Acne

Clinicians who are stumped on how to counsel patients asking about whether cannabinoids benefit various skin-related ailments are not alone.

“When you walk into places like CVS or Walgreens, you see lots of displays for CBD creams and oils,” Todd S. Anhalt, MD, said during the annual meeting of the Pacific Dermatologic Association. “The problem is, we don’t know what’s in them or who made them or how good they are. That’s going to be a problem for a while.”

According to Dr. Anhalt, clinical professor emeritus of dermatology at Stanford (Calif.) University, there are about 140 active cannabinoid compounds in cannabis, but the most important ones are THC and cannabidiol (CBD). There are three types of cannabinoids, based on where the cannabidiol is produced: endocannabinoids, which are produced in the human body; phytocannabinoids, which are derived from plants such as marijuana and hemp; and synthetic cannabinoids, which are derived in labs.

Dr. Anhalt described the endocannabinoid system as a conserved network of molecular signaling made of several components: signaling molecules (endocannabinoids), endocannabinoid receptors (CB-1 and CB-2), enzymes, and transporters. There is also overlap between cannabinoids and terpenes, which are responsible for flavor and aroma in plants and marijuana and can enhance the effects of CBD.

“For the most part, CB-1 receptors are in the central nervous system and CB-2 [receptors] are mostly in the periphery,” including the skin and digestive system, said Dr. Anhalt, who practices at the California Skin Institute in Los Altos, Calif. “This is interesting because one of the main conditions I recommend cannabidiol for is in patients with peripheral neuropathy, despite the fact they may be on all sorts of medications such as Neurontin and Lyrica or tricyclic antidepressants. Sometimes they don’t get much relief from those. I have had many patients tell me that they have had reduction of pain and increased functionality using the CBD creams.” CB-2 receptors, he noted, are located in keratinocytes, sensory receptors, sweat glands, fibroblasts, Langerhans cells, melanocytes, and sebaceous glands.

Recent research shows that the endocannabinoid system is involved in modulation of the CNS and in immune function, particularly skin homeostasis and barrier function. “We know that barrier function can be affected by the generation of oxidative species,” he said. “The stress that it causes can decrease barrier function and lead to cytokine release and itch. CBDs have been shown to enter cells, target and upregulate genes with decreased oxidation and inflammation, and protect membrane integrity in skin cells. Therefore, this might be helpful in atopic dermatitis.” Other potential uses in dermatology include wound healing, acne, hair growth modulation, skin and hair pigmentation, skin infections, psoriasis, and cutaneous malignancies, as well as neuropathic pain.

Evidence is strongest for neuropathic pain, he said, which is mediated by CB-1 receptors peripherally, followed by itch and atopic dermatitis. The authors of a 2017 systematic review concluded that “low-strength” evidence exists to suggest that cannabis alleviates neuropathic pain, with insufficient evidence for other types of pain.

Topical CBD comes in various forms: oils (usually hemp oil), creams, and lotions, Dr. Anhalt said. “I advise patients to apply it 2-4 times per day depending on how anxious or uncomfortable they are. It takes my patients 10 days to 2 weeks before they notice anything at all.”

For atopic dermatitis, it could be useful “not to use it instead of a moisturizer, but as a moisturizer,” Dr. Anhalt advised. “You can have a patient get big jars of CBD creams and lotions. They may have to try a few before they find one that they really like, but you can replace all of the other moisturizers that you’re using right now in patients who have a lot of itch.”

As for CBD’s effect on peripheral neuropathy, the medical literature is lacking, but some studies show low to moderate evidence of efficacy. For example, a Cochrane Review found that a 30% or greater pain reduction was achieved by 39% of patients who used cannabis-based treatments, vs. 33% of those on placebo.

“I would not suggest CBD as a first-line drug unless it’s very mild peripheral neuropathy, but for patients who are on gabapentin who are better but not better enough, this is an excellent adjunct,” Dr. Anhalt said. “It’s worth trying. It’s not too expensive and it’s really safe.”

The application of topical CBD to treat cutaneous malignancies has not yet shown evidence of significant efficacy, while using CBDs for acne holds promise. “The endogenous cannabinoid system is involved in the production of lipids,” he said. “Cannabinoids have an antilipogenic activity, so they decrease sebum production. CBD could help patients with mild acne who are reluctant to use other types of medications. For this and other potential dermatologic applications, lots more studies need to be done.”

Dr. Anhalt reported having no financial disclosures.

dbrunk@mdedge.com

Clinicians who are stumped on how to counsel patients asking about whether cannabinoids benefit various skin-related ailments are not alone.

“When you walk into places like CVS or Walgreens, you see lots of displays for CBD creams and oils,” Todd S. Anhalt, MD, said during the annual meeting of the Pacific Dermatologic Association. “The problem is, we don’t know what’s in them or who made them or how good they are. That’s going to be a problem for a while.”

According to Dr. Anhalt, clinical professor emeritus of dermatology at Stanford (Calif.) University, there are about 140 active cannabinoid compounds in cannabis, but the most important ones are THC and cannabidiol (CBD). There are three types of cannabinoids, based on where the cannabidiol is produced: endocannabinoids, which are produced in the human body; phytocannabinoids, which are derived from plants such as marijuana and hemp; and synthetic cannabinoids, which are derived in labs.

Dr. Anhalt described the endocannabinoid system as a conserved network of molecular signaling made of several components: signaling molecules (endocannabinoids), endocannabinoid receptors (CB-1 and CB-2), enzymes, and transporters. There is also overlap between cannabinoids and terpenes, which are responsible for flavor and aroma in plants and marijuana and can enhance the effects of CBD.

“For the most part, CB-1 receptors are in the central nervous system and CB-2 [receptors] are mostly in the periphery,” including the skin and digestive system, said Dr. Anhalt, who practices at the California Skin Institute in Los Altos, Calif. “This is interesting because one of the main conditions I recommend cannabidiol for is in patients with peripheral neuropathy, despite the fact they may be on all sorts of medications such as Neurontin and Lyrica or tricyclic antidepressants. Sometimes they don’t get much relief from those. I have had many patients tell me that they have had reduction of pain and increased functionality using the CBD creams.” CB-2 receptors, he noted, are located in keratinocytes, sensory receptors, sweat glands, fibroblasts, Langerhans cells, melanocytes, and sebaceous glands.

Recent research shows that the endocannabinoid system is involved in modulation of the CNS and in immune function, particularly skin homeostasis and barrier function. “We know that barrier function can be affected by the generation of oxidative species,” he said. “The stress that it causes can decrease barrier function and lead to cytokine release and itch. CBDs have been shown to enter cells, target and upregulate genes with decreased oxidation and inflammation, and protect membrane integrity in skin cells. Therefore, this might be helpful in atopic dermatitis.” Other potential uses in dermatology include wound healing, acne, hair growth modulation, skin and hair pigmentation, skin infections, psoriasis, and cutaneous malignancies, as well as neuropathic pain.

Evidence is strongest for neuropathic pain, he said, which is mediated by CB-1 receptors peripherally, followed by itch and atopic dermatitis. The authors of a 2017 systematic review concluded that “low-strength” evidence exists to suggest that cannabis alleviates neuropathic pain, with insufficient evidence for other types of pain.

Topical CBD comes in various forms: oils (usually hemp oil), creams, and lotions, Dr. Anhalt said. “I advise patients to apply it 2-4 times per day depending on how anxious or uncomfortable they are. It takes my patients 10 days to 2 weeks before they notice anything at all.”

For atopic dermatitis, it could be useful “not to use it instead of a moisturizer, but as a moisturizer,” Dr. Anhalt advised. “You can have a patient get big jars of CBD creams and lotions. They may have to try a few before they find one that they really like, but you can replace all of the other moisturizers that you’re using right now in patients who have a lot of itch.”

As for CBD’s effect on peripheral neuropathy, the medical literature is lacking, but some studies show low to moderate evidence of efficacy. For example, a Cochrane Review found that a 30% or greater pain reduction was achieved by 39% of patients who used cannabis-based treatments, vs. 33% of those on placebo.

“I would not suggest CBD as a first-line drug unless it’s very mild peripheral neuropathy, but for patients who are on gabapentin who are better but not better enough, this is an excellent adjunct,” Dr. Anhalt said. “It’s worth trying. It’s not too expensive and it’s really safe.”

The application of topical CBD to treat cutaneous malignancies has not yet shown evidence of significant efficacy, while using CBDs for acne holds promise. “The endogenous cannabinoid system is involved in the production of lipids,” he said. “Cannabinoids have an antilipogenic activity, so they decrease sebum production. CBD could help patients with mild acne who are reluctant to use other types of medications. For this and other potential dermatologic applications, lots more studies need to be done.”

Dr. Anhalt reported having no financial disclosures.

dbrunk@mdedge.com

Clinicians who are stumped on how to counsel patients asking about whether cannabinoids benefit various skin-related ailments are not alone.

“When you walk into places like CVS or Walgreens, you see lots of displays for CBD creams and oils,” Todd S. Anhalt, MD, said during the annual meeting of the Pacific Dermatologic Association. “The problem is, we don’t know what’s in them or who made them or how good they are. That’s going to be a problem for a while.”

According to Dr. Anhalt, clinical professor emeritus of dermatology at Stanford (Calif.) University, there are about 140 active cannabinoid compounds in cannabis, but the most important ones are THC and cannabidiol (CBD). There are three types of cannabinoids, based on where the cannabidiol is produced: endocannabinoids, which are produced in the human body; phytocannabinoids, which are derived from plants such as marijuana and hemp; and synthetic cannabinoids, which are derived in labs.

Dr. Anhalt described the endocannabinoid system as a conserved network of molecular signaling made of several components: signaling molecules (endocannabinoids), endocannabinoid receptors (CB-1 and CB-2), enzymes, and transporters. There is also overlap between cannabinoids and terpenes, which are responsible for flavor and aroma in plants and marijuana and can enhance the effects of CBD.

“For the most part, CB-1 receptors are in the central nervous system and CB-2 [receptors] are mostly in the periphery,” including the skin and digestive system, said Dr. Anhalt, who practices at the California Skin Institute in Los Altos, Calif. “This is interesting because one of the main conditions I recommend cannabidiol for is in patients with peripheral neuropathy, despite the fact they may be on all sorts of medications such as Neurontin and Lyrica or tricyclic antidepressants. Sometimes they don’t get much relief from those. I have had many patients tell me that they have had reduction of pain and increased functionality using the CBD creams.” CB-2 receptors, he noted, are located in keratinocytes, sensory receptors, sweat glands, fibroblasts, Langerhans cells, melanocytes, and sebaceous glands.

Recent research shows that the endocannabinoid system is involved in modulation of the CNS and in immune function, particularly skin homeostasis and barrier function. “We know that barrier function can be affected by the generation of oxidative species,” he said. “The stress that it causes can decrease barrier function and lead to cytokine release and itch. CBDs have been shown to enter cells, target and upregulate genes with decreased oxidation and inflammation, and protect membrane integrity in skin cells. Therefore, this might be helpful in atopic dermatitis.” Other potential uses in dermatology include wound healing, acne, hair growth modulation, skin and hair pigmentation, skin infections, psoriasis, and cutaneous malignancies, as well as neuropathic pain.

Evidence is strongest for neuropathic pain, he said, which is mediated by CB-1 receptors peripherally, followed by itch and atopic dermatitis. The authors of a 2017 systematic review concluded that “low-strength” evidence exists to suggest that cannabis alleviates neuropathic pain, with insufficient evidence for other types of pain.

Topical CBD comes in various forms: oils (usually hemp oil), creams, and lotions, Dr. Anhalt said. “I advise patients to apply it 2-4 times per day depending on how anxious or uncomfortable they are. It takes my patients 10 days to 2 weeks before they notice anything at all.”

For atopic dermatitis, it could be useful “not to use it instead of a moisturizer, but as a moisturizer,” Dr. Anhalt advised. “You can have a patient get big jars of CBD creams and lotions. They may have to try a few before they find one that they really like, but you can replace all of the other moisturizers that you’re using right now in patients who have a lot of itch.”

As for CBD’s effect on peripheral neuropathy, the medical literature is lacking, but some studies show low to moderate evidence of efficacy. For example, a Cochrane Review found that a 30% or greater pain reduction was achieved by 39% of patients who used cannabis-based treatments, vs. 33% of those on placebo.

“I would not suggest CBD as a first-line drug unless it’s very mild peripheral neuropathy, but for patients who are on gabapentin who are better but not better enough, this is an excellent adjunct,” Dr. Anhalt said. “It’s worth trying. It’s not too expensive and it’s really safe.”

The application of topical CBD to treat cutaneous malignancies has not yet shown evidence of significant efficacy, while using CBDs for acne holds promise. “The endogenous cannabinoid system is involved in the production of lipids,” he said. “Cannabinoids have an antilipogenic activity, so they decrease sebum production. CBD could help patients with mild acne who are reluctant to use other types of medications. For this and other potential dermatologic applications, lots more studies need to be done.”

Dr. Anhalt reported having no financial disclosures.

dbrunk@mdedge.com

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.¹ A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.²

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.^3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel⁵ and tazarotene foam, which have lower potential for sensitization.⁶ Allergic contact dermatitis also has been reported from retinyl palmitate^7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.⁹ Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.^10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.¹⁰ Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour¹³ and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians¹⁵ and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α₂-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.¹⁶ Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.^17,18 Ringuet and Houle¹⁹ reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.^20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.^18,20

Antimicrobials

Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.²² To date, limited case reports on ACD to topical clindamycin exist.^23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.^25,26,29

Metronidazole—Metronidazole is a bactericidal agent that disrupts nucleic acid synthesis with additional anti-inflammatory properties used in the treatment of rosacea. Allergic contact dermatitis to topical metronidazole has been reported.^30-34 In 2006, Beutner at al³⁵ patch tested 215 patients using metronidazole gel 1%, which revealed no positive reactions to indicate contact sensitization. Similarly, Jappe et al³⁶ found no positive reactions to metronidazole 2% in petrolatum in their prospective analysis of 78 rosacea patients, further highlighting the exceptionally low incidence of ACD. Cross-reaction with isothiazolinone, which shares structurally similar properties to metronidazole, has been speculated.^31,34 One patient developed an acute reaction to metronidazole gel 0.75% within 24 hours of application, suggesting that isothiazolinone may act as a sensitizer, though this relationship has not been proven.³¹

Neomycin—Neomycin blocks bacterial protein synthesis and is available in both prescription and over-the-counter (OTC) formulations. It commonly is used to treat and prevent superficial wound infections as an OTC antibiotic and also has otic, ophthalmologic, gastroenterologic, urologic, and peritoneal formulations. It also can be used in the dental and veterinary fields and is present in some animal feeds and in trace amounts in some vaccines for humans. Neomycin is a common antibiotic contact allergen, and the most recently reported 2017-2018 North American Contact Dermatitis Group data cycle placed it at number 12 with 5.4% positivity.³⁷ Co-reactions with bacitracin can occur, substantially limiting OTC topical antibiotic options for allergic patients. A safe alternative for patients with neomycin (and bacitracin and polymyxin) contact allergy is prescription mupirocin.

Bacitracin—Bacitracin interferes with peptidoglycan and cell-wall synthesis to treat superficial cutaneous infections. Similar to neomycin, it also can be found in OTC antibiotic ointments as well as in antibacterial bandages. There are several case reports of patients with both type IV delayed hypersensitivity (contact dermatitis) and type I anaphylactic reactions to bacitracin^38-40; patch testers should be aware of this rare association. Bacitracin was positive in 5.5% of patch tested patients in the 2017-2018 North American Contact Dermatitis Group data cycle,³⁷ and as with neomycin, bacitracin also is commonly patch tested in most screening patch test series.

Polymyxin—Polymyxin is a polypeptide topical antibiotic that is used to treat superficial wound infections and can be used in combination with neomycin and/or bacitracin. Historically, it is a less common antibiotic allergen; however, it is now frequently included in comprehensive patch test series, as the frequency of positive reactions seems to be increasing, probably due to polysensitization with neomycin and bacitracin.

Nystatin—Nystatin is an antifungal that binds to ergosterol and disrupts the cell wall. Cases exist of ACD to topical nystatin as well as systemic ACD from oral exposure, though both are quite rare. Authors have surmised that the overall low rates of ACD may be due to poor skin absorption of nystatin, which also can confound patch testing.^41,42 For patients with suspected ACD to nystatin, repeat open application testing also can be performed to confirm allergy.

Imidazole Antifungals—Similar to nystatins, imidazole antifungals also work by disrupting the fungal cell wall. Imidazole antifungal preparations that have been reported to cause ACD include clotrimazole, miconazole, econazole, and isoconazole, and although cross-reactivity patterns have been described, they are not always reproducible with patch testing.⁴³ In one reported case, tioconazole found in an antifungal nail lacquer triggered ACD involving not only the fingers and toes but also the trunk.⁴⁴ Erythema multiforme–like reactions also have been described from topical use.⁴⁵ Commercial patch test preparations of the most common imidazole allergens do exist. Nonimidazole antifungals remain a safe option for allergic patients.

Antihistamines

Antihistamines, or H1-receptor antagonists, are marketed to be applied topically for relief of pruritus associated with allergic cutaneous reactions. Ironically, they are known to be potent sensitizers themselves. There are 6 main chemical classes of antihistamines: phenothiazines, ethylenediamines, ethanolamines, alkylamines, piperazines, and piperidines. Goossens and Linsen⁴⁶ patch tested 12,460 patients from 1978 to 1997 and found the most positive reactions to promethazine (phenothiazine)(n=12), followed by diphenhydramine (ethanolamine)(n=8) and clemizole (benzimidazole)(n=6). The authors also noted cross-reactions between diphenhydramine derivatives and between promethazine and chlorpromazine.⁴⁶

Doxepin is a tricyclic antidepressant with antihistamine activity and is a well-documented sensitizer.^47-52 Taylor et al⁴⁷ evaluated 97 patients with chronic dermatoses, and patch testing revealed 17 (17.5%) positive reactions to doxepin cream, 13 (76.5%) of which were positive reactions to both the commercial cream and the active ingredient. Patch testing using doxepin dilution as low as 0.5% in petrolatum is sufficient to provoke a strong (++) allergic reaction.^50,51 Early-onset ACD following the use of doxepin cream suggests the possibility of prior sensitization, perhaps with a structurally similar phenothiazine drug.⁵¹ A keen suspicion for ACD in patients using doxepin cream for longer than the recommended duration can help make the diagnosis.^49,52

Topical Analgesics

Nonsteroidal Anti-inflammatory Drugs—Ketoprofen is one of the most frequent culprits of photoallergic contact dermatitis. Pruritic, papulovesicular, and bullous lesions typically develop acutely weeks after exposure. Prolonged photosensitivity is common and can last years after discontinuation of the nonsteroidal anti-inflammatory drug.⁵³ Cases of cross-reactions and co-sensitization to structurally similar substances have been reported, including to benzophenone-related chemicals in sunscreen and aldehyde groups in fragrance mix.^53,54

Diclofenac gel generally is well tolerated in the topical treatment of joint pain and inflammation. In the setting of ACD, patients typically present with dermatitis localized to the area of application.⁵⁵ Immediate cessation and avoidance of topical diclofenac are crucial components of management. Although systemic contact dermatitis has been reported with oral diclofenac use,⁵⁶ a recent report suggested that oral diclofenac may be well tolerated for some patients with topical ACD.⁵⁷

Publications on bufexamac-induced ACD mainly consist of international reports, as this medication has been discontinued in the United States. Bufexamac is a highly sensitizing agent that can lead to severe polymorphic eruptions requiring treatment with prednisolone and even hospitalization.⁵⁸ In one Australian case report, a mother developed an edematous, erythematous, papulovesicular eruption on the breast while breastfeeding her baby, who was being treated with bufexamac cream 5% for infantile eczema.⁵⁹ Carprofen-induced photoallergic contact dermatitis is associated with occupational exposure in pharmaceutical workers.^60,61 A few case reports on other nonsteroidal anti-inflammatory drugs, including etofenamate and aceclofenac, have been published.^62,63

Compounded Medications—Compounded topical analgesics, which help to control pain via multiple combined effects, have gained increasing popularity in the management of chronic neuropathic pain disorders. Only a few recent retrospective studies assessing the efficacy and safety of these medications have mentioned suspected allergic cutaneous reactions.^62,63 In 2015, Turrentine et al⁶⁴ reported a case of ACD to cyclobenzaprine in a compound containing ketamine 10%, diclofenac 5%, baclofen 2%, bupivacaine 1%, cyclobenzaprine 2%, gabapentin 6%, ibuprofen 3%, and pentoxifylline 3% in a proprietary cream base. When patients present with suspected ACD to a compounded pain medication, obtaining individual components for patch testing is key to determining the allergic ingredient(s). We suspect that we will see a rise in reports of ACD as these topical compounds become readily adopted in clinical practices.

Patch Testing for Diagnosis

When patients present with symptoms concerning for ACD to medicaments, the astute clinician should promptly stop the suspected topical medication and consider patch testing. For common allergens such as neomycin, bacitracin, or ethylenediamine, commercial patch test preparations exist and should be used; however, for drugs that do not have a commercial patch test preparation, the patient’s product can be applied as is, keeping in mind that certain preparations (such as retinoids) can cause irritant patch test reactions, which may confound the reading. Alternatively, individual ingredients in the medication’s formulation can be requested from the manufacturer or a compounding pharmacy for targeted testing. Suggested concentrations for patch testing based on the literature and expert reference are listed in the Table. The authors (M.R., A.R.A.) frequently rely on an expert reference⁶⁶ to determine ideal concentrations for patch testing. Referral to a specialized patch test clinic may be appropriate.

Final Interpretation

Although their intent is to heal, topical medicaments also can be a source of ACD. The astute clinician should consider ACD when topicals either no longer seem to help the patient or trigger new-onset dermatitis. Patch testing directly with the culprit medicament, or individual medication ingredients when needed, can lead to the diagnosis, though caution is advised. Stay tuned for part 2 of this series in which we will discuss ACD to topical steroids, immunomodulators, and anesthetic medications.

Patients with mild to moderate facial acne who underwent four treatments with a novel laser prototype known as Accure experienced an 82% reduction in acne lesions at 12 weeks and a 90% reduction at 12 months, a development that indicates the promise this has a treatment for acne in the future.

Currently, “there is no strong evidence that lasers are better than conventional treatments for acne,” Fernanda H. Sakamoto, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. Some patients struggling with acne “search for so many different options and they end up spending a lot of money,” which, she said, includes an estimated $222 million for laser treatment alone in 2019.

Unlike other existing laser and light options for acne treatment, however, Accure is the first light-based platform to selectively target and injure sebaceous glands, the main source of sebum production and the key to a durable solution for acne. The laser, which uses a 1,726-nm wavelength, is being developed by researchers at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston and was granted the European CE mark, which allows marketing of the product in Europe, in May of 2020.

In 2012, Dr. Sakamoto, a dermatologist at the center, and her Wellman colleagues were the first to describe the use of selective photothermolysis to target sebaceous glands. “We found that the peak absorption of lipids in sebaceous glands occurs between 1,700 and 1,720 nm,” she said. “Compared to water, the contrast is not high, so for us to develop a laser that is selective for acne, we needed to develop a strong cooling system and we had to create different methods to make it more selective.” She said that it took about 10 years to develop this laser.

The latest Accure prototype features a smart laser handpiece for real time thermal monitoring and precise delivery of laser emissions. “We have developed a mathematical model which permits us to predict safe and effective treatment patterns,” Dr. Sakamoto said at the meeting, which was named “Laser & Aesthetic Skin Therapy: What’s the Truth?” and was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It has a unique cooling system that can control and protect the skin.”

The clinical trial for Food and Drug Administration clearance, which was delayed because of the COVID-19 pandemic, is still underway, she said, and the hope is that the laser will cleared by the FDA by next year. She and her Wellman colleagues have been working with four veteran dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2021, more than 50 patients were enrolled in four IRB-approved studies and an additional 30 are enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the pilot facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment. The average lesion reduction at week 12 was 82% and the mean Visual Analog Scale score immediately after treatment was 2.10 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device with no adverse events.

“This laser is absorbed in the near-infrared spectrum, so there is no melanin absorption,” Dr. Sakamoto explained. “It’s pretty much a color-blind laser, so we can treat darker skin types safely, with no side effects.” In other findings, researchers observed a 45% reduction in acne lesions after one treatment session, which “keeps improving over time,” she said. “At 12 weeks, we have clearance of over 80% of the lesions.”

At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histological studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other follicular structures.

Dr. Sakamoto disclosed that she has received portions of patent royalties from Massachusetts General Hospital. Accure was cofounded by R. Rox Anderson, MD, the director of the Wellman Center.

dbrunk@mdedge.com

Patients with mild to moderate facial acne who underwent four treatments with a novel laser prototype known as Accure experienced an 82% reduction in acne lesions at 12 weeks and a 90% reduction at 12 months, a development that indicates the promise this has a treatment for acne in the future.

Currently, “there is no strong evidence that lasers are better than conventional treatments for acne,” Fernanda H. Sakamoto, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. Some patients struggling with acne “search for so many different options and they end up spending a lot of money,” which, she said, includes an estimated $222 million for laser treatment alone in 2019.

Unlike other existing laser and light options for acne treatment, however, Accure is the first light-based platform to selectively target and injure sebaceous glands, the main source of sebum production and the key to a durable solution for acne. The laser, which uses a 1,726-nm wavelength, is being developed by researchers at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston and was granted the European CE mark, which allows marketing of the product in Europe, in May of 2020.

In 2012, Dr. Sakamoto, a dermatologist at the center, and her Wellman colleagues were the first to describe the use of selective photothermolysis to target sebaceous glands. “We found that the peak absorption of lipids in sebaceous glands occurs between 1,700 and 1,720 nm,” she said. “Compared to water, the contrast is not high, so for us to develop a laser that is selective for acne, we needed to develop a strong cooling system and we had to create different methods to make it more selective.” She said that it took about 10 years to develop this laser.

The latest Accure prototype features a smart laser handpiece for real time thermal monitoring and precise delivery of laser emissions. “We have developed a mathematical model which permits us to predict safe and effective treatment patterns,” Dr. Sakamoto said at the meeting, which was named “Laser & Aesthetic Skin Therapy: What’s the Truth?” and was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It has a unique cooling system that can control and protect the skin.”

The clinical trial for Food and Drug Administration clearance, which was delayed because of the COVID-19 pandemic, is still underway, she said, and the hope is that the laser will cleared by the FDA by next year. She and her Wellman colleagues have been working with four veteran dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2021, more than 50 patients were enrolled in four IRB-approved studies and an additional 30 are enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the pilot facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment. The average lesion reduction at week 12 was 82% and the mean Visual Analog Scale score immediately after treatment was 2.10 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device with no adverse events.

“This laser is absorbed in the near-infrared spectrum, so there is no melanin absorption,” Dr. Sakamoto explained. “It’s pretty much a color-blind laser, so we can treat darker skin types safely, with no side effects.” In other findings, researchers observed a 45% reduction in acne lesions after one treatment session, which “keeps improving over time,” she said. “At 12 weeks, we have clearance of over 80% of the lesions.”

At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histological studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other follicular structures.

Dr. Sakamoto disclosed that she has received portions of patent royalties from Massachusetts General Hospital. Accure was cofounded by R. Rox Anderson, MD, the director of the Wellman Center.

dbrunk@mdedge.com

Patients with mild to moderate facial acne who underwent four treatments with a novel laser prototype known as Accure experienced an 82% reduction in acne lesions at 12 weeks and a 90% reduction at 12 months, a development that indicates the promise this has a treatment for acne in the future.

Currently, “there is no strong evidence that lasers are better than conventional treatments for acne,” Fernanda H. Sakamoto, MD, PhD, said during a virtual course on laser and aesthetic skin therapy. Some patients struggling with acne “search for so many different options and they end up spending a lot of money,” which, she said, includes an estimated $222 million for laser treatment alone in 2019.

Unlike other existing laser and light options for acne treatment, however, Accure is the first light-based platform to selectively target and injure sebaceous glands, the main source of sebum production and the key to a durable solution for acne. The laser, which uses a 1,726-nm wavelength, is being developed by researchers at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston and was granted the European CE mark, which allows marketing of the product in Europe, in May of 2020.

In 2012, Dr. Sakamoto, a dermatologist at the center, and her Wellman colleagues were the first to describe the use of selective photothermolysis to target sebaceous glands. “We found that the peak absorption of lipids in sebaceous glands occurs between 1,700 and 1,720 nm,” she said. “Compared to water, the contrast is not high, so for us to develop a laser that is selective for acne, we needed to develop a strong cooling system and we had to create different methods to make it more selective.” She said that it took about 10 years to develop this laser.

The latest Accure prototype features a smart laser handpiece for real time thermal monitoring and precise delivery of laser emissions. “We have developed a mathematical model which permits us to predict safe and effective treatment patterns,” Dr. Sakamoto said at the meeting, which was named “Laser & Aesthetic Skin Therapy: What’s the Truth?” and was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “It has a unique cooling system that can control and protect the skin.”

The clinical trial for Food and Drug Administration clearance, which was delayed because of the COVID-19 pandemic, is still underway, she said, and the hope is that the laser will cleared by the FDA by next year. She and her Wellman colleagues have been working with four veteran dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2021, more than 50 patients were enrolled in four IRB-approved studies and an additional 30 are enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the pilot facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment. The average lesion reduction at week 12 was 82% and the mean Visual Analog Scale score immediately after treatment was 2.10 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device with no adverse events.

“This laser is absorbed in the near-infrared spectrum, so there is no melanin absorption,” Dr. Sakamoto explained. “It’s pretty much a color-blind laser, so we can treat darker skin types safely, with no side effects.” In other findings, researchers observed a 45% reduction in acne lesions after one treatment session, which “keeps improving over time,” she said. “At 12 weeks, we have clearance of over 80% of the lesions.”

At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histological studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other follicular structures.

Dr. Sakamoto disclosed that she has received portions of patent royalties from Massachusetts General Hospital. Accure was cofounded by R. Rox Anderson, MD, the director of the Wellman Center.

dbrunk@mdedge.com

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

The Food and Drug Administration has approved a modification to the isotretinoin risk-mitigation program to make it more inclusive for transgender patients.

Beginning on Dec. 13, 2021, patients prescribed isotretinoin for acne will be assigned to one of two risk categories – those who can get pregnant and those who cannot for the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS). Previously, there were three risk categories: females of reproductive potential, females not of reproductive potential, and males.

In recent years, dermatologists and others have advocated for the change, hoping to make the process more inclusive and less intrusive for their transgender patients.

Isotretinoin (Accutane, Absorica, Amnesteem, Claravis, others) has a high risk of severe birth defects, and has been linked with other health issues, making it crucial for those with the ability to become pregnant to take contraceptive precautions while on the medication. Under the iPLEDGE program, physicians, patients, and pharmacies prescribing, using, or dispensing the drug must all be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy testing for patients who can become pregnant.

The FDA had given notification in June 2018 that the REMS modification and labeling change would be required, replacing the gender-specific language with gender-neutral language, according to an FDA spokesperson. The change was based on feedback that the gender-specific language can be a barrier to access for some patients. The FDA approved the modification on Oct. 8.
 

Expert reactions

“This is an exciting and welcome change from the FDA on iPLEDGE that many dermatologists, myself included, have advocated for quite a few years,” Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview.

In a report on the dermatologic care for lesbian, gay, bisexual, and transgender persons published in the Journal of the American Academy of Dermatology, Dr. Yeung and his colleagues noted that more than 10 million lesbian, gay, bisexual and transgender people live in the United States and that improving their health is a public health priority.

“For cisgender patients, nothing has changed – patients will continue to receive appropriate educational material related to isotretinoin based on their pregnancy potential,” Dr. Yeung said. “For transgender and gender diverse patients, this is a huge step forward.”

Under the previous system, doctors were asked to register patients using gender binary categories, “which were confusing when they did not reflect reality” for these patients, Dr. Yeung said. The new system, Dr. Yeung added, “will make my job easier. I no longer have to struggle between respecting the patient’s gender identity and providing medically necessary care for patients with severe acne.”

“The new terminology is not just respectful, it also is simpler and makes more sense,” agreed Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery at Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai, New York. “As it stood, a transgender man with his uterus and ovaries in place might be missed in the pregnancy surveillance system because he could simply be labeled a man and not followed further. At the same time, both transgender women and cisgender women who were at no risk of pregnancy could be subject to more medical scrutiny that might have been consider intrusive.”

The change “validates the important point that pregnancy potential is not exclusively defined by sociocultural constructs of gender and allow dermatologists to focus purely on what matters when prescribing isotretinoin – whether an individual is able to become pregnant or not, regardless of their gender identity,” Klint Peebles, MD, a dermatologist at Kaiser Permanente in Washington, D.C., and suburban Maryland, who has also advocated for the change, said in an interview.

 

FDA elaborates

The modification includes important changes for doctors, pharmacists, and patients alike, according to the FDA.

Health care providers must assign and confirm their currently enrolled patient’s risk category when they first log in to the IPLEDGE REMS website on or after Dec. 13, the effective date. They should be sure any patient whose prescription RMA (iPLEDGE authorization) expires on Dec. 11-12 is told to obtain their prescription before midnight, Eastern time, Dec. 10.

Pharmacists will be affected, too, since the iPLEDGE REMS changed to a new platform vendor and the current “switch” pharmacy management system will be removed as a method to verify authorization to dispense isotretinoin. With these changes, as of Dec. 13, pharmacists can’t use the switch system to obtain a predispense authorization, or RMA (risk management authorization). They will need to obtain an RMA online by accessing the iPLEDGE REMS website or via telephone to the PLEDGE REMS center, 866-495-0654, before dispensing the prescription.

Patients, beginning Dec. 13, will have the option of presenting a unique QR code at the pharmacy on their smartphone rather than providing the iPLEDGE identification number. The code can be accessed by logging into their account on the iPLEDGE REMS website.

Patients with an isotretinoin prescription RMA that expires Dec. 11-12, must obtain the prescription before 11:59 p.m. Eastern time on Dec. 10. If the RMA expires before the prescription is picked up, the patient must begin the authorization process all over again.

Dr. Safer, Dr. Yeung, and Dr. Peebles have no relevant disclosures.

More information on the update and the isotretinoin REMS program is available on the FDA website.

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

A ccording to the US Census Bureau, more than half of all Americans are projected to belong to a minority group, defined as any group other than non-Hispanic White alone, by 2044. ¹ Consequently, the United States rapidly is becoming a country in which the majority of citizens will have skin of color. Individuals with skin of color are of diverse ethnic backgrounds and include people of African, Latin American, Native American, Pacific Islander, and Asian descent, as well as interethnic backgrounds. ² Throughout the country, dermatologists along with primary care practitioners may be confronted with certain cutaneous conditions that have varying disease presentations or processes in patients with skin of color. It also is important to note that racial categories are socially rather than biologically constructed, and the term skin of color includes a wide variety of diverse skin types. Nevertheless, the current literature thoroughly supports unique pathophysiologic differences in skin of color as well as variations in disease manifestation compared to White patients. ^3-5 For example, the increased lability of melanosomes in skin of color patients, which increases their risk for postinflammatory hyperpigmentation, has been well documented. ^5-7 There are various dermatologic conditions that also occur with higher frequency and manifest uniquely in people with darker, more pigmented skin, ^7-9 and dermatologists, along with primary care physicians, should feel prepared to recognize and address them.

Extensive evidence also indicates that there are unique aspects to consider while managing certain skin diseases in patients with skin of color.^8,10,11 Consequently, as noted on the Skin of Color Society (SOCS) website, “[a]n increase in the body of dermatological literature concerning skin of color as well as the advancement of both basic science and clinical investigational research is necessary to meet the needs of the expanding skin of color population.”² In the meantime, current knowledge regarding cutaneous conditions that diversely or disproportionately affect skin of color should be actively disseminated to physicians in training. Although patients with skin of color should always have access to comprehensive care and knowledgeable practitioners, the current changes in national and regional demographics further underscore the need for a more thorough understanding of skin of color with regard to disease pathogenesis, diagnosis, and treatment.

Several studies have found that medical students in the United States are minimally exposed to dermatology in general compared to other clinical specialties,^12-14 which can easily lead to the underrecognition of disorders that may uniquely or disproportionately affect individuals with pigmented skin. Recent data showed that medical schools typically required fewer than 10 hours of dermatology instruction,¹² and on average, dermatologic training made up less than 1% of a medical student’s undergraduate medical education.^13,15,16 Consequently, less than 40% of primary care residents felt that their medical school curriculum adequately prepared them to manage common skin conditions.¹⁴ Although not all physicians should be expected to fully grasp the complexities of skin of color and its diagnostic and therapeutic implications, both practicing and training dermatologists have acknowledged a lack of exposure to skin of color. In one study, approximately 47% of dermatologists and dermatology residents reported that their medical training (medical school and/or residency) was inadequate in training them on skin conditions in Black patients. Furthermore, many who felt their training was lacking in skin of color identified the need for greater exposure to Black patients and training materials.¹⁵ The absence of comprehensive medical education regarding skin of color ultimately can be a disadvantage for both practitioners and patients, resulting in poorer outcomes. Furthermore, underrepresentation of skin of color may persist beyond undergraduate and graduate medical education. There also is evidence to suggest that noninclusion of skin of color pervades foundational dermatologic educational resources, including commonly used textbooks as well as continuing medical education disseminated at national conferences and meetings.¹⁷ Taken together, these findings highlight the need for more diverse and representative exposure to skin of color throughout medical training, which begins with a diverse inclusive undergraduate medical education in dermatology.

The objective of this study was to determine if the preclinical dermatology curriculum at 3 US medical schools provided adequate representation of skin of color patients in their didactic presentation slides.

Methods

Participants—Three US medical schools, a blend of private and public medical schools located across different geographic boundaries, agreed to participate in the study. All 3 institutions were current members of the American Medical Association (AMA) Accelerating Change in Medical Education consortium, whose primary goal is to create the medical school of the future and transform physician training.¹⁸ All 32 member institutions of the AMA consortium were contacted to request their participation in the study. As part of the consortium, these institutions have vowed to collectively work to develop and share the best models for educational advancement to improve care for patients, populations, and communities¹⁸ and would expectedly provide a more racially and ethnically inclusive curriculum than an institution not accountable to a group dedicated to identifying the best ways to deliver care for increasingly diverse communities.

Data Collection—Lectures were included if they were presented during dermatology preclinical courses in the 2015 to 2016 academic year. An uninvolved third party removed the names and identities of instructors to preserve anonymity. Two independent coders from different institutions extracted the data—lecture title, total number of clinical and histologic images, and number of skin of color images—from each of the anonymized lectures using a standardized coding form. We documented differences in skin of color noted in lectures and the disease context for the discussed differences, such as variations in clinical presentation, disease process, epidemiology/risk, and treatment between different skin phenotypes or ethnic groups. Photographs in which the coders were unable to differentiate whether the patient had skin of color were designated as indeterminate or unclear. Photographs appearing to represent Fitzpatrick skin types IV, V, and VI¹⁹ were categorically designated as skin of color, and those appearing to represent Fitzpatrick skin types I and II were described as not skin of color; however, images appearing to represent Fitzpatrick skin type III often were classified as not skin of color or indeterminate and occasionally skin of color. The Figure shows examples of images classified as skin of color, indeterminate, and not skin of color. Photographs often were classified as indeterminate due to poor lighting, close-up view photographs, or highlighted pathology obscuring the surrounding skin. We excluded duplicate photographs and histologic images from the analyses.

We also reviewed 19 conditions previously highlighted by the SOCS as areas of importance to skin of color patients.²⁰ The coders tracked how many of these conditions were noted in each lecture. Duplicate discussion of these conditions was not included in the analyses. Any discrepancies between coders were resolved through additional slide review and discussion. The final coded data with the agreed upon changes were used for statistical analyses. Recent national demographic data from the US Census Bureau in 2019 describe approximately 39.9% of the population as belonging to racial/ethnic groups other than non-Hispanic/Latinx White.²¹ Consequently, the standard for adequate representation for skin of color photographs was set at 35% for the purpose of this study.

Across all 3 institutions included in the study, the proportion of the total number of clinical photographs showing skin of color was 16% (290/1812). Eight percent of the total photographs (145/1812) were noted to be indeterminate (Table). For institution 1, 23.6% of photographs (155/658) showed skin of color, and 12.6% (83/658) were indeterminate. For institution 2, 13.1% (76/578) showed skin of color and 7.8% (45/578) were indeterminate. For institution 3, 10.2% (59/576) showed skin of color and 3% (17/576) were indeterminate.

Institutions 1, 2, and 3 had 18, 8, and 17 total dermatology lectures, respectively. Of the 19 conditions designated as areas of importance to skin of color patients by the SOCS, 16 (84.2%) were discussed by institution 1, 11 (57.9%) by institution 2, and 9 (47.4%) by institution 3 (eTable 1). Institution 3 did not include photographs of skin of color patients in its acne, psoriasis, or cutaneous malignancy lectures. Institution 1 also did not include any skin of color patients in its malignancy lecture. Lectures that focused on pigmentary disorders, atopic dermatitis, infectious conditions, and benign cutaneous neoplasms were more likely to display photographs of skin of color patients; for example, lectures that discussed infectious conditions, such as superficial mycoses, herpes viruses, human papillomavirus, syphilis, and atypical mycobacterial infections, were consistently among those with higher proportions of photographs of skin of color patients.

Throughout the entire preclinical dermatology course at all 3 institutions, of 2945 lecture slides, only 24 (0.8%) unique differences were noted between skin color and non–skin of color patients, with 10 total differences noted by institution 1, 6 by institution 2, and 8 by institution 3 (Table). The majority of these differences (19/24) were related to epidemiologic differences in prevalence among varying racial/ethnic groups, with only 5 instances highlighting differences in clinical presentation. There was only a single instance that elaborated on the underlying pathophysiologic mechanisms of the discussed difference. Of all 24 unique differences discussed, 8 were related to skin cancer, 3 were related to dermatitis, and 2 were related to the difference in manifestation of erythema in patients with darker skin (eTable 2).

Comment

The results of this study demonstrated that skin of color is underrepresented in the preclinical dermatology curriculum at these 3 institutions. Although only 16% of all included clinical photographs were of skin of color, individuals with skin of color will soon represent more than half of the total US population within the next 2 decades.¹ To increase representation of skin of color patients, teaching faculty should consciously and deliberately include more photographs of skin of color patients for a wider variety of common conditions, including atopic dermatitis and psoriasis, in addition to those that tend to disparately affect skin of color patients, such as pseudofolliculitis barbae or melasma. Furthermore, they also can incorporate more detailed discussions about important differences seen in skin of color patients.

More Skin of Color Photographs in Psoriasis Lectures—At institution 3, there were no skin of color patients included in the psoriasis lecture, even though there is considerable data in the literature indicating notable differences in the clinical presentation, quality-of-life impact, and treatment of psoriasis in skin of color patients.^11,22 There are multiple nuances in psoriasis manifestation in patients with skin of color, including less-conspicuous erythema in darker skin, higher degrees of dyspigmentation, and greater body surface area involvement. For Black patients with scalp psoriasis, the impact of hair texture, styling practices, and washing frequency are additional considerations that may impact disease severity and selection of topical therapy.¹¹ The lack of inclusion of any skin of color patients in the psoriasis lecture at one institution further underscores the pressing need to prioritize communities of color in medical education.

More Skin of Color Photographs in Cutaneous Malignancy Lectures—Similarly, while a lecturer at institution 2 noted that acral lentiginous melanoma accounts for a considerable proportion of melanoma among skin of color patients,²³ there was no mention of how melanoma generally is substantially more deadly in this population, potentially due to decreased awareness and inconsistent screening.²⁴ Furthermore, at institutions 1 and 3, there were no photographs or discussion of skin of color patients during the cutaneous malignancy lectures. Evidence shows that more emphasis is needed for melanoma screening and awareness in skin of color populations to improve survival outcomes,²⁴ and this begins with educating not only future dermatologists but all future physicians as well. The failure to include photographs of skin of color patients in discussions or lectures regarding cutaneous malignancies may serve to further perpetuate the harmful misperception that individuals with skin of color are unaffected by skin cancer.^25,26

Analysis of Skin of Color Photographs in Infectious Disease Lectures—In addition, lectures discussing infectious etiologies were among those with the highest proportion of skin of color photographs. This relatively disproportionate representation of skin of color compared to the other lectures may contribute to the development of harmful stereotypes or the stigmatization of skin of color patients. Although skin of color should continue to be represented in similar lectures, teaching faculty should remain mindful of the potential unintended impact from lectures including relatively disproportionate amounts of skin of color, particularly when other lectures may have sparse to absent representation of skin of color.

More Photographs Available for Education—Overall, our findings may help to inform changes to preclinical dermatology medical education at other institutions to create more inclusive and representative curricula for skin of color patients. The ability of instructors to provide visual representation of various dermatologic conditions may be limited by the photographs available in certain textbooks with few examples of patients with skin of color; however, concerns regarding the lack of skin of color representation in dermatology training is not a novel discussion.¹⁷ Although it is the responsibility of all dermatologists to advocate for the inclusion of skin of color, many dermatologists of color have been leading the way in this movement for decades, publishing several textbooks to document various skin conditions in those with darker skin types and discuss unique considerations for patients with skin of color.^27-29 Images from these textbooks can be utilized by programs to increase representation of skin of color in dermatology training. There also are multiple expanding online dermatologic databases, such as VisualDx, with an increasing focus on skin of color patients, some of which allow users to filter images by degree of skin pigmentation.³⁰ Moreover, instructors also can work to diversify their curricula by highlighting more of the SOCS conditions of importance to skin of color patients, which have since been renamed and highlighted on the Patient Dermatology Education section of the SOCS website.²⁰ These conditions, while not completely comprehensive, provide a useful starting point for medical educators to reevaluate for potential areas of improvement and inclusion.

There are several potential strategies that can be used to better represent skin of color in dermatologic preclinical medical education, including increasing awareness, especially among dermatology teaching faculty, of existing disparities in the representation of skin of color in the preclinical curricula. Additionally, all dermatology teaching materials could be reviewed at the department level prior to being disseminated to medical students to assess for instances in which skin of color could be prioritized for discussion or varying disease presentations in skin of color could be demonstrated. Finally, teaching faculty may consider photographing more clinical images of their skin of color patients to further develop a catalog of diverse images that can be used to teach students.

Study Limitations—Our study was unable to account for verbal discussion of skin of color not otherwise denoted or captured in lecture slides. Additional limitations include the utilization of Fitzpatrick skin types to describe and differentiate varying skin tones, as the Fitzpatrick scale originally was developed as a method to describe an individual’s response to UV exposure.¹⁹ The inability to further delineate the representation of darker skin types, such as those that may be classified as Fitzpatrick skin types V or VI,¹⁹ compared to those with lighter skin of color also was a limiting factor. This study was unable to assess for discussion of other common conditions affecting skin of color patients that were not listed as one of the priority conditions by SOCS. Photographs that were designated as indeterminate were difficult to elucidate as skin of color; however, it is possible that instructors may have verbally described these images as skin of color during lectures. Nonetheless, it may be beneficial for learners if teaching faculty were to clearly label instances where skin of color patients are shown or when notable differences are present.

Future studies would benefit from the inclusion of audio data from lectures, syllabi, and small group teaching materials from preclinical courses to more accurately assess representation of skin of color in dermatology training. Additionally, future studies also may expand to include images from lectures of overlapping clinical specialties, particularly infectious disease and rheumatology, to provide a broader assessment of skin of color exposure. Furthermore, repeat assessment may be beneficial to assess the longitudinal effectiveness of curricular changes at the institutions included in this study, comparing older lectures to more recent, updated lectures. This study also may be replicated at other medical schools to allow for wider comparison of curricula.

Acknowledgment—The authors wish to thank the institutions that offered and agreed to participate in this study with the hopes of improving medical education.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

One of the most commonly used organic acids used on the skin, lactic acid, has been used for over 3 decades. Originally derived from milk or plant-derived sugars, this gentle exfoliating acid can be used in peels, serums, masks, and toners, and has the additional benefit of hydrating the skin. Lactic acid is formulated in concentrations from 2% to 50%; however, because of its large molecular size, it doesn’t penetrate the deeper layers of the dermis to the same extent as the other alpha-hydroxy acids (AHAs), such as glycolic acid. Thus, it is one of the gentler exfoliants and one that can be used in sensitive skin or darker skin types.

Similar to other AHAs, lactic acid is used topically to treat hyperpigmentation, textural abnormalities, acne scars, enlarged pores, and acne. Despite its mild peeling effects, lactic acid is best used to treat xerotic skin because of its function as a humectant, drawing moisture into the stratum corneum. Similar to the other AHAs, lactic acid has also been shown to decrease melanogenesis and is a gentle treatment for skin hyperpigmentation, particularly in skin of color. Side effects include peeling, stinging, erythema, photosensitivity, and hyperpigmentation when improperly used.

Very little clinical research has been reported in the last 20 years as to the uses and benefits of lactic acid in skincare. In my clinical experience, daily use of lactic acid is more effective and has more long-term benefits for hydration and rejuvenation of the skin than the other AHAs. Concentrations of 10%-15% used daily on the skin as a mild exfoliant and humectant have shown to improve texture, decrease pigmentation and improve fine lines – without thinning of the skin seen with the deeper dermal penetrating acids.

Confusion in the market has also risen as many over-the-counter brands have included ammonium lactate in their portfolio of moisturizers. Ammonium lactate is a combination of ammonium hydroxide and lactic acid, or the salt of lactic acid. A comparative study evaluating the difference between 5% lactic acid and 12% ammonium lactate for the treatment of xerosis showed that ammonium lactate was significantly more effective at reducing xerosis. It is widely used in the treatment of keratosis pilaris, calluses, xerosis, and ichthyosis.

Widespread use of lactic acid has not gotten as much glory as that of glycolic acid. However, in clinical practice, its functions are more widespread. It is a much safer acid to use, and its added benefit of increasing hydration of the skin is crucial in its long-term use for both photoaging and the prevention of wrinkles. With any acid, the exfoliating properties must be treated with adequate hydration and barrier repair.

The intrinsic moisturizing effect of lactic acid makes it a much more well-rounded acid and that can be used for longer periods of time in a broader spectrum of patients.

Dr. Lily Talakoub and Dr. Naissan O. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at dermnews@mdedge.com. They had no relevant disclosures.

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (Figure, C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹

Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶ 

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (Figure, C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹

Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶ 

Photographs courtesy of Richard P. Usatine, MD.

THE COMPARISON

A A 27-year-old Hispanic woman with comedonal and inflammatory acne. Erythema is prominent around the inflammatory lesions. Note the pustule on the cheek surrounded by pink color.

B A teenaged Black boy with acne papules and pustules on the face. There are comedones, hyperpigmented macules, and pustules on the cheek.

C A teenaged Black girl with pomade acne. The patient used various hair care products, which obstructed the pilosebaceous units on the forehead.

Epidemiology

Acne is a leading dermatologic condition in individuals with skin of color in the United States.¹

Key clinical features in people with darker skin tones include:

• erythematous or hyperpigmented papules or comedones
• hyperpigmented macules and postinflammatory hyperpigmentation (PIH)
• increased risk for keloidal scars.²

Worth noting

• Patients with darker skin tones may be more concerned with the dark marks (also referred to as scars or manchas in Spanish) than the acne itself. This PIH may be viewed by patients as the major problem.
• Acne medications such as azelaic acid and some retinoids (when applied appropriately) can treat both acne and PIH.³
• Irritation from topical acne medications, including retinoid dermatitis, may lead to more PIH. Using noncomedogenic moisturizers and applying medication appropriately (ie, a pea-sized amount of topical retinoid per application) may help limit irritation.^4,5
• One type of acne seen more commonly, although not exclusively, in Black patients is pomade acne, which principally appears on the forehead and is associated with use of hair care and styling products (Figure, C).

Health disparity highlight

Disparities in access to health care exist for those with dermatologic concerns. According to one study, African American (28.5%) and Hispanic patients (23.9%) were less likely to be seen by a dermatologist solely for the diagnosis of a dermatologic condition compared to Asian and Pacific Islander patients (36.7%) or White patients (43.2%).¹

Noting that isotretinoin is the most potent systemic therapy for severe cystic acne vulgaris, Bell et al⁶ reported that Black patients had lower odds of receiving isotretinoin compared to White patients. Hispanic patients had lower odds of receiving a topical retinoid, tretinoin, than non-Hispanic patients.⁶ 

An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.^1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.⁴ In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.⁵ The focus of this column will be the dermatologic potential of vetiver.

Naomi Morris/EyeEm/EyeEm

Chemical constituents

Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. ³

In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).⁶

Antimicrobial activity

In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.⁷

Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.⁸In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.²

In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.⁹

Antiacne activity

In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.¹⁰ This usage points to the potential of vetiver use as an antiacne ingredient.
 

Safety

The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.¹1
 

Conclusion

Vetiver is an important ingredient in modern perfumery. It also has potential to impart benefits to the skin in topical formulations. Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.

2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.

3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.

4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.

5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.

6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.

7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.

8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.

9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.

10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].

11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.

An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.^1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.⁴ In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.⁵ The focus of this column will be the dermatologic potential of vetiver.

Naomi Morris/EyeEm/EyeEm

Chemical constituents

Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. ³

In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).⁶

Antimicrobial activity

In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.⁷

Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.⁸In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.²

In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.⁹

Antiacne activity

In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.¹⁰ This usage points to the potential of vetiver use as an antiacne ingredient.
 

Safety

The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.¹1
 

Conclusion

Vetiver is an important ingredient in modern perfumery. It also has potential to impart benefits to the skin in topical formulations. Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.

2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.

3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.

4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.

5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.

6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.

7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.

8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.

9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.

10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].

11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.

An important ingredient in the contemporary perfume and cosmetics industries, vetiver, is the only grass cultivated throughout the world to retain its essential oil, which contains sesquiterpene alcohols and hydrocarbons.^1-3 Field and glasshouse studies have revealed that vetiver grass can tolerate extreme variations in climate well, including protracted drought, floods, submergence, temperature, and soils high in acidity, alkalinity, and various heavy metals. Its heartiness may explain its continuing or even increasing use in fragrances and other products pertinent to skin health as humanity strives to adapt to climate change.⁴ In a 2017 review of various commercial essential oils as antimicrobial therapy for cutaneous disorders, Orchard and van Vuuren identified vetiver as warranting particular attention for its capacity to confer broad benefits to the skin in addressing acne, cuts, eczema, oiliness, sores, wounds, and aging skin.⁵ The focus of this column will be the dermatologic potential of vetiver.

Naomi Morris/EyeEm/EyeEm

Chemical constituents

Vetiver is thought to be one of the most complex of the essential oils owing to the hundreds of sesquiterpene derivatives with large structural diversity that contribute to its composition. ³

In a 2012 analysis of the components of South Indian vetiver oils, Mallavarapu et al. found an abundance of sesquiterpenes and oxygenated sesquiterpenes with cedrane, bisabolane, eudesmane, eremophilane, and zizaane skeletons. The primary constituents identified in the four oils evaluated included eudesma-4,6-diene (delta-selinene) + beta-vetispirene (3.9%-6.1%), beta-vetivenene (0.9%-9.4%), 13-nor-trans-eudesma-4(15),7-dien-11-one + amorph-4-en-10-ol (5.0%-6.4%), trans-eudesma-4(15),7-dien-12-ol (vetiselinenol) + (E)-opposita-4(15),7(11)-dien-12-ol (3.7%-5.9%), eremophila-1 (10),11-dien-2alpha-ol (nootkatol) + ziza-6(13)-en-12-ol (khusimol) (16.1%-19.2%), and eremophila-1(10),7(11)-dien-2alpha-ol (isonootkatol) + (E)-eremophila-1(10),7(11)-12-ol (isovalencenol) (5.6%-6.9%).⁶

Antimicrobial activity

In 2012, Saikia et al. assessed the antimycobacterial activity of Vetiveria zizanioides against Mycobacterium tuberculosis H(37)Rv and H(37)Ra strains. Their results showed that ethanolic extracts and hexane fractions displayed robust antimycobacterial properties, buttressing the traditional medical uses of the plant, as well as consideration of this agent as a modern antituberculosis agent.⁷

Two years later, Dos Santos et al. showed that Vetiveria zizanioides roots grown in Brazil exhibited notable antimicrobial effects against various pathogenic organisms.⁸In 2017, Burger et al. showed that vetiver essential oil primarily contributes its scent to cosmetic formulations but also displayed antimicrobial activity against Gram-positive bacterial strains, as well as one strain of Candida glabrata. They suggest that vetiver should be considered for its antimicrobial capacity as an added bonus to cosmetic formulations.²

In a 2018 study to ascertain the antimicrobial activity of 247 essential oil combinations against five reference strains of wound pathogens, Orchard et al. found that 26 combinations exhibited extensive antimicrobial activity. Sandalwood and vetiver were found to contribute most to antimicrobial function when used in combination. The investigators concluded that such combinations warrant consideration for wound therapy.⁹

Antiacne activity

In 2018, Orchard et al. conducted another study of the efficacy of commercial essential oil combinations against the two pathogens responsible for acne, Propionibacterium acnes and Staphlyococcus epidermidis. They investigated 408 combinations, of which 167 exhibited notable antimicrobial activity. They observed that the combination with the lowest minimum inhibitory concentration value against P. acnes and S. epidermidis was vetiver and cinnamon bark.¹⁰ This usage points to the potential of vetiver use as an antiacne ingredient.
 

Safety

The Scientific Committee on Consumer Safety (SCCS) offered a final opinion on the safety of the fragrance ingredient acetylated vetiver oil in 2019, declaring its use with 1% alpha-tocopherol in cosmetic leave-on and rinse-off products safe at proposed concentration levels. They noted that acetylated vetiver oil has been used for several years without provoking contact allergies.¹1
 

Conclusion

Vetiver is an important ingredient in modern perfumery. It also has potential to impart benefits to the skin in topical formulations. Much more research is necessary to determine just what kind of a role this perfumery powerhouse can play in dermatology.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Del Giudice L et al. Environ Microbiol. 2008 Oct;10(10):2824-41.

2. Burger P et al. Medicines (Basel). 2017 Jun 16;4(2):41.

3. Belhassen E et al. Chem Biodivers. 2014 Nov;11(11):1821–42.

4. Danh LT et al. Int J Phytoremediation. 2009 Oct-Dec;11(8):664–91.

5. Orchard A and van Vuuren S. Evid Based Complement Alternat Med. 2017;2017:4517971.

6. Mallavarapu GR et al. Nat Prod Commun. 2012 Feb;7(2):223–5.

7. Saikia D et al. Complement Ther Med. 2012 Dec;20(6):434–6.

8. Dos Santos DS et al. Acta Pharm. 2014 Dec;64(4):495-501.

9. Orchard A et al. Chem Biodivers. 2018 Dec;15(12):e1800405.

10. Orchard A et al. Int J Cosmet Sci. 2018 Mar 24. [Epub ahead of print].

11. SCCS members & External experts. Regul Toxicol Pharmacol. 2019 Oct;107:104389.

Adult women with acne describe significant impacts on their lived experience of acne, including concerns about appearance, mental and emotional health consequences, and disruption to their personal and professional lives, results from a qualitative study demonstrated.

“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”

For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.

The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).

More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.

In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.

“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”

In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”

Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”

In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”

A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”

For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”

This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.

dbrunk@mdedge.com

Adult women with acne describe significant impacts on their lived experience of acne, including concerns about appearance, mental and emotional health consequences, and disruption to their personal and professional lives, results from a qualitative study demonstrated.

“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”

For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.

The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).

More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.

In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.

“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”

In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”

Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”

In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”

A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”

For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”

This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.

dbrunk@mdedge.com

Adult women with acne describe significant impacts on their lived experience of acne, including concerns about appearance, mental and emotional health consequences, and disruption to their personal and professional lives, results from a qualitative study demonstrated.

“Nearly 50% of women experience acne in their 20s, and 35% experience acne in their 30s,” the study’s corresponding author, John S. Barbieri, MD, MBA, formerly of the department of dermatology at the University of Pennsylvania, Philadelphia, told this news organization. “While several qualitative studies have examined acne in adolescence, the lived experience of adult female acne has not been explored in detail and prior studies have included relatively few patients. As a result, we conducted a series of semistructured interviews among adult women with acne to examine the lived experience of adult acne and its treatment.”

For the study, published online July 28, 2021, in JAMA Dermatology, Dr. Barbieri and colleagues conducted voluntary, confidential phone interviews with 50 women aged between 18 and 40 years with moderate to severe acne who were recruited from the University of Pennsylvania Health System and from a private dermatology clinic in Cincinnati. They used free listing and open-ended, semistructured interviews to elicit opinions from the women on how acne affected their lives; their experience with acne treatments, dermatologists, and health care systems; as well as their views on treatment success.

The mean age of the participants was 28 years and 48% were white (10% were Black, 8% were Asian, 4% were more than one race, and the rest abstained from answering this question; 10% said they were Hispanic).

More than three-quarters (78%) reported prior treatment with topical retinoids, followed by spironolactone (70%), topical antibiotics (43%), combined oral contraceptives (43%), and isotretinoin (41%). During the free-listing part of interviews, where the women reported the first words that came to their mind when asked about success of treatment and adverse effects, the most important terms expressed related to treatment success were clear skin, no scarring, and no acne. The most important terms related to treatment adverse effects were dryness, redness, and burning.

In the semistructured interview portion of the study, the main themes expressed were acne-related concerns about appearance, including feeling less confident at work; mental and emotional health, including feelings of depression, anxiety, depression, and low self-worth during acne breakouts; and everyday life impact, including the notion that acne affected how other people perceived them. The other main themes included successful treatment, with clear skin and having a manageable number of lesions being desirable outcomes; and interactions with health care, including varied experiences with dermatologists. The researchers observed that most participants did not think oral antibiotics were appropriate treatments for their acne, specifically because of limited long-term effectiveness.

“Many patients described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne,” the authors wrote. “In contrast, those who thought their dermatologist listened to their concerns and individualized their treatment plan reported higher levels of satisfaction.”

In an interview, Dr. Barbieri, who is now with the department of dermatology at Brigham and Women’s Hospital, Boston, said that he was surprised by how many patients expressed interest in nonantibiotic treatments for acne, “given that oral antibiotics are by far the most commonly prescribed systemic treatment for acne.”

Moreover, he added, “although I have experienced many patients being hesitant about isotretinoin, I was surprised by how strong patients’ concerns were about isotretinoin side effects. Unfortunately, there are many misconceptions about isotretinoin that limit use of this treatment that can be highly effective and safe for the appropriate patient.”

In an accompanying editorial, dermatologists Diane M. Thiboutot, MD and Andrea L. Zaenglein, MD, with Penn State University, Hershey, and Alison M. Layton, MB, ChB, with the Harrogate Foundation Trust, Harrogate, North Yorkshire, England, wrote that the findings from the study “resonate with those recently reported in several international studies that examine the impacts of acne, how patients assess treatment success, and what is important to measure from a patient and health care professional perspective in a clinical trial for acne.”

A large systematic review on the impact of acne on patients, conducted by the Acne Core Outcomes Research Network (ACORN), found that “appearance-related concerns and negative psychosocial effects were found to be a major impact of acne,” they noted. “Surprisingly, only 22 of the 473 studies identified in this review included qualitative data gathered from patient interviews. It is encouraging to see the concordance between the concerns voiced by the participants in the current study and those identified from the literature review, wherein a variety of methods were used to assess acne impacts.”

For his part, Dr. Barbieri said that the study findings “justify the importance of having a discussion with patients about their unique lived experience of acne and individualizing treatment to their specific needs. Patient reported outcome measures could be a useful adjunctive tool to capture these impacts on quality of life.”

This study was funded by grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Barbieri disclosed that he received partial salary support through a Pfizer Fellowship in Dermatology Patient Oriented Research grant to the Trustees of the University of Pennsylvania. Dr. Thiboutot reported receiving consultant fees from Galderma and Novartis outside the submitted work. Dr. Layton reported receiving unrestricted educational presentation, advisory board, and consultancy fees from Galderma Honoraria; unrestricted educational presentation and advisory board honoraria from Leo; advisory board honoraria from Novartis and Mylan; consultancy honoraria from Procter and Gamble and Meda; grants from Galderma; and consultancy and advisory board honoraria from Origimm outside the submitted work.

dbrunk@mdedge.com