What it is:A chronic follicular disease that shows up as comedones (whiteheads/blackheads) and, when things get inflamed, papules, pustules, and nodules. It usually kicks off with puberty as androgens ramp up sebaceous gland activity.
The core problem:A follicle gets clogged with excess sebum and dead skin cells, then Cutibacterium acnes(formerly Propionibacterium acnes) grows in that clogged, oily environment and triggers inflammation. Everything you treat traces back to one of four steps in that chain.
What you do about it:Match the drug to the mechanism and the severity. Mild comedonal disease gets a topical retinoid. Add benzoyl peroxide once inflammation shows up. Escalate to oral antibiotics, hormonal therapy, or isotretinoin as severity climbs. Nothing here is cured, only controlled, so maintenance matters as much as induction.
Think of acne as a four-step cascade: (1) too much sebum, (2) abnormal keratinization plugs the follicle, (3) C. acnesproliferates in the plugged, sebum-rich follicle, (4) inflammation. Every drug class on this page interrupts one or more of those four steps, and knowing which step a drug hits tells you why it's combined with certain other drugs and not others.
Acne starts at puberty as gonadal development ramps up androgen production. Circulating androgens make sebaceous glands bigger and more active, which sets up everything downstream.
| Step | What happens | Drug classes that hit it |
|---|---|---|
| 1. Sebum overproduction | Androgen-driven sebaceous gland growth and activity | Isotretinoin, hormonal agents (antiandrogens, estrogens) |
| 2. Abnormal keratinization | Epidermal cells adhere to each other, forming a keratin plug (microcomedone) that traps sebum | Topical retinoids, salicylic acid, isotretinoin |
| 3. C. acnesproliferation | The anaerobic bacterium thrives in the trapped, sebum-rich follicle and produces lipase that hydrolyzes sebum triglycerides into irritating free fatty acids | Benzoyl peroxide, topical/oral antibiotics, isotretinoin |
| 4. Inflammation | Free fatty acids increase keratinization further, follicle wall ruptures, releasing keratin and lipids into the dermis, neutrophils pour in | Intralesional/oral corticosteroids, antibiotics, isotretinoin |
Isotretinoin is the only drug that hits all four steps at once, which is exactly why it's the only therapy that produces durable remission instead of just control. Everything else picks off one or two steps and has to be combined with something else to cover the rest.
Closed comedones (whiteheads)are the first visible lesion: the follicle is almost completely obstructed and prone to rupture. Open comedones (blackheads)form when the plug extends up the canal and dilates the opening (the dark color is oxidized keratin, not dirt). Once the follicle wall ruptures, you get the inflammatory lesions: papules, pustules, and nodules, driven by neutrophil recruitment and C. acnes-generated chemokines.
Noninflammatory= comedones only (open/closed), treat with keratolytics and retinoids. Inflammatory= papules, pustules, nodules, needs something that also targets C. acnesand inflammation (benzoyl peroxide, antibiotics). Grading the patient correctly is what determines whether you start with a retinoid alone or add an antimicrobial.
Lesions cluster where sebaceous glands are densest: face, back, neck, shoulders, and chest, sometimes extending to the buttocks or extremities. Whatever pattern of involvement shows up first tends to persist. Skin, scalp, and hair are frequently oily.
| Lesion type | Description |
|---|---|
| Closed comedone | Whitehead. First visible lesion, nearly fully obstructed, prone to rupture |
| Open comedone | Blackhead. Plug extends to upper canal, opening dilates |
| Papule | Small, inflamed, raised lesion |
| Pustule | Pus-filled, from neutrophil recruitment into the follicle |
| Nodule (cyst) | Deep, inflamed lesion, most likely to scar |
Nodules and deep lesions can scar permanently. Resolved inflammatory lesions can also leave erythematous or pigmented macules(hyperpigmentation) lasting months, especially in dark-skinned patients. This is why "just wait it out" is bad advice for moderate-severe disease: delaying effective treatment risks permanent marks, not just prolonged breakouts.
Acne is a clinical diagnosis: look at the lesions, grade severity, and rule out other causes such as drug-induced acne (think corticosteroids, lithium, phenytoin, isoniazid, or anabolic steroids). There's no single universal severity scale in practice, several grading systems exist, but the working categories you'll see driving treatment decisions are:
Severity grading isn't academic here, it's the entire treatment algorithm. Every "what do you start with" decision in this chapter maps directly onto which of these four categories the patient falls into.
Goals:reduce the number and severity of lesions, improve appearance, slow progression, limit duration and recurrence, prevent scarring and hyperpigmentation, and avoid the psychological toll acne takes on patients.
| Severity | First choice | Alternatives |
|---|---|---|
| Comedonal (noninflammatory) | Topical retinoid (adapalene preferred), alone or as fixed combo with benzoyl peroxide | Benzoyl peroxide, azelaic acid, or salicylic acid |
| Mild-moderate papulopustular | Fixed-dose adapalene + benzoyl peroxide, or benzoyl peroxide + topical retinoid, or azelaic acid. In moderate disease the fixed-dose combo is preferred, +/- hormonal therapy and/or antibiotic (especially if trunk involved) | Blue light monotherapy, erythromycin + tretinoin fixed combo, oral zinc. Widespread disease: oral antibiotic + topical benzoyl peroxide +/- adapalene |
| Moderately severe/severe papulopustular or moderate nodular | Oral antibiotic + fixed-dose topical combination | Add oral isotretinoin or oral hormonal therapy; if limited, oral antiandrogens + oral antibiotics or topicals |
| Nodular or conglobate | Oral isotretinoin monotherapy (females: isotretinoin + antiandrogenic hormonal therapy) | Retinoid fixed combo or oral antibiotic; retinoid fixed combo + oral antibiotic and/or oral antiandrogen |
| Maintenance (all severities) | Topical retinoid alone, or retinoid + benzoyl peroxide fixed combo | Topical azelaic acid |
Maintenance usually starts after a 12-week induction periodand runs 3-4 months, sometimes longer to prevent relapse after stopping. Long-term oral antibiotics are not recommendedfor maintenance, the point of induction therapy is to hand off to a retinoid/benzoyl peroxide regimen and get the antibiotic out of the picture to limit resistance.
Exfoliants work by inducing continuous mild drying and peeling. That irritation thickens the epidermis, increases scaling and erythema, and dries out an oily surface, which can resolve pustular lesions but is a blunter tool than retinoids or benzoyl peroxide.
Salicylic acidis OTC at 0.5-2%, comedolytic, with 3-6% being truly keratolytic (softens the horny layer, sheds scales). It has mild antibacterial activity against C. acnesand slight anti-inflammatory effect up to 5%. It's FDA-recognized as safe and effective but offers no advantage over benzoyl peroxide or topical retinoids, its real value is as an OTC first-line option for mild acne or when a patient can't tolerate retinoid irritation. Prescription strength runs 5-10%, start low and increase as tolerance develops.
Sulfur(precipitated or colloidal, 2-10%) is keratolytic with antibacterial activity, can quickly resolve pustules/papules, but use is limited by its offensive odor and the availability of better options. Often paired with salicylic acid or resorcinol for additive effect.
Resorcinolis less keratolytic than salicylic acid and, alone, is FDA category II (not generally recognized as safe/effective). Combined with sulfur 3-8% it's considered safe and effective. It's an irritant/sensitizer, avoid large areas or broken skin, and it can leave a reversible dark brown scale in dark-skinned patients.
Retinoids reverse abnormal keratinocyte desquamation, acting as true keratolytics that inhibit microcomedone formation. They work on both comedonal and inflammatoryacne, which is why they're the backbone of almost every regimen in the algorithm above. They're safe, effective, and economical for all but the most severe disease, and should be step one in moderate acne (alone or with antibiotics/benzoyl peroxide), reverting to retinoid-alone once results are achieved for maintenance.
Apply at night, about 30 minutes after cleansing. Start every other night for 1-2 weeksto let the skin adjust, only increase frequency/strength after 4-6 weeksat the lowest concentration in the least irritating vehicle. Gels and creams irritate less than solutions. Dryness, peeling, erythema, and irritation are the tradeoff for the remission retinoids can produce, and reducing frequency (not stopping) is how you manage it.
| Agent | Key points |
|---|---|
| Tretinoin | Creams, gels, pumps, various strengths. Avoid in pregnancy(fetal risk) |
| Adapalene (Differin) | As effective as, less irritating than other retinoids. 0.1% gel is OTC (age 12+, once daily); 0.3% gel by prescription. Available in fixed combos with benzoyl peroxide |
| Tazarotene (Tazorac) | As effective as adapalene applied half as often; more effective than tretinoin for inflammatory lesions. 0.05%/0.1% cream/gel, 0.1% foam. Contraindicated in pregnancy |
| Trifarotene (Aklief) | Approved age 9+. 0.005% cream, once daily evening. Avoid in pregnancy |
Benzoyl peroxideis bactericidal against C. acnes(not just bacteriostatic like antibiotics), mildly comedolytic, suppresses sebum production, and reduces the free fatty acids that drive comedogenesis and inflammation. No resistance has ever been reported, which is exactly why it's paired with antibiotics: adding benzoyl peroxide to antibiotic therapy improves efficacy and helps prevent resistance from developing in the first place.
Works on bothnoninflammatory and inflammatory acne, fast onset (can reduce inflamed lesion count within 5 days), and is standard of care for mild-moderate papulopustular acne. First choice combined with adapalene for mild-moderate inflammatory acne; second-line for pure comedonal disease. Available OTC 2.5-10% as washes, foams, creams, gels. Start at 2.5%in a water-based formulation at night, increase to 5% or switch to acetone/alcohol gel or paste once tolerated. Wash off in the morning and apply sunscreen during the day. Side effects: dryness, irritation, rare allergic contact dermatitis, and it bleaches hair, clothing, and towels(worth mentioning before they ruin a good pillowcase).
Clindamycin and erythromycinare topical macrolides, effective and well tolerated, but should be used in combinationwith benzoyl peroxide or a retinoid (never alone) to boost efficacy and cut resistance. Clindamycin is preferredover erythromycin for better efficacy and no systemic absorption; erythromycin is seldom used in practice today.
Azelaic acidhas antibacterial, anti-inflammatory, and comedolytic activity, used for mild-moderate inflammatory acne, though it has more limited efficacy than other options. It's an alternative for comedonal/inflammatory acne (particularly in combination) and an alternative to retinoids for maintenance. Well tolerated: pruritus/burning/stinging/tingling in 1-5%, erythema/dryness/peeling/irritation in under 1%. Available as 20% cream (Azelex) or 15% gel (Finacea), applied BID on clean dry skin. Most patients improve within 4 weeks.
Dapsone (Aczone)is a sulfone with antibacterial and anti-inflammatory activity, useful for patients who can't tolerate conventional agents, and can be used in sulfonamide-allergic patients (topical dapsone hasn't shown cross-reactivity the way oral sulfonamides do). 5% gel is BID, 7.5% gel is once daily. Combine with a topical retinoid if comedones are present; also used alongside adapalene or benzoyl peroxide.
Oral antibiotics are not a mild-acne drug. They're reserved for moderate-to-severe inflammatorydisease, and should always be paired with a topical retinoid combination from the start so the antibiotic can be discontinued after 3-6 monthsonce the retinoid/benzoyl peroxide regimen is carrying the maintenance load.
| Agent(s) | Role |
|---|---|
| Tetracyclines (minocycline, doxycycline) | First-line. Both antibacterial and anti-inflammatory |
| Macrolides (erythromycin, azithromycin), TMP/SMX | Acceptable alternatives. Erythromycin limited by resistance, reserve for patients who can't take a tetracycline (pregnant women, children <8 years) |
| Ciprofloxacin, trimethoprim alone | Options when other antibiotics can't be used or fail |
| Sarecycline (Seysara) | Narrow-spectrum tetracycline derivative, anti-inflammatory, approved age 9+ for non-nodular moderate-severe inflammatory acne |
Adverse effectsare generally low-incidence but worth knowing by drug: any oral antibiotic can cause vaginal candidiasis. Minocyclinecauses pigment deposition in skin/mucous membranes/teeth and can cause dose-related dizziness, urticaria, hypersensitivity syndrome, autoimmune hepatitis, a lupus-like syndrome, and serum sickness-like reactions. Doxycycline is a photosensitizer, especially at higher doses, worth a sun-protection counseling point. Choice of agent should weigh side effect profile, resistance, cost, and guideline consensus.
Intralesional triamcinoloneis effective for individual large inflammatory nodules, producing rapid improvement and less pain, but carries a risk of local skin atrophy at the injection site.
These target step one of the cascade, androgen-driven sebum overproduction, and are an option specifically in women (spironolactone is not for use in males).
| Agent | Notes |
|---|---|
| Combined oral contraceptives | Estrogen-containing OCPs help via antiandrogenic effects. FDA-approved for acne (in women who also want contraception): norgestimate/ethinyl estradiol and norethindrone acetate/ethinyl estradiol. Other estrogen-containing products may also work. Can be used alone or combined with other acne therapy |
| Spironolactone | Antiandrogen, effective in select women. Not FDA approvedfor acne and not for use in males. Watch for hyperkalemia, especially at higher doses or with cardiac/renal compromise |
| Clascoterone 1% cream (Winlevi) | Topical androgen receptor inhibitor, approved for males and females age 12+. Applied BID. Common effects: erythema, edema, scaling/dryness |
| Oral corticosteroids | High-dose, short courses can give temporary benefit in severe inflammatory acne. Low-dose prednisone (5-15 mg daily) alone or with a high-estrogen combined OCP has shown efficacy for acne/seborrhea. Long-term effects rule this out as primary therapy |
Clascoteroneis topical, FDA-approved, and works in bothsexes. Spironolactoneis oral, off-label for acne, and restricted to women only. Same mechanistic idea (block androgen receptor activity in the follicle) but very different regulatory status and eligible population, a classic exam distractor pair.
Isotretinoin is a vitamin A metabolite that decreases sebum production, inhibits C. acnesgrowth, and reduces inflammation, meaning it's the only agent that addresses all four stepsof the acne cascade at once. It's the only acne treatment that produces prolonged remission rather than just control.
Approved for:severe recalcitrant nodular acne in non-pregnant patients age 12+ with multiple inflammatory nodules ≥5 mm. Also used for moderate acne that's treatment-resistant, relapses quickly after stopping oral antibiotics, or is causing physical scarring or significant psychosocial distress.
Approved dose range: 0.5-2 mg/kg/day, usually over a 20-week course. Take with food, absorption is significantly better. Guideline-preferred approach: start at 0.5 mg/kg/day or less, increase to 1 mg/kg/dayafter the first month as tolerated, targeting a cumulative dose of 120-150 mg/kgto minimize the flare that can happen early in treatment.
Isotretinoin is a severe teratogen. Female patients of childbearing potential must be on two different forms of contraceptionstarting 1 month beforetherapy, continuing throughout, and for up to 4 months afterdiscontinuation. Everypatient (regardless of sex) must be enrolled in the iPLEDGEprogram, which mandates pregnancy testing and prescriber/pharmacist attestation to the required safety procedures before each fill.
Side effectscluster in the mucocutaneous system (most common: cheilitis, dry nose/eyes/mouth), plus musculoskeletal and ophthalmic effects, headaches, and CNS effects. Most of these are temporary and resolve after stopping. Baseline and periodic labs:triglycerides, cholesterol, transaminases, and CBC.
Mood disorders, depression, suicidal ideation, and suicide have been reported sporadically with isotretinoin, but a causal link has notbeen established. The confound is real: severe acne itself is strongly associated with depression and suicidal ideation independent of treatment. Practically, this means you screen and monitor mood throughout therapy rather than avoiding a highly effective drug based on an unproven causal link, but you still take any mood change seriously and report it.
| Class / Drug | Strength / Dose | Notes |
|---|---|---|
| Exfoliants | ||
| Salicylic acid | OTC 0.5-2%; Rx 5-10% | 3-6% is truly keratolytic |
| Sulfur | 2-10% | Precipitated or colloidal form |
| Resorcinol | 2% + sulfur 3-8% | Alone = FDA category II |
| Topical retinoids | ||
| Tretinoin | Various cream/gel/pump strengths | Avoid in pregnancy |
| Adapalene (Differin) | 0.1% gel OTC; 0.3% gel Rx | Once daily; +/- BPO fixed combo |
| Tazarotene (Tazorac) | 0.05-0.1% cream/gel; 0.1% foam | Contraindicated in pregnancy |
| Trifarotene (Aklief) | 0.005% cream | Once daily evening; age 9+ |
| Topical antibacterials | ||
| Benzoyl peroxide | Start 2.5%, titrate to 5-10% | Apply PM, wash off AM, use sunscreen |
| Clindamycin (topical) | Standard 1% preparations | Always pair with BPO or retinoid |
| Azelaic acid | 20% cream (Azelex) or 15% gel (Finacea) | BID on clean, dry skin |
| Dapsone (Aczone) | 5% gel BID or 7.5% gel once daily | OK in sulfonamide allergy |
| Oral antibiotics | ||
| Doxycycline / Minocycline | Standard tetracycline dosing | First-line; doxycycline photosensitizes |
| Sarecycline (Seysara) | Weight-based dosing | Age 9+; narrow-spectrum |
| Hormonal agents (women unless noted) | ||
| Norgestimate/ethinyl estradiol; norethindrone acetate/ethinyl estradiol | Standard OCP dosing | FDA-approved for acne + contraception |
| Spironolactone | Variable, higher doses = more hyperkalemia risk | Off-label; women only |
| Clascoterone 1% cream (Winlevi) | Apply BID | Approved both sexes, age 12+ |
| Isotretinoin | ||
| Isotretinoin | 0.5-2 mg/kg/day, ~20-week course | Take with food; cumulative goal 120-150 mg/kg; iPLEDGE required |
| Parameter | When | Watching for |
|---|---|---|
| Lesion counts / diary | Patient-tracked; clinician contact 2-3 weeks after starting therapy, then every 4-8 weeks | Objective response, adherence to the plan |
| Response benchmarks | 4-8 weeks, and 2-4 months | 10-15% lesion reduction by 4-8 weeks, >50% reduction by 2-4 months. Inflammatory lesions should resolve within a few weeks, comedones within 3-4 months |
| Mood / anxiety / depression | Ongoing, especially on isotretinoin | Should trend toward improvement within 2-4 months if present at baseline; report new or worsening symptoms |
| Triglycerides, cholesterol, LFTs, CBC | Baseline and periodically on isotretinoin | Hypertriglyceridemia, transaminitis, cytopenias |
| Pregnancy test | Monthly per iPLEDGE, on isotretinoin | Teratogenicity, contraception adherence |
| Potassium | Periodically on spironolactone, especially higher doses | Hyperkalemia |
| Skin irritation / tolerance | Each retinoid or benzoyl peroxide titration step | Dryness, peeling, erythema guiding dose/frequency changes |
| Long-term trajectory | Every visit | No progression of severity, longer acne-free stretches, no new scarring or pigmentation |