Hair & Nails

Alopecia areata (AA) is an autoimmune disease that immunopathogenetically is thought to be due to breakdown of the immune privilege of the proximal hair follicle during the anagen growth phase. Alopecia areata has been reported to have a lifetime prevalence of 1.7%.¹ Recent studies have specifically identified cytotoxic CD8⁺ NKG2D⁺ T cells as being responsible for the activation of AA.^2-4 Two interleukins—IL-2 and IL-15—have been implicated to be cytotoxic sensitizers allowing CD8⁺ T cells to secrete IFN-γ and recognize autoantigens via major histocompatibility complex class I.^5,6 Janus kinases (JAKs) are enzymes that play major roles in many different molecular processes. Specifically, JAK1/3 has been determined to arbitrate IL-15 activation of receptors on CD8⁺ T cells.⁷ These cells then interact with CD4 T cells, mast cells, and other inflammatory cells to cause destruction of the hair follicle without damage to the keratinocyte and melanocyte stem cells, allowing for reversible yet relapsing hair loss.⁸

Treatment of AA is difficult, requiring patience and strict compliance while taking into account duration of disease, age at presentation, site involvement, patient expectations, cost and insurance coverage, prior therapies, and any comorbidities. At the time of this case, no US Food and Drug Administration–approved drug regimen existed for the treatment of AA, and, to date, no treatment is preventative.⁴ We present a case of a patient with alopecia universalis of 11 years’ duration that was refractory to intralesional triamcinolone, clobetasol, minoxidil, and UVB brush therapy yet was successfully treated with tofacitinib.

Case Report

A 29-year-old otherwise-healthy woman presented to our clinic for treatment of alopecia universalis of 11 years’ duration that flared intermittently despite various treatments. Her medical history was unremarkable; however, she had a brother with alopecia universalis. She had no family history of any other autoimmune disorders. At the current presentation, the patient was known to have alopecia universalis with scant evidence of exclamation-point hairs on dermoscopy. Her treatment plan at this point consisted of intralesional triamcinolone to the active areas at 10 mg/mL every 4 weeks, plus clobetasol foam 0.05% at bedtime, minoxidil foam 5% at bedtime, and a UVB brush 3 times a week for 6 months before progressing to universalis type because of hair loss in the eyebrows and eyelashes. This treatment plan continued for 1 year with minimal improvement of the alopecia (Figure 1).

The patient was dissatisfied and wanted to discontinue therapy. Because these treatment options were exhausted with minimal benefit, the patient was then considered for treatment with tofacitinib. Baseline studies were performed, including purified protein derivative, complete blood cell count with differential, comprehensive metabolic panel, lipid profile, and liver function tests, all of which were within reference range. Insurance initially denied coverage of this therapy; a prior authorization was subsequently submitted and denied. A letter of medical necessity was then proposed, and approval for tofacitinib was finally granted. The patient was started on tofacitinib 5 mg twice daily and was monitored every 2 months with a complete blood cell count, comprehensive metabolic panel, lipid panels, and liver function tests. She had a platelet count of 112,000/μL (reference range, 150,000–450,000/μL) at baseline, and continued monitoring revealed a platelet count of 83,000 after 7 months of treatment. This platelet abnormality was evaluated by a hematologist and found to be within reference range; subsequent monitoring did not reveal any abnormalities.

Initial hair growth on the scalp was diffuse with thin, white to light brown hairs in areas of hair loss at months 1 and 2, with progressive hair growth over months 3 to 7. Eyebrow hair growth was noted beginning at month 6. One year later, only hair regrowth occurred without any adverse events (Figure 2). After 5 years of treatment, the patient had a full head of thick hair (Figure 3). The tofacitinib dosage was 5 mg twice daily at initiation, and after 1 year increased to 10 mg twice daily. Her medical insurance subsequently changed and the regimen was adjusted to an 11-mg tablet and 5-mg tablet daily. She remained on this regimen with success.

Comment

Use of JAK Inhibitors—Reports and studies have shed light on the use and efficacy of JAK inhibitors in AA (Table).^5-11 Tofacitinib is a selective JAK1/3 inhibitor that predominantly inhibits JAK3 but also inhibits JAK1, albeit to a lesser degree, which interferes with the JAK/STAT (signal transducer and activator of transcription) cascade responsible for the production, differentiation, and function of various B cells, T cells, and natural killer cells.² Although it was developed for the management of allograft rejection, tofacitinib has made headway in rheumatology for treatment of patients with moderate to severe rheumatoid arthritis who are unable to take or are not responding to methotrexate.² Since 2014, tofacitinib has been introduced to the therapeutic realm for AA but is not yet approved by the US Food and Drug Administration.^3,4

In 2014, Craiglow and King⁵ reported use of tofacitinib with dosages beginning at 10 mg/d and increasing to 15 mg/d in a patient with alopecia universalis and psoriasis. Total hair regrowth was noted after 8 months of therapy.⁵ Xing et al⁶ described 3 patients treated with ruxolitinib, a JAK1/2 inhibitor approved for the treatment of myelofibrosis, at an oral dose of 20 mg twice daily with near-complete hair regrowth after 5 months of treatment.⁶ Biopsies from lesions at baseline and after 3 months of therapy revealed a reduction in perifollicular T cells and in HLA class I and II expression in follicles.⁶ A patient in Italy with essential thrombocythemia and concurrent alopecia universalis was enrolled in a clinical trial with ruxolitinib and was treated with 15 mg twice daily. After 10 months of treatment, the patient had progressive hair regrowth that was sustained for more than 50 months of therapy.⁷ Baricitinib, a JAK1/2 inhibitor, was used in a 17-year-old adolescent boy to assess efficacy of the drug in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome.⁸ The patient also had longstanding patch-type AA that was resistance to treatment and progressed to an ophiasis pattern even though he was on immunosuppressive therapies. He was on 12 mg of prednisone daily at the start of therapy with baricitinib 7 mg daily initially. The baricitinib regimen was titrated up to 7 mg in the morning and 4 mg in the evening, with tapering of prednisone to 3 mg daily after 6 months of initiation. Within 3 months of therapy, hair regrowth occurred, with only a resultant patch on the occipital scalp that further resolved after 6 more months of therapy, resulting in total persistent hair growth.⁸ A 40-year-old woman with moderate to severe alopecia universalis was treated with tofacitinib 5 mg twice daily, revealing near-complete hair regrowth after 4 months of treatment; regrowth of eyebrows and eyelashes also was seen.⁹ However, discontinuation of treatment resulted in hair loss. Microarray analyses of biopsy specimens of lesioned sites at baseline revealed elevated IFN-γ and cytotoxic T cell-level signatures that subsequently decreased—albeit not to normal control levels—after 4 weeks of treatment.⁹ Being that IFN-γ receptors mediate their effects through JAK1/2, JAK1/3, tofacitinib, ruxolitinib, and baricitinib seem to be in sync with the immunopathogenesis of AA and thus may be the therapy of choice in the near future.

A recent retrospective study assessing response to tofacitinib in adults with AA (>40% hair loss), alopecia totalis, alopecia universalis, and stable or progressive diseases for at least 6 months determined a clinical response in 50 of 65 (77%) patients, with 13 patients exhibiting a complete response.¹⁰ Patients in this study were started on tofacitinib 5 mg twice daily with the addition of adjuvant pulsed prednisone (300 mg once monthly for 3 doses) with or without doubled dosing of tofacitinib if they had a halt in hair regrowth. This study demonstrated some benefit when pulsed prednisone was combined with the daily tofacitinib therapy. However, the study emphasized the importance of maintenance therapy, as 8 patients experienced hair loss with discontinuation after previously having hair regrowth; 5 (63%) of these patients experienced regrowth with augmentation of dosing or addition of adjuvant therapy.¹⁰

Another group of investigators assessed the efficacy of tofacitinib 5 mg in 13 adolescents aged 12 to 17 years, most with alopecia universalis (46% [6/13]); 10 of 13 (77%) patients responded to treatment with a mean duration of 6.5 months. The patients who had alopecia totalis and alopecia universalis for more than 10 years were poor responders to tofacitinib, and in fact, 1 of 13 (33%) patients in the study who did not respond to therapy had disease for 12 years.¹¹ Therefore, starting tofacitinib either long-term or intermittently should be considered in children diagnosed early with severe AA, alopecia totalis, or alopecia universalis to prevent irreversible hair loss or progressive disease^12,13; however, further data are required to assess efficacy and long-term benefits of this type of regimen.

Safety Profile—Widespread use of a medication is determined not only by its efficacy profile but also its safety profile. With any medication that exhibits immunosuppressive effects, adverse events must be considered and thoroughly discussed with patients and their primary care physicians. A prospective, open-label, single-arm trial examined the efficacy and safety of tofacitinib 5 mg twice daily in the treatment of AA and its more severe forms over 3 months.¹² Of the 66 patients who completed the trial, 64% (42/66) exhibited a positive response to tofacitinib. Relapse was noted in 8.5 weeks after discontinuation of tofacitinib, reiterating the potential need for a maintenance regimen. In this study, 25.8% (17/66) of patients experienced infections as adverse events including (in decreasing order) upper respiratory tract infections, urinary tract infections, herpes zoster, conjunctivitis, bronchitis, mononucleosis, and paronychia. No reports of new or recurrent malignancy were noted. Other more constitutional adverse events were noted including headaches, abdominal pain, acne, diarrhea, fatigue, nausea, pruritus, hot flashes, cough, folliculitis, weight gain, dry eyes, and amenorrhea. One patient with a pre-existing liver condition experienced transaminitis that resolved with weight loss. There also were noted increases in low- and high-density lipoprotein levels.¹² Our patient with baseline thrombocytopenia had mild drops in platelet count that subsequently stabilized and did not result in any bleeding abnormalities.

Duration of Therapy—Tofacitinib has demonstrated some preliminary success in the management of AA, but the appropriate duration of treatment requires further investigation. Our patient has been on tofacitinib for more than 5 years. She started at a total dosage of 10 mg/d, which increased to 16 mg/d. Initial dosing with maintenance regimens needs to be established for further widespread use to maximize benefit and minimize harm.

At what point do we decide to continue or stop treatment in patients who do not respond as expected or plateau? This is another critical question; our patient had periods of slowed growth and plateauing, but knowing the risks and benefits, she continued the medication and eventually experienced improved regrowth again.

Conclusion

Throughout the literature and in our patient, tofacitinib has demonstrated efficacy in treating AA. When other conventional therapies have failed, use of tofacitinib should be considered.

Alopecia areata (AA) is an autoimmune disease that immunopathogenetically is thought to be due to breakdown of the immune privilege of the proximal hair follicle during the anagen growth phase. Alopecia areata has been reported to have a lifetime prevalence of 1.7%.¹ Recent studies have specifically identified cytotoxic CD8⁺ NKG2D⁺ T cells as being responsible for the activation of AA.^2-4 Two interleukins—IL-2 and IL-15—have been implicated to be cytotoxic sensitizers allowing CD8⁺ T cells to secrete IFN-γ and recognize autoantigens via major histocompatibility complex class I.^5,6 Janus kinases (JAKs) are enzymes that play major roles in many different molecular processes. Specifically, JAK1/3 has been determined to arbitrate IL-15 activation of receptors on CD8⁺ T cells.⁷ These cells then interact with CD4 T cells, mast cells, and other inflammatory cells to cause destruction of the hair follicle without damage to the keratinocyte and melanocyte stem cells, allowing for reversible yet relapsing hair loss.⁸

Treatment of AA is difficult, requiring patience and strict compliance while taking into account duration of disease, age at presentation, site involvement, patient expectations, cost and insurance coverage, prior therapies, and any comorbidities. At the time of this case, no US Food and Drug Administration–approved drug regimen existed for the treatment of AA, and, to date, no treatment is preventative.⁴ We present a case of a patient with alopecia universalis of 11 years’ duration that was refractory to intralesional triamcinolone, clobetasol, minoxidil, and UVB brush therapy yet was successfully treated with tofacitinib.

Case Report

A 29-year-old otherwise-healthy woman presented to our clinic for treatment of alopecia universalis of 11 years’ duration that flared intermittently despite various treatments. Her medical history was unremarkable; however, she had a brother with alopecia universalis. She had no family history of any other autoimmune disorders. At the current presentation, the patient was known to have alopecia universalis with scant evidence of exclamation-point hairs on dermoscopy. Her treatment plan at this point consisted of intralesional triamcinolone to the active areas at 10 mg/mL every 4 weeks, plus clobetasol foam 0.05% at bedtime, minoxidil foam 5% at bedtime, and a UVB brush 3 times a week for 6 months before progressing to universalis type because of hair loss in the eyebrows and eyelashes. This treatment plan continued for 1 year with minimal improvement of the alopecia (Figure 1).

The patient was dissatisfied and wanted to discontinue therapy. Because these treatment options were exhausted with minimal benefit, the patient was then considered for treatment with tofacitinib. Baseline studies were performed, including purified protein derivative, complete blood cell count with differential, comprehensive metabolic panel, lipid profile, and liver function tests, all of which were within reference range. Insurance initially denied coverage of this therapy; a prior authorization was subsequently submitted and denied. A letter of medical necessity was then proposed, and approval for tofacitinib was finally granted. The patient was started on tofacitinib 5 mg twice daily and was monitored every 2 months with a complete blood cell count, comprehensive metabolic panel, lipid panels, and liver function tests. She had a platelet count of 112,000/μL (reference range, 150,000–450,000/μL) at baseline, and continued monitoring revealed a platelet count of 83,000 after 7 months of treatment. This platelet abnormality was evaluated by a hematologist and found to be within reference range; subsequent monitoring did not reveal any abnormalities.

Initial hair growth on the scalp was diffuse with thin, white to light brown hairs in areas of hair loss at months 1 and 2, with progressive hair growth over months 3 to 7. Eyebrow hair growth was noted beginning at month 6. One year later, only hair regrowth occurred without any adverse events (Figure 2). After 5 years of treatment, the patient had a full head of thick hair (Figure 3). The tofacitinib dosage was 5 mg twice daily at initiation, and after 1 year increased to 10 mg twice daily. Her medical insurance subsequently changed and the regimen was adjusted to an 11-mg tablet and 5-mg tablet daily. She remained on this regimen with success.

Comment

Use of JAK Inhibitors—Reports and studies have shed light on the use and efficacy of JAK inhibitors in AA (Table).^5-11 Tofacitinib is a selective JAK1/3 inhibitor that predominantly inhibits JAK3 but also inhibits JAK1, albeit to a lesser degree, which interferes with the JAK/STAT (signal transducer and activator of transcription) cascade responsible for the production, differentiation, and function of various B cells, T cells, and natural killer cells.² Although it was developed for the management of allograft rejection, tofacitinib has made headway in rheumatology for treatment of patients with moderate to severe rheumatoid arthritis who are unable to take or are not responding to methotrexate.² Since 2014, tofacitinib has been introduced to the therapeutic realm for AA but is not yet approved by the US Food and Drug Administration.^3,4

In 2014, Craiglow and King⁵ reported use of tofacitinib with dosages beginning at 10 mg/d and increasing to 15 mg/d in a patient with alopecia universalis and psoriasis. Total hair regrowth was noted after 8 months of therapy.⁵ Xing et al⁶ described 3 patients treated with ruxolitinib, a JAK1/2 inhibitor approved for the treatment of myelofibrosis, at an oral dose of 20 mg twice daily with near-complete hair regrowth after 5 months of treatment.⁶ Biopsies from lesions at baseline and after 3 months of therapy revealed a reduction in perifollicular T cells and in HLA class I and II expression in follicles.⁶ A patient in Italy with essential thrombocythemia and concurrent alopecia universalis was enrolled in a clinical trial with ruxolitinib and was treated with 15 mg twice daily. After 10 months of treatment, the patient had progressive hair regrowth that was sustained for more than 50 months of therapy.⁷ Baricitinib, a JAK1/2 inhibitor, was used in a 17-year-old adolescent boy to assess efficacy of the drug in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome.⁸ The patient also had longstanding patch-type AA that was resistance to treatment and progressed to an ophiasis pattern even though he was on immunosuppressive therapies. He was on 12 mg of prednisone daily at the start of therapy with baricitinib 7 mg daily initially. The baricitinib regimen was titrated up to 7 mg in the morning and 4 mg in the evening, with tapering of prednisone to 3 mg daily after 6 months of initiation. Within 3 months of therapy, hair regrowth occurred, with only a resultant patch on the occipital scalp that further resolved after 6 more months of therapy, resulting in total persistent hair growth.⁸ A 40-year-old woman with moderate to severe alopecia universalis was treated with tofacitinib 5 mg twice daily, revealing near-complete hair regrowth after 4 months of treatment; regrowth of eyebrows and eyelashes also was seen.⁹ However, discontinuation of treatment resulted in hair loss. Microarray analyses of biopsy specimens of lesioned sites at baseline revealed elevated IFN-γ and cytotoxic T cell-level signatures that subsequently decreased—albeit not to normal control levels—after 4 weeks of treatment.⁹ Being that IFN-γ receptors mediate their effects through JAK1/2, JAK1/3, tofacitinib, ruxolitinib, and baricitinib seem to be in sync with the immunopathogenesis of AA and thus may be the therapy of choice in the near future.

A recent retrospective study assessing response to tofacitinib in adults with AA (>40% hair loss), alopecia totalis, alopecia universalis, and stable or progressive diseases for at least 6 months determined a clinical response in 50 of 65 (77%) patients, with 13 patients exhibiting a complete response.¹⁰ Patients in this study were started on tofacitinib 5 mg twice daily with the addition of adjuvant pulsed prednisone (300 mg once monthly for 3 doses) with or without doubled dosing of tofacitinib if they had a halt in hair regrowth. This study demonstrated some benefit when pulsed prednisone was combined with the daily tofacitinib therapy. However, the study emphasized the importance of maintenance therapy, as 8 patients experienced hair loss with discontinuation after previously having hair regrowth; 5 (63%) of these patients experienced regrowth with augmentation of dosing or addition of adjuvant therapy.¹⁰

Another group of investigators assessed the efficacy of tofacitinib 5 mg in 13 adolescents aged 12 to 17 years, most with alopecia universalis (46% [6/13]); 10 of 13 (77%) patients responded to treatment with a mean duration of 6.5 months. The patients who had alopecia totalis and alopecia universalis for more than 10 years were poor responders to tofacitinib, and in fact, 1 of 13 (33%) patients in the study who did not respond to therapy had disease for 12 years.¹¹ Therefore, starting tofacitinib either long-term or intermittently should be considered in children diagnosed early with severe AA, alopecia totalis, or alopecia universalis to prevent irreversible hair loss or progressive disease^12,13; however, further data are required to assess efficacy and long-term benefits of this type of regimen.

Safety Profile—Widespread use of a medication is determined not only by its efficacy profile but also its safety profile. With any medication that exhibits immunosuppressive effects, adverse events must be considered and thoroughly discussed with patients and their primary care physicians. A prospective, open-label, single-arm trial examined the efficacy and safety of tofacitinib 5 mg twice daily in the treatment of AA and its more severe forms over 3 months.¹² Of the 66 patients who completed the trial, 64% (42/66) exhibited a positive response to tofacitinib. Relapse was noted in 8.5 weeks after discontinuation of tofacitinib, reiterating the potential need for a maintenance regimen. In this study, 25.8% (17/66) of patients experienced infections as adverse events including (in decreasing order) upper respiratory tract infections, urinary tract infections, herpes zoster, conjunctivitis, bronchitis, mononucleosis, and paronychia. No reports of new or recurrent malignancy were noted. Other more constitutional adverse events were noted including headaches, abdominal pain, acne, diarrhea, fatigue, nausea, pruritus, hot flashes, cough, folliculitis, weight gain, dry eyes, and amenorrhea. One patient with a pre-existing liver condition experienced transaminitis that resolved with weight loss. There also were noted increases in low- and high-density lipoprotein levels.¹² Our patient with baseline thrombocytopenia had mild drops in platelet count that subsequently stabilized and did not result in any bleeding abnormalities.

Duration of Therapy—Tofacitinib has demonstrated some preliminary success in the management of AA, but the appropriate duration of treatment requires further investigation. Our patient has been on tofacitinib for more than 5 years. She started at a total dosage of 10 mg/d, which increased to 16 mg/d. Initial dosing with maintenance regimens needs to be established for further widespread use to maximize benefit and minimize harm.

At what point do we decide to continue or stop treatment in patients who do not respond as expected or plateau? This is another critical question; our patient had periods of slowed growth and plateauing, but knowing the risks and benefits, she continued the medication and eventually experienced improved regrowth again.

Conclusion

Throughout the literature and in our patient, tofacitinib has demonstrated efficacy in treating AA. When other conventional therapies have failed, use of tofacitinib should be considered.

Alopecia areata (AA) is an autoimmune disease that immunopathogenetically is thought to be due to breakdown of the immune privilege of the proximal hair follicle during the anagen growth phase. Alopecia areata has been reported to have a lifetime prevalence of 1.7%.¹ Recent studies have specifically identified cytotoxic CD8⁺ NKG2D⁺ T cells as being responsible for the activation of AA.^2-4 Two interleukins—IL-2 and IL-15—have been implicated to be cytotoxic sensitizers allowing CD8⁺ T cells to secrete IFN-γ and recognize autoantigens via major histocompatibility complex class I.^5,6 Janus kinases (JAKs) are enzymes that play major roles in many different molecular processes. Specifically, JAK1/3 has been determined to arbitrate IL-15 activation of receptors on CD8⁺ T cells.⁷ These cells then interact with CD4 T cells, mast cells, and other inflammatory cells to cause destruction of the hair follicle without damage to the keratinocyte and melanocyte stem cells, allowing for reversible yet relapsing hair loss.⁸

Treatment of AA is difficult, requiring patience and strict compliance while taking into account duration of disease, age at presentation, site involvement, patient expectations, cost and insurance coverage, prior therapies, and any comorbidities. At the time of this case, no US Food and Drug Administration–approved drug regimen existed for the treatment of AA, and, to date, no treatment is preventative.⁴ We present a case of a patient with alopecia universalis of 11 years’ duration that was refractory to intralesional triamcinolone, clobetasol, minoxidil, and UVB brush therapy yet was successfully treated with tofacitinib.

Case Report

A 29-year-old otherwise-healthy woman presented to our clinic for treatment of alopecia universalis of 11 years’ duration that flared intermittently despite various treatments. Her medical history was unremarkable; however, she had a brother with alopecia universalis. She had no family history of any other autoimmune disorders. At the current presentation, the patient was known to have alopecia universalis with scant evidence of exclamation-point hairs on dermoscopy. Her treatment plan at this point consisted of intralesional triamcinolone to the active areas at 10 mg/mL every 4 weeks, plus clobetasol foam 0.05% at bedtime, minoxidil foam 5% at bedtime, and a UVB brush 3 times a week for 6 months before progressing to universalis type because of hair loss in the eyebrows and eyelashes. This treatment plan continued for 1 year with minimal improvement of the alopecia (Figure 1).

The patient was dissatisfied and wanted to discontinue therapy. Because these treatment options were exhausted with minimal benefit, the patient was then considered for treatment with tofacitinib. Baseline studies were performed, including purified protein derivative, complete blood cell count with differential, comprehensive metabolic panel, lipid profile, and liver function tests, all of which were within reference range. Insurance initially denied coverage of this therapy; a prior authorization was subsequently submitted and denied. A letter of medical necessity was then proposed, and approval for tofacitinib was finally granted. The patient was started on tofacitinib 5 mg twice daily and was monitored every 2 months with a complete blood cell count, comprehensive metabolic panel, lipid panels, and liver function tests. She had a platelet count of 112,000/μL (reference range, 150,000–450,000/μL) at baseline, and continued monitoring revealed a platelet count of 83,000 after 7 months of treatment. This platelet abnormality was evaluated by a hematologist and found to be within reference range; subsequent monitoring did not reveal any abnormalities.

Initial hair growth on the scalp was diffuse with thin, white to light brown hairs in areas of hair loss at months 1 and 2, with progressive hair growth over months 3 to 7. Eyebrow hair growth was noted beginning at month 6. One year later, only hair regrowth occurred without any adverse events (Figure 2). After 5 years of treatment, the patient had a full head of thick hair (Figure 3). The tofacitinib dosage was 5 mg twice daily at initiation, and after 1 year increased to 10 mg twice daily. Her medical insurance subsequently changed and the regimen was adjusted to an 11-mg tablet and 5-mg tablet daily. She remained on this regimen with success.

Comment

Use of JAK Inhibitors—Reports and studies have shed light on the use and efficacy of JAK inhibitors in AA (Table).^5-11 Tofacitinib is a selective JAK1/3 inhibitor that predominantly inhibits JAK3 but also inhibits JAK1, albeit to a lesser degree, which interferes with the JAK/STAT (signal transducer and activator of transcription) cascade responsible for the production, differentiation, and function of various B cells, T cells, and natural killer cells.² Although it was developed for the management of allograft rejection, tofacitinib has made headway in rheumatology for treatment of patients with moderate to severe rheumatoid arthritis who are unable to take or are not responding to methotrexate.² Since 2014, tofacitinib has been introduced to the therapeutic realm for AA but is not yet approved by the US Food and Drug Administration.^3,4

In 2014, Craiglow and King⁵ reported use of tofacitinib with dosages beginning at 10 mg/d and increasing to 15 mg/d in a patient with alopecia universalis and psoriasis. Total hair regrowth was noted after 8 months of therapy.⁵ Xing et al⁶ described 3 patients treated with ruxolitinib, a JAK1/2 inhibitor approved for the treatment of myelofibrosis, at an oral dose of 20 mg twice daily with near-complete hair regrowth after 5 months of treatment.⁶ Biopsies from lesions at baseline and after 3 months of therapy revealed a reduction in perifollicular T cells and in HLA class I and II expression in follicles.⁶ A patient in Italy with essential thrombocythemia and concurrent alopecia universalis was enrolled in a clinical trial with ruxolitinib and was treated with 15 mg twice daily. After 10 months of treatment, the patient had progressive hair regrowth that was sustained for more than 50 months of therapy.⁷ Baricitinib, a JAK1/2 inhibitor, was used in a 17-year-old adolescent boy to assess efficacy of the drug in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome.⁸ The patient also had longstanding patch-type AA that was resistance to treatment and progressed to an ophiasis pattern even though he was on immunosuppressive therapies. He was on 12 mg of prednisone daily at the start of therapy with baricitinib 7 mg daily initially. The baricitinib regimen was titrated up to 7 mg in the morning and 4 mg in the evening, with tapering of prednisone to 3 mg daily after 6 months of initiation. Within 3 months of therapy, hair regrowth occurred, with only a resultant patch on the occipital scalp that further resolved after 6 more months of therapy, resulting in total persistent hair growth.⁸ A 40-year-old woman with moderate to severe alopecia universalis was treated with tofacitinib 5 mg twice daily, revealing near-complete hair regrowth after 4 months of treatment; regrowth of eyebrows and eyelashes also was seen.⁹ However, discontinuation of treatment resulted in hair loss. Microarray analyses of biopsy specimens of lesioned sites at baseline revealed elevated IFN-γ and cytotoxic T cell-level signatures that subsequently decreased—albeit not to normal control levels—after 4 weeks of treatment.⁹ Being that IFN-γ receptors mediate their effects through JAK1/2, JAK1/3, tofacitinib, ruxolitinib, and baricitinib seem to be in sync with the immunopathogenesis of AA and thus may be the therapy of choice in the near future.

A recent retrospective study assessing response to tofacitinib in adults with AA (>40% hair loss), alopecia totalis, alopecia universalis, and stable or progressive diseases for at least 6 months determined a clinical response in 50 of 65 (77%) patients, with 13 patients exhibiting a complete response.¹⁰ Patients in this study were started on tofacitinib 5 mg twice daily with the addition of adjuvant pulsed prednisone (300 mg once monthly for 3 doses) with or without doubled dosing of tofacitinib if they had a halt in hair regrowth. This study demonstrated some benefit when pulsed prednisone was combined with the daily tofacitinib therapy. However, the study emphasized the importance of maintenance therapy, as 8 patients experienced hair loss with discontinuation after previously having hair regrowth; 5 (63%) of these patients experienced regrowth with augmentation of dosing or addition of adjuvant therapy.¹⁰

Another group of investigators assessed the efficacy of tofacitinib 5 mg in 13 adolescents aged 12 to 17 years, most with alopecia universalis (46% [6/13]); 10 of 13 (77%) patients responded to treatment with a mean duration of 6.5 months. The patients who had alopecia totalis and alopecia universalis for more than 10 years were poor responders to tofacitinib, and in fact, 1 of 13 (33%) patients in the study who did not respond to therapy had disease for 12 years.¹¹ Therefore, starting tofacitinib either long-term or intermittently should be considered in children diagnosed early with severe AA, alopecia totalis, or alopecia universalis to prevent irreversible hair loss or progressive disease^12,13; however, further data are required to assess efficacy and long-term benefits of this type of regimen.

Safety Profile—Widespread use of a medication is determined not only by its efficacy profile but also its safety profile. With any medication that exhibits immunosuppressive effects, adverse events must be considered and thoroughly discussed with patients and their primary care physicians. A prospective, open-label, single-arm trial examined the efficacy and safety of tofacitinib 5 mg twice daily in the treatment of AA and its more severe forms over 3 months.¹² Of the 66 patients who completed the trial, 64% (42/66) exhibited a positive response to tofacitinib. Relapse was noted in 8.5 weeks after discontinuation of tofacitinib, reiterating the potential need for a maintenance regimen. In this study, 25.8% (17/66) of patients experienced infections as adverse events including (in decreasing order) upper respiratory tract infections, urinary tract infections, herpes zoster, conjunctivitis, bronchitis, mononucleosis, and paronychia. No reports of new or recurrent malignancy were noted. Other more constitutional adverse events were noted including headaches, abdominal pain, acne, diarrhea, fatigue, nausea, pruritus, hot flashes, cough, folliculitis, weight gain, dry eyes, and amenorrhea. One patient with a pre-existing liver condition experienced transaminitis that resolved with weight loss. There also were noted increases in low- and high-density lipoprotein levels.¹² Our patient with baseline thrombocytopenia had mild drops in platelet count that subsequently stabilized and did not result in any bleeding abnormalities.

Duration of Therapy—Tofacitinib has demonstrated some preliminary success in the management of AA, but the appropriate duration of treatment requires further investigation. Our patient has been on tofacitinib for more than 5 years. She started at a total dosage of 10 mg/d, which increased to 16 mg/d. Initial dosing with maintenance regimens needs to be established for further widespread use to maximize benefit and minimize harm.

At what point do we decide to continue or stop treatment in patients who do not respond as expected or plateau? This is another critical question; our patient had periods of slowed growth and plateauing, but knowing the risks and benefits, she continued the medication and eventually experienced improved regrowth again.

Conclusion

Throughout the literature and in our patient, tofacitinib has demonstrated efficacy in treating AA. When other conventional therapies have failed, use of tofacitinib should be considered.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

Considerable hair regrowth can be achieved in children with alopecia areata with the use of a novel plant-based drug, according to research presented during the first late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology.

In the RAAINBOW study, a greater mean relative improvement in the Severity of Alopecia Tool (SALT) scores at 24 weeks was recorded in children who had been treated topically with coacillium (22.9%) than in those who had received a topical placebo (–8.0%), with a significant 31% overall difference (P < .0001).

“Coacillium cutaneous solution was used for the first time for treatment of alopecia areata and also for the first time used in a pediatric population,” the presenting investigator Ulrike Blume-Peytavi, MD, said at the meeting.

“It’s well tolerated, and in fact what is interesting is, it has a durable response, even after treatment discontinuation,” added Dr. Blume-Peytavi, who is the deputy head of the department of dermatology, venereology and allergology at Charité-Universitätsmedizin Berlin.
 

Backing the botanical?

Paola Pasquali, MD, a dermatologist at Pius Hospital de Valls in Spain, who cochaired the session where the findings were presented, commented, “Thank you for showing that chocolate is great! I knew it. It is fantastic to see how chocolate is used.”

Dr. Pasquali was referring to the coacillium ingredient Theobroma cacao extract. The seeds of T. cacao, or the cocoa tree, are used to make various types of chocolate products. Theobroma cacao is one of four plant extracts that make up coacillium, the others being Allium cepa (onion), Citrus limon (lemon), and Paullinia cupana (guaraná, a source of caffeine).

The four plant extracts are classified as “generally regarded as safe” (GRAS), Dr. Blume-Peytavi observed, noting that the development of coacillium fell under the category of a prescription botanical drug as set out by the U.S. Food and Drug Administration or a herbal medicinal product as set out by the European Medicines Agency.

But how does it work?

The botanical’s mode of action of acting positively on hair follicle cycling and endothelial cell activation was called into question, however, by Emma Guttman-Yassky, MD, PhD, who was in the audience.

She asked, “So how do you explain that, after three large studies with topical JAK inhibitors that did not work actually in alopecia areata because it’s very hard to penetrate the scalp for a topical [drug], this one works?”

Dr. Guttman-Yassky, professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York, added: “Looking at the ingredients, to me, it seems that it’s more like a DPCP [diphenylcyclopropenone]-like reaction.”

DPCP, which has been used to treat alopecia, purportedly works by stimulating the immune response to target the skin surface – causing an allergic reaction – rather than the hair follicle.

It’s an interesting question as to how a molecule penetrates the hair follicle, and it depends on the size of the molecule, Dr. Blume-Peytavi responded.

“We have done a lot of studies on follicular penetration, and we are quite aware that you need a certain size of the molecule,” she said. Between 14 and 200 nanometers appears to produce “the best penetrators,” she observed.

Dr. Blume-Peytavi commented that even after topical JAK inhibitors are applied, the molecules that penetrate do not remain in the local area for very long, yet still produce an inhibitory signaling effect.

No scalp irritation was seen in the trial, which suggests that coacillium is not working in the same way as DPCP, Dr. Blume-Peytavi countered.
 

Evaluating efficacy and safety: The RAAINBOW study

Dr. Blume-Peytavi acknowledged that JAK inhibitors were “a tremendous advance in treating severe and very severe alopecia areata,” but because of their benefit-to-risk ratio, there was still an unmet need for new treatments, particularly in children, in whom drug safety is of critical importance.

Having a drug that could be given safely and also have an effect early on in the disease, while it is still at a mild to moderate stage, would be of considerable value, Dr. Blume-Peytavi maintained.

The RAAINBOW study was a randomized, double-blind, phase 2/3 trial conducted at 12 sites in Germany and three other countries between March 2018 and March 2022 to evaluate the efficacy and safety of coacillium in the treatment of children and adolescents with moderate to severe alopecia areata.

In all, 62 children aged 2-18 years (mean age, 11 years) participated; 42 were treated twice daily with coacillium cutaneous solution 22.5% and 20 received placebo for 24 weeks. Treatment was then stopped, and participants followed for another 24 weeks off treatment to check for disease relapse, bringing the total study duration up to 48 weeks.

Baseline characteristics were “relatively comparable for severity,” Dr. Blume-Peytavi said. Most of the children had severe alopecia areata (57% for coacillium and 65% for placebo); the remainder had moderate disease (43% vs. 35%, respectively).

The average SALT scores at the start of treatment were 56 in the coacillium group and 62 in the placebo group, and a respective 44 and 61 at the end of 24 weeks’ treatment.

Perhaps the most important results, Dr. Blume-Peytavi said, was that at 48 weeks of follow-up, which was 24 weeks after treatment had been discontinued, the mean SALT scores were 29 for coacillium and 56 for placebo (P < .0001).

“You can see the improvement in the treated group is continuing even without treatment. However, the placebo group stays relatively about the same range,” she said.

Overall, 82% of patients treated with coacillium and 37% of those who received placebo experienced hair growth after treatment had stopped, and by week 48, a respective 46.7% vs. 9.1% had a SALT score of 20 or less, and 30.0% vs. 0% had a SALT score of 10 or less.

No safety concerns were raised, with no serious treatment-related reactions, no immunosuppressant-like reactions, and no steroidlike side effects.
 

Beyond the RAAINBOW

Larger studies are needed, Dr. Blume-Peytavi said. According to developer Legacy Healthcare’s website, coacillium cutaneous solution is not being developed just for childhood alopecia areata. It is also under investigation as a treatment for persistent chemotherapy-induced alopecia, atopic dermatitis, and psoriasis. In addition, an oral solution is being tested for cancer-related fatigue.

The study was funded by Legacy Healthcare. Dr. Blume-Peytavi has received research funding and acts as an advisor to the company, among others; four of the study’s coauthors are employees of the company. Dr. Pasquali and Dr. Guttman-Yassky were not involved in the study and had no relevant financial ties to disclose.

A version of this article first appeared on Medscape.com.

Considerable hair regrowth can be achieved in children with alopecia areata with the use of a novel plant-based drug, according to research presented during the first late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology.

In the RAAINBOW study, a greater mean relative improvement in the Severity of Alopecia Tool (SALT) scores at 24 weeks was recorded in children who had been treated topically with coacillium (22.9%) than in those who had received a topical placebo (–8.0%), with a significant 31% overall difference (P < .0001).

“Coacillium cutaneous solution was used for the first time for treatment of alopecia areata and also for the first time used in a pediatric population,” the presenting investigator Ulrike Blume-Peytavi, MD, said at the meeting.

“It’s well tolerated, and in fact what is interesting is, it has a durable response, even after treatment discontinuation,” added Dr. Blume-Peytavi, who is the deputy head of the department of dermatology, venereology and allergology at Charité-Universitätsmedizin Berlin.
 

Backing the botanical?

Paola Pasquali, MD, a dermatologist at Pius Hospital de Valls in Spain, who cochaired the session where the findings were presented, commented, “Thank you for showing that chocolate is great! I knew it. It is fantastic to see how chocolate is used.”

Dr. Pasquali was referring to the coacillium ingredient Theobroma cacao extract. The seeds of T. cacao, or the cocoa tree, are used to make various types of chocolate products. Theobroma cacao is one of four plant extracts that make up coacillium, the others being Allium cepa (onion), Citrus limon (lemon), and Paullinia cupana (guaraná, a source of caffeine).

The four plant extracts are classified as “generally regarded as safe” (GRAS), Dr. Blume-Peytavi observed, noting that the development of coacillium fell under the category of a prescription botanical drug as set out by the U.S. Food and Drug Administration or a herbal medicinal product as set out by the European Medicines Agency.

But how does it work?

The botanical’s mode of action of acting positively on hair follicle cycling and endothelial cell activation was called into question, however, by Emma Guttman-Yassky, MD, PhD, who was in the audience.

She asked, “So how do you explain that, after three large studies with topical JAK inhibitors that did not work actually in alopecia areata because it’s very hard to penetrate the scalp for a topical [drug], this one works?”

Dr. Guttman-Yassky, professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York, added: “Looking at the ingredients, to me, it seems that it’s more like a DPCP [diphenylcyclopropenone]-like reaction.”

DPCP, which has been used to treat alopecia, purportedly works by stimulating the immune response to target the skin surface – causing an allergic reaction – rather than the hair follicle.

It’s an interesting question as to how a molecule penetrates the hair follicle, and it depends on the size of the molecule, Dr. Blume-Peytavi responded.

“We have done a lot of studies on follicular penetration, and we are quite aware that you need a certain size of the molecule,” she said. Between 14 and 200 nanometers appears to produce “the best penetrators,” she observed.

Dr. Blume-Peytavi commented that even after topical JAK inhibitors are applied, the molecules that penetrate do not remain in the local area for very long, yet still produce an inhibitory signaling effect.

No scalp irritation was seen in the trial, which suggests that coacillium is not working in the same way as DPCP, Dr. Blume-Peytavi countered.
 

Evaluating efficacy and safety: The RAAINBOW study

Dr. Blume-Peytavi acknowledged that JAK inhibitors were “a tremendous advance in treating severe and very severe alopecia areata,” but because of their benefit-to-risk ratio, there was still an unmet need for new treatments, particularly in children, in whom drug safety is of critical importance.

Having a drug that could be given safely and also have an effect early on in the disease, while it is still at a mild to moderate stage, would be of considerable value, Dr. Blume-Peytavi maintained.

The RAAINBOW study was a randomized, double-blind, phase 2/3 trial conducted at 12 sites in Germany and three other countries between March 2018 and March 2022 to evaluate the efficacy and safety of coacillium in the treatment of children and adolescents with moderate to severe alopecia areata.

In all, 62 children aged 2-18 years (mean age, 11 years) participated; 42 were treated twice daily with coacillium cutaneous solution 22.5% and 20 received placebo for 24 weeks. Treatment was then stopped, and participants followed for another 24 weeks off treatment to check for disease relapse, bringing the total study duration up to 48 weeks.

Baseline characteristics were “relatively comparable for severity,” Dr. Blume-Peytavi said. Most of the children had severe alopecia areata (57% for coacillium and 65% for placebo); the remainder had moderate disease (43% vs. 35%, respectively).

The average SALT scores at the start of treatment were 56 in the coacillium group and 62 in the placebo group, and a respective 44 and 61 at the end of 24 weeks’ treatment.

Perhaps the most important results, Dr. Blume-Peytavi said, was that at 48 weeks of follow-up, which was 24 weeks after treatment had been discontinued, the mean SALT scores were 29 for coacillium and 56 for placebo (P < .0001).

“You can see the improvement in the treated group is continuing even without treatment. However, the placebo group stays relatively about the same range,” she said.

Overall, 82% of patients treated with coacillium and 37% of those who received placebo experienced hair growth after treatment had stopped, and by week 48, a respective 46.7% vs. 9.1% had a SALT score of 20 or less, and 30.0% vs. 0% had a SALT score of 10 or less.

No safety concerns were raised, with no serious treatment-related reactions, no immunosuppressant-like reactions, and no steroidlike side effects.
 

Beyond the RAAINBOW

Larger studies are needed, Dr. Blume-Peytavi said. According to developer Legacy Healthcare’s website, coacillium cutaneous solution is not being developed just for childhood alopecia areata. It is also under investigation as a treatment for persistent chemotherapy-induced alopecia, atopic dermatitis, and psoriasis. In addition, an oral solution is being tested for cancer-related fatigue.

The study was funded by Legacy Healthcare. Dr. Blume-Peytavi has received research funding and acts as an advisor to the company, among others; four of the study’s coauthors are employees of the company. Dr. Pasquali and Dr. Guttman-Yassky were not involved in the study and had no relevant financial ties to disclose.

A version of this article first appeared on Medscape.com.

Considerable hair regrowth can be achieved in children with alopecia areata with the use of a novel plant-based drug, according to research presented during the first late-breaking news session at the annual congress of the European Academy of Dermatology and Venereology.

In the RAAINBOW study, a greater mean relative improvement in the Severity of Alopecia Tool (SALT) scores at 24 weeks was recorded in children who had been treated topically with coacillium (22.9%) than in those who had received a topical placebo (–8.0%), with a significant 31% overall difference (P < .0001).

“Coacillium cutaneous solution was used for the first time for treatment of alopecia areata and also for the first time used in a pediatric population,” the presenting investigator Ulrike Blume-Peytavi, MD, said at the meeting.

“It’s well tolerated, and in fact what is interesting is, it has a durable response, even after treatment discontinuation,” added Dr. Blume-Peytavi, who is the deputy head of the department of dermatology, venereology and allergology at Charité-Universitätsmedizin Berlin.
 

Backing the botanical?

Paola Pasquali, MD, a dermatologist at Pius Hospital de Valls in Spain, who cochaired the session where the findings were presented, commented, “Thank you for showing that chocolate is great! I knew it. It is fantastic to see how chocolate is used.”

Dr. Pasquali was referring to the coacillium ingredient Theobroma cacao extract. The seeds of T. cacao, or the cocoa tree, are used to make various types of chocolate products. Theobroma cacao is one of four plant extracts that make up coacillium, the others being Allium cepa (onion), Citrus limon (lemon), and Paullinia cupana (guaraná, a source of caffeine).

The four plant extracts are classified as “generally regarded as safe” (GRAS), Dr. Blume-Peytavi observed, noting that the development of coacillium fell under the category of a prescription botanical drug as set out by the U.S. Food and Drug Administration or a herbal medicinal product as set out by the European Medicines Agency.

But how does it work?

The botanical’s mode of action of acting positively on hair follicle cycling and endothelial cell activation was called into question, however, by Emma Guttman-Yassky, MD, PhD, who was in the audience.

She asked, “So how do you explain that, after three large studies with topical JAK inhibitors that did not work actually in alopecia areata because it’s very hard to penetrate the scalp for a topical [drug], this one works?”

Dr. Guttman-Yassky, professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, New York, added: “Looking at the ingredients, to me, it seems that it’s more like a DPCP [diphenylcyclopropenone]-like reaction.”

DPCP, which has been used to treat alopecia, purportedly works by stimulating the immune response to target the skin surface – causing an allergic reaction – rather than the hair follicle.

It’s an interesting question as to how a molecule penetrates the hair follicle, and it depends on the size of the molecule, Dr. Blume-Peytavi responded.

“We have done a lot of studies on follicular penetration, and we are quite aware that you need a certain size of the molecule,” she said. Between 14 and 200 nanometers appears to produce “the best penetrators,” she observed.

Dr. Blume-Peytavi commented that even after topical JAK inhibitors are applied, the molecules that penetrate do not remain in the local area for very long, yet still produce an inhibitory signaling effect.

No scalp irritation was seen in the trial, which suggests that coacillium is not working in the same way as DPCP, Dr. Blume-Peytavi countered.
 

Evaluating efficacy and safety: The RAAINBOW study

Dr. Blume-Peytavi acknowledged that JAK inhibitors were “a tremendous advance in treating severe and very severe alopecia areata,” but because of their benefit-to-risk ratio, there was still an unmet need for new treatments, particularly in children, in whom drug safety is of critical importance.

Having a drug that could be given safely and also have an effect early on in the disease, while it is still at a mild to moderate stage, would be of considerable value, Dr. Blume-Peytavi maintained.

The RAAINBOW study was a randomized, double-blind, phase 2/3 trial conducted at 12 sites in Germany and three other countries between March 2018 and March 2022 to evaluate the efficacy and safety of coacillium in the treatment of children and adolescents with moderate to severe alopecia areata.

In all, 62 children aged 2-18 years (mean age, 11 years) participated; 42 were treated twice daily with coacillium cutaneous solution 22.5% and 20 received placebo for 24 weeks. Treatment was then stopped, and participants followed for another 24 weeks off treatment to check for disease relapse, bringing the total study duration up to 48 weeks.

Baseline characteristics were “relatively comparable for severity,” Dr. Blume-Peytavi said. Most of the children had severe alopecia areata (57% for coacillium and 65% for placebo); the remainder had moderate disease (43% vs. 35%, respectively).

The average SALT scores at the start of treatment were 56 in the coacillium group and 62 in the placebo group, and a respective 44 and 61 at the end of 24 weeks’ treatment.

Perhaps the most important results, Dr. Blume-Peytavi said, was that at 48 weeks of follow-up, which was 24 weeks after treatment had been discontinued, the mean SALT scores were 29 for coacillium and 56 for placebo (P < .0001).

“You can see the improvement in the treated group is continuing even without treatment. However, the placebo group stays relatively about the same range,” she said.

Overall, 82% of patients treated with coacillium and 37% of those who received placebo experienced hair growth after treatment had stopped, and by week 48, a respective 46.7% vs. 9.1% had a SALT score of 20 or less, and 30.0% vs. 0% had a SALT score of 10 or less.

No safety concerns were raised, with no serious treatment-related reactions, no immunosuppressant-like reactions, and no steroidlike side effects.
 

Beyond the RAAINBOW

Larger studies are needed, Dr. Blume-Peytavi said. According to developer Legacy Healthcare’s website, coacillium cutaneous solution is not being developed just for childhood alopecia areata. It is also under investigation as a treatment for persistent chemotherapy-induced alopecia, atopic dermatitis, and psoriasis. In addition, an oral solution is being tested for cancer-related fatigue.

The study was funded by Legacy Healthcare. Dr. Blume-Peytavi has received research funding and acts as an advisor to the company, among others; four of the study’s coauthors are employees of the company. Dr. Pasquali and Dr. Guttman-Yassky were not involved in the study and had no relevant financial ties to disclose.

A version of this article first appeared on Medscape.com.

Practice Gap

Pain and anxiety are common in fully conscious patients undergoing dermatologic surgery with local anesthesia. Particularly during nail surgery, pain from anesthetic injection—caused by both needle insertion and fluid infiltration—occurs because the nail unit is highly vascularized and innervated.¹ Current methods to improve patient comfort during infiltration include use of a buffered anesthetic solution, warming the anesthetic, slower technique, and direct cold application.²

Perioperative anxiety correlates with increased postoperative pain, analgesic use, and delayed recovery. Furthermore, increased perioperative anxiety reduces the pain threshold and elevates estimates of pain intensity.³ Therefore, reducing procedure-related anxiety and pain may improve quality of care and ease patient discomfort.

Distraction is a common and practical nonpharmacotherapeutic technique for reducing pain and anxiety during medical procedures. The refocusing method of distraction aims to divert attention away from pain to more pleasant stimuli to reduce pain perception.³ Several methods of distraction—using stress balls, engaging in conversation, hand-holding, applying virtual reality, and playing videos—can decrease perioperative anxiety and pain.^3-6

Procedural pain and distraction techniques have been evaluated in the pediatric population more than in adults.⁴ Nail surgery–associated pain and distraction techniques for nail surgery have been inadequately studied.⁷

We offer a distraction technique utilizing a portable massager to ensure that patients are as comfortable as possible when the local anesthetic is injected prior to the first incision.

The Technique

A portable shiatsu massager that uses heat and deep-tissue kneading is placed on the upper thigh for toenail cases or lower arm for fingernail cases during injection of anesthetic to divert the patient’s attention from the surgical site (Figure). Kneading from the massage helps distract the patient from pain by introducing a competing, more pleasant, vibrating sensation that overrides pain signals; the relaxation component helps to diminish patient anxiety during injection.

Practice Implications

Use of a portable massager may reduce pain through both distraction and vibration. In a randomized clinical trial of 115 patients undergoing hand or facial surgery, patients who viewed a distraction video during the procedure reported a lower pain score compared to the control group (mean [SD] visual analog scale of pain score, 3.4 [2.6] vs 4.5 [2.6][P=.01]).⁴ In another randomized clinical trial of 25 patients undergoing lip augmentation, 92% of patients (23/25) in the vibration-assisted arm endorsed less pain during procedures compared to the arm without vibration (mean [SD] pain score, 3.82 [1.73] vs 5.6 [1.76][P<.001]).⁸

Utilization of a portable massager is a safe means of improving the patient experience; the distracting and relaxing effects and intense pulsations simultaneously reduce anxiety and pain during nail surgery. Controlled clinical trials are needed to evaluate its efficacy in diminishing both anxiety and pain during nail procedures compared to other analgesic methods.

Practice Gap

Pain and anxiety are common in fully conscious patients undergoing dermatologic surgery with local anesthesia. Particularly during nail surgery, pain from anesthetic injection—caused by both needle insertion and fluid infiltration—occurs because the nail unit is highly vascularized and innervated.¹ Current methods to improve patient comfort during infiltration include use of a buffered anesthetic solution, warming the anesthetic, slower technique, and direct cold application.²

Perioperative anxiety correlates with increased postoperative pain, analgesic use, and delayed recovery. Furthermore, increased perioperative anxiety reduces the pain threshold and elevates estimates of pain intensity.³ Therefore, reducing procedure-related anxiety and pain may improve quality of care and ease patient discomfort.

Distraction is a common and practical nonpharmacotherapeutic technique for reducing pain and anxiety during medical procedures. The refocusing method of distraction aims to divert attention away from pain to more pleasant stimuli to reduce pain perception.³ Several methods of distraction—using stress balls, engaging in conversation, hand-holding, applying virtual reality, and playing videos—can decrease perioperative anxiety and pain.^3-6

Procedural pain and distraction techniques have been evaluated in the pediatric population more than in adults.⁴ Nail surgery–associated pain and distraction techniques for nail surgery have been inadequately studied.⁷

We offer a distraction technique utilizing a portable massager to ensure that patients are as comfortable as possible when the local anesthetic is injected prior to the first incision.

The Technique

A portable shiatsu massager that uses heat and deep-tissue kneading is placed on the upper thigh for toenail cases or lower arm for fingernail cases during injection of anesthetic to divert the patient’s attention from the surgical site (Figure). Kneading from the massage helps distract the patient from pain by introducing a competing, more pleasant, vibrating sensation that overrides pain signals; the relaxation component helps to diminish patient anxiety during injection.

Practice Implications

Use of a portable massager may reduce pain through both distraction and vibration. In a randomized clinical trial of 115 patients undergoing hand or facial surgery, patients who viewed a distraction video during the procedure reported a lower pain score compared to the control group (mean [SD] visual analog scale of pain score, 3.4 [2.6] vs 4.5 [2.6][P=.01]).⁴ In another randomized clinical trial of 25 patients undergoing lip augmentation, 92% of patients (23/25) in the vibration-assisted arm endorsed less pain during procedures compared to the arm without vibration (mean [SD] pain score, 3.82 [1.73] vs 5.6 [1.76][P<.001]).⁸

Utilization of a portable massager is a safe means of improving the patient experience; the distracting and relaxing effects and intense pulsations simultaneously reduce anxiety and pain during nail surgery. Controlled clinical trials are needed to evaluate its efficacy in diminishing both anxiety and pain during nail procedures compared to other analgesic methods.

Practice Gap

Pain and anxiety are common in fully conscious patients undergoing dermatologic surgery with local anesthesia. Particularly during nail surgery, pain from anesthetic injection—caused by both needle insertion and fluid infiltration—occurs because the nail unit is highly vascularized and innervated.¹ Current methods to improve patient comfort during infiltration include use of a buffered anesthetic solution, warming the anesthetic, slower technique, and direct cold application.²

Perioperative anxiety correlates with increased postoperative pain, analgesic use, and delayed recovery. Furthermore, increased perioperative anxiety reduces the pain threshold and elevates estimates of pain intensity.³ Therefore, reducing procedure-related anxiety and pain may improve quality of care and ease patient discomfort.

Distraction is a common and practical nonpharmacotherapeutic technique for reducing pain and anxiety during medical procedures. The refocusing method of distraction aims to divert attention away from pain to more pleasant stimuli to reduce pain perception.³ Several methods of distraction—using stress balls, engaging in conversation, hand-holding, applying virtual reality, and playing videos—can decrease perioperative anxiety and pain.^3-6

Procedural pain and distraction techniques have been evaluated in the pediatric population more than in adults.⁴ Nail surgery–associated pain and distraction techniques for nail surgery have been inadequately studied.⁷

We offer a distraction technique utilizing a portable massager to ensure that patients are as comfortable as possible when the local anesthetic is injected prior to the first incision.

The Technique

A portable shiatsu massager that uses heat and deep-tissue kneading is placed on the upper thigh for toenail cases or lower arm for fingernail cases during injection of anesthetic to divert the patient’s attention from the surgical site (Figure). Kneading from the massage helps distract the patient from pain by introducing a competing, more pleasant, vibrating sensation that overrides pain signals; the relaxation component helps to diminish patient anxiety during injection.

Practice Implications

Use of a portable massager may reduce pain through both distraction and vibration. In a randomized clinical trial of 115 patients undergoing hand or facial surgery, patients who viewed a distraction video during the procedure reported a lower pain score compared to the control group (mean [SD] visual analog scale of pain score, 3.4 [2.6] vs 4.5 [2.6][P=.01]).⁴ In another randomized clinical trial of 25 patients undergoing lip augmentation, 92% of patients (23/25) in the vibration-assisted arm endorsed less pain during procedures compared to the arm without vibration (mean [SD] pain score, 3.82 [1.73] vs 5.6 [1.76][P<.001]).⁸

Utilization of a portable massager is a safe means of improving the patient experience; the distracting and relaxing effects and intense pulsations simultaneously reduce anxiety and pain during nail surgery. Controlled clinical trials are needed to evaluate its efficacy in diminishing both anxiety and pain during nail procedures compared to other analgesic methods.

FLOTCH (leukonychia totalis-trichilemmal cysts-ciliary dystrophy syndrome) syndrome is a rare genetic cutaneous disorder primarily characterized by multiple recurrent trichilemmal pilar cysts and leukonychia. It may be associated with ciliary dystrophy, koilonychia, and/or less frequently renal calculi and pancreatitis. This disorder often presents in an autosomal-dominant pattern of inheritance. Leukonychia and associated pilar cysts originally were termed Bauer syndrome in 1920 and later described in 1986 as FLOTCH syndrome secondary to the association with ciliary dystrophy. ^1,2 The term FLOTCH was coined by Friedel et al ¹ to describe a combination of diagnoses experienced by a family in which several members had multiple pilar cysts, leukonychia, and ciliary dystrophy. We present a 25-year-old Black woman with suspected FLOTCH syndrome who was seen in our clinic for enlarging cysts. 

Case Report

A 25-year-old Black woman with no notable medical history presented to the clinic for a surgical evaluation of cysts of several years’ duration that were enlarging and tender. Physical examination revealed multiple firm, fixed, tender nodules on the left superior parietal scalp, left inferior frontal scalp (Figure 1A), right inferior parietal scalp, right central postauricular skin, and right inferior occipital scalp. Similar-appearing cysts measuring 1.5 to 2 cm were seen on the left rib cage (Figure 1B) and left lateral forearm. Upon further examination, there was homogeneous, nonblanchable, white discoloration of all 10 fingernails consistent with true leukonychia (Figure 1C). When questioned about the nails, the patient stated they had been this color her whole life. Moreover, the patient confirmed that her brother’s nails had a similar appearance.

The patient subsequently underwent elliptical excision of the cysts located on the left medial forehead and left rib cage, and histopathology revealed trichilemmal pilar cysts with dystrophic calcification, dermal fibrosis, and mild chronic inflammation (Figure 2). The pathology report also noted that the anatomic site was somewhat unusual; however, the features were otherwise typical and diagnostic. Given the presentation of multiple pilar cysts throughout the body, leukonychia totalis, and positive family history, the patient was diagnosed with FLOTCH syndrome. Unfortunately, the patient was lost to follow-up following the excision, and no further management could be provided.

Comment

Leukonychia is an abnormality of the nail that results in a visible distribution of white color across the nail plate. It can be classified as totalis when covering the entire nail or partialis when covering localized areas of the nail. The disease also is categorized as acquired or inherited. Acquired leukonychia may appear after damage to a particular area of the nail or secondary to an underlying systemic disease, clinically appearing as white puncta or transverse striae. Hereditary leukonychia is rare, primarily covering the entire nail (totalis), and often is inherited in an autosomal-dominant pattern.^3,4 The appearance of this disease can be an isolated occurrence or may be a component of a condition such as FLOTCH syndrome, as proposed in this case.

Pilar cysts (also known as trichilemmal cysts) are benign, slowly growing, firm, subcutaneous nodules that are similar to epidermoid cysts but arise from the root sheaths of hair follicles. Pilar cysts are inherited in an autosomal-dominant pattern and are caused by a mutation involving a 2-hit mechanism of variants of the phospholipase C delta 1 gene, PLCD1. Patients typically present with multiple cysts,⁵ as in our case.

This association of leukonychia and multiple pilar cysts previously has been reported in 7 family lines.^1-3,6-9 The molecular basis of FLOTCH syndrome is unknown, and these combined diagnoses may be of syndromic nature. Histologic observations of leukonychia and the mechanism of the creation of pilar cysts suggest derivation from similar abnormal keratinization in the nail beds and hair follicles, respectively.⁶

The first familial association between leukonychia totalis and sebaceous cysts was described by Bauer² in 1920. In 1975, Bushkell and Gorlin⁷ reported a similar inherited association with the addition of a history of renal calculi. In 1986, Friedel et al¹ coined the term FLOTCH syndrome when reporting a case of an affected family presenting with leukonychia, recurrent cysts, and ciliary dystrophy. Slee et al⁸ reported 2 cases of pancreatitis experienced by patients presenting with these cysts and leukonychia. The etiology of the pancreatitis was unknown, leading researchers to believe it may be a complication associated with the spectrum of diseases.⁸ In 2008, Morin et al⁶ proposed that those with linked leukonychia and trichilemmal cysts may be at risk for neuromas or spinal tumors and suggested systematic screening after observing a family member with an ependymoma and bilateral multiple acoustic tumors. Rodríguez-Lojo et al³ described a 5-generation family with leukonychia totalis and numerous pilar cysts. Mutoh et al⁹ reported another 5-generation family with associated leukonychia and multiple pilar cysts as well as koilonychia. One family member had a reported history of renal calculus.⁹

In our case, FLOTCH syndrome was suspected given the patient’s concurrent pilar and follicular infundibular cysts. No specific treatment was indicated; however, as seen in prior cases and in ours, many patients prefer to have the cysts excised. A more comprehensive investigation could have revealed other associations, such as ciliary dystrophy, renal calculi, or pancreatitis. It is possible that in conjunction with the syndrome, patients could develop other such clinical manifestations. Pilar cysts most frequently are found on the scalp, yet in patients with concurrent leukonychia, the cysts have been shown to also develop in other regions of the body, as seen in our patient and in the case reported by Mutoh et al.⁹ Given the autosomal-dominant nature of this disease and the keratinizing structures affected, we confer with the hypotheses that a general keratin dysfunction is suspected. Further investigation is needed to determine the exact altered genetic mechanism or deficiency that may be causing this abnormal keratinization as well as a more extensive examination of patients to confirm if other described symptoms may be related.

FLOTCH (leukonychia totalis-trichilemmal cysts-ciliary dystrophy syndrome) syndrome is a rare genetic cutaneous disorder primarily characterized by multiple recurrent trichilemmal pilar cysts and leukonychia. It may be associated with ciliary dystrophy, koilonychia, and/or less frequently renal calculi and pancreatitis. This disorder often presents in an autosomal-dominant pattern of inheritance. Leukonychia and associated pilar cysts originally were termed Bauer syndrome in 1920 and later described in 1986 as FLOTCH syndrome secondary to the association with ciliary dystrophy. ^1,2 The term FLOTCH was coined by Friedel et al ¹ to describe a combination of diagnoses experienced by a family in which several members had multiple pilar cysts, leukonychia, and ciliary dystrophy. We present a 25-year-old Black woman with suspected FLOTCH syndrome who was seen in our clinic for enlarging cysts. 

Case Report

A 25-year-old Black woman with no notable medical history presented to the clinic for a surgical evaluation of cysts of several years’ duration that were enlarging and tender. Physical examination revealed multiple firm, fixed, tender nodules on the left superior parietal scalp, left inferior frontal scalp (Figure 1A), right inferior parietal scalp, right central postauricular skin, and right inferior occipital scalp. Similar-appearing cysts measuring 1.5 to 2 cm were seen on the left rib cage (Figure 1B) and left lateral forearm. Upon further examination, there was homogeneous, nonblanchable, white discoloration of all 10 fingernails consistent with true leukonychia (Figure 1C). When questioned about the nails, the patient stated they had been this color her whole life. Moreover, the patient confirmed that her brother’s nails had a similar appearance.

The patient subsequently underwent elliptical excision of the cysts located on the left medial forehead and left rib cage, and histopathology revealed trichilemmal pilar cysts with dystrophic calcification, dermal fibrosis, and mild chronic inflammation (Figure 2). The pathology report also noted that the anatomic site was somewhat unusual; however, the features were otherwise typical and diagnostic. Given the presentation of multiple pilar cysts throughout the body, leukonychia totalis, and positive family history, the patient was diagnosed with FLOTCH syndrome. Unfortunately, the patient was lost to follow-up following the excision, and no further management could be provided.

Comment

Leukonychia is an abnormality of the nail that results in a visible distribution of white color across the nail plate. It can be classified as totalis when covering the entire nail or partialis when covering localized areas of the nail. The disease also is categorized as acquired or inherited. Acquired leukonychia may appear after damage to a particular area of the nail or secondary to an underlying systemic disease, clinically appearing as white puncta or transverse striae. Hereditary leukonychia is rare, primarily covering the entire nail (totalis), and often is inherited in an autosomal-dominant pattern.^3,4 The appearance of this disease can be an isolated occurrence or may be a component of a condition such as FLOTCH syndrome, as proposed in this case.

Pilar cysts (also known as trichilemmal cysts) are benign, slowly growing, firm, subcutaneous nodules that are similar to epidermoid cysts but arise from the root sheaths of hair follicles. Pilar cysts are inherited in an autosomal-dominant pattern and are caused by a mutation involving a 2-hit mechanism of variants of the phospholipase C delta 1 gene, PLCD1. Patients typically present with multiple cysts,⁵ as in our case.

This association of leukonychia and multiple pilar cysts previously has been reported in 7 family lines.^1-3,6-9 The molecular basis of FLOTCH syndrome is unknown, and these combined diagnoses may be of syndromic nature. Histologic observations of leukonychia and the mechanism of the creation of pilar cysts suggest derivation from similar abnormal keratinization in the nail beds and hair follicles, respectively.⁶

The first familial association between leukonychia totalis and sebaceous cysts was described by Bauer² in 1920. In 1975, Bushkell and Gorlin⁷ reported a similar inherited association with the addition of a history of renal calculi. In 1986, Friedel et al¹ coined the term FLOTCH syndrome when reporting a case of an affected family presenting with leukonychia, recurrent cysts, and ciliary dystrophy. Slee et al⁸ reported 2 cases of pancreatitis experienced by patients presenting with these cysts and leukonychia. The etiology of the pancreatitis was unknown, leading researchers to believe it may be a complication associated with the spectrum of diseases.⁸ In 2008, Morin et al⁶ proposed that those with linked leukonychia and trichilemmal cysts may be at risk for neuromas or spinal tumors and suggested systematic screening after observing a family member with an ependymoma and bilateral multiple acoustic tumors. Rodríguez-Lojo et al³ described a 5-generation family with leukonychia totalis and numerous pilar cysts. Mutoh et al⁹ reported another 5-generation family with associated leukonychia and multiple pilar cysts as well as koilonychia. One family member had a reported history of renal calculus.⁹

In our case, FLOTCH syndrome was suspected given the patient’s concurrent pilar and follicular infundibular cysts. No specific treatment was indicated; however, as seen in prior cases and in ours, many patients prefer to have the cysts excised. A more comprehensive investigation could have revealed other associations, such as ciliary dystrophy, renal calculi, or pancreatitis. It is possible that in conjunction with the syndrome, patients could develop other such clinical manifestations. Pilar cysts most frequently are found on the scalp, yet in patients with concurrent leukonychia, the cysts have been shown to also develop in other regions of the body, as seen in our patient and in the case reported by Mutoh et al.⁹ Given the autosomal-dominant nature of this disease and the keratinizing structures affected, we confer with the hypotheses that a general keratin dysfunction is suspected. Further investigation is needed to determine the exact altered genetic mechanism or deficiency that may be causing this abnormal keratinization as well as a more extensive examination of patients to confirm if other described symptoms may be related.

FLOTCH (leukonychia totalis-trichilemmal cysts-ciliary dystrophy syndrome) syndrome is a rare genetic cutaneous disorder primarily characterized by multiple recurrent trichilemmal pilar cysts and leukonychia. It may be associated with ciliary dystrophy, koilonychia, and/or less frequently renal calculi and pancreatitis. This disorder often presents in an autosomal-dominant pattern of inheritance. Leukonychia and associated pilar cysts originally were termed Bauer syndrome in 1920 and later described in 1986 as FLOTCH syndrome secondary to the association with ciliary dystrophy. ^1,2 The term FLOTCH was coined by Friedel et al ¹ to describe a combination of diagnoses experienced by a family in which several members had multiple pilar cysts, leukonychia, and ciliary dystrophy. We present a 25-year-old Black woman with suspected FLOTCH syndrome who was seen in our clinic for enlarging cysts. 

Case Report

A 25-year-old Black woman with no notable medical history presented to the clinic for a surgical evaluation of cysts of several years’ duration that were enlarging and tender. Physical examination revealed multiple firm, fixed, tender nodules on the left superior parietal scalp, left inferior frontal scalp (Figure 1A), right inferior parietal scalp, right central postauricular skin, and right inferior occipital scalp. Similar-appearing cysts measuring 1.5 to 2 cm were seen on the left rib cage (Figure 1B) and left lateral forearm. Upon further examination, there was homogeneous, nonblanchable, white discoloration of all 10 fingernails consistent with true leukonychia (Figure 1C). When questioned about the nails, the patient stated they had been this color her whole life. Moreover, the patient confirmed that her brother’s nails had a similar appearance.

The patient subsequently underwent elliptical excision of the cysts located on the left medial forehead and left rib cage, and histopathology revealed trichilemmal pilar cysts with dystrophic calcification, dermal fibrosis, and mild chronic inflammation (Figure 2). The pathology report also noted that the anatomic site was somewhat unusual; however, the features were otherwise typical and diagnostic. Given the presentation of multiple pilar cysts throughout the body, leukonychia totalis, and positive family history, the patient was diagnosed with FLOTCH syndrome. Unfortunately, the patient was lost to follow-up following the excision, and no further management could be provided.

Comment

Leukonychia is an abnormality of the nail that results in a visible distribution of white color across the nail plate. It can be classified as totalis when covering the entire nail or partialis when covering localized areas of the nail. The disease also is categorized as acquired or inherited. Acquired leukonychia may appear after damage to a particular area of the nail or secondary to an underlying systemic disease, clinically appearing as white puncta or transverse striae. Hereditary leukonychia is rare, primarily covering the entire nail (totalis), and often is inherited in an autosomal-dominant pattern.^3,4 The appearance of this disease can be an isolated occurrence or may be a component of a condition such as FLOTCH syndrome, as proposed in this case.

Pilar cysts (also known as trichilemmal cysts) are benign, slowly growing, firm, subcutaneous nodules that are similar to epidermoid cysts but arise from the root sheaths of hair follicles. Pilar cysts are inherited in an autosomal-dominant pattern and are caused by a mutation involving a 2-hit mechanism of variants of the phospholipase C delta 1 gene, PLCD1. Patients typically present with multiple cysts,⁵ as in our case.

This association of leukonychia and multiple pilar cysts previously has been reported in 7 family lines.^1-3,6-9 The molecular basis of FLOTCH syndrome is unknown, and these combined diagnoses may be of syndromic nature. Histologic observations of leukonychia and the mechanism of the creation of pilar cysts suggest derivation from similar abnormal keratinization in the nail beds and hair follicles, respectively.⁶

The first familial association between leukonychia totalis and sebaceous cysts was described by Bauer² in 1920. In 1975, Bushkell and Gorlin⁷ reported a similar inherited association with the addition of a history of renal calculi. In 1986, Friedel et al¹ coined the term FLOTCH syndrome when reporting a case of an affected family presenting with leukonychia, recurrent cysts, and ciliary dystrophy. Slee et al⁸ reported 2 cases of pancreatitis experienced by patients presenting with these cysts and leukonychia. The etiology of the pancreatitis was unknown, leading researchers to believe it may be a complication associated with the spectrum of diseases.⁸ In 2008, Morin et al⁶ proposed that those with linked leukonychia and trichilemmal cysts may be at risk for neuromas or spinal tumors and suggested systematic screening after observing a family member with an ependymoma and bilateral multiple acoustic tumors. Rodríguez-Lojo et al³ described a 5-generation family with leukonychia totalis and numerous pilar cysts. Mutoh et al⁹ reported another 5-generation family with associated leukonychia and multiple pilar cysts as well as koilonychia. One family member had a reported history of renal calculus.⁹

In our case, FLOTCH syndrome was suspected given the patient’s concurrent pilar and follicular infundibular cysts. No specific treatment was indicated; however, as seen in prior cases and in ours, many patients prefer to have the cysts excised. A more comprehensive investigation could have revealed other associations, such as ciliary dystrophy, renal calculi, or pancreatitis. It is possible that in conjunction with the syndrome, patients could develop other such clinical manifestations. Pilar cysts most frequently are found on the scalp, yet in patients with concurrent leukonychia, the cysts have been shown to also develop in other regions of the body, as seen in our patient and in the case reported by Mutoh et al.⁹ Given the autosomal-dominant nature of this disease and the keratinizing structures affected, we confer with the hypotheses that a general keratin dysfunction is suspected. Further investigation is needed to determine the exact altered genetic mechanism or deficiency that may be causing this abnormal keratinization as well as a more extensive examination of patients to confirm if other described symptoms may be related.

TOPLINE:

Nearly three-quarters of adults with alopecia areata (AA) were not receiving treatment 1 year after diagnosis, according to a retrospective cohort study using data from more than 45,000 individuals.

METHODOLOGY:

• The study population included 45,483 adults aged 18 years and older with new diagnoses of AA between Oct. 15, 2015, and Feb. 28, 2020. Data were from a large U.S. health care database that included medical and pharmacy claims.
• The mean age of the participants was 43.8 years, and 65.7% were female.
• The researchers measured variables that might relate to AA and its treatment patterns within 1 year of starting the study and during the first year of the study, with data collected at 1, 42, 84, and 365 days after study entry.

TAKEAWAYS:

• During the first year after diagnosis, 66.4% of patients received at least one treatment for AA at one or more time points.
• At 1 year, 71.8% of patients were not receiving any active treatment for AA.
• Among those who received treatment, intralesional injections were the most often prescribed therapy (41.8% of patients), followed by topical corticosteroids (40.9%), intramuscular corticosteroids (38.1%), and oral corticosteroids (20.6%).
• Patients diagnosed with either alopecia totalis or alopecia universalis were significantly less likely to receive intralesional steroids and significantly more likely to receive topical corticosteroids than those without these diagnoses (11.1% vs. 44.1% and 25.4% vs. 42.1, respectively).

IN PRACTICE:

The results highlight the need to determine why so many alopecia patients with AA were no longer on treatment after 1 year, although treatment trends may change with the emergence of new therapies, such as JAK inhibitors and others, according to the authors.

SOURCE:

The lead author of the study was Hemin Lee, MD, MPH, Brigham and Women’s Hospital, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The use of insurance claims data did not allow analysis of over-the-counter medications and treatments, and the lack of a single ICD-10 code for defining AA could have resulted in misclassification of outcomes.

DISCLOSURES:

The study received no outside funding, and Dr. Lee had no disclosures. One author had disclosures that included receiving personal fees from Pfizer and Concert outside of the submitted study and participating in alopecia-related trials with Lilly, Concert, Aclaris, and Incyte. Another author’s disclosures included receiving personal fees from companies that included Pfizer, Concert, Lilly, and AbbVie. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Nearly three-quarters of adults with alopecia areata (AA) were not receiving treatment 1 year after diagnosis, according to a retrospective cohort study using data from more than 45,000 individuals.

METHODOLOGY:

• The study population included 45,483 adults aged 18 years and older with new diagnoses of AA between Oct. 15, 2015, and Feb. 28, 2020. Data were from a large U.S. health care database that included medical and pharmacy claims.
• The mean age of the participants was 43.8 years, and 65.7% were female.
• The researchers measured variables that might relate to AA and its treatment patterns within 1 year of starting the study and during the first year of the study, with data collected at 1, 42, 84, and 365 days after study entry.

TAKEAWAYS:

• During the first year after diagnosis, 66.4% of patients received at least one treatment for AA at one or more time points.
• At 1 year, 71.8% of patients were not receiving any active treatment for AA.
• Among those who received treatment, intralesional injections were the most often prescribed therapy (41.8% of patients), followed by topical corticosteroids (40.9%), intramuscular corticosteroids (38.1%), and oral corticosteroids (20.6%).
• Patients diagnosed with either alopecia totalis or alopecia universalis were significantly less likely to receive intralesional steroids and significantly more likely to receive topical corticosteroids than those without these diagnoses (11.1% vs. 44.1% and 25.4% vs. 42.1, respectively).

IN PRACTICE:

The results highlight the need to determine why so many alopecia patients with AA were no longer on treatment after 1 year, although treatment trends may change with the emergence of new therapies, such as JAK inhibitors and others, according to the authors.

SOURCE:

The lead author of the study was Hemin Lee, MD, MPH, Brigham and Women’s Hospital, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The use of insurance claims data did not allow analysis of over-the-counter medications and treatments, and the lack of a single ICD-10 code for defining AA could have resulted in misclassification of outcomes.

DISCLOSURES:

The study received no outside funding, and Dr. Lee had no disclosures. One author had disclosures that included receiving personal fees from Pfizer and Concert outside of the submitted study and participating in alopecia-related trials with Lilly, Concert, Aclaris, and Incyte. Another author’s disclosures included receiving personal fees from companies that included Pfizer, Concert, Lilly, and AbbVie. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

TOPLINE:

Nearly three-quarters of adults with alopecia areata (AA) were not receiving treatment 1 year after diagnosis, according to a retrospective cohort study using data from more than 45,000 individuals.

METHODOLOGY:

• The study population included 45,483 adults aged 18 years and older with new diagnoses of AA between Oct. 15, 2015, and Feb. 28, 2020. Data were from a large U.S. health care database that included medical and pharmacy claims.
• The mean age of the participants was 43.8 years, and 65.7% were female.
• The researchers measured variables that might relate to AA and its treatment patterns within 1 year of starting the study and during the first year of the study, with data collected at 1, 42, 84, and 365 days after study entry.

TAKEAWAYS:

• During the first year after diagnosis, 66.4% of patients received at least one treatment for AA at one or more time points.
• At 1 year, 71.8% of patients were not receiving any active treatment for AA.
• Among those who received treatment, intralesional injections were the most often prescribed therapy (41.8% of patients), followed by topical corticosteroids (40.9%), intramuscular corticosteroids (38.1%), and oral corticosteroids (20.6%).
• Patients diagnosed with either alopecia totalis or alopecia universalis were significantly less likely to receive intralesional steroids and significantly more likely to receive topical corticosteroids than those without these diagnoses (11.1% vs. 44.1% and 25.4% vs. 42.1, respectively).

IN PRACTICE:

The results highlight the need to determine why so many alopecia patients with AA were no longer on treatment after 1 year, although treatment trends may change with the emergence of new therapies, such as JAK inhibitors and others, according to the authors.

SOURCE:

The lead author of the study was Hemin Lee, MD, MPH, Brigham and Women’s Hospital, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The use of insurance claims data did not allow analysis of over-the-counter medications and treatments, and the lack of a single ICD-10 code for defining AA could have resulted in misclassification of outcomes.

DISCLOSURES:

The study received no outside funding, and Dr. Lee had no disclosures. One author had disclosures that included receiving personal fees from Pfizer and Concert outside of the submitted study and participating in alopecia-related trials with Lilly, Concert, Aclaris, and Incyte. Another author’s disclosures included receiving personal fees from companies that included Pfizer, Concert, Lilly, and AbbVie. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

The Diagnosis: Monilethrix

A diagnosis of monilethrix was rendered based on the clinical and trichoscopic findings. Simple surveillance of the patient’s condition and prevention of further hair trauma were proposed as management options.

Monilethrix is a hair shaft disorder that is inherited in a predominantly autosomal-dominant pattern with variable expressiveness and penetrance resulting from heterozygous mutations in hair keratin genes KRT81, KRT83, and KRT86 in a region of chromosome 12q13.13.^1,2 An autosomalrecessive form has been described with mutation in desmoglein 4, but it differs from the classical form by the variable periodicity of the region between the nodules.^3,4

The morphologic alteration consists of the formation of fusiform nodules of normal structure alternated with narrow and dystrophic constrictions (Figure). These internodes are fragile areas that cause breakage at constricted points.⁵ Clinically, monilethrix presents as areas of focal or diffuse alopecia with frequent involvement of the terminal follicles, mainly in areas of friction. The hair is normal at birth due to the predominance of lanugo in the neonatal period, but it subsequently is replaced by abnormal hairs in the first months of life.⁶ Initial clinical signs begin to appear when the terminal hairs begin to form.⁷ Although rarer, the eyebrows and eyelashes, as well as the axillary, pubic, and body hair, may be involved.⁵

Other hair shaft anomalies merit consideration in the differential diagnosis of monilethrix, including pseudomonilethrix, pressure alopecia, trichorrhexis invaginata, ectodermal dysplasia, tinea capitis, and trichothiodystrophy.⁶ The diagnosis is reached by clinical history and physical examination. Trichoscopy and light microscopy are used to confirm the diagnosis. Trichoscopic examination shows markedly higher rates of anagen hair. The shafts examined in our patient revealed 0.7- to 1-mm intervals between nodes. Hair can be better visualized under a polarized microscope, and the condition can be distinguished from pseudomonilethrix using this approach.^5,6 In our patient, the diagnosis was made based on light microscopy and trichoscopic findings with no genetic testing; however, genetic testing for the classic mutations of the keratin genes would be desirable to confirm the diagnosis but was not done in our patient.⁶ The prognosis of monilethrix is variable; most cases persist into adulthood, though spontaneous improvement may occur with advancing age, during summer, and during pregnancy.⁸

There is no definitive therapy for monilethrix. Although there have been reports of cases treated with systemic corticosteroids, oral retinoids, topical minoxidil, vitamins, and peeling ointments (desquamative oil), the cornerstone of management is protecting the hair against traumatic procedures such as excessive combing, brushing, and friction, as well as parent and patient education about the benign nature of the condition.9 Additionally, some cases have shown improvement with minoxidil solution at 2% and 5% concentrations, oral minoxidil, or acitretin.^7-9

The Diagnosis: Monilethrix

A diagnosis of monilethrix was rendered based on the clinical and trichoscopic findings. Simple surveillance of the patient’s condition and prevention of further hair trauma were proposed as management options.

Monilethrix is a hair shaft disorder that is inherited in a predominantly autosomal-dominant pattern with variable expressiveness and penetrance resulting from heterozygous mutations in hair keratin genes KRT81, KRT83, and KRT86 in a region of chromosome 12q13.13.^1,2 An autosomalrecessive form has been described with mutation in desmoglein 4, but it differs from the classical form by the variable periodicity of the region between the nodules.^3,4

The morphologic alteration consists of the formation of fusiform nodules of normal structure alternated with narrow and dystrophic constrictions (Figure). These internodes are fragile areas that cause breakage at constricted points.⁵ Clinically, monilethrix presents as areas of focal or diffuse alopecia with frequent involvement of the terminal follicles, mainly in areas of friction. The hair is normal at birth due to the predominance of lanugo in the neonatal period, but it subsequently is replaced by abnormal hairs in the first months of life.⁶ Initial clinical signs begin to appear when the terminal hairs begin to form.⁷ Although rarer, the eyebrows and eyelashes, as well as the axillary, pubic, and body hair, may be involved.⁵

Other hair shaft anomalies merit consideration in the differential diagnosis of monilethrix, including pseudomonilethrix, pressure alopecia, trichorrhexis invaginata, ectodermal dysplasia, tinea capitis, and trichothiodystrophy.⁶ The diagnosis is reached by clinical history and physical examination. Trichoscopy and light microscopy are used to confirm the diagnosis. Trichoscopic examination shows markedly higher rates of anagen hair. The shafts examined in our patient revealed 0.7- to 1-mm intervals between nodes. Hair can be better visualized under a polarized microscope, and the condition can be distinguished from pseudomonilethrix using this approach.^5,6 In our patient, the diagnosis was made based on light microscopy and trichoscopic findings with no genetic testing; however, genetic testing for the classic mutations of the keratin genes would be desirable to confirm the diagnosis but was not done in our patient.⁶ The prognosis of monilethrix is variable; most cases persist into adulthood, though spontaneous improvement may occur with advancing age, during summer, and during pregnancy.⁸

There is no definitive therapy for monilethrix. Although there have been reports of cases treated with systemic corticosteroids, oral retinoids, topical minoxidil, vitamins, and peeling ointments (desquamative oil), the cornerstone of management is protecting the hair against traumatic procedures such as excessive combing, brushing, and friction, as well as parent and patient education about the benign nature of the condition.9 Additionally, some cases have shown improvement with minoxidil solution at 2% and 5% concentrations, oral minoxidil, or acitretin.^7-9

The Diagnosis: Monilethrix

A diagnosis of monilethrix was rendered based on the clinical and trichoscopic findings. Simple surveillance of the patient’s condition and prevention of further hair trauma were proposed as management options.

Monilethrix is a hair shaft disorder that is inherited in a predominantly autosomal-dominant pattern with variable expressiveness and penetrance resulting from heterozygous mutations in hair keratin genes KRT81, KRT83, and KRT86 in a region of chromosome 12q13.13.^1,2 An autosomalrecessive form has been described with mutation in desmoglein 4, but it differs from the classical form by the variable periodicity of the region between the nodules.^3,4

The morphologic alteration consists of the formation of fusiform nodules of normal structure alternated with narrow and dystrophic constrictions (Figure). These internodes are fragile areas that cause breakage at constricted points.⁵ Clinically, monilethrix presents as areas of focal or diffuse alopecia with frequent involvement of the terminal follicles, mainly in areas of friction. The hair is normal at birth due to the predominance of lanugo in the neonatal period, but it subsequently is replaced by abnormal hairs in the first months of life.⁶ Initial clinical signs begin to appear when the terminal hairs begin to form.⁷ Although rarer, the eyebrows and eyelashes, as well as the axillary, pubic, and body hair, may be involved.⁵

Other hair shaft anomalies merit consideration in the differential diagnosis of monilethrix, including pseudomonilethrix, pressure alopecia, trichorrhexis invaginata, ectodermal dysplasia, tinea capitis, and trichothiodystrophy.⁶ The diagnosis is reached by clinical history and physical examination. Trichoscopy and light microscopy are used to confirm the diagnosis. Trichoscopic examination shows markedly higher rates of anagen hair. The shafts examined in our patient revealed 0.7- to 1-mm intervals between nodes. Hair can be better visualized under a polarized microscope, and the condition can be distinguished from pseudomonilethrix using this approach.^5,6 In our patient, the diagnosis was made based on light microscopy and trichoscopic findings with no genetic testing; however, genetic testing for the classic mutations of the keratin genes would be desirable to confirm the diagnosis but was not done in our patient.⁶ The prognosis of monilethrix is variable; most cases persist into adulthood, though spontaneous improvement may occur with advancing age, during summer, and during pregnancy.⁸

There is no definitive therapy for monilethrix. Although there have been reports of cases treated with systemic corticosteroids, oral retinoids, topical minoxidil, vitamins, and peeling ointments (desquamative oil), the cornerstone of management is protecting the hair against traumatic procedures such as excessive combing, brushing, and friction, as well as parent and patient education about the benign nature of the condition.9 Additionally, some cases have shown improvement with minoxidil solution at 2% and 5% concentrations, oral minoxidil, or acitretin.^7-9