with subcision or collagen injection. 4 Collagen implants are temporary and must be repeated every few years. 4 Management of the different grades of acne vulgaris The management of the different grades of acne as it is stated in the South African Acne Guideline 2005 Update is summarised in Table 4. 7 Conclusion The management of acne vulgaris by non-dermatologists is increasing. 8 Pharmacists have a definite role to play in the less severe forms of acne and especially with respect to the counselling of patients with any form or severity of acne. Acne can be extremely distressing and can impact severely on the quality of life of a person. Initially mild acne should be treated with topical agents. The choice of treatment depends on whether comedonal or inflammatory lesions predominate. In more severe disease, addition of systemic drugs to topical therapy is required. Oral antibiotics are the mainstay of treatment for moderate to severe acne. Early referral of those with severe acne may prevent scarring. Acne responses to treatment vary considerably. Frequently more than one treatment modality is used concomitantly. Best results are seen when treatments are individualised on the basis of clinical presentation. The reader is strongly encouraged to consult the following sources for more detailed evidence-based information on acne: Acne Guideline 2005 Update has been developed and published in an attempt to improve the outcomes of acne treatment in South Africa (see Reference 7). Guidelines of Care for Acne Vulgaris Management published by the National Guideline Clearinghouse (levels of evidence are also indicated) (see Reference 13). The guidelines can also be consulted in the Journal of the American Academy of Dermatology (see Reference 14). Summary of Recommended Guideline: Acne Management of the Guidelines Advisory Committee (GAC) these EBM guidelines indicate different levels of evidence (see Reference 10). References: 1. Rutter P Community Pharmacy: Symptoms, Diagnosis and Treatment. Edinburgh: Churchill Livingstone. 2. Nathan A FASTtrack: Managing Symptoms in the Pharmacy. London: Pharmaceutical Press. 3. South African Medicines Formulary (SAMF) th Edition. Edited by CJ Gibbon. Claremont: Health and Medical Publishing Group of the South African Medical Association. 4. The Merck Manual of Diagnosis and Therapy th Edition. Edited by MH Beers. Whitehouse Station: Merck Research Laboratories. 5. Rutter P Symptoms, Diagnosis and Treatment: A Guide for Pharmacists and Nurses. Edinburgh: Elsevier Churchill Livingstone. 6. Harper JC & Fulton J Acne Vulgaris. emedicine, 15 July. Available on the web: print (date accessed: 15 December 2008). 7. Acne Guideline 2005 Update Compiled by W Sinclair & HF Jordaan. South African Medical Journal, 95 (11): Haider A & Shaw JC Treatment of Acne. Journal of the American Medical Association, 292: Feldman S, Careccia RE, Barham KL & Hancox J Diagnosis and Treatment of Acne. American Family Physician, 69: , Lauharanta J Guidelines Advisory Committee (GAC). Summary of Recommended Guideline: Acne Management. (EBM guidelines.) April. Available on the web: (date accessed: 15 December 2008). 11. MeReC Bulletin The Treatment of Acne Vulgaris: An Update. 10 (8). Liverpool: National Prescribing Centre. 12. Standard Treatment Guidelines and Essential Drugs List for South Africa: Primary Health Care Pretoria: The National Department of Health. 13. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK & Bhushan R Guidelines of Care for Acne Vulgaris Management. National Guideline Clearinghouse. Available on the web: summary.aspx?doc_id=10797 (date accessed: 12 December 2008). 14. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, Thiboutot DM, Van Voorhees AS, Beutner KA, Sieck CK & Bhushan R Guidelines of Care for Acne Vulgaris Management. Journal of the American Academy of Dermatology, 56 (4): Acne Vulgaris Treatment Overview Acne Health Centre. WebMD. Available on the web: acne/acne-vulgaris-treatment-overview (date accessed: 15 December 2008). Table 4: Management of the different grades of acne 7 Grade Grade 1 Grade 2 Grade 3 Grade 4 Recommended treatment This degree of acne should be managed topically. A topical retinoid will suffice in most cases, but the addition of benzoyl peroxide or azelaic acid may be necessary in resistant cases. In milder cases with superficial inflammatory papules, the same treatment as above can be followed. However, where the papules are more deeply situated, a systemic antibiotic is indicated. In these cases there is always a severe, deep inflammatory process present with a marked influx of neutrophils, necessitating systemic antibiotics. These should always be used in combination with a topical retinoid and, if the systemic treatment needs to go on for longer than three months, topical benzoyl peroxide should be added. Hormonal treatment can be used with good success at this stage in female patients who desire contraception or who have other gynaecological indications for this treatment. Systemic isotretinoin represents the treatment of choice in these patients. In females, an oral contraceptive combined with anti-androgens can sometimes be effective. Systemic antibiotics can bring about excellent improvement in these cases, but the improvement is of short duration and these medicines do not represent a long-term solution for this type of acne. Unacceptably long courses of antibiotics are usually necessary. 19