The first step in the management of acne vulgaris in skin of color patients is to take a thorough medical history of the patient's skin and hair care products and practices (). One of the objectives of the history is to evaluate the patient's potential for skin irritation. For example, the skin-care practices listed in an epidemiological study in Arab Americans included the use of olive oil to moisturize the skin, hair oils and pomades, a mixture of pure honey and sugar to exfoliate, natural lemon juice or a milk and cucumber blend to wash the face, or a mixture of herbs or Dead Sea clay to make facial masks.11
Also, in the United States, the demand for bleaching creams has facilitated a rise in the use of illegally obtained, high-concentration hydroquinone products or high-potency corticosteroids that are available over the counter in ethnic stores in major metropolitan cities.41
Many dermatologists may not be aware of these cultural practices; therefore, it is important to learn about how ethnic patients care for their skin and hair as it may impact the planned treatment strategy.
Important questions to ask during the medical history
Another aspect to be mindful of when designing a treatment regimen for skin of color patients is the importance of addressing PIH. The early initiation of PIH treatment will help hasten its resolution and prevent further darkening. However, a delicate balance exists, as cutaneous irritation from the treatment itself can cause or exacerbate PIH in these patients.39
An irritant contact dermatitis in skin of color patients can be signaled by the presence of erythema (), hyperpigmentation (), or hypopigmentation (). However, there are a multitude of depigmenting agents for the treatment of PIH including those with dual efficacy, which treat acne as well. It is also imperative to emphasize the importance of photoprotection in the treatment and prevention of PIH. In fact, a study analyzed data from the 1992 National Health Interview Survey of 1,583 African Americans regarding sun-protection behaviors and found only nine percent of respondents were very likely to use sunscreen versus 81 percent who were unlikely to use it.42
Therefore, patient education is a key component to successful treatment.
Figures 9a, 9b, 9c Erythema (a), hyperpigmentation (b), hypopigmentation (c) resulting from an irritant contact dermatitis in skin of color patients. Figures 9b and 9c are reprinted with permission from Dermatologic Therapy. 2004;17(2):184–195.© John Wiley (more ...) Medical therapy. Topical agents. Retinoids
. In general, topical retinoids are typically first-line therapy for mild-to-moderate acne in skin of color.38,39
(). Retinoids are a class of drugs that are structural and functional vitamin A analogues. These agents exert a comedolytic effect and possess anti-inflammatory and anti-keratinization properties.43
Of particular significance to skin of color patients is the ability of retinoids to treat both acne and PIH. By increasing epidermal turnover, these agents facilitate melanin dispersion and removal.44
The most common agents used are tretinoin, a first-generation retinoid, and adapalene and tazarotene, both third-generation synthetic retinoids (). The concern with using retinoids in skin of color is due to its potential to induce an irritant contact dermatitis, which could lead to PIH. However, retinoids can still be used not only safely but effectively in this patient population by starting at lower concentrations and titrating up based on treatment response and choosing more tolerable formulations (i.e., creams over gels). Tretinoin can also be formulated in a microsponge delivery system, which allows for the controlled release of tretinoin, thereby, causing less irritation.38,45
summarizes the clinical studies evaluating the safety and efficacy of topical retinoids in skin of color patients.
Figures 10a and 10b Skin of color patient with acne and PIH before (a) and after (b) 7 months of therapy with tazarotene 0.1% applied in the mornings and a fixed combination lightening agent (fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% cream) applied (more ...)
Available retinoids marketed in the United States
Clinical studies evaluating the safety and efficacy of topical retinoids for acne in skin of color
. Generally, topical antimicrobials are used in combination therapy for milder cases of acne in skin of color.38
Erythromycin, a macrolide, and clindamycin, a lincosamide, both inhibit bacterial protein synthesis and possess anti-inflammatory properties.38,46
However, these agents are typically used concurrently with benzoyl peroxide (BPO), an oxidizer of bacterial proteins, to reduce the development of bacterial re-sistance,47
and clinical studies have shown increased efficacy with combination therapy.48–50
Ko et al51
conducted a 12-week, randomized, open-label, com-parative study of clindamycin/ benzoyl peroxide (C/BPO) versus adapalene in 69 Korean patients with mild-to-moderate acne. Although both treatments were effective in reducing acne lesion counts and severity score, C/BPO produced a significantly greater reduction in inflammatory lesions than adapalene. Patients tolerated both medications equally well and had minimal side effects. BPO is also widely used as monotherapy and available in lower concentrations over the counter in a variety of formulations, such as creams, washes, foams, pads, and facial masks. However, BPO can be very drying to skin of color and can also cause an irritant contact dermatitis; therefore, it is best to start with lower concentrations and cream or lotion formulations in skin of color patients.39
Sodium sulfacetamide 10%, in the class of sulfonamides, is another topical agent that is typically formulated with sulfur (1–5%) in a cleanser, lotion, cleansing cloths, and topical suspension to treat acne.46
Other topical agents
. Azelaic acid (AA), a dicarboxylic acid, is produced from the organism responsible for Pityriasis versicolor
and is useful in the treatment of acne. Formulated in a 20% cream, AA is often used concomitantly with other topical agents, such as BPO, antibiotics, or retinoids, for greater efficacy.52
AA may be especially suited for skin of color patients given its low irritation potential and its ability as a dicarboxylic acid to inhibit tyrosinase, an enzyme necessary for the production of melanin, thereby treating the acne as well as the PIH.39,53
Salicylic acid (SA) is a beta-hydroxy acid that is available over-the-counter in concentrations up to 2% in a wide variety of formulations. Its efficacy in acne stems from its lipophilic nature, which allows it to penetrate into comedones and its mild anti-inflammatory properties.16,54
However, more clinical studies are needed evaluating the safety and efficacy of these agents in skin of color.
Dapsone, a sulfone, possesses both antimicrobial and anti-inflammatory properties, and is used today to treat a wide range of dermatoses.55
Its efficacy in the treatment of acne was first noticed when patients with leprosy, who also had acne, were treated with systemic sulfones and experienced an improvement in their acne.56
Oral dapsone has not been widely used for acne due to systemic toxicities, but studies have shown that topical 5% dapsone gel is both safe and effective for acne.57,58
Of specific concern for skin of color patients with oral dapsone was the development of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This enzyme deficiency is particularly common in patients of African, South Asian, Middle Eastern, and Mediterranean descent, and is estimated to affect about 1 in 10 African-American males in the United States.59,60
A pharmacokinetic study has shown that the total systemic exposure to dapsone and its metabolites were approximately 100-fold less for topical dapsone than for oral dapsone even in the presence of trimethoprim/sulfamethoxazole (TMP/SMX), which increases systemic absorption of dapsone,61
and plasma dapsone levels reached a steady state and did not increase with prolonged treatment. In fact, when co-administered with (TMP/SMX), the topical dapsone dose is approximately 1% of that from the 100mg oral dose.62
Piette et al63
conducted a hematological safety study of topical dapsone in 64 ethnic patients with G6PD deficiency and acne. There was a 0.32g/dL drop in hemoglobin concentration from baseline to two weeks of topical dapsone treatment; however, this finding was not accompanied by abnormalities in other laboratory indicators of hemolysis (i.e., bilirubin, haptoglobin, reticulocyte count) or clinical signs and symptoms of hemolytic anemia. Therefore, the authors concluded that the risk of hemolytic anemia with topical 5% dapsone gel is very small for patients with G6PD deficiency and can be used safely in all patients.63
Also of note is the fact that topical dapsone followed by benzoyl peroxide has been reported to cause a temporary yellow or orange discoloration of the skin or facial hair.62
. The multifactorial etiologies of acne (i.e., hyperkeratinization, increased sebum, P. acnes
, and inflammation) as well as the prevention of bacterial resistance all facilitate the need for new developments in combination acne therapy. Combining agents that target the different etiological factors of acne can help increase efficacy and response time.64
There have been multiple clinical studies showing the efficacy of using two or three different anti-acne agents, such as BPO, a topical antibiotic, and a topical retinoid; however, the majority of patients included in these studies were Caucasian.65–67
Individual agents can be applied at different times of the day in an effort to reduce the risk of irritation, which is particularly important for skin of color patients.64
Topical antibiotics, such as clindamycin and erythromycin, have been formulated with BPO to help reduce the risk of antibiotic-resistant P. acnes.
Recently, however, more fixed-combination agents are available that combine topical antimicrobials with retinoids, such as adapalene 0.1%/BPO 2.5% and clindamycin phosphate 1.2%/tretinoin 0.025% (). These agents offer greater convenience by providing comedolytic, antibacterial, and anti-inflammatory properties in a single formulation. Clinical studies with the newer fixed-combination agents in skin of color are currently underway. Even other classes of topical anti-acne agents are now being investigated for their utility in combination acne therapy. A recent clinical study evaluated the safety and efficacy of dapsone in combination with adapalene or BPO and found both combinations to be safe and well tolerated in a study population comprising 40-percent ethnic patients.68
Commonly used fixed-combination agents
Oral agents. Retinoids
. Isotretinoin (13-cis-retinoic acid) is an oral retinoid that is approved by the US Food and Drug Administration to treat severe nodulocystic acne and is the treatment of choice for this type of acne in skin of color.43,69
Although its exact mechanism of action is unknown, isotretinoin is known to affect many of the etiological factors of acne by decreasing sebum production, comedogenesis, and P. acnes
Kelly et al69
conducted a study to determine the efficacy of isotretinoin in African-American patients with recalcitrant nodulocystic acne. The authors reported specific treatment effects with isotretinoin that occurred in blacks, such as an early onset flare in areas of the face that were void of lesions prior to treatment, particularly the temporal and submandibular areas, improvement in PIH, and an ashen or grayish facial hue due to the drying and desquamative effects of the drug.69
Therefore, it is important for successful treatment to educate the patient regarding the clinical course with isotretinoin and encourage them to continue with the treatment regimen despite early acne flares. The above study by Kelly et al also noted a dramatic improvement in self esteem and social interactions in those patients who experience a resolution of their acne.69
In addition to African Americans, other clinical studies have also demonstrated the safety and efficacy of isotretinoin in Middle Eastern,70,71
patient populations. Although isotretinoin can be highly effective in treating severe acne, it is also associated with numerous mucocutaneous and serious systemic toxicities (e.g., teratogenicity, dyslipidemia, pancreatitis, and hepatotoxicity); therefore, careful patient selection and monitoring is important.43
. In skin of color patients, as with Caucasian patients, oral antibiotics are typically reserved for patients with moderate-to-severe inflammatory acne, most of whom have likely failed prior treatment with topical agents alone.16,39,64
The most common classes of oral antibiotics used in acne include macrolides (i.e., erythromycin) and tetracyclines (i.e., tetracycline, doxycycline, minocycline), which both work by inhibiting bacterial protein synthesis, and sulfonamides (i.e., TMP/SMX), which inhibit bacterial DNA synthesis.46
Not only do these agents inhibit the growth of P. acnes
but tetracyclines and erythromycin are also effective in acne due to their intrinsic anti-inflammatory properties.46,64
As with topical antibiotics, oral agents can also be used in combination with topical retinoids. Clinical studies have shown some success with the combinations of doxycycline plus adapalene74
and minocycline plus tazarotene75
; however, more studies are needed, particularly in skin of color patients. In designing a treatment regimen, it is important to weigh the benefits of clinical efficacy versus the risks of bacterial resistance and the side effects profile of the antibiotic.
As with other systemic therapies, oral antibiotics can cause a wide range of side effects from gastrointestinal upset with erythromycin or tetracycline to the uncommon Stevens-Johnson syndrome with TMP/SMX or a lupus-like syndrome with minocycline.46,76
Doxycycline can cause a photosensitivity reaction; however, in the author's opinion, this reaction is uncommon in dark-skinned patients. Tetracyclines, particularly minocycline, have been shown to cause rare but serious hypersensitivity reactions, including urticaria, hepatitis, and pneumonitis, which may occur more frequently77
and have a prolonged course78
in black patients although further studies are needed. Muller et al79
conducted a study on the susceptibility of ethnic groups to Drug Hypersensitivity Syndrome (DHS) in a mostly Afro-Caribbean study population. The annual incidence rate was approximately 1 in 100,000, and of the 28 cases included in the study, 14 percent of cases were likely caused by minocycline. Although no definite conclusions could be drawn regarding increased susceptibility in ethnic patients, DHS was the most frequent type of severe drug reaction in this population. Minocycline-induced DHS has also been reported in a Japanese patient.80
Other adverse effects with minocycline include a blue/black-grey discoloration of the skin, which has been reported in a Hispanic patient,81
oral mucosa, sclera, teeth, and nails82,83
as well as the thyroid, heart valves, and bones.84–86
Again, in the author's opinion, this complication does not appear to be common in skin of color.
Other medical therapies.
In treating all patients with acne, hormonal factors should not be overlooked, particularly in women with hirsutism. The increased sebum production stimulated by androgens can be addressed with anti-androgen agents, such as spironolactone, cyproterone acetate, and oral contraceptives.17
Other agents for the medical treatment of acne that are currently in different stages of development include retinoic acid metabolism blocking agents, ectopeptidase inhibitors, 5-lipoxygenase inhibitors, and antisense oligonucleotides.17
Surgical therapy. Chemical peels.
Chemical peeling, like retinoids, in skin of color patients is another therapeutic option that can address both acne and PIH simultaneously. Patients with FST IV to VI typically undergo superficial or medium-depth chemical peels. Their response to chemical peeling may vary and thus the selection of the peeling agent must be done with caution. There have been a number of clinical studies that show the efficacy of certain superficial chemical peels specifically in skin of color patients (). Glycolic acid (GA) is a naturally occurring alpha-hydroxy acid that works by inducing epidermolysis, dispersing basal layer melanin, and increasing dermal collagen synthesis.87,88
GA peels utilize concentrations ranging from 20 to 70 percent and require neutralization to terminate the peel. Salicylic acid (SA) causes keratolysis by disrupting intercellular lipid linkages between epithelioid cells.87,89
Superficial SA peels are usually performed with strengths ranging from 20 to 30 percent without the need for neutralization. Jessner's solution is a combination of 14g resorcinol, 14g salicylic acid, and 14g lactic acid in 95% ethanol, which causes keratolysis by decreasing corneocyte cohesion.90
It was formulated as a combination peel to decrease the concentration of any one agent used in the solution, thereby decreasing the risk for side effects while also producing a synergistic effect.87,90
Clinical studies evaluating the safety and efficacy of chemical peels for acne in skin of color
Before the chemical peel procedure, a detailed history including dermatological conditions, current oral and topical medications used, past reactions to other cosmetic procedures, a history of herpes simplex virus (HSV) infection, keloids, hypertrophic scarring or PIH, and a skin examination should be obtained. It is not uncommon for darker phototypes to develop transient PIH after chemical peeling.39
However, this sequela can be anticipated and pre-treated with hydroquinone to minimize its intensity, and patients can be given a post-treatment course as well. Other preventive measures include starting at lower peel concentrations and titrating up based on response, performing peels at less frequent intervals (2–4 weeks), stopping retinoid therapy 5 to 7 days prior to the peel procedure, and educating the patient about the importance of sun protection.39
Lasers and light-based therapies.
Lasers and light sources can be an effective adjunct to topical or systemic acne management.91
There have been numerous case reports and a few clinical studies evaluating the use of devices including blue light, diode laser, intense pulsed light (IPL), and photodynamic therapy (PDT) for the treatment of acne in skin of color.92–95
In blue light therapy, fluorescent porphyrins contained within P. acnes
are targeted and killed by the blue light.92
Tzung et al92
conducted a study of 31 Taiwanese patients (FST III-IV) and found that blue light irradiation was effective in treating mild-to-moderate acne (P
<0.001) but worsened nodulocystic acne. The 1,450nm diode laser heats the sebaceous gland, which may lead to reduced sebum production and thus decrease inflammatory acne lesions.93
A cooling device helps protect the epidermis from thermal injury and also decreases pain during treatment.93
The diode laser has been shown to be effective acne treatment in two clinical studies conducted in Asian patients (FST III-V) with only a few patients experiencing transient PIH or erythema.93,96
IPL may operate by similar mechanisms as the previous devices including photoinactivation of P. acnes
and photothermolysis of the sebaceous glands and may also possess anti-inflammatory effects.94
Kawana et al94
conducted a study of 25 Japanese patients (FST III-IV) and found that five sessions of IPL at wavelengths of 400 to 700nm and 870 to 1200nm was effective in treating moderate-to-severe acne with the majority of patients experiencing transient erythema. However, multiple previous studies in Asian patients using different IPL parameters did not show significant improvement in acne, particularly with inflammatory lesions.97–99
Therefore, further large-scale studies are needed.
PDT uses aminolevulinic acid, a photosensitizer, as it selectively induces porphyrin fluorescence of pilosebaceous units, which targets the bacteria.100
PDT has been used successfully in Asian populations,101,102
and there is a case report describing the efficacy of PDT in an African-American patient (FST V).103
Scaling and transient hyperpigmentation were reported with PDT therapy in both populations. Larger clinical studies are still needed, particularly for higher phototypes. Photopneumatic therapy is a new treatment option for acne in which the skin is gently drawn into a handpiece allowing the mechanical removal of sebaceous content by the suction pressure, and broadband light is delivered directly to the treatment site (400–1,200nm) leading to bacterial destruction.104
This device has been shown to be effective for acne and side effects including mild erythema; however, clinical studies are needed to determine the safety and efficacy of this device in skin of color patients. As with most other surgical procedures in skin of color patients, postinflammatory hyper- and hypopigmentation and keloidal or hypertrophic scarring are important sequelae of treatment to always keep in mind. There are a number of strategies that may help reduce the risk of these complications, including obtaining an adequate medical history, performing test spots, and the use of cooling devices.105
In addition, post-operative corticosteroid injections can also be helpful in reducing the risk of these complications if erythema develops at the treatment site.
Other surgical options.
The use of intralesional corticosteroid injections into inflammatory cysts or nodules can help alleviate the pain that may develop with these lesions. Triamcinolone acetonide 2.5 to 5mg/cc can be used for the injections and resolution typically occurs within 2 to 5 days.39
Higher concentrations of corticosteroid, 20 to 40mg/cc, can be used if keloids have developed and injections can be repeated every 2 to 4 weeks.39
Open or closed comedones can be manually extracted if resolution does not occur with topical retinoid therapy. Prior to acne surgery, a 6- to 8-week course of retinoid therapy can help reduce the difficulty of extracting, thereby reducing skin trauma as well as the risk of PIH.39
As with retinoids, 1 to 2 salicylic acid peels prior to acne surgery can also help ease the extraction process.
Acne management strategy in skin of color.
outlines the effective treatment options based on acne severity for skin of color patients. However, there are a few key points to emphasize for darker skin. Medical therapy should be started early in skin of color patients with acne to prevent or help decrease the severity of acne sequelae (i.e., PIH, keloids). For topical therapies with some irritation potential, start at lower concentrations and titrate up based on patient response, and choose more tolerable formulations.39
Given the lower starting doses for skin of color, treatment failures may warrant an increase in dosage or addition of another product rather than a switch to another agent. Keep those agents in mind that effectively treat both acne and PIH in a single formulation. Sun protection measures are important to the prevention and treatment of PIH as well as effective depigmenting agents.39
Combination therapy with oral antibiotics and retinoids should be prescribed to patients with inflammatory lesions, then can be discontinued once the inflammatory lesions resolve.106
If the cessation of oral antibiotics is not possible and a longer course of treatment is needed, patients should use either BPO alone or BPO/antibiotic combinations to reduce the risk of bacterial resistance. Topical retinoids can be used as maintenance therapy once antimicrobials are stopped.106
Effective agents for acne in skin of color