Hair & Nails

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.

To the Editor:
A 62-year-old woman was referred to the dermatology clinic for papules on both eyelids of 6 months’ duration. She underwent surgery for a thyroid gland adenoma 3 years prior and subsequently experienced hypothyroidism. Levothyroxine sodium was administered daily (100 µg initially; 50 µg over the last 1.5 years). Papules occurred on both eyelids 6 months prior to presentation and gradually increased in number. The center of each papule was filled with a black keratinous plug. The skin lesions became raised after the patient ate fatty foods. The lesions remained entirely asymptomatic and there was no family history of a similar disorder.

Physical examinations showed no systemic abnormalities. Dermatologic examination showed clustered 3- to 4-mm flesh-colored papules on both upper eyelids; the centers of the papules were filled with 1- to 2-mm black keratinous plugs (Figure 1A). Several similar skin lesions existed on the lower eyelids, nasal root, and right side of the nasal dorsum. On laboratory examination, the results of routine blood, urine, and stool tests, as well as renal and hepatic functions, electrolytes, and blood sugar levels, were within reference range. Indicators including triglyceride of 2.50 mmol/L (reference range, 0.40–1.90 mmol/L), total cholesterol of 6.31 mmol/L (reference range, 3.00–5.70 mmol/L), serum total thyroxine (T₄) of 5.32 µg/dL (reference range, 6.09–12.23 µg/dL), total triiodothyronine (T₃) of 64 ng/dL (reference range, 87–178 ng/dL), serum free thyroxine (FT₄) of 0.41 ng/dL (reference range, 0.61–1.12 ng/dL), serum free triiodothyronine (FT₃) of 182 pg/dL (reference range, 250–390 pg/dL), and thyrotropin of 33.75 µIU/mL (reference range, 0.34–5.60 µIU/mL) were not within reference range; however, thyroperoxidase antibodies, thyrotropin receptor antibodies, thyroglobulin antibodies, thyroglobulin, and calcitonin were within reference range. Color ultrasonography indicated post–subtotal resection of the bilateral thyroid glands.

Figure 1. Clustered flesh-colored papules on both upper eyelids; the centers of the papules were filled with black keratinous plugs (A). Following treatment with levothyroxine sodium, most of the skin lesions had resolved (B).

Histopathologic analysis of the skin lesions showed that the epidermis became atrophic and thinner, and several atrophic and cyst-dilated follicular structures existed inside the dermis. Some structures opened through the epidermis; the walls were squamous epithelium and keratin filled the structures (Figure 2). The condition was diagnosed as nevus comedonicus (NC).

The patient was referred to the endocrinology department and treated with levothyroxine sodium (100 µg daily). At 5-month follow-up, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions had resolved (Figure 1B).

Nevus comedonicus is an unusual skin lesion with a predilection for the face, neck, shoulders, upper arms, and trunk. The clinical manifestations include comedonelike papules with centers that are characterized by large, black, solid keratinous plugs. When the plugs are peeled off, volcanic craterlike pits will be left. The skin lesions usually are ribbonlike and clustered on 1 side of the body. Pathologic examination often shows that the epidermis is pitted downward, and the dilated follicular ostia are plugged with keratin.^1,2 Paige and Mendelson³ divided NC into 2 types: inflammatory and noninflammatory. Approximately half of NC patients experience cysts, abscesses, fistulae, and scars.⁴

The exact etiology of NC is unclear. Some researchers believe that it is a congenital hair follicle deformity; more specifically, that it is caused by a developmental defect in the hair follicles in the embryonic stage (ie, abnormal differentiation of epithelial stem cells that differentiate into follicles). Most incidences of NC occur at birth or before growth and development. However, few studies have reported late-onset NC.⁵

Figure 2. Several atrophic and cyst-dilated follicular structures existed inside the dermis. Some of them opened through the epidermis and were filled with keratin (A and B)(both H&E, original magnifications ×4 and ×10).

The relationship between NC and thyroid disease is unique. Clinical research has shown that hypothyroidism can result in hair loss and cracks.⁶ In animal experiments, hypothyroidism model mice often experienced degenerative changes of their hair follicles and hair papillae as well as changes in the telogen phase, such as thinning of the outer and inner root sheaths.⁷ Meanwhile, decreased cell proliferation activity in the hair follicles was observed. Therefore, it is reasonable to conclude that thyroid hormones have regulatory effects on the growth and development of hair follicles.⁷

A study on human hair follicles found that thyroid hormone receptor β1 is expressed in human hair follicles.⁸ Research on in vitro–cultured human hair follicles showed that thyroid hormones T₃ and T₄ upregulated the proliferation of hair matrix cells and downregulated their apoptosis. Thyroid hormones also prolonged the duration of the hair growth phase (anagen).⁹ Furthermore, expression of thyrotropin receptor was detected in human hair follicles. Because increased serum thyrotropin levels can lead to clinical hair loss, thyrotropin may inhibit the growth of hair follicles via thyrotropin receptor.¹⁰ In our patient, NC occurred on both eyelids when the patient experienced hypothyroidism following thyroid gland adenoma surgery. Following treatment with levothyroxine sodium, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions resolved. Therefore, the occurrence of NC may be related to hypothyroidism in this patient. The low thyroid hormone levels and elevated thyrotropin level possibly induced degenerative changes and injuries to the hair matrix cells, resulting in hair follicle obstruction and accumulation of keratin, which ultimately led to NC. However, the exact relationship between NC and thyroid diseases requires elucidation in future studies.

To the Editor:
A 62-year-old woman was referred to the dermatology clinic for papules on both eyelids of 6 months’ duration. She underwent surgery for a thyroid gland adenoma 3 years prior and subsequently experienced hypothyroidism. Levothyroxine sodium was administered daily (100 µg initially; 50 µg over the last 1.5 years). Papules occurred on both eyelids 6 months prior to presentation and gradually increased in number. The center of each papule was filled with a black keratinous plug. The skin lesions became raised after the patient ate fatty foods. The lesions remained entirely asymptomatic and there was no family history of a similar disorder.

Physical examinations showed no systemic abnormalities. Dermatologic examination showed clustered 3- to 4-mm flesh-colored papules on both upper eyelids; the centers of the papules were filled with 1- to 2-mm black keratinous plugs (Figure 1A). Several similar skin lesions existed on the lower eyelids, nasal root, and right side of the nasal dorsum. On laboratory examination, the results of routine blood, urine, and stool tests, as well as renal and hepatic functions, electrolytes, and blood sugar levels, were within reference range. Indicators including triglyceride of 2.50 mmol/L (reference range, 0.40–1.90 mmol/L), total cholesterol of 6.31 mmol/L (reference range, 3.00–5.70 mmol/L), serum total thyroxine (T₄) of 5.32 µg/dL (reference range, 6.09–12.23 µg/dL), total triiodothyronine (T₃) of 64 ng/dL (reference range, 87–178 ng/dL), serum free thyroxine (FT₄) of 0.41 ng/dL (reference range, 0.61–1.12 ng/dL), serum free triiodothyronine (FT₃) of 182 pg/dL (reference range, 250–390 pg/dL), and thyrotropin of 33.75 µIU/mL (reference range, 0.34–5.60 µIU/mL) were not within reference range; however, thyroperoxidase antibodies, thyrotropin receptor antibodies, thyroglobulin antibodies, thyroglobulin, and calcitonin were within reference range. Color ultrasonography indicated post–subtotal resection of the bilateral thyroid glands.

Figure 1. Clustered flesh-colored papules on both upper eyelids; the centers of the papules were filled with black keratinous plugs (A). Following treatment with levothyroxine sodium, most of the skin lesions had resolved (B).

Histopathologic analysis of the skin lesions showed that the epidermis became atrophic and thinner, and several atrophic and cyst-dilated follicular structures existed inside the dermis. Some structures opened through the epidermis; the walls were squamous epithelium and keratin filled the structures (Figure 2). The condition was diagnosed as nevus comedonicus (NC).

The patient was referred to the endocrinology department and treated with levothyroxine sodium (100 µg daily). At 5-month follow-up, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions had resolved (Figure 1B).

Nevus comedonicus is an unusual skin lesion with a predilection for the face, neck, shoulders, upper arms, and trunk. The clinical manifestations include comedonelike papules with centers that are characterized by large, black, solid keratinous plugs. When the plugs are peeled off, volcanic craterlike pits will be left. The skin lesions usually are ribbonlike and clustered on 1 side of the body. Pathologic examination often shows that the epidermis is pitted downward, and the dilated follicular ostia are plugged with keratin.^1,2 Paige and Mendelson³ divided NC into 2 types: inflammatory and noninflammatory. Approximately half of NC patients experience cysts, abscesses, fistulae, and scars.⁴

The exact etiology of NC is unclear. Some researchers believe that it is a congenital hair follicle deformity; more specifically, that it is caused by a developmental defect in the hair follicles in the embryonic stage (ie, abnormal differentiation of epithelial stem cells that differentiate into follicles). Most incidences of NC occur at birth or before growth and development. However, few studies have reported late-onset NC.⁵

Figure 2. Several atrophic and cyst-dilated follicular structures existed inside the dermis. Some of them opened through the epidermis and were filled with keratin (A and B)(both H&E, original magnifications ×4 and ×10).

The relationship between NC and thyroid disease is unique. Clinical research has shown that hypothyroidism can result in hair loss and cracks.⁶ In animal experiments, hypothyroidism model mice often experienced degenerative changes of their hair follicles and hair papillae as well as changes in the telogen phase, such as thinning of the outer and inner root sheaths.⁷ Meanwhile, decreased cell proliferation activity in the hair follicles was observed. Therefore, it is reasonable to conclude that thyroid hormones have regulatory effects on the growth and development of hair follicles.⁷

A study on human hair follicles found that thyroid hormone receptor β1 is expressed in human hair follicles.⁸ Research on in vitro–cultured human hair follicles showed that thyroid hormones T₃ and T₄ upregulated the proliferation of hair matrix cells and downregulated their apoptosis. Thyroid hormones also prolonged the duration of the hair growth phase (anagen).⁹ Furthermore, expression of thyrotropin receptor was detected in human hair follicles. Because increased serum thyrotropin levels can lead to clinical hair loss, thyrotropin may inhibit the growth of hair follicles via thyrotropin receptor.¹⁰ In our patient, NC occurred on both eyelids when the patient experienced hypothyroidism following thyroid gland adenoma surgery. Following treatment with levothyroxine sodium, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions resolved. Therefore, the occurrence of NC may be related to hypothyroidism in this patient. The low thyroid hormone levels and elevated thyrotropin level possibly induced degenerative changes and injuries to the hair matrix cells, resulting in hair follicle obstruction and accumulation of keratin, which ultimately led to NC. However, the exact relationship between NC and thyroid diseases requires elucidation in future studies.

To the Editor:
A 62-year-old woman was referred to the dermatology clinic for papules on both eyelids of 6 months’ duration. She underwent surgery for a thyroid gland adenoma 3 years prior and subsequently experienced hypothyroidism. Levothyroxine sodium was administered daily (100 µg initially; 50 µg over the last 1.5 years). Papules occurred on both eyelids 6 months prior to presentation and gradually increased in number. The center of each papule was filled with a black keratinous plug. The skin lesions became raised after the patient ate fatty foods. The lesions remained entirely asymptomatic and there was no family history of a similar disorder.

Physical examinations showed no systemic abnormalities. Dermatologic examination showed clustered 3- to 4-mm flesh-colored papules on both upper eyelids; the centers of the papules were filled with 1- to 2-mm black keratinous plugs (Figure 1A). Several similar skin lesions existed on the lower eyelids, nasal root, and right side of the nasal dorsum. On laboratory examination, the results of routine blood, urine, and stool tests, as well as renal and hepatic functions, electrolytes, and blood sugar levels, were within reference range. Indicators including triglyceride of 2.50 mmol/L (reference range, 0.40–1.90 mmol/L), total cholesterol of 6.31 mmol/L (reference range, 3.00–5.70 mmol/L), serum total thyroxine (T₄) of 5.32 µg/dL (reference range, 6.09–12.23 µg/dL), total triiodothyronine (T₃) of 64 ng/dL (reference range, 87–178 ng/dL), serum free thyroxine (FT₄) of 0.41 ng/dL (reference range, 0.61–1.12 ng/dL), serum free triiodothyronine (FT₃) of 182 pg/dL (reference range, 250–390 pg/dL), and thyrotropin of 33.75 µIU/mL (reference range, 0.34–5.60 µIU/mL) were not within reference range; however, thyroperoxidase antibodies, thyrotropin receptor antibodies, thyroglobulin antibodies, thyroglobulin, and calcitonin were within reference range. Color ultrasonography indicated post–subtotal resection of the bilateral thyroid glands.

Figure 1. Clustered flesh-colored papules on both upper eyelids; the centers of the papules were filled with black keratinous plugs (A). Following treatment with levothyroxine sodium, most of the skin lesions had resolved (B).

Histopathologic analysis of the skin lesions showed that the epidermis became atrophic and thinner, and several atrophic and cyst-dilated follicular structures existed inside the dermis. Some structures opened through the epidermis; the walls were squamous epithelium and keratin filled the structures (Figure 2). The condition was diagnosed as nevus comedonicus (NC).

The patient was referred to the endocrinology department and treated with levothyroxine sodium (100 µg daily). At 5-month follow-up, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions had resolved (Figure 1B).

Nevus comedonicus is an unusual skin lesion with a predilection for the face, neck, shoulders, upper arms, and trunk. The clinical manifestations include comedonelike papules with centers that are characterized by large, black, solid keratinous plugs. When the plugs are peeled off, volcanic craterlike pits will be left. The skin lesions usually are ribbonlike and clustered on 1 side of the body. Pathologic examination often shows that the epidermis is pitted downward, and the dilated follicular ostia are plugged with keratin.^1,2 Paige and Mendelson³ divided NC into 2 types: inflammatory and noninflammatory. Approximately half of NC patients experience cysts, abscesses, fistulae, and scars.⁴

The exact etiology of NC is unclear. Some researchers believe that it is a congenital hair follicle deformity; more specifically, that it is caused by a developmental defect in the hair follicles in the embryonic stage (ie, abnormal differentiation of epithelial stem cells that differentiate into follicles). Most incidences of NC occur at birth or before growth and development. However, few studies have reported late-onset NC.⁵

Figure 2. Several atrophic and cyst-dilated follicular structures existed inside the dermis. Some of them opened through the epidermis and were filled with keratin (A and B)(both H&E, original magnifications ×4 and ×10).

The relationship between NC and thyroid disease is unique. Clinical research has shown that hypothyroidism can result in hair loss and cracks.⁶ In animal experiments, hypothyroidism model mice often experienced degenerative changes of their hair follicles and hair papillae as well as changes in the telogen phase, such as thinning of the outer and inner root sheaths.⁷ Meanwhile, decreased cell proliferation activity in the hair follicles was observed. Therefore, it is reasonable to conclude that thyroid hormones have regulatory effects on the growth and development of hair follicles.⁷

A study on human hair follicles found that thyroid hormone receptor β1 is expressed in human hair follicles.⁸ Research on in vitro–cultured human hair follicles showed that thyroid hormones T₃ and T₄ upregulated the proliferation of hair matrix cells and downregulated their apoptosis. Thyroid hormones also prolonged the duration of the hair growth phase (anagen).⁹ Furthermore, expression of thyrotropin receptor was detected in human hair follicles. Because increased serum thyrotropin levels can lead to clinical hair loss, thyrotropin may inhibit the growth of hair follicles via thyrotropin receptor.¹⁰ In our patient, NC occurred on both eyelids when the patient experienced hypothyroidism following thyroid gland adenoma surgery. Following treatment with levothyroxine sodium, the T₄, T₃, FT₄, FT₃, and thyrotropin levels were within reference range and most of the skin lesions resolved. Therefore, the occurrence of NC may be related to hypothyroidism in this patient. The low thyroid hormone levels and elevated thyrotropin level possibly induced degenerative changes and injuries to the hair matrix cells, resulting in hair follicle obstruction and accumulation of keratin, which ultimately led to NC. However, the exact relationship between NC and thyroid diseases requires elucidation in future studies.

The Diagnosis: Circle Hairs

The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.

Circle hairs were first described in 1963.¹ These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.² Others propose that they are vestigial remains that once had a part in preserving body heat.³ Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.^2,4

It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.² If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.

Figure 1. Dermatoscopic view of hair.

Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40).

The Diagnosis: Circle Hairs

The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.

Circle hairs were first described in 1963.¹ These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.² Others propose that they are vestigial remains that once had a part in preserving body heat.³ Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.^2,4

It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.² If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.

Figure 1. Dermatoscopic view of hair.

Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40).

The Diagnosis: Circle Hairs

The patient’s hairs were visualized under dermoscopy (Figure 1). A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (Figure 2). The patient was diagnosed with circle hairs.

Circle hairs were first described in 1963.¹ These peculiar hairs grow in a circular horizontal distribution beneath the stratum corneum and are considered benign incidental findings. Their exact cause is unknown. If taken out and unrolled, their length and diameter tends to be smaller than surrounding hairs. It has been hypothesized that they are the result of hairs that lack the size necessary to perforate the stratum corneum.² Others propose that they are vestigial remains that once had a part in preserving body heat.³ Circle hairs tend to grow in elderly, hairy, and obese males, predominantly on the torso and thighs.^2,4

It is important to distinguish between circle hairs and rolled hairs. Rolled hairs may be found on the surface or beneath the stratum corneum and are associated with inflammation and keratinization abnormalities.² If taken together, these latter findings can help differentiate between the two. The importance stands in recognizing that both circle hairs and rolled hairs are benign; however, rolled hairs can be related to other skin disorders that need additional treatment.

Figure 1. Dermatoscopic view of hair.

Figure 2. A skin biopsy showed a terminal hair in a horizontal distribution that was located beneath the stratum corneum (A and B)(both Verhoeff-van Gieson, original magnifications ×40).

Topical efinaconazole’s ability to permeate the nail to the infection in onychomycosis is not hampered by the presence of infection or nail thickness, according to data from a multicenter, open-label study.

Adult patients with onychomycosis treated with efinaconazole 10% solution for 4 weeks had drug concentrations in both big and second toenails much higher than minimum inhibitory concentration (MIC) values for common onychomycosis pathogens, the researchers reported in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1388-92).

© istockphoto / thinkstockphotos.com

The topical triazole efinaconazole has a broad spectrum of activity that is particularly potent against the common onychomycosis pathogens Trichophyton rubrum,T. mentagrophytes, and Candida albicans, the investigators, led by Misao Sakamoto of Kaken Pharmaceutical in Tokyo, noted. The treatment is an alternative to oral antifungal therapy, which can have systemic side effects or drug interactions. However, transungual delivery of effective topical treatments has been hampered by low permeation rates. The goal of this study was to assess the transungual delivery of efinaconazole in onychomycosis and its fungicidal activity in the toenail.

A total of 40 patients treated their toenails with efinaconazole 5% or 10% topical solution once daily before bedtime for 28 days. Patients applied two drops of solution to both great toes and one drop to all other toenails. Nail samples were taken from the big toenails at weeks 2, 4, and 6. Fungicidal activity against T. rubrum in the ventral layer of the nails was assessed by using an in vitro human nail infection model. Concentrations of the antifungal in the toenail were similar at weeks 2 and 4 with 10% solution, whereas they were lower at week 2 than at week 4 with 5% treatment. For both doses, efinaconazole concentrations peaked at the end of week 4 and declined at week 6. Great-toenail concentrations at week 4 for the 5% and 10% solutions were 5.6 and 6.0 mg/g, respectively.

This finding might be explained by the drug diffusing into the nail bed, the study authors said. No differences in the concentrations were seen in normal or affected nails, suggesting that transungual delivery of efinaconazole was not influenced by the presence of disease.

Concentrations of the antifungal were similar in the great and second toenails, suggesting nail thickness did not affect drug accumulation. In the in vitro nail model, efinaconazole was effective in reducing fungal viability, which suggested that sufficient amounts of the antifungal were being delivered to the ventral layer of the nail plate, the researchers noted.

“The high efinaconazole concentrations in patients’ toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase III studies,” they concluded.

All authors work for Kaken Pharmaceutical or Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals, manufacturer of efinaconazole). The study was funded by Kaken and Valeant.

[email protected]

Topical efinaconazole’s ability to permeate the nail to the infection in onychomycosis is not hampered by the presence of infection or nail thickness, according to data from a multicenter, open-label study.

Adult patients with onychomycosis treated with efinaconazole 10% solution for 4 weeks had drug concentrations in both big and second toenails much higher than minimum inhibitory concentration (MIC) values for common onychomycosis pathogens, the researchers reported in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1388-92).

© istockphoto / thinkstockphotos.com

The topical triazole efinaconazole has a broad spectrum of activity that is particularly potent against the common onychomycosis pathogens Trichophyton rubrum,T. mentagrophytes, and Candida albicans, the investigators, led by Misao Sakamoto of Kaken Pharmaceutical in Tokyo, noted. The treatment is an alternative to oral antifungal therapy, which can have systemic side effects or drug interactions. However, transungual delivery of effective topical treatments has been hampered by low permeation rates. The goal of this study was to assess the transungual delivery of efinaconazole in onychomycosis and its fungicidal activity in the toenail.

A total of 40 patients treated their toenails with efinaconazole 5% or 10% topical solution once daily before bedtime for 28 days. Patients applied two drops of solution to both great toes and one drop to all other toenails. Nail samples were taken from the big toenails at weeks 2, 4, and 6. Fungicidal activity against T. rubrum in the ventral layer of the nails was assessed by using an in vitro human nail infection model. Concentrations of the antifungal in the toenail were similar at weeks 2 and 4 with 10% solution, whereas they were lower at week 2 than at week 4 with 5% treatment. For both doses, efinaconazole concentrations peaked at the end of week 4 and declined at week 6. Great-toenail concentrations at week 4 for the 5% and 10% solutions were 5.6 and 6.0 mg/g, respectively.

This finding might be explained by the drug diffusing into the nail bed, the study authors said. No differences in the concentrations were seen in normal or affected nails, suggesting that transungual delivery of efinaconazole was not influenced by the presence of disease.

Concentrations of the antifungal were similar in the great and second toenails, suggesting nail thickness did not affect drug accumulation. In the in vitro nail model, efinaconazole was effective in reducing fungal viability, which suggested that sufficient amounts of the antifungal were being delivered to the ventral layer of the nail plate, the researchers noted.

“The high efinaconazole concentrations in patients’ toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase III studies,” they concluded.

All authors work for Kaken Pharmaceutical or Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals, manufacturer of efinaconazole). The study was funded by Kaken and Valeant.

[email protected]

Topical efinaconazole’s ability to permeate the nail to the infection in onychomycosis is not hampered by the presence of infection or nail thickness, according to data from a multicenter, open-label study.

Adult patients with onychomycosis treated with efinaconazole 10% solution for 4 weeks had drug concentrations in both big and second toenails much higher than minimum inhibitory concentration (MIC) values for common onychomycosis pathogens, the researchers reported in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1388-92).

© istockphoto / thinkstockphotos.com

The topical triazole efinaconazole has a broad spectrum of activity that is particularly potent against the common onychomycosis pathogens Trichophyton rubrum,T. mentagrophytes, and Candida albicans, the investigators, led by Misao Sakamoto of Kaken Pharmaceutical in Tokyo, noted. The treatment is an alternative to oral antifungal therapy, which can have systemic side effects or drug interactions. However, transungual delivery of effective topical treatments has been hampered by low permeation rates. The goal of this study was to assess the transungual delivery of efinaconazole in onychomycosis and its fungicidal activity in the toenail.

A total of 40 patients treated their toenails with efinaconazole 5% or 10% topical solution once daily before bedtime for 28 days. Patients applied two drops of solution to both great toes and one drop to all other toenails. Nail samples were taken from the big toenails at weeks 2, 4, and 6. Fungicidal activity against T. rubrum in the ventral layer of the nails was assessed by using an in vitro human nail infection model. Concentrations of the antifungal in the toenail were similar at weeks 2 and 4 with 10% solution, whereas they were lower at week 2 than at week 4 with 5% treatment. For both doses, efinaconazole concentrations peaked at the end of week 4 and declined at week 6. Great-toenail concentrations at week 4 for the 5% and 10% solutions were 5.6 and 6.0 mg/g, respectively.

This finding might be explained by the drug diffusing into the nail bed, the study authors said. No differences in the concentrations were seen in normal or affected nails, suggesting that transungual delivery of efinaconazole was not influenced by the presence of disease.

Concentrations of the antifungal were similar in the great and second toenails, suggesting nail thickness did not affect drug accumulation. In the in vitro nail model, efinaconazole was effective in reducing fungal viability, which suggested that sufficient amounts of the antifungal were being delivered to the ventral layer of the nail plate, the researchers noted.

“The high efinaconazole concentrations in patients’ toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase III studies,” they concluded.

All authors work for Kaken Pharmaceutical or Dow Pharmaceutical Sciences (a division of Valeant Pharmaceuticals, manufacturer of efinaconazole). The study was funded by Kaken and Valeant.

[email protected]

The vehicle used in the topical antifungal efinaconazole 10% spread into the subungual space between the nail bed and nail plate, reaching the site of infection in patients with toenail onychomycosis, according to results from a small study.

Efinaconazole topical solution 10% has a broad spectrum of antifungal activity against the organisms most associated with toenail onychomycosis and has shown efficacy in two phase III trials, reported Dr. Boni E. Elweski of the University of Alabama, Birmingham, and her colleagues in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1394-98). The vehicle for the topical solution was developed with low surface tension to create a greater probability of nail plate permeation and access through the subungual space, the study authors wrote.

To assess the effectiveness of the solution in reaching the site of infection, the researchers applied the vehicle to the toenails of 11 adult patients with moderate to severe onychomycosis. Two drops of test material (saturated fluorescein 0.6% in vehicle solution) were applied to the distal end of the toenail, and a brush was used to spread the solution below the surface of the nail and distal skin area in contact with the nail. Standard and UV pictures of the toenails were taken after 20-30 minutes, and the process was repeated 40-45 minutes later. Approximately 1-2 mm of the affected toenail was clipped, photographed, and clipped again.

The findings showed that the vehicle had spread into the subungual space, with deposition of fluorescein seen wherever the vehicle had reached, including the nail bed. Nail clippings also showed deposition to the underside of the nail plate. The data support the instructions for the use of efinaconazole topical solution 10%, which specifically state that the solution be brushed on the skin around the nail as well as the nail plate, the authors said. However, they noted that the study was performed without the active drug, and that results could differ if efinaconazole were included.

All of the study authors are either advisers for, or employees of, Valeant Pharmaceuticals, manufacturer of topical 10% efinaconazole.

The vehicle used in the topical antifungal efinaconazole 10% spread into the subungual space between the nail bed and nail plate, reaching the site of infection in patients with toenail onychomycosis, according to results from a small study.

Efinaconazole topical solution 10% has a broad spectrum of antifungal activity against the organisms most associated with toenail onychomycosis and has shown efficacy in two phase III trials, reported Dr. Boni E. Elweski of the University of Alabama, Birmingham, and her colleagues in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1394-98). The vehicle for the topical solution was developed with low surface tension to create a greater probability of nail plate permeation and access through the subungual space, the study authors wrote.

To assess the effectiveness of the solution in reaching the site of infection, the researchers applied the vehicle to the toenails of 11 adult patients with moderate to severe onychomycosis. Two drops of test material (saturated fluorescein 0.6% in vehicle solution) were applied to the distal end of the toenail, and a brush was used to spread the solution below the surface of the nail and distal skin area in contact with the nail. Standard and UV pictures of the toenails were taken after 20-30 minutes, and the process was repeated 40-45 minutes later. Approximately 1-2 mm of the affected toenail was clipped, photographed, and clipped again.

The findings showed that the vehicle had spread into the subungual space, with deposition of fluorescein seen wherever the vehicle had reached, including the nail bed. Nail clippings also showed deposition to the underside of the nail plate. The data support the instructions for the use of efinaconazole topical solution 10%, which specifically state that the solution be brushed on the skin around the nail as well as the nail plate, the authors said. However, they noted that the study was performed without the active drug, and that results could differ if efinaconazole were included.

All of the study authors are either advisers for, or employees of, Valeant Pharmaceuticals, manufacturer of topical 10% efinaconazole.

The vehicle used in the topical antifungal efinaconazole 10% spread into the subungual space between the nail bed and nail plate, reaching the site of infection in patients with toenail onychomycosis, according to results from a small study.

Efinaconazole topical solution 10% has a broad spectrum of antifungal activity against the organisms most associated with toenail onychomycosis and has shown efficacy in two phase III trials, reported Dr. Boni E. Elweski of the University of Alabama, Birmingham, and her colleagues in the Journal of Drugs in Dermatology (J. Drugs Dermatol. 2014;13:1394-98). The vehicle for the topical solution was developed with low surface tension to create a greater probability of nail plate permeation and access through the subungual space, the study authors wrote.

To assess the effectiveness of the solution in reaching the site of infection, the researchers applied the vehicle to the toenails of 11 adult patients with moderate to severe onychomycosis. Two drops of test material (saturated fluorescein 0.6% in vehicle solution) were applied to the distal end of the toenail, and a brush was used to spread the solution below the surface of the nail and distal skin area in contact with the nail. Standard and UV pictures of the toenails were taken after 20-30 minutes, and the process was repeated 40-45 minutes later. Approximately 1-2 mm of the affected toenail was clipped, photographed, and clipped again.

The findings showed that the vehicle had spread into the subungual space, with deposition of fluorescein seen wherever the vehicle had reached, including the nail bed. Nail clippings also showed deposition to the underside of the nail plate. The data support the instructions for the use of efinaconazole topical solution 10%, which specifically state that the solution be brushed on the skin around the nail as well as the nail plate, the authors said. However, they noted that the study was performed without the active drug, and that results could differ if efinaconazole were included.

All of the study authors are either advisers for, or employees of, Valeant Pharmaceuticals, manufacturer of topical 10% efinaconazole.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

VANCOUVER, B.C. – Cicatricial alopecia should be considered a "trichologic emergency," Dr. Jerry Shapiro advised at the annual meeting of the Pacific Dermatologic Association. The hair loss may be permanent, "so it’s important to get on top of this, and not just sit out the condition."

Cicatricial alopecia is characterized by a loss of follicular ostia with replacement by fibrous tissue. Primary cicatricial alopecia targets the hair follicle and involves preferential destruction of the follicular epithelium with sparing of interfollicular dermis. In secondary cicatricial alopecia, "the follicle is an innocent bystander" that is destroyed in the course of infectious tinea capitis, infiltrative diseases such as metastatic disease and sarcoidosis, trauma such as radiation exposure and burns, and inflammatory conditions such as pemphigus vulgaris.

The North American Hair Research Society consensus classification of cicatricial alopecia is based on the infiltrate: lymphocytic, neutrophilic, mixed, or nonspecific.

"We determine our treatment decisions based on the infiltrate," said Dr. Shapiro, whose New York– and Vancouver–based practices are devoted exclusively to hair and scalp disorders. "A biopsy can be crucial when you’re managing these patients, so you know how actively inflamed the lesions are and what the primary infiltrate is. We always take a 4-mm punch biopsy, and we may take two. We’ll do one for transverse sectioning and another one for longitudinal sectioning."

"Sometimes there’s (histologic) overlap between lupus erythematosus or lichen planopilaris," he said. The clinical and pathologic findings can be variable, so the differential diagnosis is difficult. "There are no cures, and the cause of these conditions is unknown."

Discoid lupus erythematosus often presents with atrophy and extensive hair loss. A hallmark feature is central follicular hyperkeratosis. If less than 10% of the scalp is involved, Dr. Shapiro uses ultrapotent topical corticosteroids such as clobetasol with or without triamcinolone acetonide (TCA) injections (10 mg/cc for a maximum total of 2 ccs per sitting once a month). "We inject into the areas that are red as well as the surrounding areas so that it doesn’t spread," he said.

If a patient responds to this regimen he continues to use it on an as-needed basis. For nonresponders, Dr. Shapiro resorts to hydroxychloroquine 200 mg b.i.d. or isotretinoin 40 mg b.i.d. Other alternatives can include topical tacrolimus. Others have used tazarotene and imiquimod, he said, but "I find the latter two too irritating."

For patients with 10% or greater scalp involvement, Dr. Shapiro uses hydroxychloroquine plus ultrapotent topical steroids, plus TCA injections, plus bridging therapy with prednisone, usually with 40 mg prednisone tapered.

Patients with lichen planopilaris typically present with peripheral hyperkeratosis, or frontal fibrosing alopecia, which is marked by loss of a strip of hair at the front and/or the sides of the scalp. Frontal fibrosing alopecia is "a silent epidemic. In Vancouver, I’m seeing about seven cases per day of this, and three to four cases per day in New York. Sometimes, the eyebrows are the first sign of hair loss. Many times it can go completely around the scalp, so it’s [considered] marginally fibrosing," Dr. Shapiro said.

Frontal fibrosing alopecia primarily affects postmenopausal women. "We think there is a hormonal component that is causing this, but there is also a trigger in the environment," Dr. Shapiro said. "We don’t know what the trigger is, but certain countries have less of it. China does not see that much of it, nor does Saudi Arabia."

Dr. Shapiro and his associates recently published a retrospective study of 62 cases of frontal fibrosing alopecia seen between January 2004 and March 2012. Of the 62 patients, 61 were women (Int. J. Dermatol. 2014 [doi:10.1111/ijd.12479]). Their average age was 61 years and the age of onset ranged from 18 to 81 years. In terms of symptoms, 22 (35%) patients were asymptomatic, 42 (68%) had a history of female pattern hair loss, and 50 (81%) patients’ eyebrows were affected.

In Dr. Shapiro’s experience, intralesional TCA with or without oral tetracycline or hydroxychloroquine may help to halt or slow the progression of frontal fibrosing alopecia. He typically uses intralesional Kenalog 2.5 mL/cc. "I do 30 injections for 3 ccs total: 0.1 cc/injection site and I go from one ear to the other," Dr. Shapiro said. "We’ll also use clobetasol solution at the beginning and taper to a betamethasone solution. Other things to consider are tacrolimus, Cetaphil cleanser, and finasteride."

Dr. Shapiro disclosed that he is a consultant to Johnson & Johnson, GSK/Stiefel, Allergan, MSD, and Applied Biology.

[email protected]

On Twitter @dougbrunk

VANCOUVER, B.C. – Cicatricial alopecia should be considered a "trichologic emergency," Dr. Jerry Shapiro advised at the annual meeting of the Pacific Dermatologic Association. The hair loss may be permanent, "so it’s important to get on top of this, and not just sit out the condition."

Cicatricial alopecia is characterized by a loss of follicular ostia with replacement by fibrous tissue. Primary cicatricial alopecia targets the hair follicle and involves preferential destruction of the follicular epithelium with sparing of interfollicular dermis. In secondary cicatricial alopecia, "the follicle is an innocent bystander" that is destroyed in the course of infectious tinea capitis, infiltrative diseases such as metastatic disease and sarcoidosis, trauma such as radiation exposure and burns, and inflammatory conditions such as pemphigus vulgaris.

The North American Hair Research Society consensus classification of cicatricial alopecia is based on the infiltrate: lymphocytic, neutrophilic, mixed, or nonspecific.

"We determine our treatment decisions based on the infiltrate," said Dr. Shapiro, whose New York– and Vancouver–based practices are devoted exclusively to hair and scalp disorders. "A biopsy can be crucial when you’re managing these patients, so you know how actively inflamed the lesions are and what the primary infiltrate is. We always take a 4-mm punch biopsy, and we may take two. We’ll do one for transverse sectioning and another one for longitudinal sectioning."

"Sometimes there’s (histologic) overlap between lupus erythematosus or lichen planopilaris," he said. The clinical and pathologic findings can be variable, so the differential diagnosis is difficult. "There are no cures, and the cause of these conditions is unknown."

Discoid lupus erythematosus often presents with atrophy and extensive hair loss. A hallmark feature is central follicular hyperkeratosis. If less than 10% of the scalp is involved, Dr. Shapiro uses ultrapotent topical corticosteroids such as clobetasol with or without triamcinolone acetonide (TCA) injections (10 mg/cc for a maximum total of 2 ccs per sitting once a month). "We inject into the areas that are red as well as the surrounding areas so that it doesn’t spread," he said.

If a patient responds to this regimen he continues to use it on an as-needed basis. For nonresponders, Dr. Shapiro resorts to hydroxychloroquine 200 mg b.i.d. or isotretinoin 40 mg b.i.d. Other alternatives can include topical tacrolimus. Others have used tazarotene and imiquimod, he said, but "I find the latter two too irritating."

For patients with 10% or greater scalp involvement, Dr. Shapiro uses hydroxychloroquine plus ultrapotent topical steroids, plus TCA injections, plus bridging therapy with prednisone, usually with 40 mg prednisone tapered.

Patients with lichen planopilaris typically present with peripheral hyperkeratosis, or frontal fibrosing alopecia, which is marked by loss of a strip of hair at the front and/or the sides of the scalp. Frontal fibrosing alopecia is "a silent epidemic. In Vancouver, I’m seeing about seven cases per day of this, and three to four cases per day in New York. Sometimes, the eyebrows are the first sign of hair loss. Many times it can go completely around the scalp, so it’s [considered] marginally fibrosing," Dr. Shapiro said.

Frontal fibrosing alopecia primarily affects postmenopausal women. "We think there is a hormonal component that is causing this, but there is also a trigger in the environment," Dr. Shapiro said. "We don’t know what the trigger is, but certain countries have less of it. China does not see that much of it, nor does Saudi Arabia."

Dr. Shapiro and his associates recently published a retrospective study of 62 cases of frontal fibrosing alopecia seen between January 2004 and March 2012. Of the 62 patients, 61 were women (Int. J. Dermatol. 2014 [doi:10.1111/ijd.12479]). Their average age was 61 years and the age of onset ranged from 18 to 81 years. In terms of symptoms, 22 (35%) patients were asymptomatic, 42 (68%) had a history of female pattern hair loss, and 50 (81%) patients’ eyebrows were affected.

In Dr. Shapiro’s experience, intralesional TCA with or without oral tetracycline or hydroxychloroquine may help to halt or slow the progression of frontal fibrosing alopecia. He typically uses intralesional Kenalog 2.5 mL/cc. "I do 30 injections for 3 ccs total: 0.1 cc/injection site and I go from one ear to the other," Dr. Shapiro said. "We’ll also use clobetasol solution at the beginning and taper to a betamethasone solution. Other things to consider are tacrolimus, Cetaphil cleanser, and finasteride."

Dr. Shapiro disclosed that he is a consultant to Johnson & Johnson, GSK/Stiefel, Allergan, MSD, and Applied Biology.

[email protected]

On Twitter @dougbrunk

VANCOUVER, B.C. – Cicatricial alopecia should be considered a "trichologic emergency," Dr. Jerry Shapiro advised at the annual meeting of the Pacific Dermatologic Association. The hair loss may be permanent, "so it’s important to get on top of this, and not just sit out the condition."

Cicatricial alopecia is characterized by a loss of follicular ostia with replacement by fibrous tissue. Primary cicatricial alopecia targets the hair follicle and involves preferential destruction of the follicular epithelium with sparing of interfollicular dermis. In secondary cicatricial alopecia, "the follicle is an innocent bystander" that is destroyed in the course of infectious tinea capitis, infiltrative diseases such as metastatic disease and sarcoidosis, trauma such as radiation exposure and burns, and inflammatory conditions such as pemphigus vulgaris.

The North American Hair Research Society consensus classification of cicatricial alopecia is based on the infiltrate: lymphocytic, neutrophilic, mixed, or nonspecific.

"We determine our treatment decisions based on the infiltrate," said Dr. Shapiro, whose New York– and Vancouver–based practices are devoted exclusively to hair and scalp disorders. "A biopsy can be crucial when you’re managing these patients, so you know how actively inflamed the lesions are and what the primary infiltrate is. We always take a 4-mm punch biopsy, and we may take two. We’ll do one for transverse sectioning and another one for longitudinal sectioning."

"Sometimes there’s (histologic) overlap between lupus erythematosus or lichen planopilaris," he said. The clinical and pathologic findings can be variable, so the differential diagnosis is difficult. "There are no cures, and the cause of these conditions is unknown."

Discoid lupus erythematosus often presents with atrophy and extensive hair loss. A hallmark feature is central follicular hyperkeratosis. If less than 10% of the scalp is involved, Dr. Shapiro uses ultrapotent topical corticosteroids such as clobetasol with or without triamcinolone acetonide (TCA) injections (10 mg/cc for a maximum total of 2 ccs per sitting once a month). "We inject into the areas that are red as well as the surrounding areas so that it doesn’t spread," he said.

If a patient responds to this regimen he continues to use it on an as-needed basis. For nonresponders, Dr. Shapiro resorts to hydroxychloroquine 200 mg b.i.d. or isotretinoin 40 mg b.i.d. Other alternatives can include topical tacrolimus. Others have used tazarotene and imiquimod, he said, but "I find the latter two too irritating."

For patients with 10% or greater scalp involvement, Dr. Shapiro uses hydroxychloroquine plus ultrapotent topical steroids, plus TCA injections, plus bridging therapy with prednisone, usually with 40 mg prednisone tapered.

Patients with lichen planopilaris typically present with peripheral hyperkeratosis, or frontal fibrosing alopecia, which is marked by loss of a strip of hair at the front and/or the sides of the scalp. Frontal fibrosing alopecia is "a silent epidemic. In Vancouver, I’m seeing about seven cases per day of this, and three to four cases per day in New York. Sometimes, the eyebrows are the first sign of hair loss. Many times it can go completely around the scalp, so it’s [considered] marginally fibrosing," Dr. Shapiro said.

Frontal fibrosing alopecia primarily affects postmenopausal women. "We think there is a hormonal component that is causing this, but there is also a trigger in the environment," Dr. Shapiro said. "We don’t know what the trigger is, but certain countries have less of it. China does not see that much of it, nor does Saudi Arabia."

Dr. Shapiro and his associates recently published a retrospective study of 62 cases of frontal fibrosing alopecia seen between January 2004 and March 2012. Of the 62 patients, 61 were women (Int. J. Dermatol. 2014 [doi:10.1111/ijd.12479]). Their average age was 61 years and the age of onset ranged from 18 to 81 years. In terms of symptoms, 22 (35%) patients were asymptomatic, 42 (68%) had a history of female pattern hair loss, and 50 (81%) patients’ eyebrows were affected.

In Dr. Shapiro’s experience, intralesional TCA with or without oral tetracycline or hydroxychloroquine may help to halt or slow the progression of frontal fibrosing alopecia. He typically uses intralesional Kenalog 2.5 mL/cc. "I do 30 injections for 3 ccs total: 0.1 cc/injection site and I go from one ear to the other," Dr. Shapiro said. "We’ll also use clobetasol solution at the beginning and taper to a betamethasone solution. Other things to consider are tacrolimus, Cetaphil cleanser, and finasteride."

Dr. Shapiro disclosed that he is a consultant to Johnson & Johnson, GSK/Stiefel, Allergan, MSD, and Applied Biology.

[email protected]

On Twitter @dougbrunk