Fig. 8.1
A patient with papules and closed comedones consistent with mild acne
Fig. 8.2
Combined inflammatory papules with closed comedones and scarring in a patient with moderate acne
Fig. 8.3
Severe acne in a patient with numerous nodules, scarring, as well as open comedones in the ears
Acne Fulminans
Acne fulminans is the most severe form of acne, and primarily affects adolescent boys. It is characterized by the abrupt development of nodular and suppurative acne lesions in the background of mild to moderate acne. Lesions affect the face, neck, chest, back, and trunk, and often develop into painful, friable ulcerated plaques with overlying hemorrhagic crust. Significant scarring is common. Systemic manifestations include fever, arthralgias, myalgias, hepatosplenomegaly, and malaise. The systemic findings of acne fulminans overlap with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.
Acne Conglobata
Acne conglobata is a severe form of nodular acne with eruptive onset in the absence of systemic manifestations. It can be seen as part of the follicular occlusion tetrad, along with dissecting cellulitis of the scalp, hidradenitis suppurativa, and pilonidal cysts. It may also be seen as part of PAPA syndrome, an autosomal dominant disorder caused by mutations in the PSTPIP1 gene, characterized by sterile pyogenic arthritis, pyoderma gangrenosum, and acne conglobata. PAPASH syndrome includes sterile pyogenic arthritis, pyoderma gangrenosum, acne and suppurative hidradenitis. Novel mutations in the PSTPIP1 gene are also implicated [1].
Drug-Induced Acne
Drug-induced acne typically presents as monomorphous papules and pustules, and can be secondary to several medications. In the pediatric population, the most common cause is systemic or ultrapotent topical corticosteroids, and less often lithium, isoniazid, and phenytoin. Other possible agents include cyclosporine, azathioprine, and phenobarbital, as well as accidental exposure secondary to testosterone-containing agents.
Specific Investigations
For diagnosis |
Endocrine evaluation (in children under 7 years and adolescents when other signs of hyperandrogenism are present) |
For treatment |
With isotretinoin: liver function tests, lipid profile, β-hCG (females of childbearing age) |
With dapsone: complete blood count (CBC) with differential, glucose-6-phosphate dehydrogenase (G6PD) level |
Laboratory evaluation is not required in the majority of patients with acne. In patients with a suspected endocrine abnormality, such as polycystic ovarian syndrome (PCOS), congenital adrenal hyperplasia, an adrenal or gonadal tumor, baseline evaluation should be performed. Screening tests include serum total and free testosterone, dihydroepiandrosterone-sulfate (DHEA-S), and 17-hydroxyprogesterone. Lutenizing hormone (LH) and follicle-stimulating hormone (FSH) may be obtained as well. In females with PCOS, serum free testosterone typically ranges from 100 to 200 ng/dl, and may be associated with an increased LH/FSH ratio (>2–3:1). Congenital adrenal hyperplasia is usually associated with 17-hydroxyprogesterone levels of >3 ng/ml [2]. Serum testosterone >200 ng/dl raises concern for an ovarian tumor, while serum DHEA-S levels of >8,000 ng/ml may be secondary to an underlying adrenal tumor.
In patients undergoing treatment with isotretinoin, baseline laboratory tests include liver function tests and a serum lipid panel. Repeat laboratory testing should be performed at monthly intervals when the lipid response to isotretinoin is established [3]. Females of childbearing potential must have two negative pregnancy tests within a month prior to starting isotretinoin therapy, then monthly during treatment and for 1 month after cessation of therapy.
Oral dapsone therapy can cause hemolytic anemia and, uncommonly, agranulocytosis, thus warranting periodic CBCs. Its use is contraindicated in those with G6PD deficiency, and levels of the enzyme should be checked prior to starting treatment with dapsone.
Table 8.1
First line therapies
Acne type | Treatment |
|---|---|
Mild | Benzoyl peroxide or |
Topical retinoid or | |
Topical combination therapya | |
Moderate | Topical combination therapya +/− oral antibiotic |
Severe | Topical combination therapya +/− oral antibiotic or |
Isotretinoin (if severe nodular or scarring)+/− oral steroid |
Table 8.2
Second line therapies
Acne type | Treatment |
|---|---|
Mild | Add topical retinoid or BP (if not already using) or |
Alternate topical combination therapy* or | |
Azelaic acid or salicylic acid or dapsone gel | |
Moderate | Alternate oral antibiotic + alternative retinoid |
+/− BP or | |
Combined oral contraceptive or spironolactone (for females) or | |
Isotretinoin | |
Severe | High-dose oral antibiotic + alternate topical retinoid + BP or |
Combined oral contraceptive (for females) or | |
Dapsone or | |
Etanercept or systemic immunosuppressive (rarely used) |
Level of evidence | |
|---|---|
Topical retinoids | A |
Benzoyl peroxide (BPO) | B |
Combination topical retinoid + BPO | A |
Topical dapsone 5 % gel | A |
Topical azelaic acid | B |
Oral antibiotics | A |
Isotretinoin | A |
Oral contraceptives | A |
Spironolactone | A |
Oral dapsone | A |
Oral corticosteroids | C |
Table 8.3
Third line therapies
Chemical peels – A (level of evidence) |
Laser therapy – B (level of evidence) |
Intralesional steroid injections – E (level of evidence) |
Discussion of Treatment Modalities
Topical Retinoids
Topical retinoids are first-line agents in acne treatment. They should be applied to the entire acne-prone area in order help prevent future acne lesions. The most common side effect is skin dryness and irritation, especially when used in combination with other topical agents. To minimize irritation, the retinoid can be applied every 2–3 days, and increased to daily as tolerated. Additionally, moisturizer can be applied directly over top of the medication.
Three topical retinoids are available; tretinoin, adapalene, and tazarotene. Tretinoin is photolabile and susceptible to oxidation by benzoyl peroxide. It should be applied at night and should not be used at the same time of day as benzoyl peroxide. Microsphere formulations do not have these restrictions, nor does adapalene or tazarotene. Tretinoin and adapalene are labeled pregnancy category C, while topical tazarotene is pregnancy category X, and patients of childbearing potential should be counseled accordingly.
Topical Antimicrobials
Benzoyl peroxide is an effective treatment alone or when used in combination therapy. Unlike other antimicrobials, microbial resistance has not been reported to benzoyl peroxide. It is available in concentrations from 2.5 % to 10 % and in several formulations, including washes, creams, gels, lotions, soap, foams, and pads. Benzoyl peroxide can bleach towels, sheets, and clothing, and cause skin erythema and irritation. A combination adapalene 0.1 %/benzoyl peroxide 2.5 % topical gel is available.
Other topical antibiotics include clindamycin and erythromycin, which are available as gels, solutions, and pledgets. However, antibiotic resistance to these agents is increasing, so monotherapy with these agents is not recommended.
Other Topical Agents
Azelaic acid cream or gel has inhibitory properties against P. acnes and can be used to treat inflammatory acne. It has the additional benefit of providing modest improvement to the post-inflammatory hyperpigmentation from prior acne lesions.
Topical dapsone 5 % gel has anti-inflammatory and anti-microbial properties and can also be used for inflammatory acne. The most common adverse event is skin irritation or dryness, and it can cause a temporary orange-yellow discoloration of the skin and hair if used concurrently with benzoyl peroxide. Studies have shown minimal absorption of topical dapsone, and it is safe in those with G6PD deficiency [4]. There is one report of methemoglobinemia attributed to topical dapsone use [5].
Salicylic acid is present in many over-the-counter acne treatments. It can be effective in mild comedonal acne. Several formulations in concentrations up to 2 % exist, including gels, creams, lotions, foams, solutions, and washes. It is typically well tolerated, but can cause erythema and xerosis.
Oral Antibiotics
Oral antibiotics are used in combination with topical agents as first-line therapy for moderate papulopustular acne. Doxycycline and minocycline are used most commonly, and given at doses of 100 mg daily to twice daily. Once-daily extended-release formulations are available. The most common side effect is gastrointestinal upset, especially with doxycycline. Esophagitis can also occur. Doxycycline can cause phototoxicity. Pseudotumor cerebri has been associated with all of the tetracyclines, especially if combined with isotretinoin. Tetracyclines can also cause permanent discoloration of developing teeth. Doxycycline and tetracycline are thus contraindicated in children under the age of 8 years. Minocycline is indicated for those 12 years and older. It can cause dizziness, or accumulate in the skin, leading to bluish pigmentary changes. Minocycline can uncommonly lead to hypersensitivity reactions as well as various autoimmune conditions, including drug-induced lupus.
Macrolides are second-line antibiotics for inflammatory acne. Azithromycin is most often used, as Propionibacterium acnes resistance to erythromycin is exceptionally high. Azithromycin is variably dosed for acne, from 250 to 500 mg three times weekly to daily. In younger children, 5 mg/kg daily to three times weekly is used. Macrolides have many drug interactions, and a thorough medication history is warranted prior to treatment. Erythromycin is dosed at 500 mg twice daily. For younger children, a dose of 30–50 mg/kg/day, divided twice daily, is used. Gastrointestinal upset is very common, and an often limiting side effect.
Trimethoprim-sulfamethoxazole is sometimes used for recalcitrant acne or to treat secondary gram-negative folliculitis. Due to the numerous potential serious side effects, it is generally regarded as third-line treatment among antibiotics, and use should be limited. Dosing is weight-based in children, and patients are given 6–12 mg/kg of trimethoprim every 12 h up to the adult dose of one double-strength tab twice daily.
Isotretinoin
Oral isotretinoin is approved for patients with severe, nodulocystic acne refractory to treatment including oral antibiotics. It may also be used as first-line therapy in those with severe nodular acne at risk for scarring, or those with significant scarring.
Patients may start at a lower dose of isotretinoin (0.25–0.5 mg/kg daily) and titrated up to 1 mg/kg/day after 1 month. Treatment is continued until a cumulative dose of 120–150 mg/kg is reached. When used to treat acne fulminans, it is typically started concurrently with oral steroids to prevent flaring, with tapering of the steroids over a few weeks.
Isotretinoin is a potent teratogen, and females of childbearing potential must receive proper counseling and use two forms of contraception during therapy. Common side effects include xerosis, cheilitis, epistaxis, and myalgias. Dry eyes or blurred vision is sometimes reported. Isotretinoin can cause elevations in triglycerides and liver enzymes. Two possible associations link isotretinoin to inflammatory bowel disease and depression, although recent data does not support causality.
Oral Dapsone
In patients with recalcitrant nodular acne, or with contraindications to isotretinoin, oral dapsone is sometimes used at a dose of 100 mg daily.
Hormonal Therapy
Hormonal therapy is considered second-line therapy in female patients with acne, but can be used initially in those with noted perimenstrual flares or irregular periods. Oral contraceptives are the mainstay of hormonal therapy, and contraceptives containing progestins with lower androgen activity or anti-androgen activity are most effective. They are commonly used in adolescent girls, ideally after they have established menstrual cycles.
The most common side effects include nausea, vomiting, menstrual irregularities, weight gain, and breast tenderness. Rare adverse events include hypertension and thromboembolism. This rate is higher in smokers and in those >35 years of age. Decreased bone density is a concern, so low-dose estrogen contraceptives are not recommended.
Spironolactone is a second-line hormonal treatment for acne, which has additive effects when combined with oral contraceptives. Doses range from 25 to 200 mg/day divided into twice-daily dosing. The most common side effects include breast tenderness, headache, and menstrual irregularities. Postural hypotension is uncommon, and hyperkalemia is usually not seen in healthy females. It is not commonly used in younger adolescents.
Table 8.4
Third-line therapies
Third-line therapies |
Third-line acne treatments include chemical peels (usually with glycolic or salicylic acid) [6] and laser therapy. Individual nodular lesions can be injected with triamcinolone in concentrations up to 2.5 mg/cc |
Neonatal Acne
Neonatal acne, considered by some to be synonymous with neonatal cephalic pustulosis, is seen up to 20 % of healthy newborns. It is characterized by small, inflamed papules and pustules in the absence of comedones, favoring the cheeks and nasal bridge, but often extending to the forehead, chin, neck, and upper trunk. Lesions usually appear by 2 weeks of age and resolve within the first few months of life. While some support a pathogenetic role of Malassezia yeast, this remains unproven and debated.
Specific Investigations
None
Table 8.5
First-line therapies
First-line therapies |
Observation |
Neonatal acne is a self-limited condition and treatment is usually not required, unless extensive or persistent.
Table 8.6
Second-line therapies
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