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CLINICAL GUIDELINE
Acne Guideline 2005 Update
Compiled by Werner Sinclair and H Francois Jordaan and largely based on a consensus document of the Global Alliance to
Improve Outcomes in Acne
Objective. The guidelines on the management of acne vulgaris Validation. These guidelines were developed through general have been developed in an attempt to improve the outcomes of consensus by a group of about 40 internationally recognised acne treatment in South Africa. This extremely common experts in the field of acne treatment (the Global Alliance to condition has a major impact on the quality of life of South Improve Outcomes in Acne, see details below) and further African young people and it is expected that if implemented, refined for South African circumstances by the majority of these guidelines will play a role in improving this situation.
South African dermatologists who attended a series of six Recommendations. All health care workers involved in the discussions held in the major centres of South Africa during management of acne should take note of these guidelines and endeavour to implement them in clinical practice. All Guideline sponsor. The meetings of the Global Alliance to treatment methods and procedures not substantiated by Improve Outcomes in Acne as well as the South African evidence from the literature should be discontinued and discussion meetings were sponsored by Galderma.
avoided to decrease the financial burden of acne treatment.
S Afr Med J 2005; 95: 883-892.
1. Introduction
and South America were included with the European group andthe South African delegates attended most of the meetings in Acne vulgaris is an extremely prevalent skin condition,1 affecting the majority of teenagers to a certain degree at some Four meetings were held in Europe. Brussels hosted these in point. The impact on the quality of life of young people is highly November 2002 and January 2003, Seville in April 2003 and significant.2 It has a greater negative effect on the emotions and social functioning of teenagers than diseases like asthma andepilepsy.3 It is often associated with anxiety, depression and The information and recommendations originating from these unemployment.4 The impact of the condition is often difficult to meetings were published in the Journal of the American Academy determine clinically,5 but one can assume that almost all acne of Dermatology (2003; 49: S1-38) and were brought back to South
patients will experience this impact to some degree.
Africa and discussed with South African dermatologists in aseries of meetings held during March and April 2004 at six main Medical treatment can make a very big difference,6 often centres in the country. About 80% of local dermatologists clearing the condition completely, or bringing about significant attended these meetings, commented on the recommendations, improvement in those who do not experience complete and gave input on special circumstances applicable to South Africa. All the information gathered from these meetings was The ‘Global Alliance to Improve Outcomes in Acne’ was then incorporated into the guidelines as set out in the rest of this formed in 2001 as a world-wide effort to bring together a group document. The recommendations are therefore highly of recognised experts in the field of acne treatment. The aim was representative of the current global approach to the treatment of to review the current state of knowledge in this field, to work acne, and at the same time reflect the thinking of the majority of through all the relevant literature available systematically, to local dermatologists. The guidelines should carry the necessary have meetings to discuss the evidence thus collected, and to weight and authority to ensure general acceptability among all draw up a set of recommendations for acne management to be South African health care workers who manage acne cases and distributed to all participating countries where the general should therefore be applied by dermatologists, general medical implementation of these guidelines would be encouraged.
practitioners, gynaecologists, pharmacists, nurses and also Two main groups were formed, in America and Europe.
Meetings were held separately but information was shared and This review discusses use of the major classes of anti-acne there was unification of the ultimate guidelines. Africa, Australia therapy and the way it should be used, with recommendationsin each instance, and management of the different grades of Please forward all comments to: [email protected]
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the follicular epithelium in the duct of the sebaceous gland; (iv) Consensus of the Global Alliance
proliferation of Propionibacterium acnes; and (v) inflammatory Acne has very significant impact on patients
• Negative effect on emotions and social functioning It is important to realise that acne is androgen-dependent.
• Associated with anxiety, depression, unemployment The main hormone responsible for increasing sebum • Impact not always easy to assess clinically production is dihydrotestosterone, converted from testosteronein the sebaceous glands by the enzyme 5-alpha-reductase.8-10 The primary lesion in acne is the microcomedo. It is not Recommendations of the Global
visible to the naked eye but histological analysis shows Alliance
hyperkeratosis of the intrafollicular sebaceous ducts anddilatation of the sebaceous glands. In the acne-prone patient, Quality of life
about 30% of facial follicles will be in this state at any given • Effective treatment dramatically improves a patient’s time. An additional concept is that of the inflammatory microcomedo, still not visible to the naked eye, but which • Use of a simple QOL assessment tool can help clinicians shows inflammation on histological examination.11 This lesion forms an important target in the treatment of acne, especiallyas far as maintenance treatment is concerned.
2. Why Guidelines?
It has also become evident that interleukin-1-alpha, an inflammatory cytokine, plays a major role in inducing Guidelines for the treatment of acne vulgaris are necessary inflammation in the microcomedo, with resultant activation of because a huge variation exists in the approach of different dermatologists and other health care workers involved in acne P. acnes is a Gram-positive, pleomorphic, anaerobic rod; its management. Some of the methods used are not supported by important role in acne has been well proven.12 There is a very any evidence in the literature and some methods are clearly strong correlation between the number of these bacteria and detrimental to the patient, the community or the patient’s the level of sebum production16 and it has been shown that finances. A significant proportion of dermatologists also only living propionibacteria are able to induce inflammation in deviate from the accepted regimens. In our present climate of acne cysts.13-16 Humoral and cellular immune responses managed health care, health care funders are increasingly induced by this bacterium, namely the generation of relying on evidence-based decisions when deciding on extracellular enzymes,17 the production of interleukin-1-alpha,18 reimbursement of treatments. Similar trends are followed in the the generation of heat-shock proteins and a mitogenic effect on T-cells, correlate with acne severity. A positive chemotactic One should also remember that non-dermatologists treat effect on neutrophils is an important consequence of the more acne than dermatologists, hence it is particularly breakdown of sebum into free fatty acids by bacterial lipase.19,20 important for the former to have a set of practical guidelines to These bacteria are not involved in comedogenesis but they are facilitate the best possible outcomes in acne treatment.
very prominent in inducing inflammation through A further consideration is that new evidence is constantly emerging and new drugs are being developed on a regular At present there is no evidence to suggest that coagulase- basis. These factors should be taken into account when negative Staphylococcus aureus, S. epidermidis or Pityrosporum guidelines are drawn up. Guidelines can never be static, and ovale play any significant role in the pathogenesis of acne constant revision is the norm. Guidelines were published in this Journal in 1999; while many of these principles are stillapplicable, they have been largely revised here.
Consensus of the Global Alliance
3. Pathophysiology of acne vulgaris
Knowledge of pathophysiology should influence
It is very important to be knowledgeable about the treatment
pathophysiology of this condition. The pathogenetic factors • Primary pathophysiological factors in acne: represent specific targets for treatment and it has been proved that combinations of treatment directed at different pathogenetic factors will achieve better results than different • Abnormal desquamation of the follicular epithelium treatment methods aimed at the same factors.7 The main pathogenetic factors involved in acne are the following: (i) production of androgens in the body; (ii) • Treatment should target as many factors as possible excessive sebum production; (iii) abnormal desquamation of November 2005, Vol. 95, No. 11 SAMJ
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4. Clinical diagnosis of acne vulgaris
scarring would immediately be placed in a more severecategory than one without scarring. Acne vulgaris can present with a variety of skin lesions,namely comedones, both open and closed, inflammatory 6. Use of antibiotics in treatment of
papules, pustules, nodules, cysts, conglobate lesions, sinuses, acne vulgaris
scars and even ulcers. However, several other skin diseasespresent with very similar-looking skin lesions and a diagnosis Antibiotics are the most frequently used type of drug in the is not always as straightforward as it would seem. It is always treatment of acne. They can be used both topically and important to ascertain whether comedones are present because systemically, the latter being far more effective. It is generally comedones are virtually diagnostic of acne vulgaris and it is accepted that antibiotics, especially in topical form, are largely very difficult to make this diagnosis in their absence.
abused in the management of acne and many of the problemsexperienced with the use of antibiotics are due to the While acne involves mostly the face it often extends onto the inappropriate use of topical preparations.
trunk, most often the back, and can also involve the upperarms, thighs and even the buttocks. The scalp is very rarely It is not the purpose of this review to discuss the involved even though it is richly supplied with sebaceous pharmacology of these drugs in detail, but certain aspects of the mechanisms of action and the most important side-effectswill be addressed.
5. Grading of acne vulgaris
Different classes of antibiotics are used in acne management.
It is necessary to grade acne vulgaris according to severity; this Most frequently used are the tetracyclines, especially is very important in decision making when treatment is doxycycline, lymecycline, minocycline and the older first- planned. Grading can, however, be very problematic and generation tetracyclines. Erythromycin is also frequently used, highly subjective, especially when clinicians also use the both topically and systemically, and the same applies to number of different skin lesions to determine severity.
clindamycin. Co-trimoxazole is also commonly used,22,23 as it isinexpensive and often highly effective. As a rule the penicillins The simplest way of grading acne is based on the predominant type of lesion present on the skin, regardless ofnumber. This makes therapeutic sense if one assumes that, for 6.1 Mechanism of action of oral antibiotics
example, one comedo present on the face will respond as wellto treatment as a thousand comedones. The acne is therefore The cyclines are the most widely studied group of drugs in this graded according to the type of lesions present and the latter regard. They exert both antibacterial and non-antibacterial will dictate the form of therapy implemented. Grading is action in combating acne. Among the non-antibacterial always done according to the most severe lesions present.
activities, inhibition of bacterial lipases, anti-inflammatoryactivity and immunosuppression are among the most important. For the cyclines as a group, 11 different anti- inflammatory effects have been discovered, which include • Grade 2: Inflammatory papules present in addition to the among others, inhibition of neutrophil leucotaxis,24 reduction in cytokine secretion, decrease in metalloproteinase activity and • Grade 3: Pustules present in addition to any of the above direct inhibition of lymphocyte mitosis.25-28 These activities are • Grade 4: Nodules, cysts, conglobate lesions or ulcers present used in a variety of other diseases, but in acne the antibacterial effects are probably the most important.
More complicated grading systems rely heavily on the use of 6.2 Propionibacterium resistance to antibiotics used
photographs or diagrams. In such systems the clinicalappearance of the patient is compared with a standard set of photographs and severity is decided on according to Successful treatment reduces the population of P. acnes but correspondence with a particular photograph. This system is does not eradicate it. Acne is not cured, there is merely a often difficult to reproduce, highly subjective, and does not temporary reduction in the number of bacteria. Widespread always reflect the exact pathology present and therefore is not use of antibiotics has led to the emergence of resistance and reliable in indicating the exact treatment required for the therapeutic failure.29,30 Therapeutic failure can also be caused by poor compliance, incorrect use of the drug, inadequate In addition to the actual grade of the acne, one should take potency prescribed and folliculitis caused by other bacteria.
into account the extent of involvement because this will Antibiotic resistance among these bacteria has increased certainly influence the decision on the treatment method. The dramatically over the past 25 years, with a figure of 62% presence of scarring should also be noted. A patient with quoted for the UK at the moment. Resistance is now an November 2005, Vol. 95, No. 11 SAMJ
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international problem, induced by the use of antibiotics.
antibiotic when treating moderate to severe inflammatory Resistant bacteria can also be transferred to close contacts and to and from physicians, with dermatologists being particularly • Doxycycline or minocycline can be prescribed as second at risk. Several factors are at play in causing resistance. The most important of these is the prescription of prolonged • First-generation tetracyclines should be considered a third courses of antibiotics, multiple courses of antibiotics and the use of topical preparations. The edge of a topically treated area • Erythromycin can be used in children under 12 years old or will always have a zone where the concentration of antibiotic will be suboptimal, encouraging the growth of resistant • Co-trimoxazole can be considered in selected cases 6.3 How to prevent resistance
6.5 Optimal dosing of oral cyclines in acne
One should avoid the needless use of antibiotics; they are only treatment
indicated for moderate to severe acne (grades 2 - 4). They As mentioned above, the correct dosing is essential to prevent should be used in combination treatment and never as bacterial resistance, and even though low doses have been monotherapy. Minimum duration of treatment should be 6 shown to be effective this will increase bacterial resistance. It is weeks and maximum duration 12 weeks. Strict compliance by therefore encouraged that high doses be used for the full the patient is necessary, and if topical antibiotics are used they duration of treatment to increase efficiency and to reduce the should be combined with topical non-antibiotic antimicrobials Antiresistance agents that can be used include benzoyl peroxide, zinc acetate and oral isotretinoin.
Recommendations of the Global
Alliance
6.4 Which oral cyclines are used in acne treatment?
Optimal dosage for antibiotics in acne
Minocycline, doxycycline and lymecycline have similarefficacy.31 As far as side-effects are concerned, doxycycline is prone to cause phototoxicity and gastrointestinal disturbance • 100 - 200 mg per day for doxycycline and minocycline and minocycline can cause hyperpigmentation, hypersensitivity syndromes, serum sickness-like illness and • Topical antibiotics should never be used as monotherapy drug-induced lupus.32,33 These side-effects are fortunately rare,but nevertheless serious.34 It is recommended that ifminocycline is to be used for more than 3 months, liver 6.6 Optimal duration of oral antibiotic treatment
functions and ANA determination need to be done 3-monthly.35Lymecycline appears to be free of these side-effects.36 It has been shown that oral antibiotics will induceimprovement during the first 3 or 4 months of treatment, with Pharmacoeconomically, there is very little difference between little improvement thereafter, while antibiotic resistance will these 3 drugs, with doxycycline being slightly less expensive become more apparent after 4 months of treatment. It is therefore felt that courses of antibiotics for acne should be On the whole there is at the moment very little use for first- generation tetracyclines like oxytetracycline in the treatment ofacne vulgaris. Their effectiveness cannot compare with that ofthe more modern drugs and they are not significantly cheaper Recommendations of the Global
any more, giving them poor cost-effectiveness ratios.
Alliance
Duration of antibiotic treatment
Recommendations of the Global
Alliance
• Oral antibiotics should be prescribed for 3 months • An additional month can be considered if a steady Oral antibiotics for acne
improvement has been seen over the previous 3 months, • Oral cyclines should be considered as a first choice when but total clearance has not been achieved • Compliance should be checked in patients who do not • Lymecycline should be considered as a first-choice November 2005, Vol. 95, No. 11 SAMJ
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7. Use of topical retinoids in acne
8. Use of topical benzoyl peroxide in
treatment
acne treatment
Topical retinoids target the microcomedo, which forms the Benzoyl peroxide is an extremely useful preparation in the earliest precursor of visible acne lesions. These preparations management of acne. It has a mild but significant keratolytic also have very significant anti-inflammatory effects through effect, therefore acting in a comedolytic fashion, but is also a inhibition of toll-like receptors, which is not only useful in broad-spectrum antimicrobial, acting in a non-antibiotic treating inflammatory acne, but also plays a major role in fashion. It can therefore be used alone in cases of mild acne,41 in treating the inflammatory microcomedo, as mentioned in the combination with topical retinoids in severe comedonal and discussion on the pathophysiology. They can therefore be used early inflammatory acne, and as an antiresistance agent in with great success in established inflammatory acne, right from combination with systemic antibiotics when prolonged or the start of treatment,37 and they are also extremely useful in repeated courses of the latter are necessary.
maintenance therapy where long-term use can prevent the Benzoyl peroxide is available in different strengths, usually formation of new lesions and suppress the further 5% or 10% gels and creams, and in the form of facial washes.
development of inflammatory microcomedones.
The different topical retinoids available, namely tretinoin, adapalene, isotretinoin and tazarotene, have similar efficacy38 Consensus of the Global Alliance
but share a common side-effect in the form of initial irritation Benzoyl peroxide is a useful adjunctive treatment
on application.39 Of the four preparations, adapalene seems tobe the one least prone to cause significant irritation.40 This irritation effect is more pronounced on the Highveld of South • Slower-acting than systemic antibiotics Africa with its drier climate than on the coast. It is therefore important to use the cream formulations on the Highveld, • Useful in patients with mild to moderate acne while the gel formulations can be freely used at the coast.
It is also very important to realise that topical retinoids should be applied to the whole affected area and not only on Recommendations of the Global
visible lesions. This is because in addition to their therapeutic Alliance
effect on visible lesions, their main action is preventive,working on skin without apparent lesions.
Benzoyl peroxide
• Use in patients with mild to moderate acne Consensus of the Global Alliance
• Apply once or twice daily to entire affected area• Use lower strengths in persons with: Topical retinoids have multiple anti-acne actions
• Inhibits/reduces number of microcomedones • Higher concentrations and washes for: • Promotes normal desquamation of follicular epithelium• Anti-inflammatory• Enhances penetration of other drugs 9. Combination therapy for acne
• Maintains remission by inhibiting microcomedones vulgaris
Oral antibiotics and topical retinoids have been shown to have Recommendations of the Global
synergistic mechanisms through independent processes.
Alliance
Clearing of both inflammatory lesions and comedones isfaster42 and more complete with a combination of these 2 Topical retinoids in acne treatment
preparations than with antibiotics alone.43,44 The simultaneoususe of topical retinoids limits the duration of antimicrobial • Should be the primary form of treatment for most forms of therapy, enhances the penetration of antibiotics into the skin and increases the follicular cell turnover allowing more antibiotics to be transported into the sebaceous unit.41 • Add antimicrobial therapy for inflammatory lesions when Benzoyl peroxide can be added to topical retinoids and • Should be applied to the entire affected area systemic antibiotics in order to decrease resistance44 or it can be • Essential part of maintenance therapy used in combination with topical retinoids either on alternate November 2005, Vol. 95, No. 11 SAMJ
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days or on a daily basis, one being applied in the morning and treatment of choice for maintenance, as explained above, for a minimum period of 12 months after completion of the initialsystemic treatment. Benzoyl peroxide can be added to theretinoids at this stage, especially if inflammatory lesions still Consensus of the Global Alliance
appear. Topical retinoids can also be used as maintenancetreatment after completion of a course of systemic isotretinoin Combination therapy is now standard of care for
mild to moderate acne
Other preparations that can be used for long-term • Antimicrobial therapy plus topical retinoids is significantly maintenance are azelaic acid46 and salicylic acid, but these represent the second and third choices. In females the use of • Clearance of both inflammatory lesions and comedones is oral contraception, even without anti-androgen effect, also represents excellent maintenance therapy, with or without • Combination therapy allows targeting of different • Topical retinoids are likely to enhance penetration of antimicrobials, and to speed up action of antibiotics Consensus of the Global Alliance
• Topical retinoids added early, at start of treatment, give Maintenance therapy
• Antibiotic can be discontinued when inflammatory lesions • The microcomedo is the precursor of all acne lesions • The process of microcomedo formation is permanent and • If this is not possible, benzoyl peroxide or benzoyl peroxide/antibiotic combination can be used • Avoiding microcomedo formation has a preventive effect in • Success can be maintained with topical retinoids • Microcomedones are the main target of topical retinoids Recommendations of the Global
Alliance
Recommendations of the Global
Alliance
Combination therapy
• Oral antibiotics should not be used alone Maintenance therapy
• Oral antibiotics should not be combined with topical • After the acute phase of acne treatment (> 90% antibiotics (increases the risk of bacterial resistance and improvement), maintenance therapy should always be • Oral antibiotics should always be combined with a topical • Topical retinoids are the treatment of choice for retinoid from the start (3 pathogenic factors addressed) • Benzoyl peroxide can be added to topical retinoids and • Suggested duration of maintenance therapy is 6 - 12 oral antibiotics in order to lower the incidence of bacterial • Benzoyl peroxide can be added to topical retinoids to • Benzoyl peroxide should be added when longer courses of lower bacterial resistance after antibiotic treatment • Second choices for maintenance therapy are azelaic acid • Topical retinoids and benzoyl peroxide can be used in combination, either on alternate days or one in themorning and the other at night 11. Hormonal treatment of acne
10. Importance of maintenance therapy
vulgaris
Acne is an androgen-dependent condition and in females the With the exception of a full course of systemic isotretinoin, androgens can be effectively blocked or reduced, often leading other acne therapies will merely suppress the process and not to significant improvement in or clearing of the condition. It cure the condition. This is especially applicable when systemic represents an excellent choice for women who need oral antibiotics are used. It is therefore imperative that maintenance contraception and should be used early for patients with therapy be instituted in all instances.45 Topical retinoids are the moderate to severe acne who also have signs of androgen over- November 2005, Vol. 95, No. 11 SAMJ
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activity (Seborrhoea, Acne, Hirsutism, Androgenic alopecia
Used in the correct dose, it very seldom fails to clear acne (SAHA)). It is useful in combination treatment, in women with completely and it effects a permanent cure in a high percentage late-onset acne and in patients with prominent premenstrual of cases, with cure rates varying from 38% to 66%, depending Ordinary combination oral contraceptives are often effective Isotretinoin addresses all the pathophysiological factors in mild forms of acne,47 but for more severe forms antiandro- involved in acne and usually achieves dramatic results even in gens must be used. The most effective available is cyproterone more severe cases. There is no doubt that it is the drug of acetate, either in a dosage of 2 mg added to ethinylestradiol, or choice for severe acne, with benefits far outweighing the risks in a dosage of 10 mg taken for 15 days per cycle, added to a involved. It has, however, become fashionable to use the drug contraceptive48 for more severe cases. It is very important to for less severe cases where other more conservative treatments remember that cyproterone represents an effective progestogen, may have been successful, often prescribed under pressure therefore acting as effective contraception in combination with from patients. Physicians should nevertheless adhere to the ethinylestradiol and additional contraception is not necessary prescribed indications for use of this drug to prevent when this preparation is prescribed.
Some authorities feel that the routine use of a topical retinoid This drug causes numerous side-effects, some of which are in combination with hormonal therapy brings about a much serious, but most of which are not. Most patients experience quicker response than hormonal treatment alone and should be the period on this drug as very unpleasant, but they endure the regarded as an acceptable treatment option.
nuisance side-effects because they see the benefits very soonafter starting treatment. The most serious side-effect is ofcourse the teratogenic effect of the medication. This side-effect Consensus of the Global Alliance
is entirely preventable55 if the patient adheres to strict Hormonal therapy is useful in androgen-driven
contraception for a month before the start of treatment,undergoes a negative pregnancy test thereafter and starts medication on the third day of her next menstrual period.
• Excellent choice for women who need oral contraception Effective contraception has to continue for 1 month after taking the last tablet in the course. Monthly negative pregnancy tests • Should be used early for patients with moderate or severe are recommended in South Africa but are compulsory in the USA. The patient should be fully aware of the risks, and should sign written consent for use of the drug and indicating her understanding that a therapeutic abortion would becompulsory should she fall pregnant during treatment.
Consensus has not been reached on the issue of depression and suicide resulting from the use of isotretinoin. Statistically Recommendations of the Global
speaking, there is a lower incidence of suicide in patients whoare on treatment with this drug, compared with a similar Alliance
population not exposed to it. General consensus has not been Hormonal therapy
reached on whether a small subset of patients will react with adepressive response in an idiosyncratic, unpredictable way.
• Use early in female patients with clinical signs of Caution is advised in patients with a history of depression; hyperandrogenism (endocrine evaluation – mood swings should be reported by the patient and the drug dehydroepiandrosterone (DHEAS), testosterone, luteinising should be discontinued should any symptoms of depression hormone/follicle-stimulating hormone (LH/FSH) ratio)49,50 • Consider in women with normal serum androgens: • Persistent inflammatory papules, nodules on lower face The other side-effects of isotretinoin are of a less serious nature59 but the patient should be aware of the dry skin and • Mainstay of hormonal therapy: oral contraceptives, mucosae that will be experienced, the initial temporary cyproterone acetate, drospirenone, spironolactone51 worsening of the acne, the photosensitivity that occurs in 5% of 889
cases, the possibility of joint and muscle pain, the severe nightblindness that can hamper driving at night, the possibility of 12. Systemic isotretinoin as treatment
mild hair loss that may occur and the fact that liver enzymes for acne vulgaris
and triglyceride levels may become raised during treatment.
Blood tests to determine baseline liver enzyme levels and Very few authorities question the fact that this preparation triglycerides need to be done before treatment starts and represents by far the most effective anti-acne treatment.52,53 should be repeated after 1 month of treatment. Should the November 2005, Vol. 95, No. 11 SAMJ
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baseline and 1-month values both be normal, further blood Consensus of the Global Alliance
The effect of isotretinoin on bone metabolism has been under Oral isotretinoin is standard of care for severe
discussion for decades.60,61 Treatment with high dosages over prolonged periods for diseases of cornification has been • Targets all the pathophysiological factors associated with skeletal abnormalities including hyperostosis, • May achieve dramatic results even in severe disease calcification of spinal ligaments and osteoporosis. It has • May be used more frequently in moderate and recently been shown that the normal 4 - 5-month course of isotretinoin does not cause any skeletal abnormalities, but there are no data available on patients who were exposed to long- • Variable rate of recurrence; retreatment may be needed term, low-dosage use of this drug. This uncertainty, togetherwith the teratogenic effect, are the main reasons why long-termlow-dosage treatment should be strongly discouraged at thisstage.
Recommendations of the Global
At each visit the patient should be questioned about Alliance
headaches; nightly or early-morning headaches could indicate Oral isotretinoin
raised intracranial pressure which is an uncommon side-effectof this drug but which can be precipitated by the concomitant use of tetracyclines or systemic corticosteroids. These last 2 • Severe nodulocystic acne and its variants drugs should be used with circumspection in these patients.
The correct indications for isotretinoin in acne are indicated • Moderate to severe acne unresponsive to treatment with: in the ‘Recommendations of the Global Alliance’ on this page. • Three months of combination treatment including The dosage used for a full course of treatment is very • Four cycles of anti-androgen containing hormonal important.62-64 This should not be below 0.5 mg/kg per day and should not exceed 1 mg/kg per day, in order to limit side- • Acne with severe psychological distress effects. The duration of treatment is determined by the body weight of the patient and the daily dose taken. One should aim for a minimum target of 120 mg per kg as a total cumulative • Frequently relapsing acne where repeated or prolonged dose but this can be increased to 150 mg per kg if a satisfactory courses of systemic antibiotics are needed result has not been achieved once 120 mg/kg has been reached.
• Patient counselling is critical (side-effects, teratogenicity, The chances for a permanent cure are dramatically reduced if treatment is discontinued before the threshold of 120 mg/kg • Typical dosage: 0.5 - 1 mg/kg/day, cumulative dosage has been reached, even if the acne has cleared completely • Pulse-dosing permitted for relapse cases or older patients There may be an indication for the so-called pulse-dosage regimen, where 0.5 mg/kg is taken daily on the first 7 days of • Recurrence is common; a topical retinoid should be used as each month. This is usually free from side-effects, except for maintenance treatment after isotretinoin treatment the teratogenic effect, and has proved to be highly effective forpatients who relapsed after a previous full course of this drug,as well as for older patients with chronic, indolent, resistant 13. Other drugs that may be used in
acne. South African dermatologists felt that this regimen acne treatment
should be included in the accepted guidelines for this country.
Many patients, especially among the poor, may not have access A special set of circumstances in which low-dosage to expensive modern treatments for very severe inflammatory continuous isotretinoin may be used, involves young teenagers acne. In these cases a combination of co-trimoxazole and low- with very severe comedonal acne. These patients respond very dosage prednisone for a few weeks may give excellent results.
poorly to topical comedolytic agents initially, and a 4 - 6-month Another useful drug in this scenario is dapsone, which at a course of 10 - 20 mg of isotretinoin per day can lead to prompt dosage of 50 - 150 mg per day can bring about complete clearance of these lesions, whereafter maintenance with topical clearance of nodular inflammatory acne. The condition can be retinoids should be highly effective.
controlled with long-term maintenance treatment, with low- High-dosage vitamin A used to be a popular treatment for dosage dapsone being relatively safe, provided that the patient acne in the past, but evidence for its effectiveness is lacking has a normal glucose-6-phosphate dehydrogenase (G6PD) level and because of the severe potential toxicity of this medication, and that full blood counts are initially done regularly to detect its use in acne should be discouraged.
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14. Adjunctive therapies
neutrophils, necessitating systemic antibiotics. These shouldalways be used in combination with a topical retinoid and, if The most important aspect of adjunctive therapy is the the systemic treatment needs to go on for longer than 3 patient’s understanding of the treatment. This will reduce months, a topical antiresistance agent should be added.
lapses in compliance, improve outcomes and prevent problems Hormonal treatment can be used with good success at this stage in female patients who desire contraception or who have Skin care regimens are generally of very little use and never other gynaecological indications for this treatment.
cost-effective. The face should be cleansed twice daily with Grade 4. Systemic isotretinoin represents the drug of choice
water and soft soap and the use of moisturising creams should in these patients. In females, an oral contraceptive combined be limited, except in patients taking systemic isotretinoin.
with anti-androgens can sometimes be effective. Systemic Office procedures such as comedo extraction, chemical peels antibiotics can bring about excellent improvement in these and intralesional corticosteroids may be useful in selected cases cases, but the improvement is of short duration and these but cannot replace medical treatment.
drugs do not represent a long-term solution for this type ofacne; unacceptably long courses of antibiotics are usuallynecessary.
Consensus of the Global Alliance
16. Summary of Guideline principles
General acne management strategies form useful
part of therapy
• Most acne cases should receive a retinoid, either systemically • Patient understanding of therapy (use, expected results, the • Inflammatory acne responds very well to retinoids, and there is consequently no need to delay their introduction into the • Office procedures: comedo extraction, chemical peels, and • The anti-inflammatory effect of retinoids starts in the • Retinoids should be used in combination treatment from the Recommendations of the Global
• The main purpose of the retinoids is to minimise the use of Alliance
• Lymecycline appears to be the tetracycline of choice for acne General management principles
at the moment, based on its cost-effectiveness and side-effectprofile.
• Bacterial resistance involving P. acnes and other organisms is • Teach patients about gentle skin cleansing a problem; if antibiotics are needed for more than 4 months, • Show appropriate application techniques for topical one should always add benzoyl peroxide or another • Help patients to have realistic expectations of therapy • Systemic retinoids represent the treatment of choice for • Show empathy for patient’s distress due to acne • Systemic retinoids should not be given routinely for acne, 15. Management of the different grades
of acne vulgaris
• The use of topical retinoid maintenance after systemic isotretinoin depends on the response to the systemic drug.
Grade 1. This degree of acne should be managed topically. A
• Hormonal treatment can be used early and as monotherapy topical retinoid will suffice in most cases, but the addition of in females who desire contraception and as maintenance.
benzoyl peroxide or azelaic acid may be necessary in resistantcases.
17. References
Grade 2. In milder cases with superficial inflammatory
1. Cunliffe WJ, Gould DJ. Prevalence of facial acne vulgaris in late adolescence and in adults.
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