Hair & Nails

Alopecia areata sends “hundreds of thousands” of patients to the doctor every year in the United States, and six in ten of those visits end with a corticosteroid prescription, investigators reported in the Journal of Drugs in Dermatology.

In contrast, “minoxidil appears either underreported or underutilized in this population of patients, which suggests the need to educate both dermatologists and patients on the potential usefulness of this medication in alopecia areata,” wrote Michael Farhangian and his associates at Wake Forest University in Winston-Salem, N.C.

Courtesy Wikimedia Commons/Abbassyma/Public Domain

About 2% of individuals develop alopecia areata during their lives, but there are no consensus guidelines for disease in the United States. To better understand treatment patterns here, the investigators analyzed data on about 2.6 outpatient visits for alopecia areata between 2001 and 2010. The data came from two national ambulatory health care surveys (J Drugs Dermatol. 2015;14[9]:1012-14).

Patients with alopecia areata most often sought care from dermatologists (85%), the researchers reported. Providers prescribed topical and injected corticosteroids far more often (61%) than other drugs, such as minoxidil (5.9%), topical tacrolimus (5.7%), topical retinoid (3.3%), oral steroids (1.8%), or anthralin (1.8%).

The British Association of Dermatologists recommends corticosteroids for localized alopecia areata, but long-term use can lead to skin atrophy, hypopigmentation, and telangiectasia, the researchers warned. “This risk may be increased in patients who are prescribed both topical and injected corticosteroids, as was observed in 9.9% of patients,” they added.

Frequencies of minoxidil and tacrolimus use were nearly identical even though tacrolimus has been found ineffectivein alopecia areata, according to the researchers.

“Patients may be hesitant to use minoxidil since it is only FDA-approved for androgenetic alopecia and not for alopecia areata,” they wrote. Minoxidil also is available over-the-counter, which could explain its scarcity in the dataset, they added.

Galderma Laboratories helped fund the work through an unrestricted educational grant. Mr. Farhangian declared no competing interests. Senior author Dr. Steven Feldman reported relationships with Galderma, Janssen, Taro, Abbott Labs, and a number of other pharmaceutical companies. Dr. Feldman also reported holding stock in Causa Research and Medical Quality Enhancement Corporation. Another coauthor reported relationships with several pharmaceutical companies.

Alopecia areata sends “hundreds of thousands” of patients to the doctor every year in the United States, and six in ten of those visits end with a corticosteroid prescription, investigators reported in the Journal of Drugs in Dermatology.

In contrast, “minoxidil appears either underreported or underutilized in this population of patients, which suggests the need to educate both dermatologists and patients on the potential usefulness of this medication in alopecia areata,” wrote Michael Farhangian and his associates at Wake Forest University in Winston-Salem, N.C.

Courtesy Wikimedia Commons/Abbassyma/Public Domain

About 2% of individuals develop alopecia areata during their lives, but there are no consensus guidelines for disease in the United States. To better understand treatment patterns here, the investigators analyzed data on about 2.6 outpatient visits for alopecia areata between 2001 and 2010. The data came from two national ambulatory health care surveys (J Drugs Dermatol. 2015;14[9]:1012-14).

Patients with alopecia areata most often sought care from dermatologists (85%), the researchers reported. Providers prescribed topical and injected corticosteroids far more often (61%) than other drugs, such as minoxidil (5.9%), topical tacrolimus (5.7%), topical retinoid (3.3%), oral steroids (1.8%), or anthralin (1.8%).

The British Association of Dermatologists recommends corticosteroids for localized alopecia areata, but long-term use can lead to skin atrophy, hypopigmentation, and telangiectasia, the researchers warned. “This risk may be increased in patients who are prescribed both topical and injected corticosteroids, as was observed in 9.9% of patients,” they added.

Frequencies of minoxidil and tacrolimus use were nearly identical even though tacrolimus has been found ineffectivein alopecia areata, according to the researchers.

“Patients may be hesitant to use minoxidil since it is only FDA-approved for androgenetic alopecia and not for alopecia areata,” they wrote. Minoxidil also is available over-the-counter, which could explain its scarcity in the dataset, they added.

Galderma Laboratories helped fund the work through an unrestricted educational grant. Mr. Farhangian declared no competing interests. Senior author Dr. Steven Feldman reported relationships with Galderma, Janssen, Taro, Abbott Labs, and a number of other pharmaceutical companies. Dr. Feldman also reported holding stock in Causa Research and Medical Quality Enhancement Corporation. Another coauthor reported relationships with several pharmaceutical companies.

Alopecia areata sends “hundreds of thousands” of patients to the doctor every year in the United States, and six in ten of those visits end with a corticosteroid prescription, investigators reported in the Journal of Drugs in Dermatology.

In contrast, “minoxidil appears either underreported or underutilized in this population of patients, which suggests the need to educate both dermatologists and patients on the potential usefulness of this medication in alopecia areata,” wrote Michael Farhangian and his associates at Wake Forest University in Winston-Salem, N.C.

Courtesy Wikimedia Commons/Abbassyma/Public Domain

About 2% of individuals develop alopecia areata during their lives, but there are no consensus guidelines for disease in the United States. To better understand treatment patterns here, the investigators analyzed data on about 2.6 outpatient visits for alopecia areata between 2001 and 2010. The data came from two national ambulatory health care surveys (J Drugs Dermatol. 2015;14[9]:1012-14).

Patients with alopecia areata most often sought care from dermatologists (85%), the researchers reported. Providers prescribed topical and injected corticosteroids far more often (61%) than other drugs, such as minoxidil (5.9%), topical tacrolimus (5.7%), topical retinoid (3.3%), oral steroids (1.8%), or anthralin (1.8%).

The British Association of Dermatologists recommends corticosteroids for localized alopecia areata, but long-term use can lead to skin atrophy, hypopigmentation, and telangiectasia, the researchers warned. “This risk may be increased in patients who are prescribed both topical and injected corticosteroids, as was observed in 9.9% of patients,” they added.

Frequencies of minoxidil and tacrolimus use were nearly identical even though tacrolimus has been found ineffectivein alopecia areata, according to the researchers.

“Patients may be hesitant to use minoxidil since it is only FDA-approved for androgenetic alopecia and not for alopecia areata,” they wrote. Minoxidil also is available over-the-counter, which could explain its scarcity in the dataset, they added.

Galderma Laboratories helped fund the work through an unrestricted educational grant. Mr. Farhangian declared no competing interests. Senior author Dr. Steven Feldman reported relationships with Galderma, Janssen, Taro, Abbott Labs, and a number of other pharmaceutical companies. Dr. Feldman also reported holding stock in Causa Research and Medical Quality Enhancement Corporation. Another coauthor reported relationships with several pharmaceutical companies.

Onychomycosis is the most common nail disease 
in adults, representing up to 50% of all nail disorders, and is nearly always associated with tinea pedis.^1,2 Moreover, toenail onychomycosis frequently involves several nails3 and can be more challenging to treat because of the slow growth rate of nails and the difficult delivery of antifungal agents to the nail bed.^3,4

The most prevalent predisposing risk factor for developing onychomycosis is advanced age, with a reported prevalence of 18.2% in patients aged 60 to 79 years compared to 0.7% in patients younger than 19 years.² Men are up to 3 times more likely to develop onychomycosis than women, though the reasons for this gender difference are less clear.^2,5 It has been hypothesized that occupational factors may play a role,² with increased use of occlusive footwear and more frequent nail injuries contributing to a higher incidence of onychomycosis in males.⁶

Differences in hormone levels associated with gender also may result in different capacities to inhibit the growth of dermatophytes.² The risk for developing onychomycosis increases with age at a similar rate in both genders.⁷

Although onychomycosis is more common in men, the disease has been shown to have a greater impact on quality of life (QOL) in women. Studies have shown that onychomycosis was more likely to cause embarrassment in women than in men 
(83% vs 71%; N=258), and women with onychomycosis felt severely embarrassed more often than men (44% vs 26%; N=258).^8,9 Additionally, one study (N=43,593) showed statistically significant differences associated with gender among onychomycosis patients who reported experiencing pain 
(33.7% of women vs 26.7% of men; P<.001), discomfort in walking (43.1% vs 36.4%; P<.001), and embarrassment (28.8% vs 25.1%; P<.001).¹⁰ Severe cases of onychomycosis even appear to have a negative impact on patients’ intimate relationships, and lower self-esteem has been reported in female patients due to unsightly and contagious-looking nail plates.^11,12 Socks and stockings frequently may be damaged due to the constant friction from diseased nails that are sharp and dystrophic.^13,14 In one study, treatment satisfaction was related to improvement in nail condition; however, males tended to be more satisfied with the improvement than females. Females were significantly less satisfied than males based on QOL scores for discomfort in wearing shoes (61.5 vs 86.3; P=.001), restrictions in shoe options (59.0 vs 82.8; P=.001), and the need to conceal toenails (73.3 vs 89.3; P<.01).¹⁵

Numerous studies have assessed the effectiveness of antifungal drugs in treating onychomycosis; however, there are limited data available on the impact of gender on outcome variables. Results from 2 identical 52-week, prospective, multicenter, randomized, double-blind studies of a total of 1655 participants 
(age range, 18–70 years) assessing the safety and efficacy of efinaconazole topical solution 10% in the treatment of onychomycosis were reported in 2013.¹⁶ Here, a gender subgroup analysis for male and female participants with mild to moderate onychomycosis is presented.

Methods

Two 52-week, prospective, multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution 10% versus vehicle in 1655 participants aged 18 to 70 years with mild to moderate toenail onychomycosis. Participants who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1 ratio) to once-daily application of a blinded study drug on the toenails for 48 weeks, followed by a 4-week follow-up period.¹⁶

Efficacy Evaluation

The primary efficacy end point was complete cure, defined as 0% clinical involvement of target toenail and mycologic cure based on negative potassium hydroxide examination and negative fungal culture at week 52.¹⁶ Secondary and supportive efficacy end points included mycologic cure, treatment success (<10% clinical involvement of the target toenail), complete or almost complete cure (≤5% clinical involvement and mycologic cure), and change in QOL based on a self-administered QOL questionnaire. All secondary end points were assessed at week 52.¹⁶ All items in the QOL questionnaire were transferred to a 0 to 100 scale, with higher scores indicating better functioning.¹⁷

In both studies, treatment compliance was assessed through participant diaries that detailed all drug applications as well as the weight of returned product bottles. Participants were considered noncompliant if they missed more than 14 cumulative applications of the study drug in the 28 days leading up to the visit at week 48, if they missed more than 20% of the total number of expected study drug applications during the treatment period, and/or if they missed 28 or more consecutive applications of the study drug during the total treatment period.

Safety Evaluation

Safety assessments included monitoring and recording adverse events (AEs) until week 52.¹⁶

Results

The 2 studies included a total of 1275 (77.2%) male and 376 (22.8%) female participants with mild to moderate onychomycosis (intention-to-treat population). Pooled results are provided in this analysis.

At baseline, the mean area of target toenail involvement among male and female participants in the efinaconazole treatment group was 36.7% and 35.6%, respectively, compared to 36.4% and 37.9%, respectively, in the vehicle group. The mean number of affected nontarget toenails was 2.8 and 2.7 among male and female participants, respectively, in the efinaconazole group compared to 2.9 and 2.4, respectively, in the vehicle group (Table 1).

Female participants tended to be somewhat more compliant with treatment than male participants at study end. At week 52, 93.0% and 93.4% of female participants in the efinaconazole and vehicle groups, respectively, were considered compliant with treatment compared to 91.1% and 88.6% of male participants, respectively (Table 1).

Primary Efficacy End Point (Observed Case)

At 
week 52, 15.8% of male and 27.1% of female participants in the efinaconazole treatment group had a complete cure compared to 4.2% and 6.3%, respectively, of those in the vehicle group (both P<.001). Efinaconazole topical solution 10% was significantly more effective than vehicle from week 48 (P<.001 male and P=.004 female).

The differences in complete cure rates reported for male (15.8%) and female (27.1%) participants treated with efinaconazole topical solution 10% were significant at week 52 (P=.001)(Figure 1).

Figure 1. Proportion of male and female participants treated with once-daily application of efinaconazole topical solution 10% who achieved complete cure from weeks 12 to 52 (observed case; intention-to-treat population; pooled data).

Figure 2. Treatment success (defined as ≤10% clinical involvement of the target toenail) at week 52. Comparison of results with efinaconazole topical solution 10% and vehicle (observed case; intention-to-treat population; pooled data).

Secondary and Supportive Efficacy End Points (Observed Case)

At week 52, 53.7% of male participants and 64.8% of female participants in the efinaconazole group achieved mycologic cure 
compared to 14.8% and 22.5%, respectively, of those in the vehicle group (both P<.001). Mycologic cure in the efinaconazole group versus the vehicle group became statistically significant at week 12 in male participants (P=.002) and at week 24 in female participants (P<.001).

At week 52, more male and female participants in the efinaconazole group (24.9% and 36.8%, respectively) achieved complete or almost complete 
cure compared to those in the vehicle group (6.8% and 11.3%, respectively), and 43.5% and 59.1% of male and female participants, respectively, were considered treatment successes (≤10% clinical involvement of the target toenail) compared to 15.5% and 26.8%, respectively, in the vehicle group (all P<.001)(Figure 2).

Treatment satisfaction scores were higher among female participants. At week 52, the mean QOL assessment score among female participants in the efinaconazole group was 77.2 compared to 70.3 among male participants in the same group (43.0 and 41.2, respectively, in the vehicle group). All QOL assessment scores were lower (ie, worse) in female onychomycosis participants at baseline. Improvements in all QOL scores were much greater in female participants at week 52 (Table 2).

The total number of efinaconazole applications was similar among male and female participants (315.1 vs 316.7). The mean amount of efina-
conazole applied was greater in male participants 
(50.4 g vs 45.6 g), and overall compliance rates, though similar, were slightly higher in females compared to males (efinaconazole only)(93.0% 
vs 91.1%).

Safety

Overall, AE rates for efinaconazole were similar to those reported for vehicle (65.3% vs 59.8%).¹⁶ Slightly more female participants reported 1 or more AE than males (71.3% vs 63.5%). Adverse events were generally mild (50.0% in females; 53.7% in males) or moderate (46.7% in females; 41.8% in males) in severity, were not related to the study drug (89.9% in females; 93.1% in males), and resolved without sequelae. The rate of discontinuation from AEs was low (2.8% in females; 2.5% in males).

Comment

Efinaconazole topical solution 10% was significantly more effective than vehicle in both male and female participants with mild to moderate onychomycosis. It appears to be especially effective in female participants, with more than 27% of female participants achieving complete cure at week 52, and nearly 37% of female participants achieving complete or almost complete cure at week 52.

Mycologic cure is the only consistently defined efficacy parameter reported in toenail onychomycosis studies.¹⁸ It often is considered the main treatment goal, with complete cure occurring somewhat later as the nails grow out.¹⁹ Indeed, in this subgroup analysis the differences seen between the active and vehicle groups correlated well with the cure rates seen at week 52. Interestingly, significantly better mycologic cure rates (P=.002, active vs vehicle) were seen as early as week 12 in the male subgroup.

The current analysis suggests that male onychomycosis patients may be more difficult to treat, a finding noted by other investigators, though the reason is not clear.²⁰ It is known that the prevalence of onychomycosis is higher in males,^2,5 but data comparing cure rates by gender is lacking. It has been suggested that men more frequently undergo nail trauma and tend to seek help for more advanced disease.²⁰ Treatment compliance also may be an issue. In our study, mean nail involvement was similar among male and female participants treated with efinaconazole (36.7% and 35.6%, respectively). Treatment compliance 
was higher among females compared to males 
(93.0% vs 91.1%), with the lowest compliance rates seen in males in the vehicle group (where complete cure rates also were the lowest). The amount of study drug used was greater in males, possibly due to larger toenails, though toenail surface area was not measured. Although there is no evidence to suggest that male toenails grow quicker, as many factors can impact nail growth, they tend to be thicker. Patients with thick toenails may be less likely to achieve complete cure.²⁰ It also is possible that male toenails take longer to grow out fully, and they may require a longer treatment course. The 52-week duration of these studies may not have allowed for full regrowth of the nails, despite mycologic cure. Indeed, continued improvement in cure rates in onychomycosis patients with longer treatment courses have been noted by other investigators.²¹

The current analysis revealed much lower baseline QOL scores in female onychomycosis patients compared to male patients. Given that target nail involvement at baseline was similar across both groups, this finding may be indicative of greater concern about their condition among females, supporting other views that onychomycosis has a greater impact on QOL in female patients. Similar scores reported across genders at week 52 likely reflects the greater efficacy seen in females.

Conclusion

Based on this subgroup analysis, once-daily application of efinaconazole topical solution 10% may provide a useful option in the treatment of mild to moderate onychomycosis, particularly in female patients. The greater improvement in nail condition concomitantly among females translates to higher overall treatment satisfaction.

Acknowledgment—The author thanks Brian Bulley, MSc, of Inergy Limited, Lindfield, West Sussex, United Kingdom, for medical writing 
support. Valeant Pharmaceuticals North America, LLC, funded Inergy’s activities pertaining to 
the manuscript.

Onychomycosis is the most common nail disease 
in adults, representing up to 50% of all nail disorders, and is nearly always associated with tinea pedis.^1,2 Moreover, toenail onychomycosis frequently involves several nails3 and can be more challenging to treat because of the slow growth rate of nails and the difficult delivery of antifungal agents to the nail bed.^3,4

The most prevalent predisposing risk factor for developing onychomycosis is advanced age, with a reported prevalence of 18.2% in patients aged 60 to 79 years compared to 0.7% in patients younger than 19 years.² Men are up to 3 times more likely to develop onychomycosis than women, though the reasons for this gender difference are less clear.^2,5 It has been hypothesized that occupational factors may play a role,² with increased use of occlusive footwear and more frequent nail injuries contributing to a higher incidence of onychomycosis in males.⁶

Differences in hormone levels associated with gender also may result in different capacities to inhibit the growth of dermatophytes.² The risk for developing onychomycosis increases with age at a similar rate in both genders.⁷

Although onychomycosis is more common in men, the disease has been shown to have a greater impact on quality of life (QOL) in women. Studies have shown that onychomycosis was more likely to cause embarrassment in women than in men 
(83% vs 71%; N=258), and women with onychomycosis felt severely embarrassed more often than men (44% vs 26%; N=258).^8,9 Additionally, one study (N=43,593) showed statistically significant differences associated with gender among onychomycosis patients who reported experiencing pain 
(33.7% of women vs 26.7% of men; P<.001), discomfort in walking (43.1% vs 36.4%; P<.001), and embarrassment (28.8% vs 25.1%; P<.001).¹⁰ Severe cases of onychomycosis even appear to have a negative impact on patients’ intimate relationships, and lower self-esteem has been reported in female patients due to unsightly and contagious-looking nail plates.^11,12 Socks and stockings frequently may be damaged due to the constant friction from diseased nails that are sharp and dystrophic.^13,14 In one study, treatment satisfaction was related to improvement in nail condition; however, males tended to be more satisfied with the improvement than females. Females were significantly less satisfied than males based on QOL scores for discomfort in wearing shoes (61.5 vs 86.3; P=.001), restrictions in shoe options (59.0 vs 82.8; P=.001), and the need to conceal toenails (73.3 vs 89.3; P<.01).¹⁵

Numerous studies have assessed the effectiveness of antifungal drugs in treating onychomycosis; however, there are limited data available on the impact of gender on outcome variables. Results from 2 identical 52-week, prospective, multicenter, randomized, double-blind studies of a total of 1655 participants 
(age range, 18–70 years) assessing the safety and efficacy of efinaconazole topical solution 10% in the treatment of onychomycosis were reported in 2013.¹⁶ Here, a gender subgroup analysis for male and female participants with mild to moderate onychomycosis is presented.

Methods

Two 52-week, prospective, multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution 10% versus vehicle in 1655 participants aged 18 to 70 years with mild to moderate toenail onychomycosis. Participants who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1 ratio) to once-daily application of a blinded study drug on the toenails for 48 weeks, followed by a 4-week follow-up period.¹⁶

Efficacy Evaluation

The primary efficacy end point was complete cure, defined as 0% clinical involvement of target toenail and mycologic cure based on negative potassium hydroxide examination and negative fungal culture at week 52.¹⁶ Secondary and supportive efficacy end points included mycologic cure, treatment success (<10% clinical involvement of the target toenail), complete or almost complete cure (≤5% clinical involvement and mycologic cure), and change in QOL based on a self-administered QOL questionnaire. All secondary end points were assessed at week 52.¹⁶ All items in the QOL questionnaire were transferred to a 0 to 100 scale, with higher scores indicating better functioning.¹⁷

In both studies, treatment compliance was assessed through participant diaries that detailed all drug applications as well as the weight of returned product bottles. Participants were considered noncompliant if they missed more than 14 cumulative applications of the study drug in the 28 days leading up to the visit at week 48, if they missed more than 20% of the total number of expected study drug applications during the treatment period, and/or if they missed 28 or more consecutive applications of the study drug during the total treatment period.

Safety Evaluation

Safety assessments included monitoring and recording adverse events (AEs) until week 52.¹⁶

Results

The 2 studies included a total of 1275 (77.2%) male and 376 (22.8%) female participants with mild to moderate onychomycosis (intention-to-treat population). Pooled results are provided in this analysis.

At baseline, the mean area of target toenail involvement among male and female participants in the efinaconazole treatment group was 36.7% and 35.6%, respectively, compared to 36.4% and 37.9%, respectively, in the vehicle group. The mean number of affected nontarget toenails was 2.8 and 2.7 among male and female participants, respectively, in the efinaconazole group compared to 2.9 and 2.4, respectively, in the vehicle group (Table 1).

Female participants tended to be somewhat more compliant with treatment than male participants at study end. At week 52, 93.0% and 93.4% of female participants in the efinaconazole and vehicle groups, respectively, were considered compliant with treatment compared to 91.1% and 88.6% of male participants, respectively (Table 1).

Primary Efficacy End Point (Observed Case)

At 
week 52, 15.8% of male and 27.1% of female participants in the efinaconazole treatment group had a complete cure compared to 4.2% and 6.3%, respectively, of those in the vehicle group (both P<.001). Efinaconazole topical solution 10% was significantly more effective than vehicle from week 48 (P<.001 male and P=.004 female).

The differences in complete cure rates reported for male (15.8%) and female (27.1%) participants treated with efinaconazole topical solution 10% were significant at week 52 (P=.001)(Figure 1).

Figure 1. Proportion of male and female participants treated with once-daily application of efinaconazole topical solution 10% who achieved complete cure from weeks 12 to 52 (observed case; intention-to-treat population; pooled data).

Figure 2. Treatment success (defined as ≤10% clinical involvement of the target toenail) at week 52. Comparison of results with efinaconazole topical solution 10% and vehicle (observed case; intention-to-treat population; pooled data).

Secondary and Supportive Efficacy End Points (Observed Case)

At week 52, 53.7% of male participants and 64.8% of female participants in the efinaconazole group achieved mycologic cure 
compared to 14.8% and 22.5%, respectively, of those in the vehicle group (both P<.001). Mycologic cure in the efinaconazole group versus the vehicle group became statistically significant at week 12 in male participants (P=.002) and at week 24 in female participants (P<.001).

At week 52, more male and female participants in the efinaconazole group (24.9% and 36.8%, respectively) achieved complete or almost complete 
cure compared to those in the vehicle group (6.8% and 11.3%, respectively), and 43.5% and 59.1% of male and female participants, respectively, were considered treatment successes (≤10% clinical involvement of the target toenail) compared to 15.5% and 26.8%, respectively, in the vehicle group (all P<.001)(Figure 2).

Treatment satisfaction scores were higher among female participants. At week 52, the mean QOL assessment score among female participants in the efinaconazole group was 77.2 compared to 70.3 among male participants in the same group (43.0 and 41.2, respectively, in the vehicle group). All QOL assessment scores were lower (ie, worse) in female onychomycosis participants at baseline. Improvements in all QOL scores were much greater in female participants at week 52 (Table 2).

The total number of efinaconazole applications was similar among male and female participants (315.1 vs 316.7). The mean amount of efina-
conazole applied was greater in male participants 
(50.4 g vs 45.6 g), and overall compliance rates, though similar, were slightly higher in females compared to males (efinaconazole only)(93.0% 
vs 91.1%).

Safety

Overall, AE rates for efinaconazole were similar to those reported for vehicle (65.3% vs 59.8%).¹⁶ Slightly more female participants reported 1 or more AE than males (71.3% vs 63.5%). Adverse events were generally mild (50.0% in females; 53.7% in males) or moderate (46.7% in females; 41.8% in males) in severity, were not related to the study drug (89.9% in females; 93.1% in males), and resolved without sequelae. The rate of discontinuation from AEs was low (2.8% in females; 2.5% in males).

Comment

Efinaconazole topical solution 10% was significantly more effective than vehicle in both male and female participants with mild to moderate onychomycosis. It appears to be especially effective in female participants, with more than 27% of female participants achieving complete cure at week 52, and nearly 37% of female participants achieving complete or almost complete cure at week 52.

Mycologic cure is the only consistently defined efficacy parameter reported in toenail onychomycosis studies.¹⁸ It often is considered the main treatment goal, with complete cure occurring somewhat later as the nails grow out.¹⁹ Indeed, in this subgroup analysis the differences seen between the active and vehicle groups correlated well with the cure rates seen at week 52. Interestingly, significantly better mycologic cure rates (P=.002, active vs vehicle) were seen as early as week 12 in the male subgroup.

The current analysis suggests that male onychomycosis patients may be more difficult to treat, a finding noted by other investigators, though the reason is not clear.²⁰ It is known that the prevalence of onychomycosis is higher in males,^2,5 but data comparing cure rates by gender is lacking. It has been suggested that men more frequently undergo nail trauma and tend to seek help for more advanced disease.²⁰ Treatment compliance also may be an issue. In our study, mean nail involvement was similar among male and female participants treated with efinaconazole (36.7% and 35.6%, respectively). Treatment compliance 
was higher among females compared to males 
(93.0% vs 91.1%), with the lowest compliance rates seen in males in the vehicle group (where complete cure rates also were the lowest). The amount of study drug used was greater in males, possibly due to larger toenails, though toenail surface area was not measured. Although there is no evidence to suggest that male toenails grow quicker, as many factors can impact nail growth, they tend to be thicker. Patients with thick toenails may be less likely to achieve complete cure.²⁰ It also is possible that male toenails take longer to grow out fully, and they may require a longer treatment course. The 52-week duration of these studies may not have allowed for full regrowth of the nails, despite mycologic cure. Indeed, continued improvement in cure rates in onychomycosis patients with longer treatment courses have been noted by other investigators.²¹

The current analysis revealed much lower baseline QOL scores in female onychomycosis patients compared to male patients. Given that target nail involvement at baseline was similar across both groups, this finding may be indicative of greater concern about their condition among females, supporting other views that onychomycosis has a greater impact on QOL in female patients. Similar scores reported across genders at week 52 likely reflects the greater efficacy seen in females.

Conclusion

Based on this subgroup analysis, once-daily application of efinaconazole topical solution 10% may provide a useful option in the treatment of mild to moderate onychomycosis, particularly in female patients. The greater improvement in nail condition concomitantly among females translates to higher overall treatment satisfaction.

Acknowledgment—The author thanks Brian Bulley, MSc, of Inergy Limited, Lindfield, West Sussex, United Kingdom, for medical writing 
support. Valeant Pharmaceuticals North America, LLC, funded Inergy’s activities pertaining to 
the manuscript.

Onychomycosis is the most common nail disease 
in adults, representing up to 50% of all nail disorders, and is nearly always associated with tinea pedis.^1,2 Moreover, toenail onychomycosis frequently involves several nails3 and can be more challenging to treat because of the slow growth rate of nails and the difficult delivery of antifungal agents to the nail bed.^3,4

The most prevalent predisposing risk factor for developing onychomycosis is advanced age, with a reported prevalence of 18.2% in patients aged 60 to 79 years compared to 0.7% in patients younger than 19 years.² Men are up to 3 times more likely to develop onychomycosis than women, though the reasons for this gender difference are less clear.^2,5 It has been hypothesized that occupational factors may play a role,² with increased use of occlusive footwear and more frequent nail injuries contributing to a higher incidence of onychomycosis in males.⁶

Differences in hormone levels associated with gender also may result in different capacities to inhibit the growth of dermatophytes.² The risk for developing onychomycosis increases with age at a similar rate in both genders.⁷

Although onychomycosis is more common in men, the disease has been shown to have a greater impact on quality of life (QOL) in women. Studies have shown that onychomycosis was more likely to cause embarrassment in women than in men 
(83% vs 71%; N=258), and women with onychomycosis felt severely embarrassed more often than men (44% vs 26%; N=258).^8,9 Additionally, one study (N=43,593) showed statistically significant differences associated with gender among onychomycosis patients who reported experiencing pain 
(33.7% of women vs 26.7% of men; P<.001), discomfort in walking (43.1% vs 36.4%; P<.001), and embarrassment (28.8% vs 25.1%; P<.001).¹⁰ Severe cases of onychomycosis even appear to have a negative impact on patients’ intimate relationships, and lower self-esteem has been reported in female patients due to unsightly and contagious-looking nail plates.^11,12 Socks and stockings frequently may be damaged due to the constant friction from diseased nails that are sharp and dystrophic.^13,14 In one study, treatment satisfaction was related to improvement in nail condition; however, males tended to be more satisfied with the improvement than females. Females were significantly less satisfied than males based on QOL scores for discomfort in wearing shoes (61.5 vs 86.3; P=.001), restrictions in shoe options (59.0 vs 82.8; P=.001), and the need to conceal toenails (73.3 vs 89.3; P<.01).¹⁵

Numerous studies have assessed the effectiveness of antifungal drugs in treating onychomycosis; however, there are limited data available on the impact of gender on outcome variables. Results from 2 identical 52-week, prospective, multicenter, randomized, double-blind studies of a total of 1655 participants 
(age range, 18–70 years) assessing the safety and efficacy of efinaconazole topical solution 10% in the treatment of onychomycosis were reported in 2013.¹⁶ Here, a gender subgroup analysis for male and female participants with mild to moderate onychomycosis is presented.

Methods

Two 52-week, prospective, multicenter, randomized, double-blind, vehicle-controlled studies were designed to evaluate the efficacy, safety, and tolerability of efinaconazole topical solution 10% versus vehicle in 1655 participants aged 18 to 70 years with mild to moderate toenail onychomycosis. Participants who presented with 20% to 50% clinical involvement of the target toenail were randomized (3:1 ratio) to once-daily application of a blinded study drug on the toenails for 48 weeks, followed by a 4-week follow-up period.¹⁶

Efficacy Evaluation

The primary efficacy end point was complete cure, defined as 0% clinical involvement of target toenail and mycologic cure based on negative potassium hydroxide examination and negative fungal culture at week 52.¹⁶ Secondary and supportive efficacy end points included mycologic cure, treatment success (<10% clinical involvement of the target toenail), complete or almost complete cure (≤5% clinical involvement and mycologic cure), and change in QOL based on a self-administered QOL questionnaire. All secondary end points were assessed at week 52.¹⁶ All items in the QOL questionnaire were transferred to a 0 to 100 scale, with higher scores indicating better functioning.¹⁷

In both studies, treatment compliance was assessed through participant diaries that detailed all drug applications as well as the weight of returned product bottles. Participants were considered noncompliant if they missed more than 14 cumulative applications of the study drug in the 28 days leading up to the visit at week 48, if they missed more than 20% of the total number of expected study drug applications during the treatment period, and/or if they missed 28 or more consecutive applications of the study drug during the total treatment period.

Safety Evaluation

Safety assessments included monitoring and recording adverse events (AEs) until week 52.¹⁶

Results

The 2 studies included a total of 1275 (77.2%) male and 376 (22.8%) female participants with mild to moderate onychomycosis (intention-to-treat population). Pooled results are provided in this analysis.

At baseline, the mean area of target toenail involvement among male and female participants in the efinaconazole treatment group was 36.7% and 35.6%, respectively, compared to 36.4% and 37.9%, respectively, in the vehicle group. The mean number of affected nontarget toenails was 2.8 and 2.7 among male and female participants, respectively, in the efinaconazole group compared to 2.9 and 2.4, respectively, in the vehicle group (Table 1).

Female participants tended to be somewhat more compliant with treatment than male participants at study end. At week 52, 93.0% and 93.4% of female participants in the efinaconazole and vehicle groups, respectively, were considered compliant with treatment compared to 91.1% and 88.6% of male participants, respectively (Table 1).

Primary Efficacy End Point (Observed Case)

At 
week 52, 15.8% of male and 27.1% of female participants in the efinaconazole treatment group had a complete cure compared to 4.2% and 6.3%, respectively, of those in the vehicle group (both P<.001). Efinaconazole topical solution 10% was significantly more effective than vehicle from week 48 (P<.001 male and P=.004 female).

The differences in complete cure rates reported for male (15.8%) and female (27.1%) participants treated with efinaconazole topical solution 10% were significant at week 52 (P=.001)(Figure 1).

Figure 1. Proportion of male and female participants treated with once-daily application of efinaconazole topical solution 10% who achieved complete cure from weeks 12 to 52 (observed case; intention-to-treat population; pooled data).

Figure 2. Treatment success (defined as ≤10% clinical involvement of the target toenail) at week 52. Comparison of results with efinaconazole topical solution 10% and vehicle (observed case; intention-to-treat population; pooled data).

Secondary and Supportive Efficacy End Points (Observed Case)

At week 52, 53.7% of male participants and 64.8% of female participants in the efinaconazole group achieved mycologic cure 
compared to 14.8% and 22.5%, respectively, of those in the vehicle group (both P<.001). Mycologic cure in the efinaconazole group versus the vehicle group became statistically significant at week 12 in male participants (P=.002) and at week 24 in female participants (P<.001).

At week 52, more male and female participants in the efinaconazole group (24.9% and 36.8%, respectively) achieved complete or almost complete 
cure compared to those in the vehicle group (6.8% and 11.3%, respectively), and 43.5% and 59.1% of male and female participants, respectively, were considered treatment successes (≤10% clinical involvement of the target toenail) compared to 15.5% and 26.8%, respectively, in the vehicle group (all P<.001)(Figure 2).

Treatment satisfaction scores were higher among female participants. At week 52, the mean QOL assessment score among female participants in the efinaconazole group was 77.2 compared to 70.3 among male participants in the same group (43.0 and 41.2, respectively, in the vehicle group). All QOL assessment scores were lower (ie, worse) in female onychomycosis participants at baseline. Improvements in all QOL scores were much greater in female participants at week 52 (Table 2).

The total number of efinaconazole applications was similar among male and female participants (315.1 vs 316.7). The mean amount of efina-
conazole applied was greater in male participants 
(50.4 g vs 45.6 g), and overall compliance rates, though similar, were slightly higher in females compared to males (efinaconazole only)(93.0% 
vs 91.1%).

Safety

Overall, AE rates for efinaconazole were similar to those reported for vehicle (65.3% vs 59.8%).¹⁶ Slightly more female participants reported 1 or more AE than males (71.3% vs 63.5%). Adverse events were generally mild (50.0% in females; 53.7% in males) or moderate (46.7% in females; 41.8% in males) in severity, were not related to the study drug (89.9% in females; 93.1% in males), and resolved without sequelae. The rate of discontinuation from AEs was low (2.8% in females; 2.5% in males).

Comment

Efinaconazole topical solution 10% was significantly more effective than vehicle in both male and female participants with mild to moderate onychomycosis. It appears to be especially effective in female participants, with more than 27% of female participants achieving complete cure at week 52, and nearly 37% of female participants achieving complete or almost complete cure at week 52.

Mycologic cure is the only consistently defined efficacy parameter reported in toenail onychomycosis studies.¹⁸ It often is considered the main treatment goal, with complete cure occurring somewhat later as the nails grow out.¹⁹ Indeed, in this subgroup analysis the differences seen between the active and vehicle groups correlated well with the cure rates seen at week 52. Interestingly, significantly better mycologic cure rates (P=.002, active vs vehicle) were seen as early as week 12 in the male subgroup.

The current analysis suggests that male onychomycosis patients may be more difficult to treat, a finding noted by other investigators, though the reason is not clear.²⁰ It is known that the prevalence of onychomycosis is higher in males,^2,5 but data comparing cure rates by gender is lacking. It has been suggested that men more frequently undergo nail trauma and tend to seek help for more advanced disease.²⁰ Treatment compliance also may be an issue. In our study, mean nail involvement was similar among male and female participants treated with efinaconazole (36.7% and 35.6%, respectively). Treatment compliance 
was higher among females compared to males 
(93.0% vs 91.1%), with the lowest compliance rates seen in males in the vehicle group (where complete cure rates also were the lowest). The amount of study drug used was greater in males, possibly due to larger toenails, though toenail surface area was not measured. Although there is no evidence to suggest that male toenails grow quicker, as many factors can impact nail growth, they tend to be thicker. Patients with thick toenails may be less likely to achieve complete cure.²⁰ It also is possible that male toenails take longer to grow out fully, and they may require a longer treatment course. The 52-week duration of these studies may not have allowed for full regrowth of the nails, despite mycologic cure. Indeed, continued improvement in cure rates in onychomycosis patients with longer treatment courses have been noted by other investigators.²¹

The current analysis revealed much lower baseline QOL scores in female onychomycosis patients compared to male patients. Given that target nail involvement at baseline was similar across both groups, this finding may be indicative of greater concern about their condition among females, supporting other views that onychomycosis has a greater impact on QOL in female patients. Similar scores reported across genders at week 52 likely reflects the greater efficacy seen in females.

Conclusion

Based on this subgroup analysis, once-daily application of efinaconazole topical solution 10% may provide a useful option in the treatment of mild to moderate onychomycosis, particularly in female patients. The greater improvement in nail condition concomitantly among females translates to higher overall treatment satisfaction.

Acknowledgment—The author thanks Brian Bulley, MSc, of Inergy Limited, Lindfield, West Sussex, United Kingdom, for medical writing 
support. Valeant Pharmaceuticals North America, LLC, funded Inergy’s activities pertaining to 
the manuscript.

To improve patient care and outcomes, leading dermatologists offered their recommendations on the top OTC dandruff treatments. Consideration must be given to:

• Head & Shoulders Shampoo
  Procter & Gamble
  “OTC dandruff products are more for maintenance rather than active treatment, which is why many consumers and patients become frustrated with their use. I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

• Moroccanoil Treatment
  Moroccanoil
  “I think it’s great to actually put [this product] directly onto the scalp after shampooing to get any remaining scales off.”—Anthony M. Rossi, MD, New York, New York

• Neutrogena T/Gel Therapeutic Hair Care
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Neutrogena T/Sal Therapeutic Shampoo
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Nizoral A-D Ketoconazole Shampoo 1%
  McNeil-PPC, Inc
  “I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

Cutis invites readers to send us their recommendations. Eye creams, men’s shaving products, and products for babies will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to [email protected].

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on the top OTC dandruff treatments. Consideration must be given to:

• Head & Shoulders Shampoo
  Procter & Gamble
  “OTC dandruff products are more for maintenance rather than active treatment, which is why many consumers and patients become frustrated with their use. I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

• Moroccanoil Treatment
  Moroccanoil
  “I think it’s great to actually put [this product] directly onto the scalp after shampooing to get any remaining scales off.”—Anthony M. Rossi, MD, New York, New York

• Neutrogena T/Gel Therapeutic Hair Care
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Neutrogena T/Sal Therapeutic Shampoo
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Nizoral A-D Ketoconazole Shampoo 1%
  McNeil-PPC, Inc
  “I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

Cutis invites readers to send us their recommendations. Eye creams, men’s shaving products, and products for babies will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to [email protected].

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on the top OTC dandruff treatments. Consideration must be given to:

• Head & Shoulders Shampoo
  Procter & Gamble
  “OTC dandruff products are more for maintenance rather than active treatment, which is why many consumers and patients become frustrated with their use. I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

• Moroccanoil Treatment
  Moroccanoil
  “I think it’s great to actually put [this product] directly onto the scalp after shampooing to get any remaining scales off.”—Anthony M. Rossi, MD, New York, New York

• Neutrogena T/Gel Therapeutic Hair Care
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Neutrogena T/Sal Therapeutic Shampoo
  Johnson & Johnson Consumer Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Nizoral A-D Ketoconazole Shampoo 1%
  McNeil-PPC, Inc
  “I recommend to soak [this product] on the scalp skin (not hair) for 5 minutes 2 to 3 times per week.”—Adam Friedman, MD, Washington, DC

Cutis invites readers to send us their recommendations. Eye creams, men’s shaving products, and products for babies will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to [email protected].

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.

The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.

R Eko Bintoro/ThinkStockPhotos

The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.

“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”

Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.

The initial challenge is simply what to label it at the first visit.

“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”

The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.

Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.

Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.

Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.

One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.

Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.

Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”

Dr. Torgerson had no financial conflicts with regard to her presentation.

[email protected]

On Twitter @Alz_Gal

NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.

The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.

R Eko Bintoro/ThinkStockPhotos

The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.

“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”

Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.

The initial challenge is simply what to label it at the first visit.

“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”

The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.

Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.

Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.

Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.

One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.

Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.

Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”

Dr. Torgerson had no financial conflicts with regard to her presentation.

[email protected]

On Twitter @Alz_Gal

NEW YORK – Antiandrogen hormones can help stabilize, and even improve, female pattern hair loss.

The pathophysiology of the disorder is unknown, but treatment is based on the assumption that women must be like men, at least when it comes to losing their hair. Intuitively, decreasing androgens should help correct the problem.

R Eko Bintoro/ThinkStockPhotos

The answer, though, is a complicated mix of yes and maybe, Dr. Rochelle Torgerson said at the American Academy of Dermatology summer meeting.

“It used to be assumed that pattern hair loss in women was just the same as it is in men,” said Dr. Torgerson of the Mayo Clinic in Rochester, Minn. “Now there is some evidence that’s not true. In 2010, for example, this was seen in a woman with complete androgen insensitivity syndrome, so in her, androgens were not affecting hair follicles. There must be a place for estrogen.”

Further complicating the picture is the fact that no hormonal medications have FDA approval for hair loss in women, and their use has a history of conflicting data in clinical studies. Still, they remain the cornerstone for treating this physically and emotionally challenging problem.

The initial challenge is simply what to label it at the first visit.

“I have no problem with term ‘androgenetic alopecia,’ since that is what women are seeing when they first look on the Internet for information. But I do try to transition them to ‘female pattern hair loss.’ And I never – ever – use the term ‘male pattern baldness.’ It has a huge impact on women.”

The disease is a progressive miniaturization of the hair follicle over time. The growing cycle slows and the resting phase lengthens. There is progressive thinning over the vertex. Some women may keep most of their frontal hairline, but the vast majority do say it’s thinner than it was.

Spironolactone and oral contraceptives with spironolactone analogues are Dr. Torgerson’s go-to medications for first-line treatment. For spironolactone, she prefers a dose of 100-200 mg/day. Some women experience gastrointestinal upset, dizziness, cramps, breast tenderness, and spotting with these medications.

Her choice for an oral contraceptive is the combination of 20 mcg ethinyl estradiol plus drospirenone, but any oral contraceptive approved for acne may work.

Finasteride and dutasteride are approved for pattern hair loss in men, but not in women. Both inhibit 5 alpha-reductase type II. Dutasteride is more potent that finasteride and also inhibits type 1 alpha-reductase; both of these enzymes convert testosterone into the more potent dihydrotestosterone. The side-effect profile is more moderate than that of spironolactone, but both of the drugs have had mixed results in clinical trials.

One problem with the finasteride trials has been the variation in dosing. The least positive studies used the lowest dose of 1.25 mg. As the dosage increased to 2.5 mg and 5 mg, the benefit increased.

Despite her support for hormonal therapies, Dr. Torgerson doesn’t rely upon them alone – she supports them with the direct action of a 5% minoxidil foam. In addition to prescribing effective therapy, she urges women to actually be patient and to have realistic expectations.

Most women expect dramatic improvement in a short time. “I have no idea where that expectation comes from. This is a slow progressive condition. I agree with them that it’s completely unsexy to have the head of hair they do at that time. But if, in 3 years, they have this same head of hair, that’s going to be an amazing success. And once they have that expectation in their mind, they are usually happy with any other results that they see.”

Dr. Torgerson had no financial conflicts with regard to her presentation.

[email protected]

On Twitter @Alz_Gal

Changes in the appearance of the nail apparatus can be produced by a variety of conditions. Onychomatricoma is an unusual benign tumor with specific clinical characteristics that was first described more than 2 decades ago.¹ It is often and easily misdiagnosed because the condition rarely has been described. We report a case of onychomatricoma in a 54-year-old Colombian man who presented with a deformity of the nail plate on the right index finger that corresponded with the classic description of onychomatricoma. We emphasize the importance of reporting such lesions to prevent misdiagnosis and delay of proper treatment.

Case Report

A 54-year-old Colombian man presented with nail dystrophy involving the right index finger of 2 years’ duration. He did not recall any trauma prior to the onset of the nail abnormalities. Several topical treatments had previously been ineffective. Physical examination revealed a longitudinally banded thickening of the lateral half of the nail plate on the right index finger with yellowish brown discoloration, transverse overcurvature of the nail, longitudinal white lines, and splinter hemorrhages (Figure 1). Direct microscopy and fungal culture were performed to diagnose or rule out onychomycosis.

Figure 1. Clinically dystrophic nail with transverse overcurvature, thickening, yellow discoloration of the nail plate, longitudinal bands, and splinter hemorrhages on the right index finger.

A clinical diagnosis of onychomatricoma was made, and the lesion was surgically removed and sent for histopathologic study (Figure 2). The radial half of the nail plate was avulsed, and the proximal part of the removed nail plate contained a large, firmly attached, filamentous tumor arising from the nail matrix (Figure 3) with multiple fine filiform projections (Figure 4). The nail bed was cleaned with a curette to remove any debris, the ulnar half of the nail plate and nail bed was left in place, and the radial border was reconstructed. Histology confirmed the clinical diagnosis (Figure 5). No recurrences of the tumor were seen 36 months following surgery.

Figure 2. Macroscopic appearance of the removed nail plate and tumor.

Figure 3. Reflection of the proximal nail fold revealed projections arising from the nail matrix.

Figure 4. When bisected, the nail plate exhibited multiple channels formed by fine filiform projections.

Comment

Since the original report of this tumor,¹ fewer than 10 cases of onychomatricoma have been reported in Latin America,^2-5 with no more than 80 cases reported worldwide.⁶ Clinicians and academicians are becoming interested in the topic, which will result in better recognition and more reports in the literature.

The clinical differential diagnosis of onycho-matricoma is extensive,^7,8 but onychomatricoma has characteristic clinical and histopathologic features that allow its separation from other nail disorders and subungual tumors (Table).⁹ There are 4 cardinal clinical signs that suggest a diagnosis of onychomatricoma: (1) banded or diffuse thickening of the nail plate of variable widths; (2) yellowish discoloration of the involved nail plate, often showing fine splinter hemorrhages in the proximal nail portion; (3) transverse overcurvature of the nail; and (4) exposure of a filamentous tufted tumor emerging from the matrix in a funnel-shaped nail by avulsion.¹

Figure 5. Histology revealed multiple filiform projections of dense connective tissue alternating with vertically oriented invaginations covered by nail matrix epithelium (A)(H&E, original magnification ×2.5). Papillomatous cellular fibrous tissue underlying nail matrix epithelium was noted (B)(H&E, original magnification ×10).

Histologic findings of onychomatricoma typically demonstrate a fibroepithelial tumor with a biphasic growth pattern mimicking normal nail matrix histology, including a proximal zone, which corresponds to the base of the fibroepithelial tumor, and a distal zone, which is composed of multiple epithelial digitations that extend into the small cavities present in the attached nail.^10-12 Nevertheless, the anatomic tumor location, the often fragmented aspect of the tissue specimen, and the choice of the section planes may change the typical histologic features seen in onychomatricoma.¹³ Stromal prominence, cellularity, and atypia may vary in individual cases.^10-12

The etiology of onychomatricoma is not yet known. Although it has been suggested that onychomatricoma could be an epithelial and connective tissue hamartoma simulating the nail matrix structure,^1,10 the more recent concept of an epithelial onychogenic tumor with onychogenic mesenchyme will help to clarify its etiology because new histopathologic and immunohistochemical features suggest a neoplastic nature.¹⁴ On the other hand, predisposing factors such as trauma to the nail plate and onychomycosis may play a role,⁷ as the thumbs, index fingers, and great toes are more susceptible to onychomycosis and accidental trauma.

Conclusion

Our patient fulfilled the criteria of onychomatricoma.¹ Onychomatricoma should be kept in mind in the differential diagnosis of subungual or  periungual tumors to avoid misdiagnosis and erroneous treatments.

Changes in the appearance of the nail apparatus can be produced by a variety of conditions. Onychomatricoma is an unusual benign tumor with specific clinical characteristics that was first described more than 2 decades ago.¹ It is often and easily misdiagnosed because the condition rarely has been described. We report a case of onychomatricoma in a 54-year-old Colombian man who presented with a deformity of the nail plate on the right index finger that corresponded with the classic description of onychomatricoma. We emphasize the importance of reporting such lesions to prevent misdiagnosis and delay of proper treatment.

Case Report

A 54-year-old Colombian man presented with nail dystrophy involving the right index finger of 2 years’ duration. He did not recall any trauma prior to the onset of the nail abnormalities. Several topical treatments had previously been ineffective. Physical examination revealed a longitudinally banded thickening of the lateral half of the nail plate on the right index finger with yellowish brown discoloration, transverse overcurvature of the nail, longitudinal white lines, and splinter hemorrhages (Figure 1). Direct microscopy and fungal culture were performed to diagnose or rule out onychomycosis.

Figure 1. Clinically dystrophic nail with transverse overcurvature, thickening, yellow discoloration of the nail plate, longitudinal bands, and splinter hemorrhages on the right index finger.

A clinical diagnosis of onychomatricoma was made, and the lesion was surgically removed and sent for histopathologic study (Figure 2). The radial half of the nail plate was avulsed, and the proximal part of the removed nail plate contained a large, firmly attached, filamentous tumor arising from the nail matrix (Figure 3) with multiple fine filiform projections (Figure 4). The nail bed was cleaned with a curette to remove any debris, the ulnar half of the nail plate and nail bed was left in place, and the radial border was reconstructed. Histology confirmed the clinical diagnosis (Figure 5). No recurrences of the tumor were seen 36 months following surgery.

Figure 2. Macroscopic appearance of the removed nail plate and tumor.

Figure 3. Reflection of the proximal nail fold revealed projections arising from the nail matrix.

Figure 4. When bisected, the nail plate exhibited multiple channels formed by fine filiform projections.

Comment

Since the original report of this tumor,¹ fewer than 10 cases of onychomatricoma have been reported in Latin America,^2-5 with no more than 80 cases reported worldwide.⁶ Clinicians and academicians are becoming interested in the topic, which will result in better recognition and more reports in the literature.

The clinical differential diagnosis of onycho-matricoma is extensive,^7,8 but onychomatricoma has characteristic clinical and histopathologic features that allow its separation from other nail disorders and subungual tumors (Table).⁹ There are 4 cardinal clinical signs that suggest a diagnosis of onychomatricoma: (1) banded or diffuse thickening of the nail plate of variable widths; (2) yellowish discoloration of the involved nail plate, often showing fine splinter hemorrhages in the proximal nail portion; (3) transverse overcurvature of the nail; and (4) exposure of a filamentous tufted tumor emerging from the matrix in a funnel-shaped nail by avulsion.¹

Figure 5. Histology revealed multiple filiform projections of dense connective tissue alternating with vertically oriented invaginations covered by nail matrix epithelium (A)(H&E, original magnification ×2.5). Papillomatous cellular fibrous tissue underlying nail matrix epithelium was noted (B)(H&E, original magnification ×10).

Histologic findings of onychomatricoma typically demonstrate a fibroepithelial tumor with a biphasic growth pattern mimicking normal nail matrix histology, including a proximal zone, which corresponds to the base of the fibroepithelial tumor, and a distal zone, which is composed of multiple epithelial digitations that extend into the small cavities present in the attached nail.^10-12 Nevertheless, the anatomic tumor location, the often fragmented aspect of the tissue specimen, and the choice of the section planes may change the typical histologic features seen in onychomatricoma.¹³ Stromal prominence, cellularity, and atypia may vary in individual cases.^10-12

The etiology of onychomatricoma is not yet known. Although it has been suggested that onychomatricoma could be an epithelial and connective tissue hamartoma simulating the nail matrix structure,^1,10 the more recent concept of an epithelial onychogenic tumor with onychogenic mesenchyme will help to clarify its etiology because new histopathologic and immunohistochemical features suggest a neoplastic nature.¹⁴ On the other hand, predisposing factors such as trauma to the nail plate and onychomycosis may play a role,⁷ as the thumbs, index fingers, and great toes are more susceptible to onychomycosis and accidental trauma.

Conclusion

Our patient fulfilled the criteria of onychomatricoma.¹ Onychomatricoma should be kept in mind in the differential diagnosis of subungual or  periungual tumors to avoid misdiagnosis and erroneous treatments.

Changes in the appearance of the nail apparatus can be produced by a variety of conditions. Onychomatricoma is an unusual benign tumor with specific clinical characteristics that was first described more than 2 decades ago.¹ It is often and easily misdiagnosed because the condition rarely has been described. We report a case of onychomatricoma in a 54-year-old Colombian man who presented with a deformity of the nail plate on the right index finger that corresponded with the classic description of onychomatricoma. We emphasize the importance of reporting such lesions to prevent misdiagnosis and delay of proper treatment.

Case Report

A 54-year-old Colombian man presented with nail dystrophy involving the right index finger of 2 years’ duration. He did not recall any trauma prior to the onset of the nail abnormalities. Several topical treatments had previously been ineffective. Physical examination revealed a longitudinally banded thickening of the lateral half of the nail plate on the right index finger with yellowish brown discoloration, transverse overcurvature of the nail, longitudinal white lines, and splinter hemorrhages (Figure 1). Direct microscopy and fungal culture were performed to diagnose or rule out onychomycosis.

Figure 1. Clinically dystrophic nail with transverse overcurvature, thickening, yellow discoloration of the nail plate, longitudinal bands, and splinter hemorrhages on the right index finger.

A clinical diagnosis of onychomatricoma was made, and the lesion was surgically removed and sent for histopathologic study (Figure 2). The radial half of the nail plate was avulsed, and the proximal part of the removed nail plate contained a large, firmly attached, filamentous tumor arising from the nail matrix (Figure 3) with multiple fine filiform projections (Figure 4). The nail bed was cleaned with a curette to remove any debris, the ulnar half of the nail plate and nail bed was left in place, and the radial border was reconstructed. Histology confirmed the clinical diagnosis (Figure 5). No recurrences of the tumor were seen 36 months following surgery.

Figure 2. Macroscopic appearance of the removed nail plate and tumor.

Figure 3. Reflection of the proximal nail fold revealed projections arising from the nail matrix.

Figure 4. When bisected, the nail plate exhibited multiple channels formed by fine filiform projections.

Comment

Since the original report of this tumor,¹ fewer than 10 cases of onychomatricoma have been reported in Latin America,^2-5 with no more than 80 cases reported worldwide.⁶ Clinicians and academicians are becoming interested in the topic, which will result in better recognition and more reports in the literature.

The clinical differential diagnosis of onycho-matricoma is extensive,^7,8 but onychomatricoma has characteristic clinical and histopathologic features that allow its separation from other nail disorders and subungual tumors (Table).⁹ There are 4 cardinal clinical signs that suggest a diagnosis of onychomatricoma: (1) banded or diffuse thickening of the nail plate of variable widths; (2) yellowish discoloration of the involved nail plate, often showing fine splinter hemorrhages in the proximal nail portion; (3) transverse overcurvature of the nail; and (4) exposure of a filamentous tufted tumor emerging from the matrix in a funnel-shaped nail by avulsion.¹

Figure 5. Histology revealed multiple filiform projections of dense connective tissue alternating with vertically oriented invaginations covered by nail matrix epithelium (A)(H&E, original magnification ×2.5). Papillomatous cellular fibrous tissue underlying nail matrix epithelium was noted (B)(H&E, original magnification ×10).

Histologic findings of onychomatricoma typically demonstrate a fibroepithelial tumor with a biphasic growth pattern mimicking normal nail matrix histology, including a proximal zone, which corresponds to the base of the fibroepithelial tumor, and a distal zone, which is composed of multiple epithelial digitations that extend into the small cavities present in the attached nail.^10-12 Nevertheless, the anatomic tumor location, the often fragmented aspect of the tissue specimen, and the choice of the section planes may change the typical histologic features seen in onychomatricoma.¹³ Stromal prominence, cellularity, and atypia may vary in individual cases.^10-12

The etiology of onychomatricoma is not yet known. Although it has been suggested that onychomatricoma could be an epithelial and connective tissue hamartoma simulating the nail matrix structure,^1,10 the more recent concept of an epithelial onychogenic tumor with onychogenic mesenchyme will help to clarify its etiology because new histopathologic and immunohistochemical features suggest a neoplastic nature.¹⁴ On the other hand, predisposing factors such as trauma to the nail plate and onychomycosis may play a role,⁷ as the thumbs, index fingers, and great toes are more susceptible to onychomycosis and accidental trauma.

Conclusion

Our patient fulfilled the criteria of onychomatricoma.¹ Onychomatricoma should be kept in mind in the differential diagnosis of subungual or  periungual tumors to avoid misdiagnosis and erroneous treatments.

VANCOUVER – Achieving effective local anesthesia is the critical first step in successful nail surgery, Dr. Chris G. Adigun said at the World Congress of Dermatology.

“Always remember: Nail surgery hurts. Your patients will applaud you enthusiastically when they’re back home for your having used a long-acting anesthetic,” said Dr. Adigun, a dermatologist in group practice in Chapel Hill, N.C.

The three most widely used anesthetic agents in nail surgery are lidocaine (Xylocaine), bupivacaine (Marcaine), and ropivacaine (Naropin). Dr. Adigun said she strongly prefers ropivacaine. It combines the best features of the other two: lidocaine’s rapid onset along with a duration of action that’s even longer than bupivacaine’s, she noted. Ropivacaine’s duration of action is 8-12 hours – and it comes without bupivacaine’s potential for cardiotoxicity. Moreover, ropivacaine has a vasoconstrictive effect, which improves hemostasis and enhances visualization during the surgery.

She provided numerous additional tips on how to predictably achieve effective anesthesia for nail surgery:

• Buffer with sodium bicarbonate. The idea is to bring the anesthetic solution close to physiologic pH, which makes for a far less painful experience than injecting the acidic unbuffered solution.

• Warm it. Investigators have shown that warming anesthetic fluid reduces pain upon injection of both nonbuffered and buffered local anesthetics (Ann Emerg Med. 2011 Jul;58(1):86-98).

• Stick to a small-gauge needle. Dr. Adigan said she favors 30 gauge. It makes for a smaller, less painful puncture and limits the rate of flow of anesthetic fluid into the digital space.

• Inject in a perpendicular plane. This will disrupt fewer nerve endings than when going in at an angle.

“I think this is something that’s not frequently taught to residents in dermatology. I think we almost always go in at an angle, but if you go in at a perpendicular plane, you’re going to cause less pain,” according to Dr. Adigun.

• Inject just below the dermis. The dermis is nociceptor rich, and stretching those tissues by injecting a volume of fluid there will cause intense, continuous pain until the local anesthetic has time to take effect.

• Use distraction techniques liberally. Dr. Adigun said she likes to tell stories and jokes, which she calls “talkesthesia.” She also utilizes a battery-powered massager.

“Put the massager as close to your surgical field as you’re comfortable with. Under the gate theory of pain, you want to create as much sensory ‘noise’ as possible with your distraction techniques so that gate is filled with your sensory noise rather than pain,” the dermatologist explained.

There are three solid, time-tested completely acceptable techniques for getting the target digit numb: the wing block, the traditional digital block, and the transthecal digital block.

Dr. Adigun said she generally relies upon the wing block unless she is concerned that the associated blanching might cause her to lose her digital landmarks during surgery addressing a subtle abnormality. In that situation she turns mainly to the traditional digital block, which doesn’t interfere with digital landmarks and effectively anesthetizes both the paired digital and volar nerves.

The downside of the traditional digital block is it entails a 15- to 20-minute wait for the anesthetic to diffuse. So does the transthecal digital block, which has the additional shortcoming of achieving predictable results only when applied for surgery on the second, third, or fourth digits.

The wing block is an efficient infiltrative technique targeting the distal digit. It offers immediate anesthesia of the total nail unit. To achieve an excellent wing block, initially inject just 0.1-0.2 mL of anesthetic fluid subcutaneously into the proximal nail fold midway between the cuticle and the distal interphalangeal joint. Wait for a wheal to form; then wait an additional 45-60 seconds. At that point, inject obliquely along the lateral edge of the nail fold in the direction of the digital tip. The needle should be advanced while maintaining a gentle fluid bolus ahead of the needle tip in order to minimize the patient’s sensation of the moving needle. The process is then repeated on the opposite side of the digit.

“You want to keep that needle in the dermal plane and avoid filling the pulp with anesthetic fluid. If you do this correctly, only one prick is felt by the patient. I very rarely have to use a full cc of anesthetic fluid when I use a wing block,” Dr. Adigun said.

If any additional needle insertions are needed, make sure they’re placed into tissue that’s already been anesthetized, she added.

Dr. Adigun reported having no financial conflicts of interest.

[email protected]

VANCOUVER – Achieving effective local anesthesia is the critical first step in successful nail surgery, Dr. Chris G. Adigun said at the World Congress of Dermatology.

“Always remember: Nail surgery hurts. Your patients will applaud you enthusiastically when they’re back home for your having used a long-acting anesthetic,” said Dr. Adigun, a dermatologist in group practice in Chapel Hill, N.C.

The three most widely used anesthetic agents in nail surgery are lidocaine (Xylocaine), bupivacaine (Marcaine), and ropivacaine (Naropin). Dr. Adigun said she strongly prefers ropivacaine. It combines the best features of the other two: lidocaine’s rapid onset along with a duration of action that’s even longer than bupivacaine’s, she noted. Ropivacaine’s duration of action is 8-12 hours – and it comes without bupivacaine’s potential for cardiotoxicity. Moreover, ropivacaine has a vasoconstrictive effect, which improves hemostasis and enhances visualization during the surgery.

She provided numerous additional tips on how to predictably achieve effective anesthesia for nail surgery:

• Buffer with sodium bicarbonate. The idea is to bring the anesthetic solution close to physiologic pH, which makes for a far less painful experience than injecting the acidic unbuffered solution.

• Warm it. Investigators have shown that warming anesthetic fluid reduces pain upon injection of both nonbuffered and buffered local anesthetics (Ann Emerg Med. 2011 Jul;58(1):86-98).

• Stick to a small-gauge needle. Dr. Adigan said she favors 30 gauge. It makes for a smaller, less painful puncture and limits the rate of flow of anesthetic fluid into the digital space.

• Inject in a perpendicular plane. This will disrupt fewer nerve endings than when going in at an angle.

“I think this is something that’s not frequently taught to residents in dermatology. I think we almost always go in at an angle, but if you go in at a perpendicular plane, you’re going to cause less pain,” according to Dr. Adigun.

• Inject just below the dermis. The dermis is nociceptor rich, and stretching those tissues by injecting a volume of fluid there will cause intense, continuous pain until the local anesthetic has time to take effect.

• Use distraction techniques liberally. Dr. Adigun said she likes to tell stories and jokes, which she calls “talkesthesia.” She also utilizes a battery-powered massager.

“Put the massager as close to your surgical field as you’re comfortable with. Under the gate theory of pain, you want to create as much sensory ‘noise’ as possible with your distraction techniques so that gate is filled with your sensory noise rather than pain,” the dermatologist explained.

There are three solid, time-tested completely acceptable techniques for getting the target digit numb: the wing block, the traditional digital block, and the transthecal digital block.

Dr. Adigun said she generally relies upon the wing block unless she is concerned that the associated blanching might cause her to lose her digital landmarks during surgery addressing a subtle abnormality. In that situation she turns mainly to the traditional digital block, which doesn’t interfere with digital landmarks and effectively anesthetizes both the paired digital and volar nerves.

The downside of the traditional digital block is it entails a 15- to 20-minute wait for the anesthetic to diffuse. So does the transthecal digital block, which has the additional shortcoming of achieving predictable results only when applied for surgery on the second, third, or fourth digits.

The wing block is an efficient infiltrative technique targeting the distal digit. It offers immediate anesthesia of the total nail unit. To achieve an excellent wing block, initially inject just 0.1-0.2 mL of anesthetic fluid subcutaneously into the proximal nail fold midway between the cuticle and the distal interphalangeal joint. Wait for a wheal to form; then wait an additional 45-60 seconds. At that point, inject obliquely along the lateral edge of the nail fold in the direction of the digital tip. The needle should be advanced while maintaining a gentle fluid bolus ahead of the needle tip in order to minimize the patient’s sensation of the moving needle. The process is then repeated on the opposite side of the digit.

“You want to keep that needle in the dermal plane and avoid filling the pulp with anesthetic fluid. If you do this correctly, only one prick is felt by the patient. I very rarely have to use a full cc of anesthetic fluid when I use a wing block,” Dr. Adigun said.

If any additional needle insertions are needed, make sure they’re placed into tissue that’s already been anesthetized, she added.

Dr. Adigun reported having no financial conflicts of interest.

[email protected]

VANCOUVER – Achieving effective local anesthesia is the critical first step in successful nail surgery, Dr. Chris G. Adigun said at the World Congress of Dermatology.

“Always remember: Nail surgery hurts. Your patients will applaud you enthusiastically when they’re back home for your having used a long-acting anesthetic,” said Dr. Adigun, a dermatologist in group practice in Chapel Hill, N.C.

The three most widely used anesthetic agents in nail surgery are lidocaine (Xylocaine), bupivacaine (Marcaine), and ropivacaine (Naropin). Dr. Adigun said she strongly prefers ropivacaine. It combines the best features of the other two: lidocaine’s rapid onset along with a duration of action that’s even longer than bupivacaine’s, she noted. Ropivacaine’s duration of action is 8-12 hours – and it comes without bupivacaine’s potential for cardiotoxicity. Moreover, ropivacaine has a vasoconstrictive effect, which improves hemostasis and enhances visualization during the surgery.

She provided numerous additional tips on how to predictably achieve effective anesthesia for nail surgery:

• Buffer with sodium bicarbonate. The idea is to bring the anesthetic solution close to physiologic pH, which makes for a far less painful experience than injecting the acidic unbuffered solution.

• Warm it. Investigators have shown that warming anesthetic fluid reduces pain upon injection of both nonbuffered and buffered local anesthetics (Ann Emerg Med. 2011 Jul;58(1):86-98).

• Stick to a small-gauge needle. Dr. Adigan said she favors 30 gauge. It makes for a smaller, less painful puncture and limits the rate of flow of anesthetic fluid into the digital space.

• Inject in a perpendicular plane. This will disrupt fewer nerve endings than when going in at an angle.

“I think this is something that’s not frequently taught to residents in dermatology. I think we almost always go in at an angle, but if you go in at a perpendicular plane, you’re going to cause less pain,” according to Dr. Adigun.

• Inject just below the dermis. The dermis is nociceptor rich, and stretching those tissues by injecting a volume of fluid there will cause intense, continuous pain until the local anesthetic has time to take effect.

• Use distraction techniques liberally. Dr. Adigun said she likes to tell stories and jokes, which she calls “talkesthesia.” She also utilizes a battery-powered massager.

“Put the massager as close to your surgical field as you’re comfortable with. Under the gate theory of pain, you want to create as much sensory ‘noise’ as possible with your distraction techniques so that gate is filled with your sensory noise rather than pain,” the dermatologist explained.

There are three solid, time-tested completely acceptable techniques for getting the target digit numb: the wing block, the traditional digital block, and the transthecal digital block.

Dr. Adigun said she generally relies upon the wing block unless she is concerned that the associated blanching might cause her to lose her digital landmarks during surgery addressing a subtle abnormality. In that situation she turns mainly to the traditional digital block, which doesn’t interfere with digital landmarks and effectively anesthetizes both the paired digital and volar nerves.

The downside of the traditional digital block is it entails a 15- to 20-minute wait for the anesthetic to diffuse. So does the transthecal digital block, which has the additional shortcoming of achieving predictable results only when applied for surgery on the second, third, or fourth digits.

The wing block is an efficient infiltrative technique targeting the distal digit. It offers immediate anesthesia of the total nail unit. To achieve an excellent wing block, initially inject just 0.1-0.2 mL of anesthetic fluid subcutaneously into the proximal nail fold midway between the cuticle and the distal interphalangeal joint. Wait for a wheal to form; then wait an additional 45-60 seconds. At that point, inject obliquely along the lateral edge of the nail fold in the direction of the digital tip. The needle should be advanced while maintaining a gentle fluid bolus ahead of the needle tip in order to minimize the patient’s sensation of the moving needle. The process is then repeated on the opposite side of the digit.

“You want to keep that needle in the dermal plane and avoid filling the pulp with anesthetic fluid. If you do this correctly, only one prick is felt by the patient. I very rarely have to use a full cc of anesthetic fluid when I use a wing block,” Dr. Adigun said.

If any additional needle insertions are needed, make sure they’re placed into tissue that’s already been anesthetized, she added.

Dr. Adigun reported having no financial conflicts of interest.

[email protected]

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

VANCOUVER – Dr. Curtis T. Thompson is on a mission: to improve the often-shoddy quality of nail biopsy specimens submitted to pathologists.

No standardized protocols for nail specimens exist. The quality of pathologic diagnosis often suffers as a result, Dr. Thompson said at the World Congress of Dermatology.

“What often happens is the nail specimens get put into a bottle of formaldehyde, they float around and get torn up, and then when they come to the lab, we have no idea what’s proximal and dorsal. This is an issue. We’re all used to just putting a nail specimen in a bottle and sending it away, so all the grossing happens in the laboratory. What I submit to you is you need to be more involved in the grossing side so the specimen can be properly processed,” said Dr. Thompson, a dermatopathologist in group practice in Tigard, Ore.

He added that clear and concise guidelines for standardized specimen submission are needed, and he offered several specific suggestions regarding the orientation of the tissue and securing it for transport.

“Careful submission of tissue specimens is of great importance and allows for better diagnostics,” Dr. Thompson stressed. “There’s really nothing more terrifying than to be told you’re being sent a pigmented lesion and then not being able to find anything at all in the specimen. You really worry that it’s ended up in the trash can through leveling. This is why dermatopathologists don’t want to read nail biopsies very much.”

When a nail specimen is submitted properly, such mix-ups become “almost impossible,” according to the dermatopathologist.

Dr. Thompson borrowed one of his key ideas on efficient handling of nail specimens from opthalmologic pathology. Ophthalmologists routinely send delicate tissue segments and margins from the operating room, and they do so with consistent success because they place the segments on a cartoon of the eye so the pathologist can see exactly where the tissue was located on the patient.

Dermatologists and surgeons can do the same after printing out a sheaf of nail diagrams gratis at the Website for Dr. Thompson’s dermatopathology practice.

The rest of the necessary equipment is similarly simple and readily obtainable from any pathology laboratory, which routinely purchases small plastic cassettes by the tens of thousands for handling of tissue specimens.

“You don’t need to go out and buy them; just ask the lab you work with to send over 10 or so,” Dr. Thompson advised.

The cassette comes with a small fitted sponge to be placed over the tissue to keep it securely in place on the nail diagram rather than floating off. Ink one end of the specimen using the wooden end of a cotton-tip applicator so the lab knows which end is proximal and which is distal. The wooden tip provides more precise inking than the cotton-tip end. Then place the closed cassette in a larger bottle of formaldehyde for shipping.

One more thing: Separate the nail plate from the nail bed or matrix whenever possible, and place them in separate cassettes. Lab technicians typically devote a lot of attention to trying to get the nail plate to stick to a slide, but the diagnostic material is usually present in the nail bed or matrix, and keeping those soft tissues separate makes it less likely they’ll get lost in the shuffle.

“I recommend putting the nail plate cassette and the lesional tissue in the same bottle because then you don’t have two specimens with double the charge for the patient,” Dr. Thompson said.

He reported having no relevant financial conflicts.

bjancin@frontlinemedcom

Hair pigmentation is a complex phenomenon that involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu.¹ Repigmentation of gray hair has been associated with herpes zoster infection,² use of systemic corticosteroids,³ thyroid hormone therapy,⁴ or treatment with interferon and ribavirin.⁵ We report a case of repigmentation of gray hairs in lesions of annular elastolytic giant cell granuloma (AEGCG) on the scalp of a 67-year-old man.

Case Report

A 67-year-old man presented to the dermatology department for evaluation of pruritic lesions on the face and scalp of 1 year’s duration. The patient reported that hairs in the involved areas of the scalp had turned from gray to a dark color since the appearance of the lesions. The patient had a history of hypertension and type 2 diabetes mellitus. His current medications included irbesartan, atorvastatin, metformin, acetylsalicylic acid, omeprazole, and repaglinide.

Physical examination revealed plaques on the scalp and cheeks that were 2 to 10 mm in diameter. Some of the plaques had an atrophic center and a desquamative peripheral border. The patient had androgenetic alopecia. The remaining hair was dark in the areas affected by the inflammatory plaques while it remained white-gray in the uninvolved areas (Figure 1).

Figure 1. Repigmentation of gray hair in the areas affected by plaques on the scalp.

A biopsy of one of the lesions was performed. Histopathology revealed a granulomatous dermatitis involving mostly the upper and mid dermis (Figure 2). Granulomas were epithelioid with many giant cells, some of which contained many nuclei. A ringed array of nuclei was noted in some histiocytes. Elastic fibers were absent in the central zone of the granulomas, a finding that was better evidenced on orcein staining (Figure 3). On the contrary, the peripheral zone of the granulomas showed an increased amount of thick elastotic material. Elastophagocytosis was observed, but no asteroid bodies, Schaumann bodies, or mucin deposits were noted. Histochemistry for microorganisms with Ziehl-Neelsen and periodic acid–Schiff staining was negative. Other findings included a mild infiltrate of melanophages in the papillary dermis as well as a mild superficial dermal inflammatory infiltrate that was rich in plasma cells. Immunostaining for Treponema pallidum was negative. The lymphocytic infiltrate was CD4⁺predominant. A prominent dermal elastosis also was noted. Hair follicles within the plaques were small in size, penetrating just the dermis. Immunostaining for HMB-45, melan-A, and S-100 demonstrated preserved melanocytes in the hair bulbs (Figure 4). CD68 immunostaining made the infiltrate of macrophages stand out. Based on the results of the histopathologic evaluation, a diagnosis of AEGCG was made.

Figure 2. Biopsy showed granulomatous dermatitis in which many giant cells were seen. The latter contained several nuclei, sometimes in a ringed array (H&E, original magnification ×20).

Figure 3. Orcein stain demonstrated a decrease in elastic fibers in the center of the granulomas as well as an increase of elastic fibers in the periphery. Elastophagocytosis was easily observed (original magnification ×40).

Figure 4. Immunohistochemical staining for HMB-45 showed preservation of melanocytes in the hair bulbs (original magnification ×20).

Comment

Annular elastolytic giant cell granuloma is a controversial entity that was first described by O’Brien⁶ in 1975 as actinic granuloma. Hanke et al⁷ proposed the term annular elastolytic giant cell granuloma to encompass lesions previously called actinic granuloma, atypical necrobiosis lipoidica, and Miescher granuloma. Some researchers have claimed that AEGCG is an independent entity, therefore separate and distinguishable from granuloma annulare. Histopathologic clues to distinguish AEGCG from granuloma annulare have been noted in the literature.^7-9 Other investigators believe AEGCG is a type of granuloma annulare that appears on exposed skin.¹⁰ There are several variants of the classic clinical presentation of AEGCG, such as cases including presentation in unexposed areas of the skin,¹¹ a papular variant,¹² a rapidly regressive variant,¹³ a reticular variant,¹⁴ a variant of early childhood,¹⁵ a generalized variant,¹⁶ presentation in a necklace distribution,¹⁷ presentation as alopecia,¹⁸ a sarcoid variant,¹⁹ or presentation as reticulate erythema.²⁰ However, no variant has been associated with hair repigmentation.

Melanin units from the proximal hair bulb are responsible for pigmentation in adult hair follicles and are integrated by the hair matrix, melanocytes, keratinocytes, and fibroblasts.²¹ Hair bulb melanocytes are larger and more dendritic than epidermal melanocytes (Figure 5). The hair only pigments during the anagen phase; therefore, its pigmentation is cyclic, as opposed to epidermal pigmentation, which is ongoing. Hair pigmentation is the result of a complex interaction between the epithelium, the mesenchyme, and the neuroectoderm. This complex pigmentation results from the interaction between follicular melanocytes, keratinocytes, and the fibroblasts from the hair papilla.²² Hair pigmentation involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu^1,23-25 (Table), and it is regulated by autocrines, paracrines, or intracrines.²¹ Therefore, it is likely that many environmental factors may affect hair pigmentation, which may explain why repigmentation of the hair has been seen in the setting of herpes zoster infection,² use of systemic corticosteroids in the treatment of bullous pemphigoid,³ thyroid hormone therapy,⁴ treatment with interferon and ribavirin,⁵ porphyria cutanea tarda,²⁶ or lentigo maligna.²⁷ In our patient, AEGCG might have induced some changes in the dermal environment that were responsible for the repigmentation of the patient’s gray hair. It is speculated that solar radiation and other factors can transform the antigenicity of elastic fibers and induce an immune response in AEGCG.^12,15 The lymphocytic infiltrate in these lesions is predominantly CD4⁺, as seen in our patient, which is consistent with an autoimmune hypothesis.¹⁵ Nevertheless, it most likely is too simplistic to attribute the repigmentation to the influence of just these cells.

Figure 5. A hair bulb of a normal follicle showing the morphology of melanocytes, which are dendritic and large (H&amp;E,original magnification ×100).

Hair pigmentation is a complex phenomenon that involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu.¹ Repigmentation of gray hair has been associated with herpes zoster infection,² use of systemic corticosteroids,³ thyroid hormone therapy,⁴ or treatment with interferon and ribavirin.⁵ We report a case of repigmentation of gray hairs in lesions of annular elastolytic giant cell granuloma (AEGCG) on the scalp of a 67-year-old man.

Case Report

A 67-year-old man presented to the dermatology department for evaluation of pruritic lesions on the face and scalp of 1 year’s duration. The patient reported that hairs in the involved areas of the scalp had turned from gray to a dark color since the appearance of the lesions. The patient had a history of hypertension and type 2 diabetes mellitus. His current medications included irbesartan, atorvastatin, metformin, acetylsalicylic acid, omeprazole, and repaglinide.

Physical examination revealed plaques on the scalp and cheeks that were 2 to 10 mm in diameter. Some of the plaques had an atrophic center and a desquamative peripheral border. The patient had androgenetic alopecia. The remaining hair was dark in the areas affected by the inflammatory plaques while it remained white-gray in the uninvolved areas (Figure 1).

Figure 1. Repigmentation of gray hair in the areas affected by plaques on the scalp.

A biopsy of one of the lesions was performed. Histopathology revealed a granulomatous dermatitis involving mostly the upper and mid dermis (Figure 2). Granulomas were epithelioid with many giant cells, some of which contained many nuclei. A ringed array of nuclei was noted in some histiocytes. Elastic fibers were absent in the central zone of the granulomas, a finding that was better evidenced on orcein staining (Figure 3). On the contrary, the peripheral zone of the granulomas showed an increased amount of thick elastotic material. Elastophagocytosis was observed, but no asteroid bodies, Schaumann bodies, or mucin deposits were noted. Histochemistry for microorganisms with Ziehl-Neelsen and periodic acid–Schiff staining was negative. Other findings included a mild infiltrate of melanophages in the papillary dermis as well as a mild superficial dermal inflammatory infiltrate that was rich in plasma cells. Immunostaining for Treponema pallidum was negative. The lymphocytic infiltrate was CD4⁺predominant. A prominent dermal elastosis also was noted. Hair follicles within the plaques were small in size, penetrating just the dermis. Immunostaining for HMB-45, melan-A, and S-100 demonstrated preserved melanocytes in the hair bulbs (Figure 4). CD68 immunostaining made the infiltrate of macrophages stand out. Based on the results of the histopathologic evaluation, a diagnosis of AEGCG was made.

Figure 2. Biopsy showed granulomatous dermatitis in which many giant cells were seen. The latter contained several nuclei, sometimes in a ringed array (H&E, original magnification ×20).

Figure 3. Orcein stain demonstrated a decrease in elastic fibers in the center of the granulomas as well as an increase of elastic fibers in the periphery. Elastophagocytosis was easily observed (original magnification ×40).

Figure 4. Immunohistochemical staining for HMB-45 showed preservation of melanocytes in the hair bulbs (original magnification ×20).

Comment

Annular elastolytic giant cell granuloma is a controversial entity that was first described by O’Brien⁶ in 1975 as actinic granuloma. Hanke et al⁷ proposed the term annular elastolytic giant cell granuloma to encompass lesions previously called actinic granuloma, atypical necrobiosis lipoidica, and Miescher granuloma. Some researchers have claimed that AEGCG is an independent entity, therefore separate and distinguishable from granuloma annulare. Histopathologic clues to distinguish AEGCG from granuloma annulare have been noted in the literature.^7-9 Other investigators believe AEGCG is a type of granuloma annulare that appears on exposed skin.¹⁰ There are several variants of the classic clinical presentation of AEGCG, such as cases including presentation in unexposed areas of the skin,¹¹ a papular variant,¹² a rapidly regressive variant,¹³ a reticular variant,¹⁴ a variant of early childhood,¹⁵ a generalized variant,¹⁶ presentation in a necklace distribution,¹⁷ presentation as alopecia,¹⁸ a sarcoid variant,¹⁹ or presentation as reticulate erythema.²⁰ However, no variant has been associated with hair repigmentation.

Melanin units from the proximal hair bulb are responsible for pigmentation in adult hair follicles and are integrated by the hair matrix, melanocytes, keratinocytes, and fibroblasts.²¹ Hair bulb melanocytes are larger and more dendritic than epidermal melanocytes (Figure 5). The hair only pigments during the anagen phase; therefore, its pigmentation is cyclic, as opposed to epidermal pigmentation, which is ongoing. Hair pigmentation is the result of a complex interaction between the epithelium, the mesenchyme, and the neuroectoderm. This complex pigmentation results from the interaction between follicular melanocytes, keratinocytes, and the fibroblasts from the hair papilla.²² Hair pigmentation involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu^1,23-25 (Table), and it is regulated by autocrines, paracrines, or intracrines.²¹ Therefore, it is likely that many environmental factors may affect hair pigmentation, which may explain why repigmentation of the hair has been seen in the setting of herpes zoster infection,² use of systemic corticosteroids in the treatment of bullous pemphigoid,³ thyroid hormone therapy,⁴ treatment with interferon and ribavirin,⁵ porphyria cutanea tarda,²⁶ or lentigo maligna.²⁷ In our patient, AEGCG might have induced some changes in the dermal environment that were responsible for the repigmentation of the patient’s gray hair. It is speculated that solar radiation and other factors can transform the antigenicity of elastic fibers and induce an immune response in AEGCG.^12,15 The lymphocytic infiltrate in these lesions is predominantly CD4⁺, as seen in our patient, which is consistent with an autoimmune hypothesis.¹⁵ Nevertheless, it most likely is too simplistic to attribute the repigmentation to the influence of just these cells.

Figure 5. A hair bulb of a normal follicle showing the morphology of melanocytes, which are dendritic and large (H&amp;E,original magnification ×100).

Hair pigmentation is a complex phenomenon that involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu.¹ Repigmentation of gray hair has been associated with herpes zoster infection,² use of systemic corticosteroids,³ thyroid hormone therapy,⁴ or treatment with interferon and ribavirin.⁵ We report a case of repigmentation of gray hairs in lesions of annular elastolytic giant cell granuloma (AEGCG) on the scalp of a 67-year-old man.

Case Report

A 67-year-old man presented to the dermatology department for evaluation of pruritic lesions on the face and scalp of 1 year’s duration. The patient reported that hairs in the involved areas of the scalp had turned from gray to a dark color since the appearance of the lesions. The patient had a history of hypertension and type 2 diabetes mellitus. His current medications included irbesartan, atorvastatin, metformin, acetylsalicylic acid, omeprazole, and repaglinide.

Physical examination revealed plaques on the scalp and cheeks that were 2 to 10 mm in diameter. Some of the plaques had an atrophic center and a desquamative peripheral border. The patient had androgenetic alopecia. The remaining hair was dark in the areas affected by the inflammatory plaques while it remained white-gray in the uninvolved areas (Figure 1).

Figure 1. Repigmentation of gray hair in the areas affected by plaques on the scalp.

A biopsy of one of the lesions was performed. Histopathology revealed a granulomatous dermatitis involving mostly the upper and mid dermis (Figure 2). Granulomas were epithelioid with many giant cells, some of which contained many nuclei. A ringed array of nuclei was noted in some histiocytes. Elastic fibers were absent in the central zone of the granulomas, a finding that was better evidenced on orcein staining (Figure 3). On the contrary, the peripheral zone of the granulomas showed an increased amount of thick elastotic material. Elastophagocytosis was observed, but no asteroid bodies, Schaumann bodies, or mucin deposits were noted. Histochemistry for microorganisms with Ziehl-Neelsen and periodic acid–Schiff staining was negative. Other findings included a mild infiltrate of melanophages in the papillary dermis as well as a mild superficial dermal inflammatory infiltrate that was rich in plasma cells. Immunostaining for Treponema pallidum was negative. The lymphocytic infiltrate was CD4⁺predominant. A prominent dermal elastosis also was noted. Hair follicles within the plaques were small in size, penetrating just the dermis. Immunostaining for HMB-45, melan-A, and S-100 demonstrated preserved melanocytes in the hair bulbs (Figure 4). CD68 immunostaining made the infiltrate of macrophages stand out. Based on the results of the histopathologic evaluation, a diagnosis of AEGCG was made.

Figure 2. Biopsy showed granulomatous dermatitis in which many giant cells were seen. The latter contained several nuclei, sometimes in a ringed array (H&E, original magnification ×20).

Figure 3. Orcein stain demonstrated a decrease in elastic fibers in the center of the granulomas as well as an increase of elastic fibers in the periphery. Elastophagocytosis was easily observed (original magnification ×40).

Figure 4. Immunohistochemical staining for HMB-45 showed preservation of melanocytes in the hair bulbs (original magnification ×20).

Comment

Annular elastolytic giant cell granuloma is a controversial entity that was first described by O’Brien⁶ in 1975 as actinic granuloma. Hanke et al⁷ proposed the term annular elastolytic giant cell granuloma to encompass lesions previously called actinic granuloma, atypical necrobiosis lipoidica, and Miescher granuloma. Some researchers have claimed that AEGCG is an independent entity, therefore separate and distinguishable from granuloma annulare. Histopathologic clues to distinguish AEGCG from granuloma annulare have been noted in the literature.^7-9 Other investigators believe AEGCG is a type of granuloma annulare that appears on exposed skin.¹⁰ There are several variants of the classic clinical presentation of AEGCG, such as cases including presentation in unexposed areas of the skin,¹¹ a papular variant,¹² a rapidly regressive variant,¹³ a reticular variant,¹⁴ a variant of early childhood,¹⁵ a generalized variant,¹⁶ presentation in a necklace distribution,¹⁷ presentation as alopecia,¹⁸ a sarcoid variant,¹⁹ or presentation as reticulate erythema.²⁰ However, no variant has been associated with hair repigmentation.

Melanin units from the proximal hair bulb are responsible for pigmentation in adult hair follicles and are integrated by the hair matrix, melanocytes, keratinocytes, and fibroblasts.²¹ Hair bulb melanocytes are larger and more dendritic than epidermal melanocytes (Figure 5). The hair only pigments during the anagen phase; therefore, its pigmentation is cyclic, as opposed to epidermal pigmentation, which is ongoing. Hair pigmentation is the result of a complex interaction between the epithelium, the mesenchyme, and the neuroectoderm. This complex pigmentation results from the interaction between follicular melanocytes, keratinocytes, and the fibroblasts from the hair papilla.²² Hair pigmentation involves many hormones, neurotransmitters, cytokines, growth factors, eicosanoids, cyclic nucleotides, nutrients, and a physicochemical milieu^1,23-25 (Table), and it is regulated by autocrines, paracrines, or intracrines.²¹ Therefore, it is likely that many environmental factors may affect hair pigmentation, which may explain why repigmentation of the hair has been seen in the setting of herpes zoster infection,² use of systemic corticosteroids in the treatment of bullous pemphigoid,³ thyroid hormone therapy,⁴ treatment with interferon and ribavirin,⁵ porphyria cutanea tarda,²⁶ or lentigo maligna.²⁷ In our patient, AEGCG might have induced some changes in the dermal environment that were responsible for the repigmentation of the patient’s gray hair. It is speculated that solar radiation and other factors can transform the antigenicity of elastic fibers and induce an immune response in AEGCG.^12,15 The lymphocytic infiltrate in these lesions is predominantly CD4⁺, as seen in our patient, which is consistent with an autoimmune hypothesis.¹⁵ Nevertheless, it most likely is too simplistic to attribute the repigmentation to the influence of just these cells.

Figure 5. A hair bulb of a normal follicle showing the morphology of melanocytes, which are dendritic and large (H&amp;E,original magnification ×100).

VANCOUVER, B.C. – The interleukin-17A inhibitor secukinumab demonstrated the greatest improvement in nail psoriasis ever reported from a randomized, placebo-controlled trial in the phase IIIb TRANSFIGURE study, Dr. Kristian Reich reported at the World Congress of Dermatology.

At 198 patients, TRANSFIGURE is the largest-ever prospective study in patients with moderate to severe chronic plaque psoriasis and significant nail involvement. And while only the 16-week results are available thus far, when TRANSFIGURE is completed after a planned 132 weeks of treatment, it will also be the longest-ever study in the treatment of nail psoriasis, noted Dr. Reich, a dermatologist in group practice in Hamburg, Germany.

Elsewhere at WCD 2015, Dr. Alice B. Gottlieb presented the week 16 results of the phase IIIb GESTURE study, in which 205 psoriasis patients with moderate to severe psoriasis of the palms and soles were randomized to subcutaneous secukinumab (Cosentyx) at 150 or 300 mg or placebo. Dosing was weekly for the first 5 weeks and monthly thereafter.

The primary endpoint, a palmoplantar Investigator’s Global Assessment scale score of 0 or 1 – clear or almost clear – at week 16 was 33.3% with secukinumab at 300 mg, 22.1% at 150 mg, and 1.5% with placebo. The average reduction in palmoplantar PASI (Psoriasis Area Severity Index) score from baseline was 54.6% with high-dose and 35.3% with low-dose secukinumab, compared with 4.1% in placebo-treated controls, reported Dr. Gottlieb, professor and chair of dermatology at Tufts University, Boston.

Like the TRANSFIGURE trial, GESTURE will continue for 132 weeks, with the initial placebo-treated controls being randomized to secukinumab at 150 or 300 mg after week 16.

Dr. Reich reported that by 16 weeks in TRANSFIGURE, mean scores on the Nail Psoriasis Severity Index had improved by 45.3%, compared with baseline, in patients on secukinumab 300 mg, 37.9% in those on secukinumab 150 mg, and 10.8% with placebo.

The results on the skin were dramatic: a PASI 75 rate of 87.1% with secukinumab 300 mg, 77% with secukinumab 150 mg, and 5.1% with placebo. The PASI 100 response rate – meaning totally clear skin – was 31.9% with high-dose and 25.2% with lower-dose secukinumab, while there was a zero PASI 100 rate in controls.

The only adverse events more common than with placebo were nasopharyngitis and upper respiratory infections.

Dr. Reich predicted that as the ongoing TRANSFIGURE study continues well beyond 16 weeks, the nail psoriasis response rates will climb, since nails are so slow growing.

TRANSFIGURE and GESTURE are sponsored by Novartis, which markets secukinumab. Dr. Reich and Dr. Gottlieb reported having financial relationships with Novartis and numerous other pharmaceutical companies.

bjancin@frontlinemedcom

VANCOUVER, B.C. – The interleukin-17A inhibitor secukinumab demonstrated the greatest improvement in nail psoriasis ever reported from a randomized, placebo-controlled trial in the phase IIIb TRANSFIGURE study, Dr. Kristian Reich reported at the World Congress of Dermatology.

At 198 patients, TRANSFIGURE is the largest-ever prospective study in patients with moderate to severe chronic plaque psoriasis and significant nail involvement. And while only the 16-week results are available thus far, when TRANSFIGURE is completed after a planned 132 weeks of treatment, it will also be the longest-ever study in the treatment of nail psoriasis, noted Dr. Reich, a dermatologist in group practice in Hamburg, Germany.

Elsewhere at WCD 2015, Dr. Alice B. Gottlieb presented the week 16 results of the phase IIIb GESTURE study, in which 205 psoriasis patients with moderate to severe psoriasis of the palms and soles were randomized to subcutaneous secukinumab (Cosentyx) at 150 or 300 mg or placebo. Dosing was weekly for the first 5 weeks and monthly thereafter.

The primary endpoint, a palmoplantar Investigator’s Global Assessment scale score of 0 or 1 – clear or almost clear – at week 16 was 33.3% with secukinumab at 300 mg, 22.1% at 150 mg, and 1.5% with placebo. The average reduction in palmoplantar PASI (Psoriasis Area Severity Index) score from baseline was 54.6% with high-dose and 35.3% with low-dose secukinumab, compared with 4.1% in placebo-treated controls, reported Dr. Gottlieb, professor and chair of dermatology at Tufts University, Boston.

Like the TRANSFIGURE trial, GESTURE will continue for 132 weeks, with the initial placebo-treated controls being randomized to secukinumab at 150 or 300 mg after week 16.

Dr. Reich reported that by 16 weeks in TRANSFIGURE, mean scores on the Nail Psoriasis Severity Index had improved by 45.3%, compared with baseline, in patients on secukinumab 300 mg, 37.9% in those on secukinumab 150 mg, and 10.8% with placebo.

The results on the skin were dramatic: a PASI 75 rate of 87.1% with secukinumab 300 mg, 77% with secukinumab 150 mg, and 5.1% with placebo. The PASI 100 response rate – meaning totally clear skin – was 31.9% with high-dose and 25.2% with lower-dose secukinumab, while there was a zero PASI 100 rate in controls.

The only adverse events more common than with placebo were nasopharyngitis and upper respiratory infections.

Dr. Reich predicted that as the ongoing TRANSFIGURE study continues well beyond 16 weeks, the nail psoriasis response rates will climb, since nails are so slow growing.

TRANSFIGURE and GESTURE are sponsored by Novartis, which markets secukinumab. Dr. Reich and Dr. Gottlieb reported having financial relationships with Novartis and numerous other pharmaceutical companies.

bjancin@frontlinemedcom

VANCOUVER, B.C. – The interleukin-17A inhibitor secukinumab demonstrated the greatest improvement in nail psoriasis ever reported from a randomized, placebo-controlled trial in the phase IIIb TRANSFIGURE study, Dr. Kristian Reich reported at the World Congress of Dermatology.

At 198 patients, TRANSFIGURE is the largest-ever prospective study in patients with moderate to severe chronic plaque psoriasis and significant nail involvement. And while only the 16-week results are available thus far, when TRANSFIGURE is completed after a planned 132 weeks of treatment, it will also be the longest-ever study in the treatment of nail psoriasis, noted Dr. Reich, a dermatologist in group practice in Hamburg, Germany.

Elsewhere at WCD 2015, Dr. Alice B. Gottlieb presented the week 16 results of the phase IIIb GESTURE study, in which 205 psoriasis patients with moderate to severe psoriasis of the palms and soles were randomized to subcutaneous secukinumab (Cosentyx) at 150 or 300 mg or placebo. Dosing was weekly for the first 5 weeks and monthly thereafter.

The primary endpoint, a palmoplantar Investigator’s Global Assessment scale score of 0 or 1 – clear or almost clear – at week 16 was 33.3% with secukinumab at 300 mg, 22.1% at 150 mg, and 1.5% with placebo. The average reduction in palmoplantar PASI (Psoriasis Area Severity Index) score from baseline was 54.6% with high-dose and 35.3% with low-dose secukinumab, compared with 4.1% in placebo-treated controls, reported Dr. Gottlieb, professor and chair of dermatology at Tufts University, Boston.

Like the TRANSFIGURE trial, GESTURE will continue for 132 weeks, with the initial placebo-treated controls being randomized to secukinumab at 150 or 300 mg after week 16.

Dr. Reich reported that by 16 weeks in TRANSFIGURE, mean scores on the Nail Psoriasis Severity Index had improved by 45.3%, compared with baseline, in patients on secukinumab 300 mg, 37.9% in those on secukinumab 150 mg, and 10.8% with placebo.

The results on the skin were dramatic: a PASI 75 rate of 87.1% with secukinumab 300 mg, 77% with secukinumab 150 mg, and 5.1% with placebo. The PASI 100 response rate – meaning totally clear skin – was 31.9% with high-dose and 25.2% with lower-dose secukinumab, while there was a zero PASI 100 rate in controls.

The only adverse events more common than with placebo were nasopharyngitis and upper respiratory infections.

Dr. Reich predicted that as the ongoing TRANSFIGURE study continues well beyond 16 weeks, the nail psoriasis response rates will climb, since nails are so slow growing.

TRANSFIGURE and GESTURE are sponsored by Novartis, which markets secukinumab. Dr. Reich and Dr. Gottlieb reported having financial relationships with Novartis and numerous other pharmaceutical companies.

bjancin@frontlinemedcom