Acne: the Chemical Basis

SKIN

• To understand the mode of action of common ACNE treatments 

• To understand the chemical basis of the side-effects of common ACNE treatments 

• To be able to identify patient at risk of phototoxicity

• To be able to offer appropriate advice to patients using common ACNE treatments

Learning Outcomes: 4

• Whiteheads – closed pore clogged with sebum + dead skin

• Blackheads – open pore with oxidised oil

• Papules – small red tender bumps

• Pimples (pustules) – pus-filled papules

• Nodules – large painful lumps under skin

• Cystic lesions – pus-filled nodules

  

What causes acne lesions? (6 points)

• Benzoyl peroxide

• Azelaic acid

• Tetracyclines (e.g., doxycycline)

• Macrolides (e.g., erythromycin), , Usually for those who cannot take tetracyclines e.g., pregnant women, breastfeeding women and children under 8 years old

Antibacterial treatments for acne (4 points)

1. When tetracyclines cannot be used

2. In pregnancy

3. In breastfeeding or children under 8

When are macrolides used? (3 points)

1. Breaks into benzoic acid free radicals

2. Free radicals react with bacterial components

3. Damages proteins, lipids, DNA

4. Kills bacteria without resistance

Benzoyl peroxide mechanism of action (4 points)

• UV light breaks peroxide bond

• Free radicals react with skin → damage

Why is benzoyl peroxide phototoxic? (2 points)

1. Inhibits thioredoxin reductase, which is part of the cellular antioxidant system

2. Disrupts antioxidant system

3. Causes ROS formation

4. Leads to bacterial DNA damage ( Gram +)

• the acid functional group is a skin irritant

  

Azelaic acid mechanism (4 points)

1. Redness, itching, burning

2. Caused by acidic irritation

Side effects of azelaic acid (2 points)

1. Produces superoxide radicals

2. Kills bacteria

They are phototoxic as superoxide production increases UV damage

Tetracycline mechanism (2 points) and why are they phototoxic?

1. Damages DNA, proteins, lipids

2. Acute → sunburn

3. Chronic → skin cancer

Effects of UV exposure (3 points)

1. Fair skin / freckles

2. High UV exposure (sunbeds)

3. Use of phototoxic drugs

Phototoxicity risk factors (3 points)

1. Warn about sunburn risk

2. Explainsome medicines increase UV damage: for acne, these are benzoyl peroxides and tetracyclines

3. Advise sun protection

Advice for phototoxic drugs (3 points)

1. Both phototoxicity & sunburn produce ROS

2. ROS causes cellular damage

• phototoxic medicines amplify the effect of the sun and sunburn

Why is this advice important? (2 points)

• Topical retinoids

• Oral retinoids

• Azelaic acid

Exfoliating acne treatments (3 points)

1. Tretinoin (topical)

2. Adapalene (topical)

3. Isotretinoin (oral)

Types of retinoids (3 points)

1. Contraindicated in pregnancy

2. Contraindicated in breastfeeding

3. Isotretinoin requires specialist prescribing

Retinoid safety considerations (3 points)

1. Activate retinoic acid receptors, a nuclear receptor that promotes cell proliferation

2. Increase in epithelial turnover

hence explains contraindication in pregnancy and lactation

Retinoid mechanism of action (3 points)

1. Combined oral contraceptive pill ( •oestrogen and progestin)

2. Co-cyprindiol (ethinylestradiol and cyproterone acetate)

3. Hormonal regulation therapy

Hormonal treatments for acne (3 points)

• Androgens increase sebum ( sebum is the primary cause of acne)

• Oestrogen/progestin reduce testosterone

• Reduced sebum production

How hormonal therapy works (3 points)

1. Irritant → physical damage

2. Sensitiser → immune response

3. Often similar symptoms

Skin irritation vs contact dermatitis (3 points)

Patch testing

How to identify contact dermatitis (1)

1. Chemicals reacting with skin proteins

2. Triggers immune response

3. Sensitisation is lifelong

4. Avoidance is only cure

Causes of contact dermatitis (4 points)

• Nickel

• Hair dye (PPD)

• Fragrance aldehydes

• Preservatives

What are 4 examples of sensitising chemicals?

It generates highly reactive free radicals that damage bacterial structures

Why can’t bacteria develop resistance to benzoyl peroxide?

UV light cleaves the peroxide bond, producing reactive radicals

What mechanism explains the phototoxicity of benzoyl peroxide?

Inhibition of thioredoxin reductase leading to ROS formation

Azelaic acid’s antibacterial effect is mainly due to:

Skin irritation due to acidity

Which side effect of azelaic acid directly relates to its chemical structure?

Doxycycline

Which acne drug is most associated with phototoxicity due to superoxide formation?

Patients with fair skin or who use sunbeds

Which patients are at highest risk of phototoxicity from benzoyl peroxide or tetracyclines?

They activate nuclear receptors altering cell proliferation

Why are retinoids contraindicated in pregnancy?

It has severe teratogenic risks

Why is isotretinoin specialist‑prescribing only?

Reduce androgen levels, lowering sebum production

How do combined oral contraceptives improve acne symptoms?

Sensitisers cause immune‑mediated reactions and lifelong sensitivity

What distinguishes a skin sensitiser from a simple irritant?