CPD 69: ASSESSING AND TREATING THE ACNE PATIENT Biography - Amy Louise Oates. I qualified from the Robert Gordon University Aberdeen with a Master in Phamacy in 2011. I then undertook my pre-registration year with Gordons Chemists in Edinburgh. After registration I moved back home, where I am now working for Johnstons Pharmacy in Longford Town, Lanesborough and Ballygar, Co. Galway. I also recently completed a Cardiology in Clinical Pharmacy Practice module with Trinity College Dublin.
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Acne, known medically as acne vulgaris, is an inflammatory and chronic disease, aggravated by various factors such as genetic, microbial and environmental. Acne is characterised by androgen-induced increased production of sebum, hyperkeratinisation, inflammation and altered adaptive immune response. Acne commonly affects the face in 99% of cases and, less frequently it also affects the back (60%) and chest (15%).1 Acne is one of the most common skin diseases. Epidemiological studies in Western industrialized countries estimated the prevalence of acne in adolescents to be between 50% and 95%,1 Acne is triggered in children with the initiation of androgen production by the adrenal glands and gonads. It usually subsides after adolescence, at the end of growth. However, in some cases acne can persist beyond, particularly in women. Even after the disease has ended, acne scars and pigmentation are common outcomes. Some acne can be caused through genetic factors, with a high tendency towards severe acne in patients with a positive family history for acne. SIGNS AND SYMPTOMS There are six main types of spot caused by acne: 1. Blackheads - small black or yellowish bumps that develop on the skin; they are not filled with dirt but are black because the inner lining of the hair follicle produces pigmentation (colouring) 2. Whiteheads - similar to blackheads but they are firmer and will not empty when squeezed
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Assessing and Treating the Acne Patient INTRODUCTION
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3. Papules - small red bumps that may feel tender or sore 4. Pustules - similar to papules but have a white tip in the centre caused by a build-up of pus 5. Nodules - the most severe type of spot caused by acne; they are large pus-filled lumps that look similar to boils and carry the greatest risk of causing severe scarring. 6. Cysts - These are large pus filled lumps that are similar and look very similar to boils. Cysts are acne lesions in their most severe form. They are a result of untreated nodules that have advanced in growth and development. Other symptoms are associated with Acne, such as: • Low self-esteem: Many people who have acne don’t feel good about themselves and it may lead to other mental problems Depression: Many people who have acne suffer from more than low self-esteem. Acne can lead to depression, with many people suffering from suicidal thoughts. • Dark spots on the skin: These spots appear when the acne heals. It can take months or years for dark spots to disappear. • Scars: People who get acne cysts and nodules often see scars when the acne clears. These scars can be prevented by visiting a dermatologist for treatment early on or if the sufferer is a youngster between 8 and 12 years old. Treating acne before cysts and nodules appear can prevent scars.
60 Second Summary Acne, known medically as acne vulgaris, is an inflammatory and chronic disease, aggravated by various factors such as genetic, microbial and environmental. Acne is characterised by androgeninduced increased production of sebum, hyperkeratinisation, inflammation and altered adaptive immune response. Acne is most commonly associated with changes in hormone levels during puberty but can start at any age. It affects the greaseproducing glands next to the hair follicles in the skin. Certain hormones cause the production of larger amounts of oil, abnormal sebum. Treatment should be started as soon as possible to prevent scarring. The choice of treatment depends on the type of acne, its severity and whether it is mostly inflammatory or comedonal. Topical mono-therapy is recommended, usually with retinods, azelaic acid or benzoyl peroxide. Topical retinoids such as tretinoin, isotretinoin and adapalene are used to treat comedones and inflammatory lesions in mild to moderate acne. Topical antibacterials are used to treat mild to moderate inflammatory acne. Preparations of Erythromycin (e.g. Zineryt) and Clindamycin (Dalacin C) are effective for treating inflammatory acne. Side effects of topical antibacterials include skin irritation and sensitisation, and GI disturbances, particularly with topical clindamycin. Patients should be counselled on the importance of good hygiene. Twice daily washing is enough, as more frequent water exposure and medications can result in overdrying and rebound production of sebum. Non-medicated soaps should be used if topical medications are prescribed. Abrasive sponges and clothes should be avoided as they can create portals for the entry of bacteria.
CPD 69: ASSESSING AND TREATING THE ACNE PATIENT has been demonstrated in clinical practice.5 Alternatives include systemic antibiotics in combination with adapalene, the fixed dose combination of adapalene with benzoyl peroxide or with azelaic acid. Conglobate Acne Oral isotretinoin is more effective than oral antibiotics in combination with topical treatments. Other options include oral hormonal therapies, such as combined oral contraceptives, which are beneficial in more severe grades of acne in combination with other topical or systemic treatments. Topical Retinoids Topical retinoids such as tretinoin, isotretinoin and adapalene are used to treat comedones and inflammatory lesions in mild to moderate acne.4 They have direct immunomodulatory effect without inducing bacterial resistance.5 Topical retinoids should be avoided in severe acne covering large areas. The preparations should be applied thinly once or twice daily. Accumulation in sensitive areas of the neck and in angles of the nose should be avoided. Topical retinoid preparations include Isotrex and adapalene, a retinoid-like drug, includes preparations such as Differin. It is also important to avoid contact with the eyes, nostrils, mouth and mucous membranes as well as broken or sunburned skin. Side effects of topical retinoids include skin irritation, redness, dry and peeling. These side effects usually improve as treatment continues, however if severe irritation occurs, treatment should be reduced and, if it persists, treatment should be discontinued.6 Topical Antibacterials
Acne is most commonly associated with changes in hormone levels during puberty but can start at any age. It affects the greaseproducing glands next to the hair follicles in the skin. Certain hormones cause the production of larger amounts of oil, abnormal sebum. This abnormal sebum changes the activity of a usually harmless skin bacterium called P acnes, which becomes more aggressive and causes inflammation and pus. The hormones also thicken the inner lining of the hair follicle, causing blockage of the pores. Cleaning the skin does not help remove this blockage.2
Treatment should be started as soon as possible to prevent scarring.4 The choice of treatment depends on the type of acne, its severity and whether it is mostly inflammatory or comedonal
Acne is caused by the interaction of 4 different factors:3 1. Excess sebum production 2. Obstruction of the outlet of the sebaceous follicle due to excess production of keratinocytes
Mild to moderate comedonal acne Topical mono-therapy is recommended, usually with retinods, azelaic acid or benzoyl peroxide.5 Mild to moderate papulopustular acne Fixed dose combinations of benzoyl peroxide with adapalene or benzoyl peroxide and clindamycin is the recommended treatment for this type of acne. This combination of topical retinoids or antimicrobials with complement modes of action greatly enhances efficacy against inflammatory lesions, resulting in faster clinical improvement. Fixed dose combinations can further optimise improvements by enhancing patient compliance and adherence.5
Topical antibacterials are used to treat mild to moderate inflammatory acne. Preparations of Erythromycin (e.g. Zineryt) and Clindamycin (Dalacin C) are effective for treating inflammatory acne. Side effects of topical antibacterials include skin irritation and sensitisation, and GI disturbances, particularly with topical clindamycin.4 Propionibacterium acnes is showing signs of antibacterial resistance. To avoid development of resistance, the use of non-antibiotic antimicrobials, such as benzoyl peroxide or azelaic acid is recommended. Benzoyl peroxide is a lipophilic non-antibiotic antimicrobial with mild comedolytic effects.5 Benzoyl peroxide induces bactericide effects against P acnes without inducing bacterial resistance. Concomitant treatment with oral and topical antibacterials should be avoided, with topical antibacterial use reserved for patients who cannot tolerate oral antibiotics or who wish to avoid them. Treatment with topical antibacterials should be continued for at least 6 months if the patient is responding to treatment. However, caution is needed and they should not be continued for longer than is necessary. OTHER TOPICAL TREATMENTS
3. Increased proliferation of the Propionibacterium acnes bacteria
Severe Papulopustualar Acne and Moderate Nodular Acne
4. Inflammation due to sebum escaping into the surrounding skin
Oral isotretinoin (Roaccutane) is recommended for these types of acne. Very good efficacy
Benzoyl Peroxide (e.g. Acnecide) is effective in treating mild to moderate acne. Both
CPD 69: ASSESSING AND TREATING THE ACNE PATIENT comedones and inflammatory lesions respond well to treatment with benzoyl peroxide, with little difference in efficacy between higher and lower concentrations.4 Treatment should, however start at the lowest concentration and increase gradually. Benzoyl peroxide should be applied once or twice daily, after washing with soap and water. Side effects include localised skin irritation and redness, particularly when starting treatment. If the acne does not respond to treatment after 2 months, a topical antimicrobial should be considered. Azelaic Acid Treatment with azelaic acid can be considered as an alternative to benzoyl peroxide for treating mild to moderate acne. Azelaic acid (e.g. Skinoren) has both antimicrobial and anticomedonal properties. Patients are less likely to suffer local skin irritation, compared with benzoyl peroxide. Oral Antibiotics Treatment with oral antibacterials can be used for inflammatory acne if topical treatment is not effective or if it is not suitable. Tetracycline, doxycycline, erythromycin, lymecycline and minocycline are all effective. in treating acne, particularly minocycline and doxycycline with their potent anti-inflammatory effects.5 The tetracyclines are broad spectrum antibiotics, used to treat a variety of infections and indication including acne. Micro-biologically, there is little to choose between the various tetracyclines, except for minocycline, which has a broader spectrum. In comparison to the other tetracyclines, minocycline also is associated with a greater risk of lupus-erythematosus- like syndrome and can cause irreversible pigmentation. Erythromycin
A dose of erythromycin 500mg twice daily is an option for the management of acne. However, resistant strains are becoming widespread and resulting in poor response.
Co-cyprindiol (Dianette) is licensed for the treatment of moderate to severe acne in women, who have not responded well to topical treatments or oral antibacterials. The pilosebaceous unit, which consists of the sebaceous gland and the hair follicle is an androgen-sensitive skin component. Acne and seborrhea are clinical conditions that result from aberrations of this target organ, which may be caused by increased sensitivity or higher plasma levels of androgen. The two drug components contained in Dianette beneficially influences the hyperandrogenic state. Cyproterone acetate is a competitive antagonist of the androgen receptor. The antiandrogen cyproterone acetate and its efficacy in acne is mostly due to decreased sebum secretion, which is under androgen control. The other component ethinylestradiol, up-regulates as well the synthesises the Sexual-HormoneBinding-Globulin (SHBG) in plasma. This works to reduce free, biologically available androgen in the circulation.6 Co--cyprindiol patients have an increased risk of venous thromboembolism, especially in the first year of use and are also at an increased risk of cardiovascular disease.
Isotretinoin (Roaccutane) exhibits activity against all the major etiologic factors involved in the pathogenesis of acne.5 Isotretinoin can only be prescribed by, or under the supervision of, a physician with experience in the use or oral retinoids for the treatment of acne and who fully understands the risk associated with this therapy and the monitoring requirements.
Minocycline Minocycline in a dose of 100mg once daily for 50mg twice daily is effective for the treatment of acne. However, minocycline is associated with an increased risk of lupus-erythematosus-like syndrome and irreversible pigmentation. Doxycyline A dose of 100mg of doxycycline daily is used as a treatment option for acne. Lymycycline A dose of 408mg lymecycline twice daily is indicated for the treatment of acne. Treatment should be continued for at least 8 weeks. 408Mg Lymecycline is equivalent to 300mg Tetracycline.
Roaccutane use results in a significant reduction in sebum production, influences comedogenesis, lowers surface and ductal P acnes and has anti-inflammatory properties.7 The EU Acne Guidelines consider Roaccutane to be the treatment of choice in severe papulopustular, moderate nodular and severe nodular acne. Quick reduction of inflammation may prevent the occurrence of both clinical and psychological scarring. The recommended dose of Roaccutane is 0.3-0.5mg/kg for severe papulopustular acne and moderate nodular acne and 0.5mg/kg for conglobate acne. Treatment should be continued for a least 6 months.7 Most patients who receive oral isotretinoin will be free of acne by the end of
CPD 69: ASSESSING AND TREATING THE ACNE PATIENT • The patients acknowledges that she has understood the hazards and necessary precautions associated with the use of Roaccutane.6 Pharmacist Advice • Patients should be counselled on the importance of good hygiene. Twice daily washing is enough, as more frequent water exposure and medications can result in overdrying and rebound production of sebum. Non-medicated soaps should be used if topical medications are prescribed. Abrasive sponges and clothes should be avoided as they can create portals for the entry of bacteria. • Any topical medication prescribed will initially worsen the acne as irritation and redness are common early side effects. Advise the patient that this will usually last for about two weeks. • Improvement should become apparent after 4 weeks of therapy, if used as directed. 4–6 months of treatment, depending on the dose administered.5 The half-life of Roaccutane is 22 hours and has a bioavailability of 25%. Absorption of isotretinoin is markedly affected by the presence of fat and pharmacokinetic studies show that absorption can be doubled by taking isotretinoin with, or after, a meal compared with the fasting state. Patients should be counselled to take the capsules with food at the same time of day.6 Side effects of Roaccutane include mucocutaneous, musculoskeletal, ophthalmic and headaches.7 These side effects are dose dependent and are usually rendered tolerable with dose modification.6 Mood changes including depression are common in adolescents and have been reported in acne patients treated with isotretinoin.6 Acne itself is associated with suicidal ideation and social impairment in adolescents and often reflects the burden of substantial acne rather that the effects of the medication.5 If significant depression is identified, a psychiatric referral may be indicated. If there is any doubt, treatment should be stopped.7 Roaccutane is teratogenic.
Teratogenicity is well recognized and regarded as one of the most serious potential adverse effects. Fifty percent of pregnancies spontaneously abort and, of the remainder about half of the infants are born with cardiovascular or skeletal deformities.7 Pregnancy is an absolute contraindication to treatment with isotretinoin. Women of childbearing potential are required to use effective contraception during and up to one month after treatment. If pregnancy does occur in spite of these precautions during treatment with Roaccutane or in the month following, there is a great risk of very severe and serious malformation of the foetus.6 If
pregnancy occurs in a woman treated with isotretinoin, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice. Women of childbearing potential can only be treated whilst adhering to the Pregnancy Prevention Programme.5 This has been implemented in many countries for the treatment with Roaccutane. It requires mandatory registration of all patients receiving the drug. The following conditions of the Pregnancy Prevention Programme (PPP) need to be met: • The patient has severe acne, which fails to respond to adequate courses of standard therapy with systemic anti-biotics and topical therapy. • The patient understands the teratogenic risk. • The patient understands the need for rigorous follow-up, on a monthly basis. • The patients understands and accepts the need for effective contraception, one month before starting treatment, throughout the duration of treatment and one month after completion of treatment. • The patient is informed and fully understands the potential consequences and risks of pregnancy and the need to rapidly consult if there is a risk of pregnancy. • The patients understands the need and accepts to undergo pregnancy testing before, during and 5 weeks after the end of treatment.
• Medication adherence plays a vital role in the success of treatment and all patients should be counselled of its importance. Skincare products have also been proven to prevent some types of mild acne, Bioderma have developed a formula to target imbalances in problem skin which treats acne-prone skin by regulating sebum quality, protecting the squalene from oxidation and keeping it from thickening which prevent the formation of blackheads, pimples and other blemishes. Acne Out is a care lotion suitable for skin suffering from mild and moderate to severe acne pustules on the face, back and neck. It is suitable for oily skin which is prone to frequent bacterial infections. REFERENCES 1. European Dermatology Forum, European Evidence Based (S3), Guidelines for the treatment of acne, 2011. Accessed online from: http://www.euroderm. org/edf/index.php/edf-guidelines/category/4guidelines-acne 2. NHS Choices. Accessed online from: http://www. nhs.uk/Conditions/Acne/Pages/Symptoms.aspx 3. WOODARD, I. et al, Adolescent Acne: A Stepwise Approach to Management, 2002. Accessed online from: www.medscape.com/viewarticle/430534_ 4. British Nation Formulary 67 5. Recent Therapeutic Developments for Acne: Evidence-Based Acne Therapy Guidelines , 2013. Accessed online from: http://www.medscape.org/ viewarticle/778129_3 6. Summary of Product Characteristics for all medicines accessed online from: www.medicines.ie November 2015. 7. LAYTON, A,The Use of Isotretinoin in Acne, Dermato Endocrinology, 2009. Accessed online from: http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2835909/