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Clinical clarity grows about toenail disorder, experts report
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
AT AAD 2022
New trial data show hair growth in more alopecia areata patients
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
AT AAD 2022
Platelet-rich plasma for hair regrowth requires art and science
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2022
COVID-19–alopecia areata link? Review doesn’t find much evidence
A new
If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”
The review was published in JAAD International.
While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.
Systematic review
The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”
However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.
For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).
Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.
The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.
The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”
In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.
Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”
However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.
“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”
No study funding is reported. The review authors and Dr. King report no relevant disclosures.
A new
If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”
The review was published in JAAD International.
While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.
Systematic review
The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”
However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.
For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).
Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.
The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.
The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”
In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.
Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”
However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.
“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”
No study funding is reported. The review authors and Dr. King report no relevant disclosures.
A new
If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”
The review was published in JAAD International.
While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.
Systematic review
The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”
However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.
For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).
Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.
The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.
The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”
In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.
Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”
However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.
“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”
No study funding is reported. The review authors and Dr. King report no relevant disclosures.
FROM JAAD INTERNATIONAL
Oral tofacitinib produces hair regrowth in children with alopecia areata
and published in Pediatric Dermatology.
The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.
“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.
“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.
The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.
Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
Study details
Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.
The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.
Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.
The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.
Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.
“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
Other research
In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.
Mechanisms, concerns
The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.
A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.
Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.
At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.
Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.
Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.
A version of this article first appeared on Medscape.com.
and published in Pediatric Dermatology.
The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.
“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.
“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.
The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.
Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
Study details
Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.
The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.
Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.
The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.
Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.
“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
Other research
In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.
Mechanisms, concerns
The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.
A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.
Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.
At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.
Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.
Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.
A version of this article first appeared on Medscape.com.
and published in Pediatric Dermatology.
The 11 pediatric patients, ages 8-18 years, all with a diagnosis of AA, were treated with tofacitinib. Eight patients, or nearly 73%, experienced hair regrowth, while the other three (27.3%) did not, as the investigators reported in the retrospective chart review.
“A success rate of 73% is very good,” said lead author Cory A. Dunnick, MD, professor of dermatology and director of clinical trials at the University of Colorado at Denver, Aurora. No serious adverse events occurred, and adverse events of any kind were limited, the researchers found.
“It is important to get information into the literature about potential treatments for severe alopecia areata because there is no [Food and Drug Administration]–approved therapy at the present time,” Dr. Dunnick told this news organization. Patients’ insurance plans often deny non–FDA-approved therapies unless there are data to support their use.
The researchers found no correlation between the dose, duration of treatment, or the presence of comorbidities and clinical response.
Oral tofacitinib has been shown to be effective and well tolerated for AA in adults, the researchers said. They referred to recent studies that have used JAK inhibitors, including tofacitinib, “in an effort to inhibit T-cell activation and halt disease progression in adult and pediatric patients” with AA.
Study details
Of the 11 patients evaluated, 6 had alopecia universalis, 1 had alopecia totalis, and 4 had patchy AA. Concomitant medical conditions known to be associated with AA affected four patients. These included atopic dermatitis, autoimmune hypothyroidism, and asthma. One patient reported having two brothers with AA.
The median disease duration was 6 years. “In my experience, JAK inhibitors are less effective for patients with longstanding – more than 10 years – alopecia totalis or alopecia universalis,” Dr. Dunnick said.
Previously, patients had been given methotrexate, oral prednisone, intralesional triamcinolone, topical corticosteroids, and topical diphenylcyclopropenone. During treatment with tofacitinib, 5 of the 11 patients also received topical steroid treatment.
The study was a retrospective chart review, so dosing was not standardized, the researchers said. Most took 5-10 mg twice daily. Median treatment time was 32 months, with a range of 5-39 months.
Patients with a complete or near complete clinical response were categorized as responders; subjectively, these were the patients who had persistent hair regrowth over more than 50% of affected areas. Five patients had complete regrowth of hair on the scalp, eyebrows, and body during treatment. Others had incomplete responses. For instance, one patient had improved growth of eyelashes and eyebrows but not on the scalp. Once the medication was increased to 15 mg daily, the patient had complete regrowth of body hair, eyelashes, and eyebrows but slow regrowth on the scalp after 1 year of treatment.
“Patients are very happy with regrowth of their hair,” Dr. Dunnick said, noting that severe AA affects self-esteem and quality of life.
Other research
In a retrospective study that looked at the effects of oral tofacitinib given to 14 preadolescent patients with AA, 9 experienced “clinically significant improvement” in their Severity of Alopecia Tool score. Three had complete remission, and seven (63.6%) had more than a 50% improvement in the score.
Mechanisms, concerns
The researchers of the current study explained that interferon signaling activity through the JAK pathways is a key mediator of the inflammation and cytotoxic T-cell response in AA. That modulation of the signaling may decrease disease progression, as the results of the current chart review suggest.
A main concern, the researchers wrote, is the potential for significant adverse events. Although this chart review did not find any, the researchers did see some transient lab abnormalities. One study found lab abnormalities in such measures as triglycerides and cholesterol.
Asked to comment on the study results, Brett King, MD, PHD, associate professor of dermatology at Yale University, New Haven, Conn., said that the study “is an important addition to a series of articles dating back to 2017 showing efficacy of tofacitinib in the pediatric age group.” The results are similar to those of previous studies, “showing that severe AA can be treated effectively with tofacitinib. Cumulatively, there is significant data to support treatment of this age group with JAK inhibitors,” he said.
At the 2021 European Academy of Dermatology and Venereology meeting, Dr. King presented the results of two phase 3 studies, which found that treatment with the oral JAK inhibitor baricitinib resulted in substantial hair growth in adults with AA. He and colleagues have also reported positive results of tofacitinib in treating AA in four children ages 8-10, with alopecia totalis and alopecia universalis, and in adolescents with AA.
Currently, three large, randomized, phase 3 clinical trials of other JAK inhibitors for AA are underway – ritlecitinib, baricitinib, and ruxolitinib – and the ritlecitinib trial includes adolescents (ages 12 years and older). “It is the results of these trials that we eagerly await, because FDA approval will bring greater access to these treatments,” Dr. King said.
Dr. Dunnick has disclosed no relevant financial relationships. Dr. King has served on advisory boards and/or is a consultant and/or a clinical trial investigator for AbbVie, Bristol-Myers Squibb, Concert Pharmaceuticals, Eli Lilly, Incyte, Pfizer, and others. He is on speaker bureaus for AbbVie, Incyte, Pfizer, and others.
A version of this article first appeared on Medscape.com.
FROM PEDIATRIC DERMATOLOGY
Male alopecia agents ranked by efficacy in meta-analysis
While up to 90% of men experience AGA in their lifetime, only three therapies are currently approved for treatment of the condition by the Food and Drug Administration – topical minoxidil, oral finasteride 1 mg, and low-level light therapy.
However, with common use of off-label oral minoxidil, as well as oral dutasteride and higher doses of oral finasteride, the latter two being 5-alpha reductase inhibitors, Aditya K. Gupta, MD, PhD, of Mediprobe Research, in London, Ont., and colleagues sought to compare the data on the three agents. Their results were published in JAMA Dermatology.
They note that, while there have been recent comparisons between oral and topical minoxidil, “to our knowledge no study has determined the comparative effectiveness of these 2 [formulations] with that of local and systemic dutasteride and finasteride.”
For the meta-analysis, the authors identified 23 studies meeting their criteria, involving patients with mean ages ranging from 22.8 to 41.8 years.
For the primary endpoint of the greatest increases in total hair count at 24 weeks, the analysis showed the 0.5-mg/day dose of dutasteride topped the list, with significantly greater efficacy, compared with 1 mg/day of finasteride (mean difference, 7.1 hairs per cm2).
The 0.5-mg/d dutasteride dose also showed higher efficacy than oral minoxidil at 0.25 mg/day (mean difference, 23.7 hairs per cm2) and 5 mg/day (mean difference, 15.0 hairs per cm2) and topical minoxidil at 2% (mean difference, 8.5 hairs per cm2).
For the secondary endpoint of the greatest increase in terminal hair count at 24 weeks, the 5-mg/day dose of minoxidil had significantly greater efficacy compared with the 0.25-mg/day dose of the drug, as well as with minoxidil’s 2% and 5% topical formulations.
The minoxidil 5-mg/day dose was also significantly more effective than 1 mg/day of finasteride for terminal hair count at 24 weeks.
In longer-term outcomes at 48 weeks, the greatest increase in total hair count at 48 weeks was observed with 5 mg/day of finasteride, which was significantly more effective, compared with 2% topical minoxidil.
And the greatest increase in terminal hair count at 48 weeks was observed with 1 mg/day of oral finasteride, which was significantly more effective than 2% as well as 5% topical minoxidil.
Based on the results, the authors ranked the agents in a decreasing order of efficacy: 0.5 mg/day of oral dutasteride, 5 mg/day of oral finasteride, 5 mg/day of oral minoxidil, 1 mg/day of oral finasteride, 5% topical minoxidil, 2% topical minoxidil, and 0.25 mg/day of oral minoxidil.
Commenting on the analysis in an accompanying editorial, Kathie P. Huang, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, and Maryanne M. Senna, MD, of the department of dermatology, Massachusetts General Hospital, Boston, said the results, in general, are consistent with their experiences, noting that 2% minoxidil is typically not used in men.
They noted that, “although topical minoxidil ranked higher than the very-low-dose 0.25 mg oral minoxidil, our personal experience is that oral minoxidil at doses of 1.25 mg to 5 mg are far superior to topical minoxidil for treating AGA.”
Adverse event considerations important
Importantly, however, strong consideration needs to be given to adverse-event profiles, as well as patient comorbidities in selecting agents, the editorial authors asserted.
With 1 mg finasteride, for instance, potential adverse events include decreased libido, erectile dysfunction, decreased ejaculatory volume, reduction in sperm count, testicular pain, depression, and gynecomastia, they noted.
And while finasteride appears to be associated with a decreased risk of prostate cancer, those receiving the drug who do develop prostate cancer may be diagnosed with higher-grade prostate cancer; however, that “might be related to tissue sampling artifact,” the editorial authors said.
Less has been published on dutasteride’s adverse-event profile, and that, in itself, is a concern.
Overall, “as more direct-to-consumer companies treating male AGA emerge, it is especially important that the potential risks of these medications be made clear to patients,” they added.
Further commenting on the analysis to this news organization, Antonella Tosti, MD, the Fredric Brandt Endowed Professor of Dermatology and Cutaneous Surgery at the University of Miami, said the study offers some important insights – and caveats.
“I think this is a very interesting study, but you have to consider what works for your patients,” she said.
Dr. Tosti noted that the 5-mg dose of minoxidil is a concern in terms of side effects. “That dose is pretty high and could feasibly cause some hypertrichosis, which can be a concern to men as well as women.”
She agrees that the lack of data on side effects with dutasteride is also a concern, especially in light of some of the known side effects with other agents.
“That’s why I don’t use it very much in younger patients – because I’m afraid it could potentially affect their fertility,” Dr. Tosti said.
In general, Dr. Tosti said she finds a combination of agents provides the best results, as many clinicians use.
“I find dutasteride (0.5 mg/day) plus oral minoxidil (1-2.5 mg/day) plus topical 5% minoxidil is the best combination,” she said.
The authors and Dr. Tosti disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
While up to 90% of men experience AGA in their lifetime, only three therapies are currently approved for treatment of the condition by the Food and Drug Administration – topical minoxidil, oral finasteride 1 mg, and low-level light therapy.
However, with common use of off-label oral minoxidil, as well as oral dutasteride and higher doses of oral finasteride, the latter two being 5-alpha reductase inhibitors, Aditya K. Gupta, MD, PhD, of Mediprobe Research, in London, Ont., and colleagues sought to compare the data on the three agents. Their results were published in JAMA Dermatology.
They note that, while there have been recent comparisons between oral and topical minoxidil, “to our knowledge no study has determined the comparative effectiveness of these 2 [formulations] with that of local and systemic dutasteride and finasteride.”
For the meta-analysis, the authors identified 23 studies meeting their criteria, involving patients with mean ages ranging from 22.8 to 41.8 years.
For the primary endpoint of the greatest increases in total hair count at 24 weeks, the analysis showed the 0.5-mg/day dose of dutasteride topped the list, with significantly greater efficacy, compared with 1 mg/day of finasteride (mean difference, 7.1 hairs per cm2).
The 0.5-mg/d dutasteride dose also showed higher efficacy than oral minoxidil at 0.25 mg/day (mean difference, 23.7 hairs per cm2) and 5 mg/day (mean difference, 15.0 hairs per cm2) and topical minoxidil at 2% (mean difference, 8.5 hairs per cm2).
For the secondary endpoint of the greatest increase in terminal hair count at 24 weeks, the 5-mg/day dose of minoxidil had significantly greater efficacy compared with the 0.25-mg/day dose of the drug, as well as with minoxidil’s 2% and 5% topical formulations.
The minoxidil 5-mg/day dose was also significantly more effective than 1 mg/day of finasteride for terminal hair count at 24 weeks.
In longer-term outcomes at 48 weeks, the greatest increase in total hair count at 48 weeks was observed with 5 mg/day of finasteride, which was significantly more effective, compared with 2% topical minoxidil.
And the greatest increase in terminal hair count at 48 weeks was observed with 1 mg/day of oral finasteride, which was significantly more effective than 2% as well as 5% topical minoxidil.
Based on the results, the authors ranked the agents in a decreasing order of efficacy: 0.5 mg/day of oral dutasteride, 5 mg/day of oral finasteride, 5 mg/day of oral minoxidil, 1 mg/day of oral finasteride, 5% topical minoxidil, 2% topical minoxidil, and 0.25 mg/day of oral minoxidil.
Commenting on the analysis in an accompanying editorial, Kathie P. Huang, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, and Maryanne M. Senna, MD, of the department of dermatology, Massachusetts General Hospital, Boston, said the results, in general, are consistent with their experiences, noting that 2% minoxidil is typically not used in men.
They noted that, “although topical minoxidil ranked higher than the very-low-dose 0.25 mg oral minoxidil, our personal experience is that oral minoxidil at doses of 1.25 mg to 5 mg are far superior to topical minoxidil for treating AGA.”
Adverse event considerations important
Importantly, however, strong consideration needs to be given to adverse-event profiles, as well as patient comorbidities in selecting agents, the editorial authors asserted.
With 1 mg finasteride, for instance, potential adverse events include decreased libido, erectile dysfunction, decreased ejaculatory volume, reduction in sperm count, testicular pain, depression, and gynecomastia, they noted.
And while finasteride appears to be associated with a decreased risk of prostate cancer, those receiving the drug who do develop prostate cancer may be diagnosed with higher-grade prostate cancer; however, that “might be related to tissue sampling artifact,” the editorial authors said.
Less has been published on dutasteride’s adverse-event profile, and that, in itself, is a concern.
Overall, “as more direct-to-consumer companies treating male AGA emerge, it is especially important that the potential risks of these medications be made clear to patients,” they added.
Further commenting on the analysis to this news organization, Antonella Tosti, MD, the Fredric Brandt Endowed Professor of Dermatology and Cutaneous Surgery at the University of Miami, said the study offers some important insights – and caveats.
“I think this is a very interesting study, but you have to consider what works for your patients,” she said.
Dr. Tosti noted that the 5-mg dose of minoxidil is a concern in terms of side effects. “That dose is pretty high and could feasibly cause some hypertrichosis, which can be a concern to men as well as women.”
She agrees that the lack of data on side effects with dutasteride is also a concern, especially in light of some of the known side effects with other agents.
“That’s why I don’t use it very much in younger patients – because I’m afraid it could potentially affect their fertility,” Dr. Tosti said.
In general, Dr. Tosti said she finds a combination of agents provides the best results, as many clinicians use.
“I find dutasteride (0.5 mg/day) plus oral minoxidil (1-2.5 mg/day) plus topical 5% minoxidil is the best combination,” she said.
The authors and Dr. Tosti disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
While up to 90% of men experience AGA in their lifetime, only three therapies are currently approved for treatment of the condition by the Food and Drug Administration – topical minoxidil, oral finasteride 1 mg, and low-level light therapy.
However, with common use of off-label oral minoxidil, as well as oral dutasteride and higher doses of oral finasteride, the latter two being 5-alpha reductase inhibitors, Aditya K. Gupta, MD, PhD, of Mediprobe Research, in London, Ont., and colleagues sought to compare the data on the three agents. Their results were published in JAMA Dermatology.
They note that, while there have been recent comparisons between oral and topical minoxidil, “to our knowledge no study has determined the comparative effectiveness of these 2 [formulations] with that of local and systemic dutasteride and finasteride.”
For the meta-analysis, the authors identified 23 studies meeting their criteria, involving patients with mean ages ranging from 22.8 to 41.8 years.
For the primary endpoint of the greatest increases in total hair count at 24 weeks, the analysis showed the 0.5-mg/day dose of dutasteride topped the list, with significantly greater efficacy, compared with 1 mg/day of finasteride (mean difference, 7.1 hairs per cm2).
The 0.5-mg/d dutasteride dose also showed higher efficacy than oral minoxidil at 0.25 mg/day (mean difference, 23.7 hairs per cm2) and 5 mg/day (mean difference, 15.0 hairs per cm2) and topical minoxidil at 2% (mean difference, 8.5 hairs per cm2).
For the secondary endpoint of the greatest increase in terminal hair count at 24 weeks, the 5-mg/day dose of minoxidil had significantly greater efficacy compared with the 0.25-mg/day dose of the drug, as well as with minoxidil’s 2% and 5% topical formulations.
The minoxidil 5-mg/day dose was also significantly more effective than 1 mg/day of finasteride for terminal hair count at 24 weeks.
In longer-term outcomes at 48 weeks, the greatest increase in total hair count at 48 weeks was observed with 5 mg/day of finasteride, which was significantly more effective, compared with 2% topical minoxidil.
And the greatest increase in terminal hair count at 48 weeks was observed with 1 mg/day of oral finasteride, which was significantly more effective than 2% as well as 5% topical minoxidil.
Based on the results, the authors ranked the agents in a decreasing order of efficacy: 0.5 mg/day of oral dutasteride, 5 mg/day of oral finasteride, 5 mg/day of oral minoxidil, 1 mg/day of oral finasteride, 5% topical minoxidil, 2% topical minoxidil, and 0.25 mg/day of oral minoxidil.
Commenting on the analysis in an accompanying editorial, Kathie P. Huang, MD, of the department of dermatology, Brigham and Women’s Hospital, Boston, and Maryanne M. Senna, MD, of the department of dermatology, Massachusetts General Hospital, Boston, said the results, in general, are consistent with their experiences, noting that 2% minoxidil is typically not used in men.
They noted that, “although topical minoxidil ranked higher than the very-low-dose 0.25 mg oral minoxidil, our personal experience is that oral minoxidil at doses of 1.25 mg to 5 mg are far superior to topical minoxidil for treating AGA.”
Adverse event considerations important
Importantly, however, strong consideration needs to be given to adverse-event profiles, as well as patient comorbidities in selecting agents, the editorial authors asserted.
With 1 mg finasteride, for instance, potential adverse events include decreased libido, erectile dysfunction, decreased ejaculatory volume, reduction in sperm count, testicular pain, depression, and gynecomastia, they noted.
And while finasteride appears to be associated with a decreased risk of prostate cancer, those receiving the drug who do develop prostate cancer may be diagnosed with higher-grade prostate cancer; however, that “might be related to tissue sampling artifact,” the editorial authors said.
Less has been published on dutasteride’s adverse-event profile, and that, in itself, is a concern.
Overall, “as more direct-to-consumer companies treating male AGA emerge, it is especially important that the potential risks of these medications be made clear to patients,” they added.
Further commenting on the analysis to this news organization, Antonella Tosti, MD, the Fredric Brandt Endowed Professor of Dermatology and Cutaneous Surgery at the University of Miami, said the study offers some important insights – and caveats.
“I think this is a very interesting study, but you have to consider what works for your patients,” she said.
Dr. Tosti noted that the 5-mg dose of minoxidil is a concern in terms of side effects. “That dose is pretty high and could feasibly cause some hypertrichosis, which can be a concern to men as well as women.”
She agrees that the lack of data on side effects with dutasteride is also a concern, especially in light of some of the known side effects with other agents.
“That’s why I don’t use it very much in younger patients – because I’m afraid it could potentially affect their fertility,” Dr. Tosti said.
In general, Dr. Tosti said she finds a combination of agents provides the best results, as many clinicians use.
“I find dutasteride (0.5 mg/day) plus oral minoxidil (1-2.5 mg/day) plus topical 5% minoxidil is the best combination,” she said.
The authors and Dr. Tosti disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Hairstyling Practices to Prevent Hair Damage and Alopecia in Women of African Descent
Central centrifugal cicatricial alopecia (CCCA), traction alopecia, and acquired proximal trichorrhexis nodosa are 3 forms of alopecia that disproportionately affect women of African descent.1 Central centrifugal cicatricial alopecia is characterized by a shiny smooth patch of hair loss over the vertex of the scalp that spreads centrifugally (Figure 1).1-4 Traction alopecia results from prolonged or repeated tension on the hair root that causes mechanical damage, hair loss, and shortening of hairs along the frontotemporal line (the so-called fringe sign)(Figure 2).1,3,5 Acquired proximal trichorrhexis nodosa, a result of trauma, is identified by a substantial number of hairs breaking off midshaft during a hair pull test.1 By understanding the unique structural properties and grooming methods of hair in women of African descent, physicians can better manage and stop the progression of hair loss before it becomes permanent.1,4,5
The characterization of hair between and within ethnic groups is challenging and lies on a spectrum.6,7 Many early studies broadly differentiated hair in 3 ethnic subgroups: African, Asian, and Caucasian6-8; older descriptions of hair texture also included terms such as straight, wavy, curly, and kinky.6 However, defining hair texture should be based on an approach that is more objective than an inaccurate ethnicity-based classification or the use of subjective, ill-defined, and overlapping descriptive terms.7 The segmentation tree analysis method (STAM) is an objective classification system that, when applied to hair, yields 8 curl-type groups (I=straight; VIII=tightly curly) based on curve diameter, curl index, number of waves, and twists.6-9 (We discuss the “tightly coiled” [group VII] through “tight, interwoven small curls” [group VIII] groups in the STAM classification of hair.)
Highly textured hair has been found to be more susceptible to breakage than other hair types because of an increased percentage of spirals and relatively fewer elastic fibers anchoring hair follicles to the dermis.1-4,10,11 In a cross-section, the hair shaft of individuals of African descent tends to be more elliptical and kidney shaped than the hair shaft of Asian individuals, which is round and has a large diameter, and the hair shaft of Caucasian individuals, which structurally lies between African and Asian hair.1,2,4,11 This axial asymmetry and section size contributes to points of lower tensile strength and increased fragility, which are exacerbated by everyday combing and grooming. Curvature of the hair follicle leads to the characteristic curly and spiral nature of African hair, which can lead to increased knotting.2,4
Practice Gap
Among women of African descent, a variety of hairstyles and hair treatments frequently are employed to allow for ease of management and self-expression.1 Many of these practices have been implicated as risk factors for alopecia. Simply advising patients to avoid tight hairstyles is ineffective because tension is subjective and difficult to quantify.5 Furthermore, it might be unreasonable to ask a patient to discontinue a hairstyle or treatment when they are unaware of less damaging alternatives.3,5
We provide an overview of hairstyles for patients who have highly textured hair so that physicians can better identify high-risk hairstyles and provide individualized recommendations for safer alternatives.1,3,5
Techniques for Hair Straightening
Traditional thermal straightening uses a hot comb or flat iron1,2,4,12 to temporarily disrupt hydrogen bonds within the hair shafts, which is reversible with exposure to moisture.1,2,4,5 Patients repeat this process every 1 or 2 weeks to offset the effects of normal perspiration and environmental humidity.5,12 Thermal straightening techniques can lead to increased fragility of the hair shaft and loss of tensile strength.11
Alternate methods of hair straightening use lye (sodium hydroxide) or nonlye (lithium and guanidine hydroxide) “relaxers” to permanently disrupt hydrogen and disulfide bonds in the hair shaft, which can damage and weaken hair.1-5,11,12 Touch-ups to the roots often are performed every 6 to 8 weeks.1,2
Chemical relaxers historically have been associated with CCCA but have not been definitively implicated as causative.2,3,4,13 Most studies have not demonstrated a statistically significant association between chemical relaxers and CCCA because, with a few exceptions,13 studies have either been based on surveys or have not employed trichoscopy or scalp biopsy. In one of those studies, patients with CCCA were determined to be 12.37 times more likely to have used a chemical relaxer in the past (P<.001).13 In another study of 39 women in Nigeria, those who had frequent and prolonged use of a chemical relaxer developed scarring alopecia more often than those who did not use a chemical relaxer (P<.0001). However, it is now known that the pathogenesis of CCCA may be related to an upregulation in genes implicated in fibroproliferative disorders (FPDs), a group of conditions characterized by aberrant wound healing, low-grade inflammation and irritation, and excessive fibrosis.14 They include systemic sclerosis, keloids, atherosclerosis, and uterine fibroids. The risk for certain FPDs is increased in individuals of African descent, and this increased risk is thought to be secondary to the protective effect that profibrotic alleles offer against helminths found in sub-Saharan Africa. A study of 5 patients with biopsy-proven CCCA found that there was increased expression of platelet-derived growth factor gene, PDGF; collagen I gene, COL I; collagen III gene, COL III; matrix metallopeptidase 1 gene, MMP1; matrix metallopeptidase 2 gene, MMP2; matrix metallopeptidase 7 gene, MMP7; and matrix metallopeptidase 9 gene, MMP9, in an affected scalp compared with an unaffected scalp.14 Still, chemical relaxers weaken the hair shaft and follicle structure, increasing the possibility of hair breakage and allowing for inflammation and trauma to render negative follicular effects.3,13
The following interventions can be recommended to patients who thermally or chemically treat their hair to prevent hair damage:
- Decrease the frequency of thermal straightening.
- Use lower heat settings on flat irons and blow-dryers.
- Thermally straighten only clean dry hair.
- Regularly trim split ends.
- Use moisturizing shampoos and conditioners.
- Have a trained professional apply a chemical relaxer, if affordable.
- Consider decreasing (1) the frequency of chemical relaxer touch-up (to every 8 to 10 weeks) and (2) the overall manipulation of hair. There is a fine balance between not treating often enough and treating too often: The transition point between chemically processed hair and grown-out roots is a high-tension breakage point.
- Apply a thick protective emollient (known as scalp basing) to the scalp before applying a relaxer1,5; this protects the scalp from irritation.
Techniques for Braids, Weaves, and Twists
Braids and cornrows, sewn-in or glued-on extensions and weaves, and twists are popular hairstyles. When applied improperly, however, they also can lead to alopecia.1-5,11,12 When braids are too tight, the patient might complain of headache. Characteristic tenting—hair pulled so tight that the scalp is raised—might be observed.3,5 Twists are achieved by interlocking 2 pieces of hair, which are held together by styling gel.1,4 When twists remain over many months, hair eventually knots or tangles into a permanent locking pattern (also known as dreadlocks, dreads, or locs).1,2,4 In some cases, the persistent weight of dreadlocks results in hair breakage.1,3,5
The following recommendations can be made to patients who style their hair with braids or cornrows, extensions or weaves, twists, or dreadlocks:
- Apply these styles with as little traction as possible.
- Change the direction in which braids and cornrows are styled frequently to avoid constant tension over the same areas.
- Opt for larger-diameter braids and twists.
- Leave these styles in place no longer than 2 or 3 months; consider removing extensions and weaves every 3 or 4 weeks.
- Remove extensions and weaves if they cause pain or irritation.
- Avoid the use of glue; opt for loosely sewn-in extensions and weaves.
- Consider the alternative of crochet braiding; this is a protective way to apply extensions to hair and can be worn straight, curly, braided, or twisted.5,12
Techniques for Other Hairstyling Practices
Low-hanging ponytails or buns, wigs, and natural hairstyles generally are considered safe when applied correctly.1,5 The following recommendations can be made to patients who have a low-hanging ponytail, bun, wig, or other natural hairstyle:
- Before a wig is applied, hold the hair against the scalp with a cotton, nylon, or satin wig cap and with clips, tapes, or bonds. Because satin does not cause constant friction or absorb moisture, it is the safest material for a wig cap.5
- Achieve a natural hairstyle by cutting off chemically processed hair and allowing hair to grow out.5
- Hair that has not been thermally or chemically processed better withstands the stresses of traction, pulling, and brushing.5
- For women with natural hair, wash hair at least every 2 weeks and moisturize frequently.5,12
- Caution patients that adding synthetic or human hair (ie, extensions, weaves) to any hairstyle to increase volume or length using glue or sewing techniques1-4,11 can cause problems. The extra weight and tension of extensions and weaves can lead to alopecia. Glue can trigger an irritant or allergic reaction, especially in women who have a latex allergy.1,4,5,11
Practice Implications
Women of African descent might be more susceptible to alopecia because of the distinctive structural properties of their hair and the various hair treatments and styles they often employ. Physicians should be knowledgeable when counseling these patients on their hair care practices. It also is important to understand that it might not be feasible for a patient to completely discontinue a hair treatment or style. In that situation, be prepared to make recommendations for safer hairstyling practices.
- Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther. 2004;17:164-176. doi:10.1111/j.1396-0296.2004.04017.x
- Herskovitz I, Miteva M. Central centrifugal cicatricial alopecia: challenges and solutions. Clin Cosmet Investig Dermatol. 2016;9:175-181. doi:10.2147/CCID.S100816
- Tanus A, Oliveira CCC, Villarreal DJ, et al. Black women’s hair: the main scalp dermatoses and aesthetic practices in women of African ethnicity. An Bras Dermatol. 2015;90:450-465. doi:10.1590/abd1806-4841.20152845
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668. doi:10.1016/j.jaad.2008.09.066
- Haskin A, Aguh C. All hairstyles are not created equal: what the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75:606-611. doi:10.1016/j.jaad.2016.02.1162
- Loussouarn G, Garcel A-L, Lozano I, et al. Worldwide diversity of hair curliness: a new method of assessment. Int J Dermatol. 2007;46(suppl 1):2-6. doi:10.1111/j.1365-4632.2007.03453.x
- De la Mettrie R, Saint-Léger D, Loussouarn G, et al. Shape variability and classification of human hair: a worldwide approach. Hum Biol. 2007;79:265-281. doi:10.1353/hub.2007.0045
- Takahashi T. Unique hair properties that emerge from combinations of multiple races. Cosmetics. 2019;6:36. https://doi.org/10.3390/cosmetics6020036
- Cloete E, Khumalo NP, Ngoepe MN. The what, why and how of curly hair: a review. Proc Math Phys Eng Sci. 2019;475:20190516. doi:10.1098/rspa.2019.0516
- Westgate GE, Ginger RS, Green MR. The biology and genetics of curly hair. Exp Dermatol. 2017;26:483-490. doi:10.1111/exd.13347
- McMichael AJ. Ethnic hair update: past and present. J Am Acad Dermatol. 2003;48(6 suppl):S127-S133. doi:10.1067/mjd.2003.278
- Roseborough IE, McMichael AJ. Hair care practices in African-American patients. Semin Cutan Med Surg. 2009;28:103-108. doi:10.1016/j.sder.2009.04.007
- Narasimman M, De Bedout V, Castillo DE, et al. Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia. Int J Trichology. 2020;12:176-181. doi:10.4103/ijt.ijt_37_20
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904-912.e901. doi:10.1016/j.jaad.2018.05.1257
Central centrifugal cicatricial alopecia (CCCA), traction alopecia, and acquired proximal trichorrhexis nodosa are 3 forms of alopecia that disproportionately affect women of African descent.1 Central centrifugal cicatricial alopecia is characterized by a shiny smooth patch of hair loss over the vertex of the scalp that spreads centrifugally (Figure 1).1-4 Traction alopecia results from prolonged or repeated tension on the hair root that causes mechanical damage, hair loss, and shortening of hairs along the frontotemporal line (the so-called fringe sign)(Figure 2).1,3,5 Acquired proximal trichorrhexis nodosa, a result of trauma, is identified by a substantial number of hairs breaking off midshaft during a hair pull test.1 By understanding the unique structural properties and grooming methods of hair in women of African descent, physicians can better manage and stop the progression of hair loss before it becomes permanent.1,4,5
The characterization of hair between and within ethnic groups is challenging and lies on a spectrum.6,7 Many early studies broadly differentiated hair in 3 ethnic subgroups: African, Asian, and Caucasian6-8; older descriptions of hair texture also included terms such as straight, wavy, curly, and kinky.6 However, defining hair texture should be based on an approach that is more objective than an inaccurate ethnicity-based classification or the use of subjective, ill-defined, and overlapping descriptive terms.7 The segmentation tree analysis method (STAM) is an objective classification system that, when applied to hair, yields 8 curl-type groups (I=straight; VIII=tightly curly) based on curve diameter, curl index, number of waves, and twists.6-9 (We discuss the “tightly coiled” [group VII] through “tight, interwoven small curls” [group VIII] groups in the STAM classification of hair.)
Highly textured hair has been found to be more susceptible to breakage than other hair types because of an increased percentage of spirals and relatively fewer elastic fibers anchoring hair follicles to the dermis.1-4,10,11 In a cross-section, the hair shaft of individuals of African descent tends to be more elliptical and kidney shaped than the hair shaft of Asian individuals, which is round and has a large diameter, and the hair shaft of Caucasian individuals, which structurally lies between African and Asian hair.1,2,4,11 This axial asymmetry and section size contributes to points of lower tensile strength and increased fragility, which are exacerbated by everyday combing and grooming. Curvature of the hair follicle leads to the characteristic curly and spiral nature of African hair, which can lead to increased knotting.2,4
Practice Gap
Among women of African descent, a variety of hairstyles and hair treatments frequently are employed to allow for ease of management and self-expression.1 Many of these practices have been implicated as risk factors for alopecia. Simply advising patients to avoid tight hairstyles is ineffective because tension is subjective and difficult to quantify.5 Furthermore, it might be unreasonable to ask a patient to discontinue a hairstyle or treatment when they are unaware of less damaging alternatives.3,5
We provide an overview of hairstyles for patients who have highly textured hair so that physicians can better identify high-risk hairstyles and provide individualized recommendations for safer alternatives.1,3,5
Techniques for Hair Straightening
Traditional thermal straightening uses a hot comb or flat iron1,2,4,12 to temporarily disrupt hydrogen bonds within the hair shafts, which is reversible with exposure to moisture.1,2,4,5 Patients repeat this process every 1 or 2 weeks to offset the effects of normal perspiration and environmental humidity.5,12 Thermal straightening techniques can lead to increased fragility of the hair shaft and loss of tensile strength.11
Alternate methods of hair straightening use lye (sodium hydroxide) or nonlye (lithium and guanidine hydroxide) “relaxers” to permanently disrupt hydrogen and disulfide bonds in the hair shaft, which can damage and weaken hair.1-5,11,12 Touch-ups to the roots often are performed every 6 to 8 weeks.1,2
Chemical relaxers historically have been associated with CCCA but have not been definitively implicated as causative.2,3,4,13 Most studies have not demonstrated a statistically significant association between chemical relaxers and CCCA because, with a few exceptions,13 studies have either been based on surveys or have not employed trichoscopy or scalp biopsy. In one of those studies, patients with CCCA were determined to be 12.37 times more likely to have used a chemical relaxer in the past (P<.001).13 In another study of 39 women in Nigeria, those who had frequent and prolonged use of a chemical relaxer developed scarring alopecia more often than those who did not use a chemical relaxer (P<.0001). However, it is now known that the pathogenesis of CCCA may be related to an upregulation in genes implicated in fibroproliferative disorders (FPDs), a group of conditions characterized by aberrant wound healing, low-grade inflammation and irritation, and excessive fibrosis.14 They include systemic sclerosis, keloids, atherosclerosis, and uterine fibroids. The risk for certain FPDs is increased in individuals of African descent, and this increased risk is thought to be secondary to the protective effect that profibrotic alleles offer against helminths found in sub-Saharan Africa. A study of 5 patients with biopsy-proven CCCA found that there was increased expression of platelet-derived growth factor gene, PDGF; collagen I gene, COL I; collagen III gene, COL III; matrix metallopeptidase 1 gene, MMP1; matrix metallopeptidase 2 gene, MMP2; matrix metallopeptidase 7 gene, MMP7; and matrix metallopeptidase 9 gene, MMP9, in an affected scalp compared with an unaffected scalp.14 Still, chemical relaxers weaken the hair shaft and follicle structure, increasing the possibility of hair breakage and allowing for inflammation and trauma to render negative follicular effects.3,13
The following interventions can be recommended to patients who thermally or chemically treat their hair to prevent hair damage:
- Decrease the frequency of thermal straightening.
- Use lower heat settings on flat irons and blow-dryers.
- Thermally straighten only clean dry hair.
- Regularly trim split ends.
- Use moisturizing shampoos and conditioners.
- Have a trained professional apply a chemical relaxer, if affordable.
- Consider decreasing (1) the frequency of chemical relaxer touch-up (to every 8 to 10 weeks) and (2) the overall manipulation of hair. There is a fine balance between not treating often enough and treating too often: The transition point between chemically processed hair and grown-out roots is a high-tension breakage point.
- Apply a thick protective emollient (known as scalp basing) to the scalp before applying a relaxer1,5; this protects the scalp from irritation.
Techniques for Braids, Weaves, and Twists
Braids and cornrows, sewn-in or glued-on extensions and weaves, and twists are popular hairstyles. When applied improperly, however, they also can lead to alopecia.1-5,11,12 When braids are too tight, the patient might complain of headache. Characteristic tenting—hair pulled so tight that the scalp is raised—might be observed.3,5 Twists are achieved by interlocking 2 pieces of hair, which are held together by styling gel.1,4 When twists remain over many months, hair eventually knots or tangles into a permanent locking pattern (also known as dreadlocks, dreads, or locs).1,2,4 In some cases, the persistent weight of dreadlocks results in hair breakage.1,3,5
The following recommendations can be made to patients who style their hair with braids or cornrows, extensions or weaves, twists, or dreadlocks:
- Apply these styles with as little traction as possible.
- Change the direction in which braids and cornrows are styled frequently to avoid constant tension over the same areas.
- Opt for larger-diameter braids and twists.
- Leave these styles in place no longer than 2 or 3 months; consider removing extensions and weaves every 3 or 4 weeks.
- Remove extensions and weaves if they cause pain or irritation.
- Avoid the use of glue; opt for loosely sewn-in extensions and weaves.
- Consider the alternative of crochet braiding; this is a protective way to apply extensions to hair and can be worn straight, curly, braided, or twisted.5,12
Techniques for Other Hairstyling Practices
Low-hanging ponytails or buns, wigs, and natural hairstyles generally are considered safe when applied correctly.1,5 The following recommendations can be made to patients who have a low-hanging ponytail, bun, wig, or other natural hairstyle:
- Before a wig is applied, hold the hair against the scalp with a cotton, nylon, or satin wig cap and with clips, tapes, or bonds. Because satin does not cause constant friction or absorb moisture, it is the safest material for a wig cap.5
- Achieve a natural hairstyle by cutting off chemically processed hair and allowing hair to grow out.5
- Hair that has not been thermally or chemically processed better withstands the stresses of traction, pulling, and brushing.5
- For women with natural hair, wash hair at least every 2 weeks and moisturize frequently.5,12
- Caution patients that adding synthetic or human hair (ie, extensions, weaves) to any hairstyle to increase volume or length using glue or sewing techniques1-4,11 can cause problems. The extra weight and tension of extensions and weaves can lead to alopecia. Glue can trigger an irritant or allergic reaction, especially in women who have a latex allergy.1,4,5,11
Practice Implications
Women of African descent might be more susceptible to alopecia because of the distinctive structural properties of their hair and the various hair treatments and styles they often employ. Physicians should be knowledgeable when counseling these patients on their hair care practices. It also is important to understand that it might not be feasible for a patient to completely discontinue a hair treatment or style. In that situation, be prepared to make recommendations for safer hairstyling practices.
Central centrifugal cicatricial alopecia (CCCA), traction alopecia, and acquired proximal trichorrhexis nodosa are 3 forms of alopecia that disproportionately affect women of African descent.1 Central centrifugal cicatricial alopecia is characterized by a shiny smooth patch of hair loss over the vertex of the scalp that spreads centrifugally (Figure 1).1-4 Traction alopecia results from prolonged or repeated tension on the hair root that causes mechanical damage, hair loss, and shortening of hairs along the frontotemporal line (the so-called fringe sign)(Figure 2).1,3,5 Acquired proximal trichorrhexis nodosa, a result of trauma, is identified by a substantial number of hairs breaking off midshaft during a hair pull test.1 By understanding the unique structural properties and grooming methods of hair in women of African descent, physicians can better manage and stop the progression of hair loss before it becomes permanent.1,4,5
The characterization of hair between and within ethnic groups is challenging and lies on a spectrum.6,7 Many early studies broadly differentiated hair in 3 ethnic subgroups: African, Asian, and Caucasian6-8; older descriptions of hair texture also included terms such as straight, wavy, curly, and kinky.6 However, defining hair texture should be based on an approach that is more objective than an inaccurate ethnicity-based classification or the use of subjective, ill-defined, and overlapping descriptive terms.7 The segmentation tree analysis method (STAM) is an objective classification system that, when applied to hair, yields 8 curl-type groups (I=straight; VIII=tightly curly) based on curve diameter, curl index, number of waves, and twists.6-9 (We discuss the “tightly coiled” [group VII] through “tight, interwoven small curls” [group VIII] groups in the STAM classification of hair.)
Highly textured hair has been found to be more susceptible to breakage than other hair types because of an increased percentage of spirals and relatively fewer elastic fibers anchoring hair follicles to the dermis.1-4,10,11 In a cross-section, the hair shaft of individuals of African descent tends to be more elliptical and kidney shaped than the hair shaft of Asian individuals, which is round and has a large diameter, and the hair shaft of Caucasian individuals, which structurally lies between African and Asian hair.1,2,4,11 This axial asymmetry and section size contributes to points of lower tensile strength and increased fragility, which are exacerbated by everyday combing and grooming. Curvature of the hair follicle leads to the characteristic curly and spiral nature of African hair, which can lead to increased knotting.2,4
Practice Gap
Among women of African descent, a variety of hairstyles and hair treatments frequently are employed to allow for ease of management and self-expression.1 Many of these practices have been implicated as risk factors for alopecia. Simply advising patients to avoid tight hairstyles is ineffective because tension is subjective and difficult to quantify.5 Furthermore, it might be unreasonable to ask a patient to discontinue a hairstyle or treatment when they are unaware of less damaging alternatives.3,5
We provide an overview of hairstyles for patients who have highly textured hair so that physicians can better identify high-risk hairstyles and provide individualized recommendations for safer alternatives.1,3,5
Techniques for Hair Straightening
Traditional thermal straightening uses a hot comb or flat iron1,2,4,12 to temporarily disrupt hydrogen bonds within the hair shafts, which is reversible with exposure to moisture.1,2,4,5 Patients repeat this process every 1 or 2 weeks to offset the effects of normal perspiration and environmental humidity.5,12 Thermal straightening techniques can lead to increased fragility of the hair shaft and loss of tensile strength.11
Alternate methods of hair straightening use lye (sodium hydroxide) or nonlye (lithium and guanidine hydroxide) “relaxers” to permanently disrupt hydrogen and disulfide bonds in the hair shaft, which can damage and weaken hair.1-5,11,12 Touch-ups to the roots often are performed every 6 to 8 weeks.1,2
Chemical relaxers historically have been associated with CCCA but have not been definitively implicated as causative.2,3,4,13 Most studies have not demonstrated a statistically significant association between chemical relaxers and CCCA because, with a few exceptions,13 studies have either been based on surveys or have not employed trichoscopy or scalp biopsy. In one of those studies, patients with CCCA were determined to be 12.37 times more likely to have used a chemical relaxer in the past (P<.001).13 In another study of 39 women in Nigeria, those who had frequent and prolonged use of a chemical relaxer developed scarring alopecia more often than those who did not use a chemical relaxer (P<.0001). However, it is now known that the pathogenesis of CCCA may be related to an upregulation in genes implicated in fibroproliferative disorders (FPDs), a group of conditions characterized by aberrant wound healing, low-grade inflammation and irritation, and excessive fibrosis.14 They include systemic sclerosis, keloids, atherosclerosis, and uterine fibroids. The risk for certain FPDs is increased in individuals of African descent, and this increased risk is thought to be secondary to the protective effect that profibrotic alleles offer against helminths found in sub-Saharan Africa. A study of 5 patients with biopsy-proven CCCA found that there was increased expression of platelet-derived growth factor gene, PDGF; collagen I gene, COL I; collagen III gene, COL III; matrix metallopeptidase 1 gene, MMP1; matrix metallopeptidase 2 gene, MMP2; matrix metallopeptidase 7 gene, MMP7; and matrix metallopeptidase 9 gene, MMP9, in an affected scalp compared with an unaffected scalp.14 Still, chemical relaxers weaken the hair shaft and follicle structure, increasing the possibility of hair breakage and allowing for inflammation and trauma to render negative follicular effects.3,13
The following interventions can be recommended to patients who thermally or chemically treat their hair to prevent hair damage:
- Decrease the frequency of thermal straightening.
- Use lower heat settings on flat irons and blow-dryers.
- Thermally straighten only clean dry hair.
- Regularly trim split ends.
- Use moisturizing shampoos and conditioners.
- Have a trained professional apply a chemical relaxer, if affordable.
- Consider decreasing (1) the frequency of chemical relaxer touch-up (to every 8 to 10 weeks) and (2) the overall manipulation of hair. There is a fine balance between not treating often enough and treating too often: The transition point between chemically processed hair and grown-out roots is a high-tension breakage point.
- Apply a thick protective emollient (known as scalp basing) to the scalp before applying a relaxer1,5; this protects the scalp from irritation.
Techniques for Braids, Weaves, and Twists
Braids and cornrows, sewn-in or glued-on extensions and weaves, and twists are popular hairstyles. When applied improperly, however, they also can lead to alopecia.1-5,11,12 When braids are too tight, the patient might complain of headache. Characteristic tenting—hair pulled so tight that the scalp is raised—might be observed.3,5 Twists are achieved by interlocking 2 pieces of hair, which are held together by styling gel.1,4 When twists remain over many months, hair eventually knots or tangles into a permanent locking pattern (also known as dreadlocks, dreads, or locs).1,2,4 In some cases, the persistent weight of dreadlocks results in hair breakage.1,3,5
The following recommendations can be made to patients who style their hair with braids or cornrows, extensions or weaves, twists, or dreadlocks:
- Apply these styles with as little traction as possible.
- Change the direction in which braids and cornrows are styled frequently to avoid constant tension over the same areas.
- Opt for larger-diameter braids and twists.
- Leave these styles in place no longer than 2 or 3 months; consider removing extensions and weaves every 3 or 4 weeks.
- Remove extensions and weaves if they cause pain or irritation.
- Avoid the use of glue; opt for loosely sewn-in extensions and weaves.
- Consider the alternative of crochet braiding; this is a protective way to apply extensions to hair and can be worn straight, curly, braided, or twisted.5,12
Techniques for Other Hairstyling Practices
Low-hanging ponytails or buns, wigs, and natural hairstyles generally are considered safe when applied correctly.1,5 The following recommendations can be made to patients who have a low-hanging ponytail, bun, wig, or other natural hairstyle:
- Before a wig is applied, hold the hair against the scalp with a cotton, nylon, or satin wig cap and with clips, tapes, or bonds. Because satin does not cause constant friction or absorb moisture, it is the safest material for a wig cap.5
- Achieve a natural hairstyle by cutting off chemically processed hair and allowing hair to grow out.5
- Hair that has not been thermally or chemically processed better withstands the stresses of traction, pulling, and brushing.5
- For women with natural hair, wash hair at least every 2 weeks and moisturize frequently.5,12
- Caution patients that adding synthetic or human hair (ie, extensions, weaves) to any hairstyle to increase volume or length using glue or sewing techniques1-4,11 can cause problems. The extra weight and tension of extensions and weaves can lead to alopecia. Glue can trigger an irritant or allergic reaction, especially in women who have a latex allergy.1,4,5,11
Practice Implications
Women of African descent might be more susceptible to alopecia because of the distinctive structural properties of their hair and the various hair treatments and styles they often employ. Physicians should be knowledgeable when counseling these patients on their hair care practices. It also is important to understand that it might not be feasible for a patient to completely discontinue a hair treatment or style. In that situation, be prepared to make recommendations for safer hairstyling practices.
- Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther. 2004;17:164-176. doi:10.1111/j.1396-0296.2004.04017.x
- Herskovitz I, Miteva M. Central centrifugal cicatricial alopecia: challenges and solutions. Clin Cosmet Investig Dermatol. 2016;9:175-181. doi:10.2147/CCID.S100816
- Tanus A, Oliveira CCC, Villarreal DJ, et al. Black women’s hair: the main scalp dermatoses and aesthetic practices in women of African ethnicity. An Bras Dermatol. 2015;90:450-465. doi:10.1590/abd1806-4841.20152845
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668. doi:10.1016/j.jaad.2008.09.066
- Haskin A, Aguh C. All hairstyles are not created equal: what the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75:606-611. doi:10.1016/j.jaad.2016.02.1162
- Loussouarn G, Garcel A-L, Lozano I, et al. Worldwide diversity of hair curliness: a new method of assessment. Int J Dermatol. 2007;46(suppl 1):2-6. doi:10.1111/j.1365-4632.2007.03453.x
- De la Mettrie R, Saint-Léger D, Loussouarn G, et al. Shape variability and classification of human hair: a worldwide approach. Hum Biol. 2007;79:265-281. doi:10.1353/hub.2007.0045
- Takahashi T. Unique hair properties that emerge from combinations of multiple races. Cosmetics. 2019;6:36. https://doi.org/10.3390/cosmetics6020036
- Cloete E, Khumalo NP, Ngoepe MN. The what, why and how of curly hair: a review. Proc Math Phys Eng Sci. 2019;475:20190516. doi:10.1098/rspa.2019.0516
- Westgate GE, Ginger RS, Green MR. The biology and genetics of curly hair. Exp Dermatol. 2017;26:483-490. doi:10.1111/exd.13347
- McMichael AJ. Ethnic hair update: past and present. J Am Acad Dermatol. 2003;48(6 suppl):S127-S133. doi:10.1067/mjd.2003.278
- Roseborough IE, McMichael AJ. Hair care practices in African-American patients. Semin Cutan Med Surg. 2009;28:103-108. doi:10.1016/j.sder.2009.04.007
- Narasimman M, De Bedout V, Castillo DE, et al. Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia. Int J Trichology. 2020;12:176-181. doi:10.4103/ijt.ijt_37_20
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904-912.e901. doi:10.1016/j.jaad.2018.05.1257
- Callender VD, McMichael AJ, Cohen GF. Medical and surgical therapies for alopecias in black women. Dermatol Ther. 2004;17:164-176. doi:10.1111/j.1396-0296.2004.04017.x
- Herskovitz I, Miteva M. Central centrifugal cicatricial alopecia: challenges and solutions. Clin Cosmet Investig Dermatol. 2016;9:175-181. doi:10.2147/CCID.S100816
- Tanus A, Oliveira CCC, Villarreal DJ, et al. Black women’s hair: the main scalp dermatoses and aesthetic practices in women of African ethnicity. An Bras Dermatol. 2015;90:450-465. doi:10.1590/abd1806-4841.20152845
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668. doi:10.1016/j.jaad.2008.09.066
- Haskin A, Aguh C. All hairstyles are not created equal: what the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75:606-611. doi:10.1016/j.jaad.2016.02.1162
- Loussouarn G, Garcel A-L, Lozano I, et al. Worldwide diversity of hair curliness: a new method of assessment. Int J Dermatol. 2007;46(suppl 1):2-6. doi:10.1111/j.1365-4632.2007.03453.x
- De la Mettrie R, Saint-Léger D, Loussouarn G, et al. Shape variability and classification of human hair: a worldwide approach. Hum Biol. 2007;79:265-281. doi:10.1353/hub.2007.0045
- Takahashi T. Unique hair properties that emerge from combinations of multiple races. Cosmetics. 2019;6:36. https://doi.org/10.3390/cosmetics6020036
- Cloete E, Khumalo NP, Ngoepe MN. The what, why and how of curly hair: a review. Proc Math Phys Eng Sci. 2019;475:20190516. doi:10.1098/rspa.2019.0516
- Westgate GE, Ginger RS, Green MR. The biology and genetics of curly hair. Exp Dermatol. 2017;26:483-490. doi:10.1111/exd.13347
- McMichael AJ. Ethnic hair update: past and present. J Am Acad Dermatol. 2003;48(6 suppl):S127-S133. doi:10.1067/mjd.2003.278
- Roseborough IE, McMichael AJ. Hair care practices in African-American patients. Semin Cutan Med Surg. 2009;28:103-108. doi:10.1016/j.sder.2009.04.007
- Narasimman M, De Bedout V, Castillo DE, et al. Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia. Int J Trichology. 2020;12:176-181. doi:10.4103/ijt.ijt_37_20
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904-912.e901. doi:10.1016/j.jaad.2018.05.1257
Severe Acute Systemic Reaction After the First Injections of Ixekizumab
Case Report
A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.
Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.
Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.
At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×103/μL (reference range, 3.54–9.06×103/μL) and thrombocytopenia at 114×103/μL (reference range, 165–415×103/μL).1 Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×103/μL and platelet count at 159×103/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).
Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.
One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.
Comment
Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.2
Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.3
Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.4 Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.
Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al5 reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—fo
The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.6 Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.7
IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,8 which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.9 Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.4 Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.
Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.
- Kratz A, Pesce MA, Basner RC, et al. Laboratory values of clinical importance. In: Kasper D, Fauci A, Hauser S, et al, eds. Harrison’s Principles of Internal Medicine. 19th ed. McGraw-Hill; 2014.
- Ixekizumab. Package insert. Eli Lilly & Co; 2017.
- Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
- Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190-1199.
- Sfikakis PP, Iliopoulos A, Elezoglou A, et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum. 2005;52:2513-2518.
- Berg EL, Yoshino T, Rott LS, et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991;174:1461-1466.
- Flier J, Boorsma DM, van Beek PJ, et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol. 2001;194:398-405.
- Zrioual S, Ecochard R, Tournadre A, et al. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112-3120.
- Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep. 2009;11:365-370.
Case Report
A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.
Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.
Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.
At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×103/μL (reference range, 3.54–9.06×103/μL) and thrombocytopenia at 114×103/μL (reference range, 165–415×103/μL).1 Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×103/μL and platelet count at 159×103/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).
Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.
One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.
Comment
Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.2
Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.3
Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.4 Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.
Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al5 reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—fo
The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.6 Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.7
IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,8 which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.9 Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.4 Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.
Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.
Case Report
A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.
Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.
Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.
At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×103/μL (reference range, 3.54–9.06×103/μL) and thrombocytopenia at 114×103/μL (reference range, 165–415×103/μL).1 Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×103/μL and platelet count at 159×103/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).
Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.
One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.
Comment
Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.2
Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.3
Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.4 Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.
Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al5 reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—fo
The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.6 Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.7
IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,8 which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.9 Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.4 Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.
Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.
- Kratz A, Pesce MA, Basner RC, et al. Laboratory values of clinical importance. In: Kasper D, Fauci A, Hauser S, et al, eds. Harrison’s Principles of Internal Medicine. 19th ed. McGraw-Hill; 2014.
- Ixekizumab. Package insert. Eli Lilly & Co; 2017.
- Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
- Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190-1199.
- Sfikakis PP, Iliopoulos A, Elezoglou A, et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum. 2005;52:2513-2518.
- Berg EL, Yoshino T, Rott LS, et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991;174:1461-1466.
- Flier J, Boorsma DM, van Beek PJ, et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol. 2001;194:398-405.
- Zrioual S, Ecochard R, Tournadre A, et al. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112-3120.
- Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep. 2009;11:365-370.
- Kratz A, Pesce MA, Basner RC, et al. Laboratory values of clinical importance. In: Kasper D, Fauci A, Hauser S, et al, eds. Harrison’s Principles of Internal Medicine. 19th ed. McGraw-Hill; 2014.
- Ixekizumab. Package insert. Eli Lilly & Co; 2017.
- Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-356.
- Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190-1199.
- Sfikakis PP, Iliopoulos A, Elezoglou A, et al. Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum. 2005;52:2513-2518.
- Berg EL, Yoshino T, Rott LS, et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med. 1991;174:1461-1466.
- Flier J, Boorsma DM, van Beek PJ, et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol. 2001;194:398-405.
- Zrioual S, Ecochard R, Tournadre A, et al. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112-3120.
- Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep. 2009;11:365-370.
Practice Points
- Psoriasis is an autoimmune disorder with a predominance of CD4+ and CD8+ T cells that release cytokines, such as tumor necrosis factor 11α and interleukins, which promote inflammation in the skin and joints and is associated with systemic inflammation predisposing patients to cardiovascular disease.
- Common adverse effects of most biologic medications for psoriasis include injection-site pain and rash, fever, malaise, back pain, urticaria and flushing, edema, dyspnea, and nausea.
- Ixekizumab is a humanized IL-17A antagonist intended for adults with moderate to severe psoriasis. Certain rare side effects specific to ixekizumab include inflammatory bowel disease, thrombocytopenia, severe injection-site reactions, and candidiasis.
- Acute onycholysis and acute exacerbation of arthritis/dactylitis are rare side effects of ixekizumab therapy.
Telemedicine Alopecia Assessment: Highlighting Patients With Skin of Color
Practice Gap
In accordance with World Health Organization guidelines on social distancing to limit transmission of SARS-CoV-2, dermatologists have relied on teledermatology (TD) to develop novel adaptations of traditional workflows, optimize patient care, and limit in-person appointments during the COVID-19 pandemic. Pandemic-induced physical and emotional stress were anticipated to increase the incidence of dermatologic diseases with psychologic triggers.
The connection between hair loss and emotional stress is well documented for telogen effluvium and alopecia areata.1,2 As anticipated, dermatology visits increased during the COVID-19 pandemic for the diagnosis of alopecia1-4; a survey performed during the pandemic found that alopecia was one of the most common diagnoses dermatologists made through telehealth platforms.5
This article provides a practical guide for dermatology practitioners to efficiently and accurately assess alopecia by TD in all patients, with added considerations for skin of color patients.
Diagnostic Tools
The intersection of TD, as an effective mechanism for the diagnosis and treatment of dermatologic disorders, and the increase in alopecia observed during the COVID-19 pandemic prompted us to develop a workflow for conducting virtual scalp examinations. Seven dermatologists (A.M., A.A., O.A., N.E., V.C., C.M.B., S.C.T.) who are experts in hair disorders contributed to developing workflows to optimize the assessment of alopecia through a virtual scalp examination, with an emphasis on patients of color. These experts completed a 7-question survey (Table) detailing their approach to the virtual scalp examination. One author (B.N.W.) served as an independent reviewer and collated responses into the following workflows.
Telemedicine Previsit Workflow
Components of the previsit workflow include:
• Instruct patients to provide all laboratory values and biopsy reports before the appointment.
• Test for a stable Wi-Fi connection using a speed test (available at https://www.speedtest.net/). A speed of 10 megabits/second or more is required for high-quality video via TD.6
• Provide a handout illustrating the required photographs of the anterior hairline; the mid scalp, including vertex, bilateral parietal, and occipital scalp; and posterior hairline. Photographs should be uploaded 2 hours before the visit. Figures 1 and 2 are examples of photographs that should be requested.
• Request images with 2 or 3 different angles of the area of the scalp with the greatest involvement to help appreciate primary and secondary characteristics.
• Encourage patients to present with clean, recently shampooed, dried, and detangled natural hair, unless they have an itchy or flaky scalp.
• For concerns of scalp, hairline, eyebrow, or facial flaking and scaling, instruct the patient to avoid applying a moisturizer before the visit.
• Instruct the patient to remove false eyelashes, eyelash extensions, eyebrow pencil, hair camouflage, hair accessories, braids, extensions, weaves, twists, and other hairstyles so that the hair can be maneuvered to expose the scalp surface.
• Instruct the patient to have a comb, pic, or brush, or more than one of these implements, available during the visit.
Telemedicine Visit Workflow
Components of the visit workflow include:
• If a stable Wi-Fi connection cannot be established, switch to an audio-only visit to collect a pertinent history. Advise the patient that in-person follow-up must be scheduled.
• Confirm that (1) the patient is in a private setting where the scalp can be viewed and (2) lighting is positioned in front of the patient.
• Ensure that the patient’s hairline, full face, eyebrows, and eyelashes and, upon request, the vertex and posterior scalp, are completely visible.
• Initiate the virtual scalp examination by instructing the patient how to perform a hair pull test. Then, examine the pattern and distribution of hair loss alongside supplemental photographs.
• Instruct the patient to apply pressure with the fingertips throughout the scalp to help localize tenderness, which, in combination with the pattern of hair loss observed, might inform the diagnosis.
• Instruct the patient to scan the scalp with the fingertips for “bumps” to locate papules, pustules, and keloidal scars.
Diagnostic Pearls
Distribution of Alopecia—The experts noted that the pattern, distribution, and location of hair loss determined from the telemedicine alopecia assessment provided important clues to distinguish the type of alopecia.
Diagnostic clues for diffuse or generalized alopecia include:
• Either of these findings might be indicative of telogen effluvium or acquired trichorrhexis nodosa. Results of the hair pull test can help distinguish between these diagnoses.
• Recent stressful life events along with the presence of telogen hairs extracted during a hair pull test support the diagnosis of telogen effluvium.
• A history of external stress on the hair—thermal, traction, or chemical—along with broken hair shafts following the hair pull test support the diagnosis of acquired trichorrhexis nodosa.
Diagnostic clues for focal or patchy alopecia include:
• Alopecia areata generally presents as focal hair loss in an annular distribution; pruritus, erythema, and scale are absent.
• Seborrheic dermatitis can present as pruritic erythematous patches with scale distributed on the scalp and, in some cases, in the eyebrows, nasolabial folds, or paranasal skin.7 Some skin of color patients present with petaloid seborrheic dermatitis—pink or hypopigmented polycyclic coalescing rings with minimal scale.7,8
• Discoid lupus erythematosus, similar to seborrheic dermatitis, might present as pruritic, scaly, hypopigmented patches. However, in the experience of the experts, a more common presentation is tender erythematous patches of hair loss with central hypopigmentation and surrounding hyperpigmentation.
Diagnostic clues for vertex and mid scalp alopecia include:
• Androgenetic alopecia typically presents as a reduction of terminal hair density in the vertex and mid scalp regions (with widening through the midline part) and fine hair along the anterior hairline.9 Signs of concomitant hyperandrogenism, including facial hirsutism, acne, and obesity, might be observed.10
• Central centrifugal cicatricial alopecia typically affects the vertex and mid scalp with a shiny scalp appearance and follicular dropout.
Diagnostic clues for frontotemporal alopecia include:
• Frontal fibrosing alopecia (FFA) often presents with spared single terminal hairs (lonely hair sign).
• Traction alopecia commonly presents with the fringe hair sign.
Scalp Symptoms—The experts noted that the presence of symptoms (eg, pain, tenderness, pruritus) in conjunction with the pattern of hair loss might support the diagnosis of an inflammatory scarring alopecia.
When do symptoms raise suspicion of central centrifugal cicatricial alopecia?
• Suspected in the setting of vertex alopecia associated with tenderness, pain, or itching.
When do symptoms raise suspicion of FFA?
• Suspected when patients experience frontotemporal tenderness, pain, or burning associated with alopecia.
• The skin hue of the affected area might be lighter in color than, and contrast with, the darker hue of the photoaged upper forehead.11
• The lonely hair sign can aid in diagnosing FFA and distinguish it from the fringe sign of traction alopecia.
• Concurrent madarosis, flesh-colored papules on the cheeks, or lichen planus pigmentosus identified by visual inspection of the face confirms the diagnosis.9,12 Madarosis of the eyebrow was frequently cited by the experts as an associated symptom of FFA.
When do symptoms raise suspicion of lichen planopilaris?
• Suspected in the presence of pruritus, burning, tenderness, or pain associated with perifollicular erythema and scale in the setting of vertex and parietal alopecia.13
• Anagen hair release is observed during the hair pull test.11,14• The experts cited flesh-colored papules and lichen planus pigmentosus as frequently associated symptoms of lichen planopilaris.
Practice Implications
There are limitations to a virtual scalp examination—the inability to perform a scalp biopsy or administer certain treatments—but the consensus of the expert panel is that an initial alopecia assessment can be completed successfully utilizing TD. Although TD is not a replacement for an in-person dermatology visit, this technology has allowed for the diagnosis, treatment, and continuing care of many common dermatologic conditions without the patient needing to travel to the office.5
With the increased frequency of hair loss concerns documented over the last year and more patients seeking TD, it is imperative that dermatologists feel confident performing a virtual hair and scalp examination on all patients.1,3,4
- Kutlu Ö, Aktas¸ H, I·mren IG, et al. Short-term stress-related increasing cases of alopecia areata during the COVID-19 pandemic. J Dermatolog Treat. 2020;1. doi:10.1080/09546634.2020.1782820
- Cline A, Kazemi A, Moy J, et al. A surge in the incidence of telogen effluvium in minority predominant communities heavily impacted by COVID-19. J Am Acad Dermatol. 2021;84:773-775. doi:10.1016/j.jaad.2020.11.032
- Kutlu Ö, Metin A. Relative changes in the pattern of diseases presenting in dermatology outpatient clinic in the era of the COVID-19 pandemic. Dermatol Ther. 2020;33:e14096. doi:10.1111/dth.14096
- Tanacan E, Aksoy Sarac G, Emeksiz MAC, et al. Changing trends in dermatology practice during COVID-19 pandemic: a single tertiary center experience. Dermatol Ther. 2020;33:e14136. doi:10.1111/dth.14136
- Sharma A, Jindal V, Singla P, et al. Will teledermatology be the silver lining during and after COVID-19? Dermatol Ther. 2020;33:e13643. doi:10.1111/dth.13643
- Iscrupe L. How to receive virtual medical treatment while under quarantine. Allconnect website. Published March 26, 2020. Accessed December 9, 2021. https://www.allconnect.com/blog/online-doctor-visit-faq
- Elgash M, Dlova N, Ogunleye T, et al. Seborrheic dermatitis in skin of color: clinical considerations. J Drugs Dermatol. 2019;18:24-27.
- McLaurin CI. Annular facial dermatoses in blacks. Cutis. 1983;32:369-370, 384.
- Suchonwanit P, Hector CE, Bin Saif GA, McMichael AJ. Factors affecting the severity of central centrifugal cicatricial alopecia. Int J Dermatol. 2016;55:e338-343. doi:10.1111/ijd.13061
- Gabros S, Masood S. Central centrifugal cicatricial alopecia. StatPearls [Internet]. StatPearls Publishing; 2021. Updated July 20, 2021. Accessed December 9, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559187/
- Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias. J Am Acad Dermatol. 2005;53:1-37. doi:10.1016/j.jaad.2004.06.015
- Cobos G, Kim RH, Meehan S, et al. Lichen planus pigmentosus and lichen planopilaris. Dermatol Online J. 2016;22:13030/qt7hp8n6dn.
- Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279. doi:10.3109/09546634.2014.933165
- Tan E, Martinka M, Ball N, et al. Primary cicatricial alopecias: clinicopathology of 112 cases. J Am Acad Dermatol. 2004;50:25-32. doi:10.1016/j.jaad.2003.04.001
Practice Gap
In accordance with World Health Organization guidelines on social distancing to limit transmission of SARS-CoV-2, dermatologists have relied on teledermatology (TD) to develop novel adaptations of traditional workflows, optimize patient care, and limit in-person appointments during the COVID-19 pandemic. Pandemic-induced physical and emotional stress were anticipated to increase the incidence of dermatologic diseases with psychologic triggers.
The connection between hair loss and emotional stress is well documented for telogen effluvium and alopecia areata.1,2 As anticipated, dermatology visits increased during the COVID-19 pandemic for the diagnosis of alopecia1-4; a survey performed during the pandemic found that alopecia was one of the most common diagnoses dermatologists made through telehealth platforms.5
This article provides a practical guide for dermatology practitioners to efficiently and accurately assess alopecia by TD in all patients, with added considerations for skin of color patients.
Diagnostic Tools
The intersection of TD, as an effective mechanism for the diagnosis and treatment of dermatologic disorders, and the increase in alopecia observed during the COVID-19 pandemic prompted us to develop a workflow for conducting virtual scalp examinations. Seven dermatologists (A.M., A.A., O.A., N.E., V.C., C.M.B., S.C.T.) who are experts in hair disorders contributed to developing workflows to optimize the assessment of alopecia through a virtual scalp examination, with an emphasis on patients of color. These experts completed a 7-question survey (Table) detailing their approach to the virtual scalp examination. One author (B.N.W.) served as an independent reviewer and collated responses into the following workflows.
Telemedicine Previsit Workflow
Components of the previsit workflow include:
• Instruct patients to provide all laboratory values and biopsy reports before the appointment.
• Test for a stable Wi-Fi connection using a speed test (available at https://www.speedtest.net/). A speed of 10 megabits/second or more is required for high-quality video via TD.6
• Provide a handout illustrating the required photographs of the anterior hairline; the mid scalp, including vertex, bilateral parietal, and occipital scalp; and posterior hairline. Photographs should be uploaded 2 hours before the visit. Figures 1 and 2 are examples of photographs that should be requested.
• Request images with 2 or 3 different angles of the area of the scalp with the greatest involvement to help appreciate primary and secondary characteristics.
• Encourage patients to present with clean, recently shampooed, dried, and detangled natural hair, unless they have an itchy or flaky scalp.
• For concerns of scalp, hairline, eyebrow, or facial flaking and scaling, instruct the patient to avoid applying a moisturizer before the visit.
• Instruct the patient to remove false eyelashes, eyelash extensions, eyebrow pencil, hair camouflage, hair accessories, braids, extensions, weaves, twists, and other hairstyles so that the hair can be maneuvered to expose the scalp surface.
• Instruct the patient to have a comb, pic, or brush, or more than one of these implements, available during the visit.
Telemedicine Visit Workflow
Components of the visit workflow include:
• If a stable Wi-Fi connection cannot be established, switch to an audio-only visit to collect a pertinent history. Advise the patient that in-person follow-up must be scheduled.
• Confirm that (1) the patient is in a private setting where the scalp can be viewed and (2) lighting is positioned in front of the patient.
• Ensure that the patient’s hairline, full face, eyebrows, and eyelashes and, upon request, the vertex and posterior scalp, are completely visible.
• Initiate the virtual scalp examination by instructing the patient how to perform a hair pull test. Then, examine the pattern and distribution of hair loss alongside supplemental photographs.
• Instruct the patient to apply pressure with the fingertips throughout the scalp to help localize tenderness, which, in combination with the pattern of hair loss observed, might inform the diagnosis.
• Instruct the patient to scan the scalp with the fingertips for “bumps” to locate papules, pustules, and keloidal scars.
Diagnostic Pearls
Distribution of Alopecia—The experts noted that the pattern, distribution, and location of hair loss determined from the telemedicine alopecia assessment provided important clues to distinguish the type of alopecia.
Diagnostic clues for diffuse or generalized alopecia include:
• Either of these findings might be indicative of telogen effluvium or acquired trichorrhexis nodosa. Results of the hair pull test can help distinguish between these diagnoses.
• Recent stressful life events along with the presence of telogen hairs extracted during a hair pull test support the diagnosis of telogen effluvium.
• A history of external stress on the hair—thermal, traction, or chemical—along with broken hair shafts following the hair pull test support the diagnosis of acquired trichorrhexis nodosa.
Diagnostic clues for focal or patchy alopecia include:
• Alopecia areata generally presents as focal hair loss in an annular distribution; pruritus, erythema, and scale are absent.
• Seborrheic dermatitis can present as pruritic erythematous patches with scale distributed on the scalp and, in some cases, in the eyebrows, nasolabial folds, or paranasal skin.7 Some skin of color patients present with petaloid seborrheic dermatitis—pink or hypopigmented polycyclic coalescing rings with minimal scale.7,8
• Discoid lupus erythematosus, similar to seborrheic dermatitis, might present as pruritic, scaly, hypopigmented patches. However, in the experience of the experts, a more common presentation is tender erythematous patches of hair loss with central hypopigmentation and surrounding hyperpigmentation.
Diagnostic clues for vertex and mid scalp alopecia include:
• Androgenetic alopecia typically presents as a reduction of terminal hair density in the vertex and mid scalp regions (with widening through the midline part) and fine hair along the anterior hairline.9 Signs of concomitant hyperandrogenism, including facial hirsutism, acne, and obesity, might be observed.10
• Central centrifugal cicatricial alopecia typically affects the vertex and mid scalp with a shiny scalp appearance and follicular dropout.
Diagnostic clues for frontotemporal alopecia include:
• Frontal fibrosing alopecia (FFA) often presents with spared single terminal hairs (lonely hair sign).
• Traction alopecia commonly presents with the fringe hair sign.
Scalp Symptoms—The experts noted that the presence of symptoms (eg, pain, tenderness, pruritus) in conjunction with the pattern of hair loss might support the diagnosis of an inflammatory scarring alopecia.
When do symptoms raise suspicion of central centrifugal cicatricial alopecia?
• Suspected in the setting of vertex alopecia associated with tenderness, pain, or itching.
When do symptoms raise suspicion of FFA?
• Suspected when patients experience frontotemporal tenderness, pain, or burning associated with alopecia.
• The skin hue of the affected area might be lighter in color than, and contrast with, the darker hue of the photoaged upper forehead.11
• The lonely hair sign can aid in diagnosing FFA and distinguish it from the fringe sign of traction alopecia.
• Concurrent madarosis, flesh-colored papules on the cheeks, or lichen planus pigmentosus identified by visual inspection of the face confirms the diagnosis.9,12 Madarosis of the eyebrow was frequently cited by the experts as an associated symptom of FFA.
When do symptoms raise suspicion of lichen planopilaris?
• Suspected in the presence of pruritus, burning, tenderness, or pain associated with perifollicular erythema and scale in the setting of vertex and parietal alopecia.13
• Anagen hair release is observed during the hair pull test.11,14• The experts cited flesh-colored papules and lichen planus pigmentosus as frequently associated symptoms of lichen planopilaris.
Practice Implications
There are limitations to a virtual scalp examination—the inability to perform a scalp biopsy or administer certain treatments—but the consensus of the expert panel is that an initial alopecia assessment can be completed successfully utilizing TD. Although TD is not a replacement for an in-person dermatology visit, this technology has allowed for the diagnosis, treatment, and continuing care of many common dermatologic conditions without the patient needing to travel to the office.5
With the increased frequency of hair loss concerns documented over the last year and more patients seeking TD, it is imperative that dermatologists feel confident performing a virtual hair and scalp examination on all patients.1,3,4
Practice Gap
In accordance with World Health Organization guidelines on social distancing to limit transmission of SARS-CoV-2, dermatologists have relied on teledermatology (TD) to develop novel adaptations of traditional workflows, optimize patient care, and limit in-person appointments during the COVID-19 pandemic. Pandemic-induced physical and emotional stress were anticipated to increase the incidence of dermatologic diseases with psychologic triggers.
The connection between hair loss and emotional stress is well documented for telogen effluvium and alopecia areata.1,2 As anticipated, dermatology visits increased during the COVID-19 pandemic for the diagnosis of alopecia1-4; a survey performed during the pandemic found that alopecia was one of the most common diagnoses dermatologists made through telehealth platforms.5
This article provides a practical guide for dermatology practitioners to efficiently and accurately assess alopecia by TD in all patients, with added considerations for skin of color patients.
Diagnostic Tools
The intersection of TD, as an effective mechanism for the diagnosis and treatment of dermatologic disorders, and the increase in alopecia observed during the COVID-19 pandemic prompted us to develop a workflow for conducting virtual scalp examinations. Seven dermatologists (A.M., A.A., O.A., N.E., V.C., C.M.B., S.C.T.) who are experts in hair disorders contributed to developing workflows to optimize the assessment of alopecia through a virtual scalp examination, with an emphasis on patients of color. These experts completed a 7-question survey (Table) detailing their approach to the virtual scalp examination. One author (B.N.W.) served as an independent reviewer and collated responses into the following workflows.
Telemedicine Previsit Workflow
Components of the previsit workflow include:
• Instruct patients to provide all laboratory values and biopsy reports before the appointment.
• Test for a stable Wi-Fi connection using a speed test (available at https://www.speedtest.net/). A speed of 10 megabits/second or more is required for high-quality video via TD.6
• Provide a handout illustrating the required photographs of the anterior hairline; the mid scalp, including vertex, bilateral parietal, and occipital scalp; and posterior hairline. Photographs should be uploaded 2 hours before the visit. Figures 1 and 2 are examples of photographs that should be requested.
• Request images with 2 or 3 different angles of the area of the scalp with the greatest involvement to help appreciate primary and secondary characteristics.
• Encourage patients to present with clean, recently shampooed, dried, and detangled natural hair, unless they have an itchy or flaky scalp.
• For concerns of scalp, hairline, eyebrow, or facial flaking and scaling, instruct the patient to avoid applying a moisturizer before the visit.
• Instruct the patient to remove false eyelashes, eyelash extensions, eyebrow pencil, hair camouflage, hair accessories, braids, extensions, weaves, twists, and other hairstyles so that the hair can be maneuvered to expose the scalp surface.
• Instruct the patient to have a comb, pic, or brush, or more than one of these implements, available during the visit.
Telemedicine Visit Workflow
Components of the visit workflow include:
• If a stable Wi-Fi connection cannot be established, switch to an audio-only visit to collect a pertinent history. Advise the patient that in-person follow-up must be scheduled.
• Confirm that (1) the patient is in a private setting where the scalp can be viewed and (2) lighting is positioned in front of the patient.
• Ensure that the patient’s hairline, full face, eyebrows, and eyelashes and, upon request, the vertex and posterior scalp, are completely visible.
• Initiate the virtual scalp examination by instructing the patient how to perform a hair pull test. Then, examine the pattern and distribution of hair loss alongside supplemental photographs.
• Instruct the patient to apply pressure with the fingertips throughout the scalp to help localize tenderness, which, in combination with the pattern of hair loss observed, might inform the diagnosis.
• Instruct the patient to scan the scalp with the fingertips for “bumps” to locate papules, pustules, and keloidal scars.
Diagnostic Pearls
Distribution of Alopecia—The experts noted that the pattern, distribution, and location of hair loss determined from the telemedicine alopecia assessment provided important clues to distinguish the type of alopecia.
Diagnostic clues for diffuse or generalized alopecia include:
• Either of these findings might be indicative of telogen effluvium or acquired trichorrhexis nodosa. Results of the hair pull test can help distinguish between these diagnoses.
• Recent stressful life events along with the presence of telogen hairs extracted during a hair pull test support the diagnosis of telogen effluvium.
• A history of external stress on the hair—thermal, traction, or chemical—along with broken hair shafts following the hair pull test support the diagnosis of acquired trichorrhexis nodosa.
Diagnostic clues for focal or patchy alopecia include:
• Alopecia areata generally presents as focal hair loss in an annular distribution; pruritus, erythema, and scale are absent.
• Seborrheic dermatitis can present as pruritic erythematous patches with scale distributed on the scalp and, in some cases, in the eyebrows, nasolabial folds, or paranasal skin.7 Some skin of color patients present with petaloid seborrheic dermatitis—pink or hypopigmented polycyclic coalescing rings with minimal scale.7,8
• Discoid lupus erythematosus, similar to seborrheic dermatitis, might present as pruritic, scaly, hypopigmented patches. However, in the experience of the experts, a more common presentation is tender erythematous patches of hair loss with central hypopigmentation and surrounding hyperpigmentation.
Diagnostic clues for vertex and mid scalp alopecia include:
• Androgenetic alopecia typically presents as a reduction of terminal hair density in the vertex and mid scalp regions (with widening through the midline part) and fine hair along the anterior hairline.9 Signs of concomitant hyperandrogenism, including facial hirsutism, acne, and obesity, might be observed.10
• Central centrifugal cicatricial alopecia typically affects the vertex and mid scalp with a shiny scalp appearance and follicular dropout.
Diagnostic clues for frontotemporal alopecia include:
• Frontal fibrosing alopecia (FFA) often presents with spared single terminal hairs (lonely hair sign).
• Traction alopecia commonly presents with the fringe hair sign.
Scalp Symptoms—The experts noted that the presence of symptoms (eg, pain, tenderness, pruritus) in conjunction with the pattern of hair loss might support the diagnosis of an inflammatory scarring alopecia.
When do symptoms raise suspicion of central centrifugal cicatricial alopecia?
• Suspected in the setting of vertex alopecia associated with tenderness, pain, or itching.
When do symptoms raise suspicion of FFA?
• Suspected when patients experience frontotemporal tenderness, pain, or burning associated with alopecia.
• The skin hue of the affected area might be lighter in color than, and contrast with, the darker hue of the photoaged upper forehead.11
• The lonely hair sign can aid in diagnosing FFA and distinguish it from the fringe sign of traction alopecia.
• Concurrent madarosis, flesh-colored papules on the cheeks, or lichen planus pigmentosus identified by visual inspection of the face confirms the diagnosis.9,12 Madarosis of the eyebrow was frequently cited by the experts as an associated symptom of FFA.
When do symptoms raise suspicion of lichen planopilaris?
• Suspected in the presence of pruritus, burning, tenderness, or pain associated with perifollicular erythema and scale in the setting of vertex and parietal alopecia.13
• Anagen hair release is observed during the hair pull test.11,14• The experts cited flesh-colored papules and lichen planus pigmentosus as frequently associated symptoms of lichen planopilaris.
Practice Implications
There are limitations to a virtual scalp examination—the inability to perform a scalp biopsy or administer certain treatments—but the consensus of the expert panel is that an initial alopecia assessment can be completed successfully utilizing TD. Although TD is not a replacement for an in-person dermatology visit, this technology has allowed for the diagnosis, treatment, and continuing care of many common dermatologic conditions without the patient needing to travel to the office.5
With the increased frequency of hair loss concerns documented over the last year and more patients seeking TD, it is imperative that dermatologists feel confident performing a virtual hair and scalp examination on all patients.1,3,4
- Kutlu Ö, Aktas¸ H, I·mren IG, et al. Short-term stress-related increasing cases of alopecia areata during the COVID-19 pandemic. J Dermatolog Treat. 2020;1. doi:10.1080/09546634.2020.1782820
- Cline A, Kazemi A, Moy J, et al. A surge in the incidence of telogen effluvium in minority predominant communities heavily impacted by COVID-19. J Am Acad Dermatol. 2021;84:773-775. doi:10.1016/j.jaad.2020.11.032
- Kutlu Ö, Metin A. Relative changes in the pattern of diseases presenting in dermatology outpatient clinic in the era of the COVID-19 pandemic. Dermatol Ther. 2020;33:e14096. doi:10.1111/dth.14096
- Tanacan E, Aksoy Sarac G, Emeksiz MAC, et al. Changing trends in dermatology practice during COVID-19 pandemic: a single tertiary center experience. Dermatol Ther. 2020;33:e14136. doi:10.1111/dth.14136
- Sharma A, Jindal V, Singla P, et al. Will teledermatology be the silver lining during and after COVID-19? Dermatol Ther. 2020;33:e13643. doi:10.1111/dth.13643
- Iscrupe L. How to receive virtual medical treatment while under quarantine. Allconnect website. Published March 26, 2020. Accessed December 9, 2021. https://www.allconnect.com/blog/online-doctor-visit-faq
- Elgash M, Dlova N, Ogunleye T, et al. Seborrheic dermatitis in skin of color: clinical considerations. J Drugs Dermatol. 2019;18:24-27.
- McLaurin CI. Annular facial dermatoses in blacks. Cutis. 1983;32:369-370, 384.
- Suchonwanit P, Hector CE, Bin Saif GA, McMichael AJ. Factors affecting the severity of central centrifugal cicatricial alopecia. Int J Dermatol. 2016;55:e338-343. doi:10.1111/ijd.13061
- Gabros S, Masood S. Central centrifugal cicatricial alopecia. StatPearls [Internet]. StatPearls Publishing; 2021. Updated July 20, 2021. Accessed December 9, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559187/
- Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias. J Am Acad Dermatol. 2005;53:1-37. doi:10.1016/j.jaad.2004.06.015
- Cobos G, Kim RH, Meehan S, et al. Lichen planus pigmentosus and lichen planopilaris. Dermatol Online J. 2016;22:13030/qt7hp8n6dn.
- Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279. doi:10.3109/09546634.2014.933165
- Tan E, Martinka M, Ball N, et al. Primary cicatricial alopecias: clinicopathology of 112 cases. J Am Acad Dermatol. 2004;50:25-32. doi:10.1016/j.jaad.2003.04.001
- Kutlu Ö, Aktas¸ H, I·mren IG, et al. Short-term stress-related increasing cases of alopecia areata during the COVID-19 pandemic. J Dermatolog Treat. 2020;1. doi:10.1080/09546634.2020.1782820
- Cline A, Kazemi A, Moy J, et al. A surge in the incidence of telogen effluvium in minority predominant communities heavily impacted by COVID-19. J Am Acad Dermatol. 2021;84:773-775. doi:10.1016/j.jaad.2020.11.032
- Kutlu Ö, Metin A. Relative changes in the pattern of diseases presenting in dermatology outpatient clinic in the era of the COVID-19 pandemic. Dermatol Ther. 2020;33:e14096. doi:10.1111/dth.14096
- Tanacan E, Aksoy Sarac G, Emeksiz MAC, et al. Changing trends in dermatology practice during COVID-19 pandemic: a single tertiary center experience. Dermatol Ther. 2020;33:e14136. doi:10.1111/dth.14136
- Sharma A, Jindal V, Singla P, et al. Will teledermatology be the silver lining during and after COVID-19? Dermatol Ther. 2020;33:e13643. doi:10.1111/dth.13643
- Iscrupe L. How to receive virtual medical treatment while under quarantine. Allconnect website. Published March 26, 2020. Accessed December 9, 2021. https://www.allconnect.com/blog/online-doctor-visit-faq
- Elgash M, Dlova N, Ogunleye T, et al. Seborrheic dermatitis in skin of color: clinical considerations. J Drugs Dermatol. 2019;18:24-27.
- McLaurin CI. Annular facial dermatoses in blacks. Cutis. 1983;32:369-370, 384.
- Suchonwanit P, Hector CE, Bin Saif GA, McMichael AJ. Factors affecting the severity of central centrifugal cicatricial alopecia. Int J Dermatol. 2016;55:e338-343. doi:10.1111/ijd.13061
- Gabros S, Masood S. Central centrifugal cicatricial alopecia. StatPearls [Internet]. StatPearls Publishing; 2021. Updated July 20, 2021. Accessed December 9, 2021. https://www.ncbi.nlm.nih.gov/books/NBK559187/
- Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias. J Am Acad Dermatol. 2005;53:1-37. doi:10.1016/j.jaad.2004.06.015
- Cobos G, Kim RH, Meehan S, et al. Lichen planus pigmentosus and lichen planopilaris. Dermatol Online J. 2016;22:13030/qt7hp8n6dn.
- Lyakhovitsky A, Amichai B, Sizopoulou C, et al. A case series of 46 patients with lichen planopilaris: demographics, clinical evaluation, and treatment experience. J Dermatolog Treat. 2015;26:275-279. doi:10.3109/09546634.2014.933165
- Tan E, Martinka M, Ball N, et al. Primary cicatricial alopecias: clinicopathology of 112 cases. J Am Acad Dermatol. 2004;50:25-32. doi:10.1016/j.jaad.2003.04.001
A Contrasting Dark Background for Nail Sampling
Practice Gap
Mycologic testing is necessary and cost-effective1 for appropriate diagnosis and treatment of onychomycosis. Empiric treatment of onychodystrophy for presumed onychomycosis can result in misdiagnosis, treatment failure, or potential adverse effects caused by medications.2 Collection of ample subungual debris facilitates the sensitivity and specificity of fungal culture and fungal polymerase chain reaction. However, the naturally pale hue of subungual debris makes specimen estimation challenging, particularly when using a similarly light-colored gauze or piece of paper for collection (Figure, A).
The Technique
A sheet from a black sticky notepad (widely available and cost-effective) can be adapted for making a diagnosis of onychomycosis (Figure, B).
Practical Implication
Use of a dark background that contrasts with light-hued nail debris is valuable to ensure an adequate specimen for fungal culture and polymerase chain reaction.
- Gupta AK, Versteeg SG, Shear NH. Confirmatory testing prior to initiating onychomycosis therapy is cost effective. J Cutan Med Surg. 2018;22:129-141. doi:10.1177/1203475417733461
- Lipner SR, Scher RK. Onychomycosis—a small step for quality of care. Curr Med Res Opin. 2016;32:865-867. doi:10.1185/03007995.2016.1147026
Practice Gap
Mycologic testing is necessary and cost-effective1 for appropriate diagnosis and treatment of onychomycosis. Empiric treatment of onychodystrophy for presumed onychomycosis can result in misdiagnosis, treatment failure, or potential adverse effects caused by medications.2 Collection of ample subungual debris facilitates the sensitivity and specificity of fungal culture and fungal polymerase chain reaction. However, the naturally pale hue of subungual debris makes specimen estimation challenging, particularly when using a similarly light-colored gauze or piece of paper for collection (Figure, A).
The Technique
A sheet from a black sticky notepad (widely available and cost-effective) can be adapted for making a diagnosis of onychomycosis (Figure, B).
Practical Implication
Use of a dark background that contrasts with light-hued nail debris is valuable to ensure an adequate specimen for fungal culture and polymerase chain reaction.
Practice Gap
Mycologic testing is necessary and cost-effective1 for appropriate diagnosis and treatment of onychomycosis. Empiric treatment of onychodystrophy for presumed onychomycosis can result in misdiagnosis, treatment failure, or potential adverse effects caused by medications.2 Collection of ample subungual debris facilitates the sensitivity and specificity of fungal culture and fungal polymerase chain reaction. However, the naturally pale hue of subungual debris makes specimen estimation challenging, particularly when using a similarly light-colored gauze or piece of paper for collection (Figure, A).
The Technique
A sheet from a black sticky notepad (widely available and cost-effective) can be adapted for making a diagnosis of onychomycosis (Figure, B).
Practical Implication
Use of a dark background that contrasts with light-hued nail debris is valuable to ensure an adequate specimen for fungal culture and polymerase chain reaction.
- Gupta AK, Versteeg SG, Shear NH. Confirmatory testing prior to initiating onychomycosis therapy is cost effective. J Cutan Med Surg. 2018;22:129-141. doi:10.1177/1203475417733461
- Lipner SR, Scher RK. Onychomycosis—a small step for quality of care. Curr Med Res Opin. 2016;32:865-867. doi:10.1185/03007995.2016.1147026
- Gupta AK, Versteeg SG, Shear NH. Confirmatory testing prior to initiating onychomycosis therapy is cost effective. J Cutan Med Surg. 2018;22:129-141. doi:10.1177/1203475417733461
- Lipner SR, Scher RK. Onychomycosis—a small step for quality of care. Curr Med Res Opin. 2016;32:865-867. doi:10.1185/03007995.2016.1147026
