A 16-year-old boy (Figure 118-1) with severe nodulocystic acne and scarring presents for treatment. After trying oral antibiotics, topical retinoids, and topical benzoyl peroxide with no significant benefit, the patient and his mother requested isotretinoin (Accutane). After 4 months of isotretinoin, the nodules and cysts cleared, and only a few papules remained (Figure 118-2). He is much happier and more confident with his appearance. His skin cleared fully after 6 months of isotretinoin.
Severe nodulocystic acne with scarring in a 16-year-old boy. (Reproduced with permission from Richard P. Usatine, MD.)
A happier boy now that his nodules and cysts have cleared at the start of the fifth month of isotretinoin treatment. (Reproduced with permission from Richard P. Usatine, MD.)
Acne is an obstructive and inflammatory disease of the pilosebaceous unit predominantly found on the face, but it may also involve the trunk. It can occur at any age, but it is most common during adolescence.
Acne vulgaris affects more than 80% of teenagers and persists beyond the age of 25 in 3% of men and 12% of women.1 Neonatal acne is most often benign cephalic pustulosis. It is temporary and thought to be related to Malassezia species (Figure 118-3) (see Chapter 114, Normal Skin Changes).
Neonatal acne in a healthy 2-week-old infant that resolved without treatment. (Reproduced with permission from Richard P. Usatine, MD.)
ETIOLOGY AND PATHOPHYSIOLOGY
The four most important steps in acne pathogenesis are:
Sebum overproduction related to androgenic hormones and genetics
Abnormal desquamation of the follicular epithelium (keratin plugging)
Propionibacterium acnes proliferation
Follicular obstruction, which can lead to inflammation and follicular disruption
Acne can be precipitated by mechanical pressure such as a helmet strap (Figure 118-4) and medications such as phenytoin and lithium (Figure 118-5).
Inflammatory acne showing pustules and nodules in a 17-year-old boy who uses a helmet while playing football in high school. (Reproduced with permission from Richard P. Usatine, MD.)
Severe inflammatory acne in a young adult. His acne worsened when he was started on phenytoin for his seizure disorder. (Reproduced with permission from Richard P. Usatine, MD.)
Some studies suggest that consumption of large quantities of milk (especially skim milk) and foods with a high glycemic index increase the risk for acne.2 SORⒷ However, a systematic review did not find sufficient evidence to support diet changes for acne.3
Morphology of acne includes comedones, papules, pustules, nodules, and cysts.
Obstructive acne = comedonal acne = noninflammatory acne consisting only of comedones (Figure 118-6).
Open comedones are called blackheads, and closed comedones are called whiteheads and look like small pink papules.
Inflammatory acne consists of papules, pustules, nodules, and cysts in addition to comedones (see Figure 118-5).
Comedonal acne in a 15-year-old girl. Open comedones (blackheads) and closed comedones (whiteheads) are visible on her forehead. (Reproduced with permission from Richard P. Usatine, MD.)
Face, back, chest, and neck.
None, unless suspecting androgen excess and/or polycystic ovarian syndrome (PCOS).4 SORⒷ Obtain testosterone and DHEA-S levels if you suspect androgen excess and/or PCOS. Consider also adding follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels if suspecting PCOS.
Acne conglobata is an uncommon and unusually severe form of acne characterized by multiple comedones, cysts, sinus tracts, and abscesses. The inflammatory lesions and scars can lead to significant disfigurement.5 Sinus tracks can form with multiple openings that drain foul-smelling purulent material (Figures 118-7, 118-8, 118-9). The comedones and nodules are usually found on the chest, shoulders, back, buttocks, and face. In some cases, acne conglobata is part of a follicular occlusion triad along with hidradenitis and dissecting cellulitis of the scalp (Figure 118-9).
Acne fulminans is characterized by sudden onset ulcerative crusting cystic acne found mostly on the chest and back (Figures 118-10 and 118-11).6 Fever, malaise, nausea, arthralgia, myalgia, and weight loss are common. Leukocytosis and elevated erythrocyte sedimentation rate are usually present. There may also be focal osteolytic lesions. The term acne fulminans may also be used in cases of severe aggravation of acne without systemic features.5
Rosacea can resemble acne due to the presence of papules and pustules on the face. It is usually seen in older adults with prominent erythema and telangiectasias. Rosacea does not include comedones and may have ocular or nasal manifestations (Chapter 119, Rosacea). Rosacea fulminans or pyoderma faciale has features of severe acne and rosacea (Figure 118-12).
Folliculitis on the back may be confused with acne. Look for hairs centrally located in the inflammatory papules to help distinguish it from acne. Acne on the back usually accompanies acne on the face (Chapter 123, Folliculitis).
Acne keloidalis nuchae consists of papules, pustules, nodules, and keloidal tissue found at the posterior hairline. It is most often seen in men of color after shaving the hair at the nape of the neck (Chapter 120, Pseudofolliculitis and Acne Keloidalis Nuchae).
Actinic comedones (blackheads, Favre and Racouchot disease) are related to sun exposure and are seen later in life (Figure 118-13).
A. Acne conglobata in a 16-year-old boy. He has severe cysts on his face with sinus tracts between them. He required many weeks of oral prednisone before isotretinoin was started. His acne cleared completely with his treatment. B. Acne conglobata cleared with minimal scarring after oral prednisone and 5 months of isotretinoin therapy. (Reproduced with permission from Richard P. Usatine, MD.)
Acne conglobata in a 42-year-old woman showing communicating sinus tracts between cysts. There is pus draining from one of the sinus tracts on the right side of the neck. (Reproduced with permission from Richard P. Usatine, MD.)
Acne conglobata in a 53-year-old man covered with open comedones and cysts on his back. He has the follicular occlusion triad including hidradenitis, dissecting cellulitis of the scalp, and acne conglobata. (Reproduced with permission from Richard P. Usatine, MD.)
Acne fulminans in a 17-year-old boy. He was on isotretinoin when he developed worsening of his acne with polymyalgia and arthralgia. He presented with numerous nodules and cysts covered by hemorrhagic crusts on his chest and back. (Reproduced with permission from Grunwald MH, Amichai B. Nodulo-cystic eruption with musculoskeletal pain. J Fam Pract. 2007;56:205-206. Frontline Medical Communications, Inc.)
Acne fulminans with severe rapidly worsening truncal acne in a 15-year-old boy. He did not have fever or bone pain but had a white blood cell count of 17,000. He responded rapidly to prednisone and was started on isotretinoin. The ulcers and granulation tissue worsened initially on isotretinoin, but prednisone helped to get this under control. (Reproduced with permission from Richard P. Usatine, MD.)
Pyoderma faciale is almost exclusively seen in adult women. It can present with severe cystic facial acne often in a malar distribution. It also is called rosacea fulminans. It started abruptly 6 months before, and is not related to cutaneous lupus. (Reproduced with permission from Richard P. Usatine, MD.)
Actinic comedones related to sun exposure in an older man. These are typically seen on the side of the face clustering around the eyes. (Reproduced with permission from Richard P. Usatine, MD.)
Treatment is based on acne type and severity. Therapies include topical retinoids, topical antimicrobials, systemic antimicrobials, hormonal therapy, oral isotretinoin, and injection therapy.
Benzoyl peroxide (2.5%, 5%, 10%)—Antimicrobial effect (gel, cream, lotion), available over the counter (OTC); 10% benzoyl peroxide causes more irritation and is not more effective.1 SORⒶ
Topical antibiotics—Clindamycin and erythromycin are the mainstays of treatment. SORⒶ
Erythromycin—Solution, gel.3 SORⒶ
Clindamycin—Solution, gel, lotion.3 SORⒶ
Benzamycin gel—Erythromycin 3%, benzoyl peroxide 5%.3 SORⒶ
BenzaClin gel—Clindamycin 1%, benzoyl peroxide 5%.3 SORⒶ
Dapsone 5% gel.7 SORⒶ
Azelaic acid—Useful to treat post-inflammatory hyperpigmentation and acne (Figure 118-14).3 SORⒶ
Obstructive or comedonal acne with spotty hyperpigmentation. Azelaic acid was helpful to treat the acne and the hyperpigmentation. (Reproduced with permission from Richard P. Usatine, MD.)
Tretinoin (Retin-A) gel, cream, liquid, micronized.1 SORⒶ
Adapalene gel (Differin)—Less irritating than tretinoin.1 SORⒶ Now available OTC. The OTC 0.1% adapalene gel is less expensive than generic and brand-name tretinoin, and this is a game changer for acne therapy in patients without health insurance.
Tazarotene (Tazorac)—Strongest topical retinoid with greatest risk of irritation.8 SORⒶ
Topical retinoids will often result in skin irritation during the first 2 to 3 months of treatment, but new systematic reviews do not demonstrate that they worsen acne lesion counts during the initial period of use.2
Doxycycline 40 to 100 mg qd-bid—Well tolerated, can take with food (but not foods high in calcium), and increases sun sensitivity.3 SORⒶ
Minocycline 50 to 100 mg qd-bid—Not proven to be better than other systemic antibiotics, including tetracycline.3,9 SORⒶ
Tetracycline 500 mg qd-bid—Absorbed best on an empty stomach.3 SORⒶ
Erythromycin 250 to 500 mg bid—Frequent gastrointestinal (GI) disturbance but can be used in pregnancy.3 SORⒶ
Trimethoprim/sulfamethoxazole DS bid—Effective but poses risk of Stevens-Johnson syndrome. Reserve for short courses in particularly severe and resistant cases.3 SORⒷ
Oral azithromycin has been prescribed in pulse dosing for acne in a number of small studies and has not been found to be inferior to oral doxycyline.10 The two most common dosing variations are 500 mg daily for 3 days each month or 250 mg every other day on an ongoing basis. It is a viable alternative to doxycycline, as the price for generic azithromycin has come down and it does not cause photosensitivity. SORⒸ
Isotretinoin (originally known as Accutane, but this brand name has been discontinued) is the most powerful treatment for acne. It is especially useful for cystic and scarring acne that has not responded to other therapies.3 SORⒶ Dosed at approximately 1 mg/kg per day for 6 months. Women of childbearing age must be completely abstinent from sex or use two forms of contraception. Monitor for dry skin, muscle aches, dry eyes, depression, and GI side effects.11 Patients should have baseline comprehensive metabolic profile and lipid panel, then repeat 1 month after being on isotretinoin to monitor for elevated liver enzymes and triglycerides. Monthly lab tests are no longer recommended.12 SORⒷ
Oral contraceptives only for females—Choose ones with low androgenic effect.3 SORⒶ FDA-approved oral contraceptives for acne include Ortho Tri-Cyclen, Yaz, and Estrostep. Other oral contraceptives with similar formulations also help to treat acne in women even though these have not received FDA approval for this indication. Note that Yaz and Yasmin have the progestin drospirenone,13 which is derived from 17α-spironolactone. It shares an antiandrogenic effect with spironolactone.
Spironolactone is another systemic option in females over the age of 12 years.3,14 This may be especially useful if the patient has hirsutism but this is not a requirement for use. Start with 25 mg daily and go to 50 mg daily as needed. It is best absorbed with food. Sometimes 50 mg bid is needed (max dose is 100 mg bid). The risk of hyperkalemia increases with a higher dose, but there is no proven value to monitoring for hyperkalemia in healthy young women not taking other potassium-sparing medications.15 Monitor potassium if the woman is over age 45 years if using higher doses. Titrate up as needed and tolerated.3 SORⒷ The most common side effects are diuresis, breast tenderness, and menstrual irregularities, which are dose dependent. One systematic review failed to show a benefit for spironolactone in acne even though it was found to decrease hirsutism.16 Despite the lack of published data, relying on available evidence, experience, and expert opinion, the American Academy of Dermatology work group supports the use of spironolactone in the management of acne in select women (American Academy of Dermatology Acne Clinical Guideline: https://www.aad.org/practice-tools/quality-care/clinical-guidelines/acne).
One small prospective study of 27 women with severe papular and nodulocystic acne used a combination of EE/DRSP (Yasmin) and spironolactone 100 mg daily. Eighty-five percent of subjects were entirely clear of acne lesions or had excellent improvement with no significant elevation of serum potassium.17
Steroid injection therapy—For painful nodules and cysts. SORⒸ Be careful to avoid producing skin atrophy. Dilute 0.1 mL of 10 mg/mL triamcinolone acetonide (Kenalog) with 0.4 mL of sterile saline for a 2 mg/mL suspension. Inject 0.1 mL with a 1-mL tuberculin syringe into each nodule using a 30-gauge needle (Figure 118-15).
Injection of acne nodules with 2 mg/mL triamcinolone acetonide. (Reproduced with permission from Richard P. Usatine, MD.)
COMPLEMENTARY AND ALTERNATIVE THERAPY
Comedonal acne (Figure 118-6)
Topical antibiotics and benzoyl peroxide.
Topical retinoid or azelaic acid.
May add oral antibiotics if topical agents are not working.
Papulopustular or nodulocystic acne—moderate to severe—inflammatory
Topical retinoid, benzoyl peroxide, and oral antibiotic.
Oral antibiotics or hormonal therapy for women are often essential at this stage.
Azelaic acid if simultaneously treating unwanted hyperpigmentation.
Steroid injection therapy—for painful nodules and cysts.
Severe cystic or scarring acne
Acne fulminans (see Figures 118-9, 118-10, 118-11)
Start with systemic steroids (prednisone 40 to 60 mg/day—approximately 1 mg/kg per day).20 SORⒸ
Systemic steroid treatment rapidly controls the skin lesions and systemic symptoms. The duration of steroid treatment in one Finnish series was 2 to 4 months to avoid relapses.20 SORⒸ
Therapy with isotretinoin, antibiotics, or both was often combined with steroids.20 SORⒸ
One British series used oral prednisolone 0.5 to 1 mg/kg daily for 4 to 6 weeks (thereafter slowly reduced to zero).21 SORⒸ
Oral isotretinoin was added to the regimen at the fourth week, initially at 0.5 mg/kg daily and gradually increased to achieve complete clearance.21 SORⒸ
Consider introducing isotretinoin at approximately 4 weeks in addition to the oral prednisone if there are no contraindications. SORⒸ
Acne conglobata and pyoderma faciale may be treated like acne fulminans, but the course of oral prednisone does not need to be as long. SORⒸ
Combination therapy with multiple topical agents can be more effective than single agents.3 SORⒶ
Topical retinoids and topical antibiotics are more effective when used in combination than when either are used alone.3 SORⒶ
Benzoyl peroxide and topical antibiotics used in combination are effective treatment for acne by helping to minimize antibiotic resistance.3 SORⒶ
The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability.3 SORⒶ
Combination therapy with topical retinoids and oral antibiotics can be helpful at the start of acne therapy. However, maintenance therapy with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance compared to tazarotene alone.22
The most affordable medications for acne include OTC topical benzoyl peroxide and OTC topical adapalene gel 0.1%. Even generic tretinoin has become very expensive. The most expensive acne medications are the brand-name combination products of existing topical medications. These medications are convenient for those with insurance that covers them (Epiduo contains benzoyl peroxide and adapalene; Ziana contains clindamycin and tretinoin). Unfortunately, previously affordable oral antibiotics in the tetracycline family have become more expensive. While they continue to play an important role in acne therapy, they are often only affordable to those patients fortunate enough to have medical insurance without large deductibles. Isotretinoin is also very expensive even though it has been generic for many years. Using the smartphone app GoodRx is one method to find the best price for a particular prescription acne medication in the local area.
NEWER EXPENSIVE MODES OF THERAPY
Intense pulsed light (IPL) and photodynamic therapy (PDT) are options for people in whom using oral and topical treatment is ineffective, inconvenient, poorly tolerated, or harmful.21 However, these therapies are often expensive, and data do not suggest that these should be first-line therapies at this time. Light and laser treatments have been shown to be of short-term benefit if patients can afford therapy and tolerate some discomfort, but the usefulness of red light or blue light as standard therapy for patients with moderate to severe acne carries low certainty.23 Thus, these therapies have not been shown to be better than simple topical treatments.2 One comparative trial demonstrated that PDT was less effective than topical adapalene in the short-term reduction of inflammatory lesions.2 Chemical peels with glycolic acid or salicylic acid can also be used to treat acne. Studies have demonstrated that chemical peels are well tolerated despite some mild discomfort.24
Isotretinoin requires monthly follow-up visits, but other therapies can be monitored every few months at first and then once to twice per year. Keep in mind that many treatments for acne take months to work, so quick follow-up visits may be disappointing.
Adherence to medication regimens is crucial for therapy success. Adequate face washing twice per day is sufficient. Do not scrub the face with abrasive physical or chemical agents. Scrubbing and picking the skin can worsen acne. If benzoyl peroxide is not being used as a leave-on product, it can be purchased to use for face washing.
S, de Berker
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KM. Acne and nutrition: a systematic review. Acta Derm Venereol.
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MG. The efficacy and tolerability of dapsone
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plus 20 microg ethinylestradiol in the treatment of acne vulgaris: lesion counts, investigator ratings and subject self-assessment. J Drugs Dermatol.
JE. A review of hormone-based therapies to treat adult acne vulgaris in women. Int J Womens Dermatol.
A. Low usefulness of potassium monitoring among healthy young women taking spironolactone
for acne. JAMA Dermatol.
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versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev.
F. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study. Indian J Dermatol Venereol Leprol.
RF. Aqueous extract of dried fruit of Berberis vulgaris
L. in acne vulgaris, a clinical trial. J Diet Suppl.
SL. Acne fulminans: report of clinical findings and treatment of twenty-four patients. J Am Acad Dermatol.
WJ. The treatment of acne fulminans: a review of 25 cases. Br J Dermatol.
et al. Light therapies for acne: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol.
C. Efficacy and safety of superficial chemical peeling in treatment of active acne vulgaris. An Bras Dermatol.