Acne Vulgaris - pathology, therapeutics, guidelines PDF

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Summary

Notes on acne from a pharmaceutical perspective, including symptoms, pathophysiology, and treatments (such as benzoyl peroxide, isotretinoin)....

Description

Acne Vulgaris Epidemiology: Affects 90% of people during teenage years, and 25% of teenagers experience severe acne. Teenage boys are affected more than girls – but more women are affected than men. Pathophysiology:  High levels of androgens increase the production of sebum and change its composition and thicken the lining of pilosebaceous follicles (PSF).  The high levels of sebum increase the growth of Cutibacterium acnes, this bacterium releases fatty acids which cause comedogenesis: o Cutibacterium acnes stimulates keratinocytes to proliferate and block pilosebaceous follicles, forming comedones. o Release of inflammatory mediators (such as TNFα) attracts neutrophils which causes inflammation and damage. Symptoms:  Non-inflammatory lesions (comedones): must be present for diagnosis! o open (blackheads) – black due to oxidation of Risk factors: tyrosine residues within sebum. o closed (whiteheads).  Genetics  High glycaemic index foods  Inflammatory lesions:  Medications (like steroids, o Papules (tender red bumps) and pustules (papules Li) with pus) – superficial raised lesions (less than 5  PCOS (high androgens) mm in diameter).  Smoking o Nodules or cysts (larger than 5mm in diameter) –  Stress deeper, palpable lesions which are often painful.  Comedogenic cosmetics High risk of scarring.  Seborrhoea, scarring, pigmentation. Treatment

Severity Mild

Description Predominantly non-inflamed lesions (open and closed comedones) with few inflammatory lesions. More widespread with an increased number of inflammatory papules and pustules. Widespread inflammatory papules, pustules and nodules or cysts. Scarring may be present.

For mild to moderate acne:  Benzoyl peroxide: o Forms free radicals; comedolytic, antibacterial, anti- Moderate inflammatory. o Titrate up: start od, work up to Severe bd. May increase %. o Safe in pregnancy/BF. o May bleach bedding etc.  Topical retinoids (ie adapalene) – alone or in combination with BP. o Comedolytic, anti-inflammatory, reduces sebum production.  Bind to retinoic acid receptors, which bind to promotor regions of genes to promote normal keratinocyte differentiation, block hyperproliferation (by downregulating ornithine decarboxylase), suppress sebum production and inhibit prostaglandin synthesis. o Apply pea-sized drop then wash off after 30-60 minutes. o Not in pregnancy/breast feeding.  Topical antibiotics – often combinations; clindamycin + BP – mops up resistant bacteria. o Avoid in pregnancy.

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Azelaic acid 20%: o Comedolytic, anti-inflammatory. o Some antimicrobial properties. Nicotinamides: o Anti-inflammatory, regulates sebum production. o Not in pregnancy/BF.

May take 6-8 weeks for benefit – may be irritation at start of treatment.

For moderate acne:  If (>3) topical preparations are insufficient, consider adding an oral antibiotic (tetracyclines, like lymecycline or doxycycline) – switch if little response after 2 months of tetracycline. Treat for 6 months for most benefit. Avoid in pregnancy.  Combined oral contraceptives may be beneficial – progesterone only may exacerbate acne. For severe acne: Refer to dermatologist.  Isotretinoin reduces sebum excretion by 90% after 6 weeks – this reduces the amount of Cutibacterium acnes, reduces hyperkeratinisation and is anti-inflammatory. o 16 week course – only prescribed by consultant dermatologists if unresponsive to other topical and oral therapies. o Bind to retinoic acid receptors, which bind to promotor regions of genes to promote normal keratinocyte differentiation, block hyperproliferation (by downregulating ornithine decarboxylase), suppress sebum production and inhibit prostaglandin synthesis. o Risks:  Teratogenic: requires PPP 1 month before and after Tx.  Depression, anxiety and suicidal ideation: cautioned if history, stop if deterioration.  Impaired night vision: may need to inform DVLA.  Dry skin and mucous membranes: emollients.  Joint pain.  Fragile skin: sun screen, avoid skin treatments 6 months after.  Abnormal LFTs: monitor LFTs and serum lipids - reduce dose or discontinue if transaminase or serum lipids persistently raised. Measure LFTs and serum lipids before Tx, 1 month after starting then every 3 months.  Sexual dysfunction: erectile dysfunction, decreased libido. Lifestyle advice:  Don’t overclean – wash bd.  Don’t pick due to risk of scarring.  Avoid oily and comedogenic cosmetics.  Reduce sugar intake.  Use fragrance-free emollients.  Wash hair regularly.  Don’t use toothpaste.  Use non-comedogenic sun screen.  Apply treatments to whole area. BNF:  To avoid development of resistance: o Use non antibiotic antimicrobials (BP, azelaic acid) o Avoid concomitant use of different oral and topical antibiotcs. o If particular antibiotic is useful, use it for repeat courses (short intervening courses of BP/AA o Don’t use for longer than necessary.

NICE Guidance:  In mild acne, where open and closed comedones predominate, with few inflammatory lesions, consider: o Topical retinoid: adapalene o Benzoyl peroxide. o Or if these are poorly tolerated, azelaic acid. o Topical antibiotics should be prescribed in combination with benzoyl peroxide.  In moderate acne, where inflammatory lesions (papules and pustules) predominate and is more wide spread, or where acne not responsive to topical preparations. o Oral tetracyclines + retinoid/BP to reduce resistance risk – avoid macrolides due to resistance of P. acnes but may be used if tetracyclines are contraindicated (ie pregnancy). o Do not use 2 different oral and topical antibiotics. o If no response to 2 antibiotics, refer to dermatology. o COCs may be considered in female patients.  If acne is severe (widespread, nodules, cysts, scarring, hyperpigmentation), multiple treatments have failed, there is significant distress caused (regardless of actual severity) or where there is diagnostic uncertainty – refer to dermatology. 

Follow ups should be arranged 8-12 weeks after initiation of each step. o If responsive, continue treatment for at least 12 weeks. o If acne cleared, maintenance therapy with retinoids or azelaic acid....