Acne Vulgaris Introduction What is acne? Factors implicated in the development of acne

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1 Acne Vulgaris Introduction Acne is a common condition, affecting about 85% of people between the ages of years. Although the majority of sufferers grow out of their acne, about 12% of women and 3% of men will continue to have acne until 44 years of age. Most of the prevalence studies on acne have been done on predominantly Caucasian groups. Specific studies undertaken in blacks (from the USA and UK), demonstrate that acne occurs at an equally high prevalence in this cohort. As overall health is often not impaired, acne is erroneously considered a trivial disease. In fact, acne poses significant psychosocial burden on sufferers, with individuals more likely to be socially withdrawn and more prone to depression, anxiety and anger compared to the normal population. In blacks, pigmentary changes (dark spots and patches) and keloidal scarring are important potentially preventable sequelae that can leave devastating psychological scars on an individual. What is acne? To understand what acne is, we must review the normal hair follicle anatomy and discuss the process by which inflammation occurs in this structure. Hair follicles have sebaceous glands and arrector pili muscle attached, together this is called the pilosebaceous unit. Acne sufferers often have an increase in oil (sebum) excretion by the sebaceous glands (often caused by increased sensitivity of the sebaceous glands to circulating sex hormones). In addition, the skin cells lining the hair follicle, which are normally shed and excreted from the follicle, become sticky and stay in the follicle in acne sufferers. This leads to the formation of a plug that blocks the hair follicle, forming the comedone, the precursor of all acne lesions. Together with follicular occlusion and oil (sebum) excretion, there is also an overgrowth of normal bacteria, with subsequent inflammation. This leads to the formation of acne spots, which can manifest as papules, pustules, nodules and cysts. There is insufficient evidence in the literature to indicate that the pathogenesis of acne differs in between races Factors implicated in the development of acne Genetics Acne is a multi-factorial disease, and genetics probably contributes to the development of acne. Studies indicate that the size, number and activity of sebaceous glands are genetically determined. In addition, the concordance rate of acne in identical twins is high, confirming the role of genetics in the development of acne. Diet There are several studies, which have addressed the role of diet in the development of acne. A recent study, concluded that diary products contribute to the pathogenesis of acne. This is postulated to be mediated via the synthetic hormones used in cows in the milk industry. Caution must be used in interpreting such studies and the general recommendations remains for individuals to eat a well-balanced diet.

2 Hormones Sebaceous gland excretion may be stimulated by male sex and adrenal gland hormones. During puberty, the level of these hormones are not elevated, but the sebaceous glands are more sensitive to them (this may be due to an increase number of receptors on the glands). There are certain medical conditions (listed in box 1) which can lead to inappropriately high levels of male sex hormones, thereby producing acne. Although the majority of individuals with acne do not have underlying hormonal problems, physicians can exclude this by careful history taking and physical examination. Appropriate investigative tests will be directed by the clinical findings. Polycystic ovarian syndrome (commonest) Cushing s syndrome Congenital adrenal hyperplasia Testosterone secreting tumours of the ovary, testes and adrenal glands Box1. Medical causes of acne vulgaris Drugs Acneform eruptions can occur as an adverse drug eruption, and stopping the offending drug will often alleviate the problem. This must be done in consultation with the prescribing physician, with a detailed review of risks and benefits of stopping the offending medication undertaken. Check the information leaflet of the drug to see if acne is listed as a side effect. Examples of drugs causing acne include steroids and lithium. Hair grooming agents-pomade acne Excessive use of hair pomades (also known as hair moisturizers, hair styling products and hair grease), which are often part of the hair care regime of blacks, can lead to the development of acne. This occurs especially around the hairline and forehead. Counselling and review of the hair care regime can alleviate pomade acne. Cosmetics Acne can result from heavy cosmetic use and the associated pigmentation changes maybe exacerbated by harsh agents applied to the skin as part of an individual s grooming practise. Furthermore, vigorous washing of the skin with rubbing and scrubbing, or using puffs or abrasive sponges can also cause or worsen acne. Thus, it is important that the skin care regime of the acne sufferer be reviewed by their dermatologist, with specific advice given regarding the use of non-irritating and non-comedogenic products. Clinical presentation of acne The clinical lesions of acne often occur in sites with a large number of sebaceous glandstypically the face (forehead, nose, chin and jawline), chest and back. In blacks, acne distributed primarily on the forehead may be a complication of the use of oily substances

3 in the hair(pomade acne-see above). Unusual distribution sites of acneform lesions can occur secondary to drugs (oral steroids may cause a generalised acneform eruption) or occlusion (for example under the chin, in a violin player). The clinical lesions of acne are: Open comedones-blackheads Closed Comedones-whiteheads Papules-solid red acne bumps Pustules-red bumps with white or yellow pus Nodules & Cysts-much larger, pus filled A study done at a center in the USA, showed that most black people with acne presented clinically with papules and acne hyperpigmented macules (darkened flat areas under 1 cm in diameter). Acne Variants Acne fulminans and acne conglobata Acne fulminans (a very severe form of cystic ace with fevers, joint pains and other systemic manifestations) and acne conglobata (severe nodulocystic acne without the systemic manifestations) are not so common in black people. Management will need dermatological input with the use of drugs such as, oral steroids, antibiotics, isotretinoin and dapsone. Acne excoriée des jeunes filles This variant is seen in young women, who present with comedones and papules, but often contribute to the pigmentary changes and lesions by scratching and picking at their lesions. Often sufferers are at risk of anxiety, obsessive- compulsive or personality disorders and for this reason, treatment should include psychotherapy. Occupational acne Exposure to certain chemicals in the work-place can produce acne as a complication- this includes cutting oils, petroleum based products, chlorinated hydrocarbons and coal tar derivatives. Comedones often dominate the clinical picture in such situations. Furthermore, exposure to high temperatures at work (such as furnace workers) maybe associated with acne. Tropical acne Acneform eruptions may occur because of extreme heat-for example in tropical climates. Clinical mimickers of acne vulgaris Physicians must distinguish acne vulgaris from a range of skin disorders, which produce follicular papules and pustules. The key distinguishing factor is the presence of comedones, which is characteristic for acne vulgaris. Gram-negative folliculitis Infection of the hair follicles can produce papules and pustules, which resembles acne. One such example is Gram-negative bacterial folliculitis, which may occur as a complication of

4 acne treatment. The prolonged antibiotic therapy given to some acne sufferers can lead to a change in the normal bacteria flora of the nose, with an overgrowth of specific bacteria known as Gram-negative bacteria. This can in turn lead to infection of the hair follicles, with clinical development of pustules around the nose, and on the cheeks and chin. This diagnosis can often be made based on the clinical history and physical examination. Confirmation will be based on swabs and bacterial culture of the pustules. It is best to stop the antibiotic treatment for the acne vulgaris and to use either isotretinoin or a different antibiotic that is guided by the results of bacterial culture of swabs of pustules. Gramnegative organisms often require a moist environment to grow, which is normally produced by the excessive sebum production in some acne sufferers. The drug isotretinoin works by decreasing sebum production, which inhibits growth of the Gram-negative organisms. Often antibiotics are only a suppressive therapy, as often the problem recurs when the drug is stopped. Once the Gram-negative folliculitis is cured, any residual acne may be treated by other therapies. Peri-oral dermatitis This occurs often in young women typically as a result of inappropriate use of topical steroids. They develop acneform lesions distributed around the mouth and sometimes around the eyes. Treatment is with antibiotics and discontinuation of the topical steroids. Rosacea This is a rare condition in blacks and is more commonly associated with Celtic ancestry. There is erythema (redness) of the face, with telangiectasia (dilated blood vessels) with or without papules and pustules. Again, no comedones are seen in this disorder. FACE This is an acronym for Facial Afro-Caribbean Childhood Eruption. This condition was first described in 1974 and is commonly seen in black children. Clinically monomorphic (looks the same) flesh- coloured or hypopigmented papules are present on the face (especially around the mouth, eyelids and ears). The lack of comedones, age of onset and unusual distribution sites differentiate this entity from acne vulgaris. It is self-limiting, resolving after several months without scarring. Management of acne A wide variety of topical and systemic agents are available for the management of acne. Their mechanism of action is by either one or a combination of the different modes of action listed below: reduction of sebum production reduction of the increased layer of cells lining the hair follicles (follicular hyperkeratosis) reduction of bacterial overgrowth and associated inflammation. Often several combination medications (topicals with systemic agents) are required to achieve optimal control. Furthermore, although significant improvement occurs with treatment, acne cannot be cured completely. Hence, it is important that patients and their dermatologists set realistic end goals.

5 There are important differences influencing the management of acne in blacks compared to Caucasians. First, black people often demonstrate higher levels of inflammation (seen under the microscope) of acne lesions, often out of proportion with the clinical presentation. Second, pigmentation changes (dark spots and patches) and keloid formation are much more common in black people. The implications of these differences are that physicians treating acne in blacks need to have a lower threshold to initiate early aggressive treatment. However, this cohort is paradoxically at a higher risk of skin irritation (with subsequent development of dark patches) with the use of some topical antiacne medications. Thus, the need for early aggressive treatment, must be balanced by the potential risks associated with the use of some of these medications and strategies to minimize skin irritation should be implemented (Box 2). Finally, some of the anti-acne medications discussed below can cause abnormalities to the unborn child and for this reason, pregnant women or those trying to conceive are best advised to check this risk with the prescribing dermatologist, prior to using any of these agents (topical or systemic). Topical antimicrobials Topical antibiotics Topical erythromycin or clindamycin can eliminate bacteria associated with the pilosebaceous units, thereby reducing the inflammation associated with acne vulgaris. When used as single therapy, resistance can develop and for this reason, they are often combined with other topical anti-acne treatments (including benzoyl peroxide). Benzoyl peroxide This is an oxidising agent with marked antibacterial activity, available in various strengths. It is effective in use with other topical antibiotics as it limits the development of bacterial resistance to these agents. The main side effect profile of this agent is similar to topical retinoids, namely dryness and irritation of the skin, a problem that may lead to lack of patient compliance. Another disadvantage is that it bleaches hair and clothing. It is important that one discusses the most appropriate use of these agents with the prescribing physician. Topical retinoids Studies have shown that topical adapalene, tretinoin and tazarotene (all topical retinoids) are effective in the treatment of acne and the associated pigmentation changes seen in blacks as a complication of this disorder. A small pea sized amount should be applied to the whole face and not just on the spots. Their side effects include sensitivity to sunlight and skin irritation. The latter problem may paradoxically lead to increased pigmentation of skin. This can be minimized by careful selection of the formulation (creams are better than gels) and starting concentration of these agents. In addition the dosing frequency can be started as alternate nights for two weeks and if tolerated nightly.

6 Azelaic acid Azelaic acid is another topical therapy used to treat acne and its associated pigmentary changes. It has a lower potential to cause skin irritation and hence may be suitable for those with sensitive skin or in individuals with a previous history of excessive pigmentation of the skin, related to injury or inflammation. It is also efficacious in the management of acne on the back or trunk. Hydroquinones This agent is used to treat dark pigmentation of the skin, occurring as a complication of acne. It is available in many over the counter preparations at low concentrations of 1-2%. Higher concentrations of 4% or more can be prescribed by a dermatologist for the treatment of excessive pigmentation of the skin following acne. This should be used under the supervision of a skin specialist, as there is a risk of paradoxical increased pigmentation (called ochronosis) with long-term or higher concentration usage. Sunscreens Daily use of a broad spectrum UVA and UVB cream or lotion sunscreen is important in managing individuals with excessive pigmentation of the skin and hence is of use in treating the pigmentary changes associated with acne. Dosing and titration Formulation Adjunctive agents Low-dose initial therapy Slow upward titration as needed Every-other-day dosing as initial therapy Use of cream and lotion vehicles Use of moisturizers prior to application of Topical agents Use of gentle cleansing agents Avoid use of astringents and toners Avoid use of harsh soaps/cleansers Box 2. Strategies to minimize skin irritation with topical anti-acne therapy Systemic Medications Oral antibiotics Oral antibiotics are the treatment of choice for individuals suffering from moderate-tosevere acne that has not responded to topical therapies. Especially in blacks, a lower threshold is required to initiate therapy. Often long-term usage of antibiotics are more efficacious (a minimum of six months) and combination with topical retinoids is desirable. The antibiotics commonly prescribed for the management of acne are shown in Box 3.

7 Lymecycline Oxytetracycline Doxycycline Minocycline Erythromycin Trimethoprim Box 3. Systemic antibiotics used to treat acne The commonest antibiotics used in acne are the tetracyclines, these include oxytetracycline, doxycycline, minocycline and lymecycline. Erythromycin can also be used, however, there is often a higher bacterial resistance to this agent and for this reason, trimethoprim is increasingly used as a second line agent. All oral antibiotics used in the management of acne can cause gastro- intestinal side effects (including nausea and diarrhoea) and vaginal yeast infections. In addition, they may affect the metabolism of the oral contraceptive pill. It is important that this is discussed in detail with the prescribing physician and other appropriate contraceptive agents used, according to the guidance of the physician. Dairy products and other agents (such as, antacids and iron) can inhibit tetracycline absorption form the gastro-intestinal tract. For this reason, this antibiotic should be taken on an empty stomach and the prescribing physician should give instructions about this. All tetracyclines can cause sensitivity to sunlight, although this is much more severe with doxycycline. Tetracylines should also never be given to children under the age of 12, due to their effect on teeth and bone Rarely, the tetracylines can cause increased pressure in the brain (benign intracranial hypertension) associated with the development of headaches. Long-term usage of minocycline is associated with the development of lupus and a slate-grey pigmentation of the skin. The common side effect associated with the use of trimethoprim includes adverse skin rashes. Please check the information leaflet present with each drug for full information about their side effects. You can also discuss this issue with the prescribing physician. Hormonal treatment Hormonal treatment can be used as an adjunctive therapy in women with: acne which has not responded adequately to systemic antibiotics women with polycystic ovarian syndrome Contraceptive pills, with both low dose estrogens, progesterone and anti-androgenic effects (like Dianette, a combination of ethinyl estradiol with cyproterone acetate), may be used for this purpose. The major limiting factor of Dianette is the association with deep vein thromboses (clots in the leg) and the potential to cause severe flare-ups of the acne after cessation of the medication. Other agents, which may be of use, include spironolactone, which has an anti-androgenic effect. Spironolactone can in some cases cause a high blood potassium level.

8 Isotretinoin Isotretinoin is indicated in people with severe nodular-cystic acne or with severe acne that does not respond to conventional therapy (as discussed above). It works by: Reduction of sebum excretion Prevention of follicular hyperkeratosis Killing of bacteria associated with acne development, with reduction of inflammation This agent is taken as a tablet, with the dosage being calculated based on an individual s weight. It is an efficacious drug and following one course of isotretinoin, approximately 40% of sufferers will remain free of acne, 40% will have a recurrence of low severity that responds to medications to which the acne had previously been resistant and 20% will need repeat treatment with isotretinoin at a future time. Patients with severe acne on the trunk and adult women are more likely to have a relapse following treatment with isotretinoin. It is important that repeated courses of isotretinoin be avoided due to its potential side effect. The most common side effect is dryness of the skin, including dry lips and eyes. A worrisome side effect is its teratogenicity (ability to cause abnormalities to the unborn child) and for this reason, women of child-bearing age must use an adequate contraception during and up to one month after treatment. There are strict guidelines in place to ensure that pregnancy is avoided with oral isotretinoin therapy; in some countries, the government monitors doctors prescribing these agents. Another side effect associated with isotretinoin is depression, suicidal ideation and psychosis. There have been a number of reports about young adults who have taken the drug and then committed suicide while on the drug. Although some have argued that acne is itself associated with depression, the general consensus is that this agent should be avoided in individuals with a history of mental health disorders. Furthermore, enquiries should be made by prescribing physicians as to the mental well-being of individuals taking this drug. Other important side effects include bone problems, hyperlipidaemia (high levels of fat in the blood), hepatitis (inflammation of the liver) and rarely benign intracranial hypertension (raised pressure in the brain), this is especially likely to occur when used in conjunction with a tetracycline, thus this combination of drugs is contra-indicated. Other therapies Specific therapies may be used to treat keloidal scarring and this is discussed in detail in a separate article on keloids. Other types of scars may also occur as a complication of the acne. Various cosmetic procedures and lasers are available for managing such acne scars. Furthermore, light, laser, and photodynamic therapy are also alternative therapies on offer for the management of acne. Blacks are at risk of pigmentary changes as a complication of these procedures, thus caution must be used when selecting these modalities of treatment (for an in-depth review please read the articles lasers and light therapy in blacks and cosmetic procedures in blacks ).

9 Scientific References 1. Bolognia JL. Jorizzo JL, Rapini R. Dermatology. Chapter Taylor S, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris in skin of color. J Am Acad Dermatol 2002 Feb;46(2 Suppl Understanding):S Callender VD. Acne in ethnic skin: special considerations for therapy. Dermatol Ther 2004;17(2): Halder RM, Richards GM. Management of dyschromias in ethnic skin. Dermatol Ther 2004;17(2): James WD. Acne. N Engl J Med 2005;352(14): Tarlow A, Piela S, Wiederkehr M, Schwartz RA. Gram-negative folliculitis. emedicine website at updated January 2007 Medicine is a science and an art form, which is constantly evolving and changing because of ongoing research. Nonetheless, the author of this article and Black Health Matters have provided to their best ability an overview of the topic discussed, based on a review of the scientific literature. However, neither the author or Black Health Matters warrants that the information provided in this article is complete or accurate, nor are they responsible for any omissions or errors in this article. We advice all readers to confirm the information in this article from other sources prior to use. For more information, please see our full terms and conditions of use of this website. Copyright Black Health Matters April 2007

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