Acne is the most common skin disease in the US and affects 80% of the population at some point in life.
Pathophysiology of Acne Vulgaris
Acne occurs through the interplay of 4 major factors:
Excess sebum production
Follicular plugging with sebum and keratinocytes
Colonization of follicles by Cutibacterium acnes (formerly Propionibacterium acnes), a normal human anaerobe
Release of multiple inflammatory mediators
Acne can be classified as
Noninflammatory: Characterized by comedones
Inflammatory: Characterized by papules, pustules, nodules, and cysts
Comedones are sebaceous plugs impacted within follicles. They are termed open or closed depending on whether the follicle is dilated or closed at the skin surface. Plugs are easily extruded from open comedones but are more difficult to remove from closed comedones. Closed comedones are the precursor lesions to inflammatory acne.
Papules and pustules occur when C. acnes colonizes the closed comedones, breaking down sebum into free fatty acids that irritate the follicular epithelium and eliciting an inflammatory response by neutrophils and then lymphocytes, which further disrupts the epithelium. The inflamed follicle ruptures into the dermis (sometimes precipitated by physical manipulation or harsh scrubbing), where the comedone contents elicit a further local inflammatory reaction, producing papules. If the inflammation is intense, grossly purulent pustules occur.
Nodules and cysts are other manifestations of inflammatory acne. Nodules are deeper lesions that may involve > 1 follicle, and cysts are large fluctuant nodules.
Etiology of Acne Vulgaris
The most common trigger is
During puberty, surges in androgens stimulate sebum production and hyperproliferation of keratinocytes.
Other triggers include
Hormonal changes that occur with pregnancy or the menstrual cycle
Occlusive cosmetics, cleansers, lotions, and clothing
High humidity and sweating
Associations between acne exacerbations and inadequate face washing, masturbation, and sex are unfounded. Some studies suggest a possible association with milk products and high-glycemic diets. Acne may abate in summer months because of sunlight’s anti-inflammatory effects. Proposed associations between acne and hyperinsulinism require further investigation. Some drugs (eg, corticosteroids, lithium, phenytoin, isoniazid) worsen acne or cause acneiform eruptions.
Symptoms and Signs of Acne Vulgaris
Skin lesions and scarring can be a source of significant emotional distress. Nodules and cysts can be painful. Lesion types frequently coexist at different stages.
Comedones appear as whiteheads or blackheads. Whiteheads (closed comedones) are flesh-colored or whitish palpable lesions 1 to 3 mm in diameter; blackheads (open comedones) are similar in appearance but with a dark center.
Papules and pustules are red lesions 2 to 5 mm in diameter. Papules are relatively deep. Pustules are more superficial.
Nodules are larger, deeper, and more solid than papules. Such lesions resemble inflamed epidermoid cysts Cutaneous Cysts Epidermal inclusion cysts are the most common cutaneous cysts. Milia are small epidermal inclusion cysts. Pilar cysts are usually on the scalp and may be familial. Benign cutaneous cysts are... read more , although they lack true cystic structure.
Cysts are suppurative nodules. Rarely, cysts form deep abscesses. Long-term cystic acne can cause scarring that manifests as tiny and deep pits (icepick scars), larger pits, shallow depressions, or hypertrophic scarring or keloids Keloids Keloids are smooth overgrowths of fibroblastic tissue that arise in an area of injury (eg, lacerations, surgical scars, truncal acne) or, occasionally, spontaneously. Keloids are more frequent... read more .
Acne conglobata is the most severe form of acne vulgaris, affecting men more than women. Patients have abscesses, draining sinuses, fistulated comedones, and keloidal and atrophic scars. The back and chest are severely involved. The arms, abdomen, buttocks, and even the scalp may be affected.
Acne fulminans is acute, febrile, ulcerative acne, characterized by the sudden appearance of confluent abscesses leading to hemorrhagic necrosis. Leukocytosis and joint pain and swelling may also be present.
Pyoderma faciale (also called rosacea fulminans) occurs suddenly on the midface of young women. It may be analogous to acne fulminans. The eruption consists of erythematous plaques and pustules, involving the chin, cheeks, and forehead. Papules and nodules may develop and become confluent.
Diagnosis of Acne Vulgaris
Assessment for contributing factors (eg, hormonal, mechanical, or drug-related)
Determination of severity (mild, moderate, severe)
Assessment of psychosocial impact
Diagnosis of acne vulgaris is by examination.
Differential diagnosis includes rosacea Symptoms and Signs Rosacea is a chronic inflammatory disorder characterized by facial flushing, telangiectasias, erythema, papules, pustules, and, in severe cases, rhinophyma. Diagnosis is based on the characteristic... read more (in which no comedones are seen), corticosteroid-induced acne (which lacks comedones and in which pustules are usually in the same stage of development), perioral dermatitis Perioral Dermatitis Perioral dermatitis is an erythematous, papulopustular facial eruption that resembles acne and/or rosacea but typically starts around the mouth. Diagnosis is by appearance. Treatment includes... read more (usually with a more perioral and periorbital distribution), and acneiform drug eruptions (see Table: Types of Drug Reactions and Typical Causative Agents Types of Drug Reactions and Typical Causative Agents ). Acne severity is graded mild, moderate, or severe based on the number and type of lesions; one example of a standardized system is outlined in table Classification of Acne Severity Classification of Acne Severity .
Prognosis for Acne Vulgaris
Acne of any severity usually remits spontaneously by the early to mid 20s, but a substantial minority of patients, usually women, may have acne into their 40s; options for treatment may be limited because of childbearing. Many adults occasionally develop mild, isolated acne lesions. Noninflammatory and mild inflammatory acne usually heals without scars. Moderate to severe inflammatory acne heals but often leaves scarring. Scarring is not only physical; acne may be a huge emotional stressor for adolescents who may withdraw, using the acne as an excuse to avoid difficult personal adjustments. Supportive counseling for patients and parents may be indicated in severe cases.
Treatment of Acne Vulgaris
Comedones: Topical tretinoin
Mild inflammatory acne: Topical retinoid alone or with a topical antibiotic, benzoyl peroxide, or both
Moderate acne: Oral antibiotic plus topical therapy as for mild acne
Severe acne: Oral isotretinoin
Cystic acne: Intralesional triamcinolone
It is important to treat acne to reduce the extent of disease, scarring, and psychologic distress.
Treatment of acne involves a variety of topical and systemic agents directed at reducing sebum production, comedone formation, inflammation, and bacterial counts and at normalizing keratinization (see Figure: How various drugs work in treating acne How various drugs work in treating acne ). Selection of treatment is generally based on severity; options are summarized in table Drugs Used to Treat Acne Drugs Used to Treat Acne . See also the 2016 guidelines of care for the management of acne vulgaris from the American Academy of Dermatology.
Affected areas should be cleansed once or twice a day, but extra washing, use of antibacterial soaps, and scrubbing confer no added benefit.
A lower glycemic diet and moderation of milk intake might be considered for treatment-resistant adolescent acne, but the effectiveness of these measures in treating acne remains controversial (1 Treatment references Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more ).
Peeling agents such as sulfur, salicylic acid, glycolic acid, and resorcinol can be useful therapeutic adjuncts.
Oral contraceptives are effective in treating inflammatory and noninflammatory acne, and spironolactone (beginning at 50 mg orally once a day, increased to 100 to 150 mg [maximum 200 mg] orally once a day after a few months if needed) is another antiandrogen that is occasionally useful in women.
Various light therapies, with and without topical photosensitizers, have been used effectively, mostly for inflammatory acne.
Treatment should involve educating the patient and tailoring the plan to one that is realistic for the patient. Treatment failure can frequently be attributed to lack of adherence to the plan and also to lack of follow-up. Consultation with a specialist may be necessary.
How various drugs work in treating acne
Treatment of mild acne should be continued for 6 weeks or until lesions respond. Maintenance treatment may be necessary to maintain control.
Single-agent therapy is generally sufficient for comedonal acne. A mainstay of treatment for comedones is daily topical tretinoin as tolerated. Daily adapalene gel, tazarotene cream or gel, azelaic acid cream, and glycolic or salicylic acid are alternatives for patients who cannot tolerate topical tretinoin. Adverse effects include erythema, burning, stinging, and peeling. Adapalene and tazarotene are retinoids; like tretinoin, they tend to be somewhat irritating and photosensitizing. Azelaic acid has comedolytic and antibacterial properties by an unrelated mechanism and may be synergistic with retinoids.
Dual therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both) should be used to treat mild papulopustular (inflammatory) acne. The topical antibiotic is usually erythromycin or clindamycin. Combining benzoyl peroxide with these antibiotics may help limit development of resistance. Glycolic acid may be used instead of or in addition to tretinoin but is no longer used commonly. Treatments have no significant adverse effects other than drying and irritation (and rare allergic reactions to benzoyl peroxide).
Physical extraction of comedones using a comedone extractor is an option for patients unresponsive to topical treatment. Comedone extraction may be done by a physician, nurse, or physician assistant. One end of the comedone extractor is like a blade or bayonet that punctures the closed comedone. The other end exerts pressure to extract the comedone.
Oral antibiotics (eg, tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical.
Clascoterone is the first topical androgen receptor inhibitor for the treatment of acne. It can be used in patients 12 years of age and older. Clascoterone 1% cream is applied 2 times a day. Adverse effects include redness, scaling or dryness, and itching;although hyperkalemia and hypothalamic-pituitary-adrenal axis suppression have been predicted based on its mechanism, these effects have not been noticed clinically (3 Treatment references Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more ).
Oral systemic therapy with antibiotics is the best way to treat moderate acne. Antibiotics effective for acne include tetracycline, minocycline, erythromycin, doxycycline, and sarecycline. Full benefit takes ≥ 12 weeks.
Topical therapy as for mild acne is usually used concomitantly with oral antibiotics.
Doxycycline and minocycline are first-line drugs; both can be taken with food. Tetracycline is also a good first choice, but it cannot be taken with food and may have lower efficacy than doxycycline and minocycline. Doxycycline and minocycline dosage is 50 to 100 mg orally 2 times a day. Doxycycline may cause photosensitivity, and minocycline may have more adverse effects with chronic use, including drug-induced lupus and hyperpigmentation. Tetracycline dosage is 250 or 500 mg orally 2 times a day between meals. To reduce the development of antibiotic resistance after control is achieved (usually 2 to 3 months), the dose is tapered as much as possible to maintain control. Sarecycline is a new tetracycline antibiotic. The dosages are weight-based: 33 to 54 kg, 60 mg orally once a day; 55 to 84 kg, 100 mg orally once a day; and 85 to 136 kg, 150 mg orally once a day. Antibiotics may be discontinued if topical therapy maintains control.
Erythromycin and azithromycin are other options, but they can cause gastrointestinal adverse effects and antibiotic resistance develops more often. Some physicians also use trimethoprim/sulfamethoxazole, but antibacterial resistance may develop and this combination can cause rare adverse drug reactions.
Long-term use of antibiotics may cause a gram-negative pustular folliculitis around the nose and in the center of the face. This uncommon superinfection may be difficult to clear and is best treated with oral isotretinoin after discontinuing the oral antibiotic. Ampicillin is an alternative treatment for gram-negative folliculitis. In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped.
If the patient is female and unresponsive to oral antibiotics, a trial of oral antiandrogens (oral contraceptives and/or spironolactone) may be considered.
Oral isotretinoin is the best treatment for patients with moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne. Dosage of isotretinoin is usually 1 mg/kg once a day for 16 to 20 weeks, but the dosage may be increased to 2 mg/kg once a day. If adverse effects make this dosage intolerable, it may be reduced to 0.5 mg/kg once a day. After therapy, acne may continue to improve.
Many patients do not require a 2nd course of treatment; when needed, it is resumed only after the drug has been stopped for 4 months, except in severe cases when it may be resumed earlier. Retreatment is required more often if the initial dosage is low (0.5 mg/kg). With this dosage (which is very popular in Europe), fewer adverse effects occur, but prolonged therapy is usually required. Cumulative dosing has gained support; a total dosage of 120 to 150 mg/kg resulted in lower recurrence rates, and some experts suggest a higher cumulative dose of 220 mg/kg (4 Treatment references Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more ).
Isotretinoin is nearly always effective, but use is limited by adverse effects, including dryness of conjunctivae and mucosae of the genitals, chapped lips, arthralgias, depression, elevated lipid levels, and the risk of birth defects if treatment occurs during pregnancy. Hydration with water followed by petrolatum application usually alleviates mucosal and cutaneous dryness. Arthralgias (mostly of large joints or the lower back) often occur. Increased risk of depression and suicide is much publicized but probably rare. Although risk of new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis) has been proposed to be associated with use of isotretinoin, such an association now appears unlikely (5 Treatment references Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more ).
Complete blood count, liver tests, triglyceride, and cholesterol levels should be determined before treatment. Each should be reassessed at 4 weeks and, unless abnormalities are noted, need not be repeated until the end of treatment. Triglycerides rarely increase to a level at which the drug should be stopped. Liver function is seldom affected. Because isotretinoin is teratogenic, women of childbearing age are told that they are required to use 2 methods of contraception for 1 month before treatment, during treatment, and for at least 1 month after stopping treatment. Pregnancy tests should be done before beginning therapy and monthly until 1 month after therapy stops.
Intralesional injection of 0.1 mL triamcinolone acetonide suspension 2.5 mg/mL (the 10 mg/mL suspension must be diluted) is indicated for patients with firm (cystic) acne who seek quick clinical improvement with reduced scarring. Local atrophy may occur but is usually transient. For isolated, very boggy lesions, incision and drainage are often beneficial but may result in residual scarring.
Other forms of acne
Pyoderma faciale is treated with oral corticosteroids and isotretinoin.
Acne fulminans is commonly treated with oral corticosteroids and systemic antibiotics.
Acne conglobata is treated with oral isotretinoin and systemic corticosteroids if severe and if systemic antibiotics fail.
For acne caused by endocrine abnormalities (eg, polycystic ovary syndrome, virilizing adrenal tumors in females), antiandrogens are indicated. Spironolactone, which has some antiandrogen effects, is sometimes prescribed to treat acne at a dose of 50 to 150 mg (maximum 200 mg) orally once a day. Cyproterone acetate is used in Europe. When other measures fail, an estrogen/progesterone–containing contraceptive may be tried; therapy ≥ 6 months is needed to evaluate effect.
Small scars can be treated with chemical peels, laser resurfacing, or dermabrasion. Deeper, discrete scars can be excised. Wide, shallow depressions can be treated with subcision or injection of collagen or another filler. Fillers, including collagen, hyaluronic acid, and polymethylmethacrylate, are temporary and must be repeated periodically.
1. Dall'Oglio F, Nasca M, Fiorentini F, Micali G: Diet and acne: Review of the evidence from 2009 to 2020. Int J Dermatol 60(6):672–685, 2021. doi: 10.1111/ijd.15390.
2. Bienenfeld A, Nagler AR, Orlow SJ: Oral antibacterial therapy for acne vulgaris: An evidence-based review. Am J Clin Dermatol 18(4):469–490, 2017. doi: 10.1007/s40257-017-0267-z
3. Hebert A, Thiboutot D, Stein Gold L, et al: Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: Two phase 3 randomized clinical trials. JAMA Dermatol 156(6):621–630, 2020. doi:10.1001/jamadermatol.2020.0465
4. Blasiak RC, Stamey CR, Burkhart CN, et al: High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris. JAMA Dermatol 149(12):1392–1398, 2013. doi: 10.1001/jamadermatol.2013.6746
5. Lee SY, Jamal MM, Nguyen ET, et al: Does exposure to isotretinoin increase the risk for the development of inflammatory bowel disease? A meta-analysis. Eur J Gastroenterol Hepatol 28(2):210–216, 2016. doi: 10.1097/MEG.0000000000000496
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
American Academy of Dermatology: Guidelines of care for the management of acne vulgaris (2016)
If noninflammatory, acne is characterized by comedones and, if inflammatory, by papules, pustules, nodules, and cysts.
Mild and moderate acne usually heals without scarring by the mid 20s.
Recommend that patients avoid triggers (eg, occlusive cosmetics and clothing, cleansers, lotions, high humidity, some drugs and chemicals, possibly a high intake of milk products or a high-glycemic diet).
Consider the psychologic as well as the physical effects of acne.
Prescribe a topical comedolytic (eg, tretinoin) plus, for inflammatory acne, benzoyl peroxide, a topical antibiotic, or both.
Prescribe an oral antibiotic for moderate acne and oral isotretinoin for severe acne.
Treat cystic acne with intralesional triamcinolone as needed for acute lesions.
Drugs Mentioned In This Article
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