Contents: The treatment of acne vulgaris: an update
The treatment of acne vulgaris: an update While acne vulgaris affects 80% of adolescents, it can also occur later in life.1 It may lead to
* The main aims of acne treatment are to reduce the
scarring or hyperpigmentation
number of lesions, reduce the impact of psychological
and substantial disfigurement.2 Acne sufferers are also more
stress and prevent scarring. Patient counselling is an
likely to be depressed or anx-
important part of disease management. ious.1 This Bulletin discusses the general approach to acne
* Treatment should be started as early as possible with
management and considers
patients reassessed every two to three months initially. recent issues surrounding treatment. It will not attempt
A response may take months and in some cases
to evaluate every possible
treatment may need to be continued for several years. drug combination in acne.
* Early referral of patients with severe acne, for treatment
by a dermatologist, may help to prevent scarring. What causes acne?
* Mild acne should initially be treated with topical
agents. Drug choice depends on whether comedonal
or inflammatory lesions predominate. Benzoyl peroxide or a topical retinoid are first choice agents,
sebum production and keratinousdebris cause a blockage of
depending on tolerance, formulation and cost.
the pilosebaceous duct. Thisproduces a lesion called a
* Oral antibiotics should be added to topical therapy
in moderate to severe acne. Tetracycline or oxytetracycline are first choice agents as they are
(whitehead). Some comedonesevolve into inflammatory lesions
effective and inexpensive. An adequate dose of an oral
antibiotic should be given for at least three months
before deciding a patient has failed to respond.
Inflammation may be causedby proliferation of the anaerobe
* Minocycline and doxycycline have not been shown to
Propionibacteriumacnes.3Diet (e.g. chocolate) or poor skin
be more effective than tetracycline or oxytetracycline
cleansing do not worsen acne.1
and are more expensive. As reports of P. acnesresistance to minocycline are rare, it may be tried inpatients who fail to repond to first choice agents. How should acne be managed?
* Erythromycin is best reserved for patients in whom
other antibiotics are unsuitable, as propionibacterial
resistance to this drug is relatively common.
management of acne requires anunderstanding of the cause, the
Clindamycin and erythromycin
topical antibiotics. Tetracycline Limitations of evidence
and isotretinoin10 to be aseffective as tretinoin. However,
evidence for azelaic acid and nicotinamide, their place in
compared benzoyl peroxide
gel for four weeks) and tretinoin
(0.1% cream, not available in theUK) in 147 patients with acne
Choice of topical agent Topical retinoids or benzoyl peroxide are first choice agents benzoyl peroxide is the topical agent of choice. The place in
therapy of topical antibiotics is How should mild acne be treated?
not well defined. Some specialistsrecommend using a topical
Mild acne consists of open and
Topical benzoyl peroxide is an
(see table 1). Patients with mild How should moderate to severe
While topical antibiotics reduce acne be treated?
numbers of P. acnes within hairfollicles, their precise mechanism
Moderate acne encompasses
The topical retinoids (vitamin A
derivatives), tretinoin, isotretinoin and adapalene Severe acne also includes tretinoin causes a low-grade Oral antibiotics are the mainstay of systemic therapy.
• P. acnes resistance to antibiotics has been associated with a poor treatment
• In 1996, a GP study of 1,000 skin swabs taken from acne patients found that 25%
of swabs had strains of P. acnes which were resistant to antibiotics.
• Most data on resistance relate to in vitro measurements and are difficult to interpret
in terms of clinical effect. Minocycline is unstable in bacteriological culture medium
and so measurement of resistance to minocycline is unreliable. Reported resist-
• Most tetracycline resistant strains of P. acnes are cross-resistant to doxycycline.
Most erythromycin resistant strains are cross-resistant to clindamycin. Measures to minimise antibiotic resistance
• Do not prescribe antibiotics if a non-antibiotic topical preparation will suffice. tetracycline or oxytetracycline
•. Use adequate doses of antibiotics.
• Avoid concomitant oral and topical use of antibiotics from different classes.
• Do not continue treatment for longer than necessary (but give an adequate course
Minocycline (100mg daily, in
• If acne returns, reuse the same drug if the previous response was satisfactory with
doxycycline (100mg daily) are
more expensive (see table 2)
• Stress to patients the importance of good compliance.
and have not been shown to bemore effective than tetracycline
Table 1. Antibiotic resistance.8,12-14
or oxytetracycline. However, theymay be useful when compliance
table 1). There is evidence that P. acnes.20 This is also the case for
Minocycline has been the
effects, minocycline should be reserved for patients who fail to respond to tetracycline
years or more.8 An adequate or oxytetracycline.8,15 dose of oral antibiotic should
resistant strains of P. acnes. be given for at least three months before deciding a patient has failed to respond. Anti-androgen therapy may
menstrual flare.2 Dianette
prescribe oral isotretinoin. Erythromycin (500mg twice Treatment duration and referral
As it is highly teratogenic, womenof childbearing age should use
Other reasons for referralinclude: scarring, pigmentation,
Table 2. Comparative costs of some oral antibiotics for acne.
(Prices are based on Chemist & Druggist and the Drug Tariff, October 1999). Cost of 28 days therapy
acne or unpleasant side-effectsfrom current acne therapy. Tetracycline - 500mg twice a day Patient counselling Oxytetracycline - 500mg twice a day Doxycycline - 100mg once a day
likely timescale for improvementand that treatment may be needed
Vibramycin Acne Pack capsules 50mg
Vibramycin-D dispersible tablets 100mg
Patients should avoid abrasive Minocycline-100mg daily in one or two divided doses cleansers and vigorous scrub- bing, as this may worsen acne by provoking inflammation.3 Minocin MR modified-release capsules 100mg
Erythromycin - 500mg twice a day
acceptable to the patient,otherwise they may not be used.
Generally, gels and solutions are
sensitive or dry skin. Creams are
'greasy'. Lotions are thinner N.B. Doses quoted are those recommended in the BNF for acne treatment. Conclusions
Sykes NL, Webster GF. Acne: a review of opt-
imum treatment. Drugs 1994; 48(1): 59-70
20 Eady EA, Bojar RA, et al. The effects of acne
September 1999; 38
peroxide and erythromycin on skin carriage of
Cunliffe WJ, Poncet M, et al. A comparison of
erythromycin-resistant propionibacteria. Br J
the efficacy and tolerability of adapalene 0.1%
Dermatol 1996; 134: 107-113
gel versus tretinoin 0.025% gel in patients with
21 Chalker DK, Shalita A, et al. A double-blind
study of the effectiveness of a 3% erythromycin
and 5% benzoyl peroxide combination in the
139(Suppl 52): 48-56
10 Dominguez J, Hojyo MT, et al. Topical isotretin-
Dermatol 1983; 9: 933-936
oin vs. topical retinoic acid in the treatment of
22 Draelos ZK. Patient compliance: enhancing
acne vulgaris. Int J Dermatol 1998; 37: 54-55
clinician abilities and strategies. J Am Acad
11 Lyons RE. Comparative effectiveness of benzoyl
Dermatol 1995; 32: S42-S48
peroxide and tretinoin in acne vulgaris. Int J
Dermatol 1978; 17: 246-251
12 Eady EA. Bacterial resistance in acne. Useful information sources
Dermatology 1998; 196: 59-66
13 Cunliffe W, Eady A. GP acne survey: results
Acne Support Group
and recommendations. Prescriber 1996; 7(4):
14 Cunliffe WJ. Rapid resolutions in the primary
care management of acne: Round table series
62, The Royal Society of Medicine Press Ltd,
15 Ferner RE, Moss C. Minocycline for acne: first
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The National Prescribing Centre, The Infirmary, 70 Pembroke Place, Liverpool, L69 3GF. Telephone: 0151-794 8146/8140/8143/8145 Fax: 0151-794-8139/44
Anexo I al acta de la Reunión del Consejo de Administración de 10.8.2009 de Itaú Unibanco Holding S.A. ITAÚ UNIBANCO HOLDING S.A. (nueva denominación de ITAÚ UNIBANCO BANCO MÚLTIPLO S.A.) POLÍTICA DE DIVULGACIÓN DE ACTO O HECHO RELEVANTE 1. PRINCIPIOS GENERALES 1.1. Escopo 1.2. Comité de Divulgación y Negociación CONCEPTO DE ACTO O HECHO RELEVANTE 2.1. Act
Human Reproduction, Vol.24, No.6 pp. 1330 – 1338, 2009Advanced Access publication on February 26, 2009Pregnancies conceived using assistedreproductive technologies (ART) havelow levels of pregnancy-associatedplasma protein-A (PAPP-A) leading toa high rate of false-positive resultsin first trimester screeningfor Down syndromeD.J. Amor1,2,3,4,8, J.X. Xu1,2, J.L. Halliday1,2, I. Francis3, D.L