Acne Vulgaris

Pathogenesis

Clinical presentation

Non-inflammatory lesion (NIL): open (blackheads) & closed (whiteheads) comedones

• Open comedones (blackheads) have dilated follicular opening, where the keratin plug darkens due to oxidized lipid and melanin.

Inflammatory lesion (IL): papules, pustules, nodules & cysts

Comedone

Inflammatory lesions

Severity assessment

Using the Comprehensive Acne Severity Scale (CASS)

Treatment (topical) – Mainstay

Commonly used:

1. Topical Benzoyl Peroxide (BPO)
2. Topical Retinoids
3. Topical Antibiotics
4. Fixed Combination Therapy

Topical agents are the mainstay of treatment in mild-moderate acne vulgaris.
The commonly used agents are topical BPO, retinoids, Abx & fixed combination preparations.
Combination treatment with either topical BPO, retinoids or topical Abx is more effective than monotherapy

Topical Benzoyl Peroxide (BPO)

• Available in 2.5%, 5% & 10% concentrations
• Topical BPO monotherapy or in combination with other topical therapy should be given in mild to moderate acne vulgaris.
• Practical advice on topical BPO:
  – Start at lower concentration of 2.5% & titrate gradually to 5 – 10% if no improvement.
  – Apply once daily on affected areas only. (May increased up to twice daily if needed)
  – If skin irritation develops, withhold treatment & restart on alternate days once AE has subsided.
  – Concomitant use of moisturizer may improve tolerability.
  – Bleaching of clothes may occur & the pt should be advised accordingly.

Topical retinoids (synthetic derivatives of Vitamin A)

• Include tretinoin, adapalene, tazarotene & isotretinoin.
• In Malaysia, only topical tretinoin & adapalene are currently available.
• Topical retinoids (e.g. tretinoin & adapalene) monotherapy should be used in non-inflammatory acne vulgaris or in combination with other therapies in inflammatory acne vulgaris.
• Contraindicated in pregnancy
• Practical advice:
  – It can cause photosensitivity, thus should be applied at night.
  – Apply a thin layer on the affected areas or the entire face.
  – If skin irritation develops, withhold treatment & restart on alternate days once the AE has subsided.
  – Concomitant use of moisturiser may improve tolerability.
  – Adequate sun protection (e.g. using broad-spectrum sunscreen, umbrella or hat) is advisable.th other topical therapy should be given in mild to moderate acne vulgaris.

Topical Antibiotics

• Useful in treatment of mild-moderate inflammatory acne.
• The use of topical Abx as monotherapy should be avoided to prevent bacterial resistance.
• Topical clindamycin & erythromycin are the most widely prescribed Abx. (Only topical clindamycin is available in Malaysia for the treatment of acne).

Fixed combination therapy

Available options:

Clindamycin/BPO ; Adapalene/BPO ; Erythromycin/BPO ; Clindamycin/Tretinoin

Other topical agents

• Topical Azelaic Acid (anti-microbial & anti-comedonal properties)
  – Also inhibits tyrosinase, thus effective for post-inflammatory hyperpigmentation
• Topical Salicylic Acid (keratolytic & comedolytic effects)

Treatment (systemic)

1. Oral antibiotics
2. Oral isotretinoin (prescribed only by dermatologist)
3. COCP (may be beneficial in female patient especially those with hyperandrogenism)
4. Spironolactone (anti-androgen & aldosterone antagonist) – competes with DHT for androgen receptors in the skin
5. Metformin (may be beneficial as adjuvant treatment; enhances insulin sensitivity –> reduce androgenic hormone)

Oral antibiotics

• Indicated for moderate-severe papulopustular/inflammatory acne vulgaris.
• Topical retinoid, BPO or AA should be used after discontinuation of Abx.
• Commonly used:
  – Tetracycline group (1st line) – contraindicated in pregnancy, lactation, age < 8 y/o or allergic to tetracyclines.
  – To reduce the AE of doxycycline, pt should be advised to take medication after meal with plenty of water; practice adequate sun protection.
  – Macrolides (Erythromycin, Azithromycin)- safe to be used in pregnancy & lactation
  – Trimethoprim-sulfamethoxazole (Co-trimoxazole) – should only be used when other Abx have failed or are contraindicated because of its potential serious AEs.
• Oral abx in combination with other topical treatment e.g. BPO, retinoid & AA is advocated as it prevents development of bacterial resistance, achieves faster resolution of lesions & targets multiple pathogenesis of acne.
• Oral doxycycline, tetracycline or erythromycin should be used for moderated to severe acne vulgaris.
• Response to these Abx should be evaluated at 6 – 8 weeks.
• Target duration therapy should not exceed 3 – 4 months to reduce resistance.

Oral isotretinoin

• Reduces sebaceous glands activity & size markedly, normalises follicular keratinisation, indirectly inhibits C. acnes growth in hair follicle & exerts an anti-inflammatory action.
• Should be prescribed for nodulocystic or severe acne vulgaris & treatment-resistant moderate acne vulgaris.
• Should only be prescribed by dermatologists
• Teratogenic & strict contraceptive practice is required for females who may become pregnant.

Cosmeceuticals

• May be used as an adjunct in the management of acne vulgaris.
• However, stronger evidence is warranted before cosmeceuticals can be recommended.
• Types: cleanser, sonic cleansing device, moisturiser, sunscreen (UVB cause inflammation, increase sebum production & proliferation of keratinocytes), hydrocolloid acne patches
• Active ingredients in Cosmeceutical for Acne Vulgaris:
  – Comeolytics – e.g. retinaldehyde, retinol. AHA (e.g. GA), beta-hydroxy acids (e.g. salicylic acid) & polyhydroxy acids (e.g. lactobionic acid & gluconolactone)
  – Sebum controller with anti-inflammatory properties – e.g. nicotinamide/niacinamide
  – Antibacterial agents – e.g. tyrothricin, tea tree oil, aloe vera, propolis, licochalcone A & cedar
  – Antioxidant – e.g. Green tea extract
  – Vitamin C (ascorbic acid)

Summary on mode of action of topical and systemic treatment

Management for special groups

Pregnant and lactating women

Hormonal therapy, tetracyclines, co-trimoxazole & isotretinoin should be avoided.

Adolescent

• Topical BPO & topical retinoids (tretinoin & adapalene) may be used safely in adolescents.
• Oral tetracycline derivatives (e.g. tetracycline, doxycycline, & minocycline) should not be used in patients aged < 8 y/o.
• Oral isotretinon can be used safely in patients ≥ 12 y/o.

Complications

Referral

Urgent: within 24 hours

• Acne fulminans (rare skin disorder)
  – Acute, painful, ulcerating & haemorrhagic form of acne.
  +- systemic Sx e.g. fever & polyarthritis
  +- bone lesions & laboratory abnormalities.
• Urgent referral to PSY if have major depression/exhibiting suicidal behaviour

Seen early: within 2 weeks

• Moderate to severe acne (e.g. nodulocystic acne)
• Severe social or psychological problems including a morbid fear of deformity (dysmorphophobia)

Non-urgent: based on available date

a) Diagnostic uncertainties, e.g.

• Suspected rosacea
• Suspected drug-induced acne
• Suspected occupational causes
• Suspected underlying endocrinological cause (e.g. PCOS) requiring further assessment
• Suspected Staph folliculitis, pityrosporum folliculitis or gram -ve folliculitis
• Rare variants of acne e.g. acne excoriae & chloracne

b) Dermatologist consultation & services.

• Failed oral Abx therapy
• Resistance or intolerance to current treatment
• Scarring or pigmentary changes
• Pregnancy with moderate & severe acne vulgaris
• Indication for specialised physical treatment (e.g. incision, drainage of cysts & laser)

Summary

Mild cases

• Topical bpo – apply in the morning OD, staining of shirt
• Topical retinoid (adapalene) – active lesion with pigmentation, not to be used in pregnancy and lactation, photosensitive – use at night
• Apply moisturizer before/after topical treatment to reduce irritation
• Do not use topical abx as monotherapy

Moderate to severe acne

• Oral abx, review in 6 to 8 weeks, if effective, consider taking for up to 3 to 4 months. Not to be used for more than 4 months. Used with topical bpo and retinoids
• If not responding to systemic abx, refer derm kiv to start isotretinoin.
• Consider start with oral tetracycline group (for more than 8 years above)
• Oral erythromycin can be used for all age group
• Reserved macrolide for pregnant patient
• Oral isotretinoin – only prescribed by dermatologist

Algorithm

Reference

Ministry of Health Malaysia. (2022). Clinical practice guidelines: Management of acne vulgaris (2nd ed.). Malaysian Health Technology Assessment Section (MaHTAS).