Dermatology

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Initial evidence suggests that the deliberate delays in melanoma care that occurred during the COVID-19 shelter-in-place lockdown last spring had a significant negative impact on patient outcomes, Rebecca I. Hartman, MD, MPH, said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medication Education.

This is not what National Comprehensive Cancer Network officials expected when they issued short-term recommendations on how to manage cutaneous melanoma during the first wave of the COVID-19 pandemic. Those recommendations for restriction of care, which Dr. Hartman characterized as “pretty significant changes from how we typically practice melanoma care in the U.S.,” came at a time when there was justifiable concern that the first COVID-19 surge would strain the U.S. health care system beyond the breaking point.

The rationale given for the NCCN recommendations was that most time-to-treat studies have shown no adverse patient outcomes for 90-day delays in treatment, even for thicker melanomas. But those studies, all retrospective, have been called into question. And the first real-world data on the impact of care restrictions during the lockdown, reported by Italian dermatologists, highlights adverse effects with potentially far-reaching consequences, noted Dr. Hartman, director of melanoma epidemiology at Brigham and Women’s Hospital and a dermatologist, Harvard University, Boston.

Analysis of the impact of lockdown-induced delays in melanoma care is not merely an academic exercise, she added. While everyone hopes that the spring 2020 COVID-19 shelter-in-place was a once-in-a-lifetime event, there’s no guarantee that will be the case. Moreover, the lockdown provides a natural experiment addressing the possible consequences of melanoma care delays on patient outcomes, a topic that for ethical reasons could never be addressed in a randomized trial.

The short-term NCCN recommendations included the use of excisional biopsies for melanoma diagnosis whenever possible; and delay of up to 3 months for wide local excision of in situ melanoma, any invasive melanoma with negative margins, and even T1 melanomas with positive margins provided the bulk of the lesion had been excised. The guidance also suggested delaying sentinel lymph node biopsy (SLNB), along with increased use of neoadjuvant therapy in patients with clinically palpable regional lymph nodes in order to delay surgery for up to 8 weeks. Single-agent systemic therapy at the least-frequent dosing was advised in order to minimize toxicity and reduce the need for additional health care resources: for example, nivolumab (Opdivo) at 480 mg every 4 weeks instead of every 2 weeks, and pembrolizumab (Keytruda) at 400 mg every 6 weeks, rather than every 3 weeks.

So, that’s what the NCCN recommended. Here’s what actually happened during shelter-in-place as captured in Dr. Hartman’s survey of 18 U.S. members of the Melanoma Prevention Working Group, all practicing dermatology in centers particularly hard-hit in the first wave of the pandemic: In-person new melanoma patient visits plunged from an average of 4.83 per week per provider to 0.83 per week. Telemedicine visits with new melanoma patients went from zero prepandemic to 0.67 visits per week per provider, which doesn’t come close to making up for the drop in in-person visits. Interestingly, two respondents reported turning to gene-expression profile testing for patient prognostication because of delays in SLNB.

Wide local excision was delayed by an average of 6 weeks in roughly one-third of melanoma patients with early tumor stage disease, regardless of margin status. For patients with stage T1b disease, wide local excision was typically performed on time during shelter-in-place; however, SLNB was delayed by an average of 5 weeks in 22% of patients with positive margins and 28% of those with negative margins. In contrast, 80% of patients with more advanced T2-T4 melanoma underwent on-schedule definitive management with wide local excision and SLNB, Dr. Hartman reported.

Critics have taken issue with the NCCN’s conclusion that most time-to-treatment studies show no harm arising from 90-day treatment delays. A review of the relevant published literature by Dr. Hartman’s Harvard colleagues, published in July, found that the evidence is mixed. “There is insufficient evidence to definitively conclude that delayed wide resection after gross removal of the primary melanoma is without harm,” they concluded in the review.

Spanish dermatologists performed a modeling study in order to estimate the potential impact of COVID-19 lockdowns on 5- and 10-year survival of melanoma patients. Using the growth rate of a random sample of 1,000 melanomas to model estimates of tumor thickness after various delays, coupled with American Joint Committee on Cancer survival data for different T stages, they estimated that 5-year survival would be reduced from 94.2% to 92.3% with a 90-day delay in diagnosis, and that 10-year survival would drop from 90.0% to 87.6%.

But that’s merely modeling. Francesco Ricci, MD, PhD, and colleagues from the melanoma unit at the Istituto Dermopatico dell’Immacolata, Rome, have provided a first look at the real-world impact of the lockdown. In the prelockdown period of January through March 9th, 2020, the referral center averaged 2.3 new melanoma diagnoses per day. During the Rome lockdown, from March 10th through May 3rd, this figure dropped to a mean of 0.6 melanoma diagnoses per day. Postlockdown, from May 4th to June 6th, the average climbed to 1.3 per day. The rate of newly diagnosed nodular melanoma was 5.5-fold greater postlockdown, compared with prelockdown; the rate of ulcerated melanoma was 4.9-fold greater.

“We can hypothesize that this may have been due to delays in diagnosis and care,” Dr. Hartman commented. “This is important because we know that nodular melanoma as well as ulceration tend to have a worse prognosis in terms of mortality.”

The mean Breslow thickness of newly diagnosed melanomas was 0.88 mm prelockdown, 0.66 mm during lockdown, and 1.96 mm postlockdown. The investigators speculated that the reduced Breslow thickness of melanomas diagnosed during lockdown might be explained by a greater willingness of more health-conscious people to defy the shelter-in-place instructions because of their concern about a suspicious skin lesion. “Though it is way too early to gauge the consequences of such diagnostic delay, should this issue be neglected, dermatologists and their patients may pay a higher price later with increased morbidity, mortality, and financial burden,” according to the investigators.

Dr. Hartman observed that it will be important to learn whether similar experiences occurred elsewhere during lockdown.

Another speaker, John M. Kirkwood, MD, said he has seen several melanoma patients referred from outside centers who had delays of up to 3 months in sentinel lymph node management of T2 and T3 tumors during lockdown who now have widespread metastatic disease.

“Now, is that anecdotal? I don’t know, it’s just worrisome to me,” commented Dr. Kirkwood, professor of medicine, dermatology, and translational science at the University of Pittsburgh.

Merrick Ross, MD, professor of surgical oncology at M.D. Anderson Cancer Center, Houston, recalled, “There was a period of time [during the lockdown] when we weren’t allowed to do certain elective procedures, if you want to call cancer surgery elective.”

“It’s too soon to talk about outcomes because a lot of patients are still in the process of being treated after what I would consider a significant delay in diagnosis,” the surgeon added.

An audience member asked if there will be an opportunity to see data on the damage done by delaying melanoma management as compared to lives saved through the lockdown for COVID-19. Dr. Ross replied that M.D. Anderson is in the midst of an institution-wide study analyzing the delay in diagnosis of a range of cancers.

“In our melanoma center it is absolutely clear, although we’re still collecting data, that the median tumor thickness is much higher since the lockdown,” Dr. Ross commented.

Dr. Hartman said she and her coinvestigators in the Melanoma Prevention Working Group are attempting to tally up the damage done via the lockdown by delaying melanoma diagnosis and treatment. But she agreed with the questioner that the most important thing is overall net lives saved through shelter-in-place.

“I’m sure that, separately, nondermatologists – perhaps infectious disease doctors and internists – are looking at how many lives were saved by the lockdown policy. So I do think all that data will come out,” Dr. Hartman predicted.

She reported having no financial conflicts regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.
 

bjancin@mdedge.com

SOURCE: Hartman, R. Cutaneous malignancies forum.

Initial evidence suggests that the deliberate delays in melanoma care that occurred during the COVID-19 shelter-in-place lockdown last spring had a significant negative impact on patient outcomes, Rebecca I. Hartman, MD, MPH, said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medication Education.

This is not what National Comprehensive Cancer Network officials expected when they issued short-term recommendations on how to manage cutaneous melanoma during the first wave of the COVID-19 pandemic. Those recommendations for restriction of care, which Dr. Hartman characterized as “pretty significant changes from how we typically practice melanoma care in the U.S.,” came at a time when there was justifiable concern that the first COVID-19 surge would strain the U.S. health care system beyond the breaking point.

The rationale given for the NCCN recommendations was that most time-to-treat studies have shown no adverse patient outcomes for 90-day delays in treatment, even for thicker melanomas. But those studies, all retrospective, have been called into question. And the first real-world data on the impact of care restrictions during the lockdown, reported by Italian dermatologists, highlights adverse effects with potentially far-reaching consequences, noted Dr. Hartman, director of melanoma epidemiology at Brigham and Women’s Hospital and a dermatologist, Harvard University, Boston.

Analysis of the impact of lockdown-induced delays in melanoma care is not merely an academic exercise, she added. While everyone hopes that the spring 2020 COVID-19 shelter-in-place was a once-in-a-lifetime event, there’s no guarantee that will be the case. Moreover, the lockdown provides a natural experiment addressing the possible consequences of melanoma care delays on patient outcomes, a topic that for ethical reasons could never be addressed in a randomized trial.

The short-term NCCN recommendations included the use of excisional biopsies for melanoma diagnosis whenever possible; and delay of up to 3 months for wide local excision of in situ melanoma, any invasive melanoma with negative margins, and even T1 melanomas with positive margins provided the bulk of the lesion had been excised. The guidance also suggested delaying sentinel lymph node biopsy (SLNB), along with increased use of neoadjuvant therapy in patients with clinically palpable regional lymph nodes in order to delay surgery for up to 8 weeks. Single-agent systemic therapy at the least-frequent dosing was advised in order to minimize toxicity and reduce the need for additional health care resources: for example, nivolumab (Opdivo) at 480 mg every 4 weeks instead of every 2 weeks, and pembrolizumab (Keytruda) at 400 mg every 6 weeks, rather than every 3 weeks.

So, that’s what the NCCN recommended. Here’s what actually happened during shelter-in-place as captured in Dr. Hartman’s survey of 18 U.S. members of the Melanoma Prevention Working Group, all practicing dermatology in centers particularly hard-hit in the first wave of the pandemic: In-person new melanoma patient visits plunged from an average of 4.83 per week per provider to 0.83 per week. Telemedicine visits with new melanoma patients went from zero prepandemic to 0.67 visits per week per provider, which doesn’t come close to making up for the drop in in-person visits. Interestingly, two respondents reported turning to gene-expression profile testing for patient prognostication because of delays in SLNB.

Wide local excision was delayed by an average of 6 weeks in roughly one-third of melanoma patients with early tumor stage disease, regardless of margin status. For patients with stage T1b disease, wide local excision was typically performed on time during shelter-in-place; however, SLNB was delayed by an average of 5 weeks in 22% of patients with positive margins and 28% of those with negative margins. In contrast, 80% of patients with more advanced T2-T4 melanoma underwent on-schedule definitive management with wide local excision and SLNB, Dr. Hartman reported.

Critics have taken issue with the NCCN’s conclusion that most time-to-treatment studies show no harm arising from 90-day treatment delays. A review of the relevant published literature by Dr. Hartman’s Harvard colleagues, published in July, found that the evidence is mixed. “There is insufficient evidence to definitively conclude that delayed wide resection after gross removal of the primary melanoma is without harm,” they concluded in the review.

Spanish dermatologists performed a modeling study in order to estimate the potential impact of COVID-19 lockdowns on 5- and 10-year survival of melanoma patients. Using the growth rate of a random sample of 1,000 melanomas to model estimates of tumor thickness after various delays, coupled with American Joint Committee on Cancer survival data for different T stages, they estimated that 5-year survival would be reduced from 94.2% to 92.3% with a 90-day delay in diagnosis, and that 10-year survival would drop from 90.0% to 87.6%.

But that’s merely modeling. Francesco Ricci, MD, PhD, and colleagues from the melanoma unit at the Istituto Dermopatico dell’Immacolata, Rome, have provided a first look at the real-world impact of the lockdown. In the prelockdown period of January through March 9th, 2020, the referral center averaged 2.3 new melanoma diagnoses per day. During the Rome lockdown, from March 10th through May 3rd, this figure dropped to a mean of 0.6 melanoma diagnoses per day. Postlockdown, from May 4th to June 6th, the average climbed to 1.3 per day. The rate of newly diagnosed nodular melanoma was 5.5-fold greater postlockdown, compared with prelockdown; the rate of ulcerated melanoma was 4.9-fold greater.

“We can hypothesize that this may have been due to delays in diagnosis and care,” Dr. Hartman commented. “This is important because we know that nodular melanoma as well as ulceration tend to have a worse prognosis in terms of mortality.”

The mean Breslow thickness of newly diagnosed melanomas was 0.88 mm prelockdown, 0.66 mm during lockdown, and 1.96 mm postlockdown. The investigators speculated that the reduced Breslow thickness of melanomas diagnosed during lockdown might be explained by a greater willingness of more health-conscious people to defy the shelter-in-place instructions because of their concern about a suspicious skin lesion. “Though it is way too early to gauge the consequences of such diagnostic delay, should this issue be neglected, dermatologists and their patients may pay a higher price later with increased morbidity, mortality, and financial burden,” according to the investigators.

Dr. Hartman observed that it will be important to learn whether similar experiences occurred elsewhere during lockdown.

Another speaker, John M. Kirkwood, MD, said he has seen several melanoma patients referred from outside centers who had delays of up to 3 months in sentinel lymph node management of T2 and T3 tumors during lockdown who now have widespread metastatic disease.

“Now, is that anecdotal? I don’t know, it’s just worrisome to me,” commented Dr. Kirkwood, professor of medicine, dermatology, and translational science at the University of Pittsburgh.

Merrick Ross, MD, professor of surgical oncology at M.D. Anderson Cancer Center, Houston, recalled, “There was a period of time [during the lockdown] when we weren’t allowed to do certain elective procedures, if you want to call cancer surgery elective.”

“It’s too soon to talk about outcomes because a lot of patients are still in the process of being treated after what I would consider a significant delay in diagnosis,” the surgeon added.

An audience member asked if there will be an opportunity to see data on the damage done by delaying melanoma management as compared to lives saved through the lockdown for COVID-19. Dr. Ross replied that M.D. Anderson is in the midst of an institution-wide study analyzing the delay in diagnosis of a range of cancers.

“In our melanoma center it is absolutely clear, although we’re still collecting data, that the median tumor thickness is much higher since the lockdown,” Dr. Ross commented.

Dr. Hartman said she and her coinvestigators in the Melanoma Prevention Working Group are attempting to tally up the damage done via the lockdown by delaying melanoma diagnosis and treatment. But she agreed with the questioner that the most important thing is overall net lives saved through shelter-in-place.

“I’m sure that, separately, nondermatologists – perhaps infectious disease doctors and internists – are looking at how many lives were saved by the lockdown policy. So I do think all that data will come out,” Dr. Hartman predicted.

She reported having no financial conflicts regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.
 

bjancin@mdedge.com

SOURCE: Hartman, R. Cutaneous malignancies forum.

Initial evidence suggests that the deliberate delays in melanoma care that occurred during the COVID-19 shelter-in-place lockdown last spring had a significant negative impact on patient outcomes, Rebecca I. Hartman, MD, MPH, said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medication Education.

This is not what National Comprehensive Cancer Network officials expected when they issued short-term recommendations on how to manage cutaneous melanoma during the first wave of the COVID-19 pandemic. Those recommendations for restriction of care, which Dr. Hartman characterized as “pretty significant changes from how we typically practice melanoma care in the U.S.,” came at a time when there was justifiable concern that the first COVID-19 surge would strain the U.S. health care system beyond the breaking point.

The rationale given for the NCCN recommendations was that most time-to-treat studies have shown no adverse patient outcomes for 90-day delays in treatment, even for thicker melanomas. But those studies, all retrospective, have been called into question. And the first real-world data on the impact of care restrictions during the lockdown, reported by Italian dermatologists, highlights adverse effects with potentially far-reaching consequences, noted Dr. Hartman, director of melanoma epidemiology at Brigham and Women’s Hospital and a dermatologist, Harvard University, Boston.

Analysis of the impact of lockdown-induced delays in melanoma care is not merely an academic exercise, she added. While everyone hopes that the spring 2020 COVID-19 shelter-in-place was a once-in-a-lifetime event, there’s no guarantee that will be the case. Moreover, the lockdown provides a natural experiment addressing the possible consequences of melanoma care delays on patient outcomes, a topic that for ethical reasons could never be addressed in a randomized trial.

The short-term NCCN recommendations included the use of excisional biopsies for melanoma diagnosis whenever possible; and delay of up to 3 months for wide local excision of in situ melanoma, any invasive melanoma with negative margins, and even T1 melanomas with positive margins provided the bulk of the lesion had been excised. The guidance also suggested delaying sentinel lymph node biopsy (SLNB), along with increased use of neoadjuvant therapy in patients with clinically palpable regional lymph nodes in order to delay surgery for up to 8 weeks. Single-agent systemic therapy at the least-frequent dosing was advised in order to minimize toxicity and reduce the need for additional health care resources: for example, nivolumab (Opdivo) at 480 mg every 4 weeks instead of every 2 weeks, and pembrolizumab (Keytruda) at 400 mg every 6 weeks, rather than every 3 weeks.

So, that’s what the NCCN recommended. Here’s what actually happened during shelter-in-place as captured in Dr. Hartman’s survey of 18 U.S. members of the Melanoma Prevention Working Group, all practicing dermatology in centers particularly hard-hit in the first wave of the pandemic: In-person new melanoma patient visits plunged from an average of 4.83 per week per provider to 0.83 per week. Telemedicine visits with new melanoma patients went from zero prepandemic to 0.67 visits per week per provider, which doesn’t come close to making up for the drop in in-person visits. Interestingly, two respondents reported turning to gene-expression profile testing for patient prognostication because of delays in SLNB.

Wide local excision was delayed by an average of 6 weeks in roughly one-third of melanoma patients with early tumor stage disease, regardless of margin status. For patients with stage T1b disease, wide local excision was typically performed on time during shelter-in-place; however, SLNB was delayed by an average of 5 weeks in 22% of patients with positive margins and 28% of those with negative margins. In contrast, 80% of patients with more advanced T2-T4 melanoma underwent on-schedule definitive management with wide local excision and SLNB, Dr. Hartman reported.

Critics have taken issue with the NCCN’s conclusion that most time-to-treatment studies show no harm arising from 90-day treatment delays. A review of the relevant published literature by Dr. Hartman’s Harvard colleagues, published in July, found that the evidence is mixed. “There is insufficient evidence to definitively conclude that delayed wide resection after gross removal of the primary melanoma is without harm,” they concluded in the review.

Spanish dermatologists performed a modeling study in order to estimate the potential impact of COVID-19 lockdowns on 5- and 10-year survival of melanoma patients. Using the growth rate of a random sample of 1,000 melanomas to model estimates of tumor thickness after various delays, coupled with American Joint Committee on Cancer survival data for different T stages, they estimated that 5-year survival would be reduced from 94.2% to 92.3% with a 90-day delay in diagnosis, and that 10-year survival would drop from 90.0% to 87.6%.

But that’s merely modeling. Francesco Ricci, MD, PhD, and colleagues from the melanoma unit at the Istituto Dermopatico dell’Immacolata, Rome, have provided a first look at the real-world impact of the lockdown. In the prelockdown period of January through March 9th, 2020, the referral center averaged 2.3 new melanoma diagnoses per day. During the Rome lockdown, from March 10th through May 3rd, this figure dropped to a mean of 0.6 melanoma diagnoses per day. Postlockdown, from May 4th to June 6th, the average climbed to 1.3 per day. The rate of newly diagnosed nodular melanoma was 5.5-fold greater postlockdown, compared with prelockdown; the rate of ulcerated melanoma was 4.9-fold greater.

“We can hypothesize that this may have been due to delays in diagnosis and care,” Dr. Hartman commented. “This is important because we know that nodular melanoma as well as ulceration tend to have a worse prognosis in terms of mortality.”

The mean Breslow thickness of newly diagnosed melanomas was 0.88 mm prelockdown, 0.66 mm during lockdown, and 1.96 mm postlockdown. The investigators speculated that the reduced Breslow thickness of melanomas diagnosed during lockdown might be explained by a greater willingness of more health-conscious people to defy the shelter-in-place instructions because of their concern about a suspicious skin lesion. “Though it is way too early to gauge the consequences of such diagnostic delay, should this issue be neglected, dermatologists and their patients may pay a higher price later with increased morbidity, mortality, and financial burden,” according to the investigators.

Dr. Hartman observed that it will be important to learn whether similar experiences occurred elsewhere during lockdown.

Another speaker, John M. Kirkwood, MD, said he has seen several melanoma patients referred from outside centers who had delays of up to 3 months in sentinel lymph node management of T2 and T3 tumors during lockdown who now have widespread metastatic disease.

“Now, is that anecdotal? I don’t know, it’s just worrisome to me,” commented Dr. Kirkwood, professor of medicine, dermatology, and translational science at the University of Pittsburgh.

Merrick Ross, MD, professor of surgical oncology at M.D. Anderson Cancer Center, Houston, recalled, “There was a period of time [during the lockdown] when we weren’t allowed to do certain elective procedures, if you want to call cancer surgery elective.”

“It’s too soon to talk about outcomes because a lot of patients are still in the process of being treated after what I would consider a significant delay in diagnosis,” the surgeon added.

An audience member asked if there will be an opportunity to see data on the damage done by delaying melanoma management as compared to lives saved through the lockdown for COVID-19. Dr. Ross replied that M.D. Anderson is in the midst of an institution-wide study analyzing the delay in diagnosis of a range of cancers.

“In our melanoma center it is absolutely clear, although we’re still collecting data, that the median tumor thickness is much higher since the lockdown,” Dr. Ross commented.

Dr. Hartman said she and her coinvestigators in the Melanoma Prevention Working Group are attempting to tally up the damage done via the lockdown by delaying melanoma diagnosis and treatment. But she agreed with the questioner that the most important thing is overall net lives saved through shelter-in-place.

“I’m sure that, separately, nondermatologists – perhaps infectious disease doctors and internists – are looking at how many lives were saved by the lockdown policy. So I do think all that data will come out,” Dr. Hartman predicted.

She reported having no financial conflicts regarding her presentation.

Global Academy for Medical Education and this news organization are owned by the same company.
 

bjancin@mdedge.com

SOURCE: Hartman, R. Cutaneous malignancies forum.

Pruritus, defined as a sensation that induces a desire to scratch¹ and classified as acute or chronic (lasting > 6 weeks),² is one of the most common complaints among primary care patients: Approximately 1% of ambulatory visits in the United States are linked to pruritus.³

Chronic pruritus impairs quality of life; its impact has been compared to that of chronic pain.⁴ Treatment should therefore be instituted promptly. Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition, as we describe here. When persistent pruritus is refractory to treatment, systemic causes should be fully explored.

In this article, we discuss the pathogenesis and management of pruritus without skin eruption in the adult nonpregnant patient. We also present practice recommendations to help you determine whether your patient’s pruritus is indicative of a serious systemic condition.

An incomplete understanding of the pathophysiology of pruritus

The pathophysiology of pruritus is not fully understood. It is generally recognized, however, that pruritus starts in the peripheral nerves located in the dermal–epidermal junction of the skin.⁵ The sensation is then transmitted along unmyelinated slow-conducting C fibers to the dorsal horn of the spinal cord.^5,6 There are 2 types of C fibers that transmit the itch impulse⁶: A histamine-dependent type and a non-­histamine-dependent type, which might explain why pruritus can be refractory to antihistamine treatment.⁶

Once the itch impulse has moved from the spinal cord, it travels along the spinothalamic tract up to the contralateral thalamus.¹ From there, the impulse ascends to the cerebral cortex.¹ In the cortex, the impulse triggers multiple areas of the brain, such as those responsible for sensation, motor function, reward, memory, and emotion.⁷

Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition.

Several chemical mediators have been found to be peripheral and central inducers of pruritus: histamine, endogenous opioids, substance P, and serotonin.² There are indications that certain receptors, such as mu-opioid receptors and kappa-opioid receptors, are key contributors to itch as well.²

A diverse etiology

The International Forum for the Study of Itch (IFSI) has established 6 main categories of causes of pruritus(TABLE 1)²:

• dermatologic
• systemic
• neurologic
• psychogenic
• mixed
• other.

Continue to: In this review...

 

In this review, we focus on the work-up and management of 3 of those categories: systemic, neurologic, and psychogenic causes of pruritus.

Systemic causes

Research has shown that 14% to 24% of patients who seek the care of a dermatologist for chronic itch without skin lesions have a systemic illness.⁸

Renal disease. Approximately 40% of patients with end-stage renal disease who are on hemodialysis or peritoneal dialysis have uremic pruritus.2 The itch is mostly generalized but can be pronounced on the back. For most patients, the itch is worse at night, causing a major impact on quality of life.⁶

Liver disease. In hepatic disease, there is often impairment in the secretion of bile, which can lead to cholestatic pruritus.² This condition commonly affects the hands and feet first; later, it becomes generalized.² Cholestatic pruritus can be elicited by tight-fitting clothing. Relief is not achieved by scratching.⁹ This type of itch effects 70% of patients with primary biliary cirrhosis and 15% of patients with hepatitis C infection.⁹

Hematologic disorders. Pruritus is a hallmark symptom of polycythemia rubra vera. Almost 50% of patients with this disorder report pruritus that occurs after exposure to water⁹; aquagenic pruritus can precede the formal diagnosis of polycythemia rubra vera by years.² It has been speculated that platelet aggregation in this disorder leads to release of serotonin and histamine, which, in turn, causes itch.⁹

Continue to: Endocrine disorders

 

Endocrine disorders. Approximately 4% to 11% of patients with thyrotoxicosis have pruritus.¹ It has been suggested that vasodilation, increased skin temperature, and a decreased itch threshold from untreated Graves disease might be inciting factors.

Malignancy. In generalized chronic pruritus without a known cause, strongly consider the likelihood of underlying malignancy^8,10; for 10% of these patients, their chronic pruritus is a paraneoplastic sign. Paraneoplastic pruritus is characterized as an itch that predates clinical onset, or occurs early in the course, of a malignancy.⁹ The condition is most strongly linked to cancers of the liver, gallbladder, biliary tract, hematologic system, and skin.¹¹

Palpate the liver, spleen, lymph nodes, and thyroid for organomegaly, which could indicate a serious systemic condition as the cause of pruritus.

Chronic pruritus affects 30% of patients with Hodgkin lymphoma.⁹ General pruritus can precede this diagnosis by months, even years.¹ In Hodgkin lymphoma patients who are in remission, a return of pruritic symptoms can be a harbinger of recurrence.⁹

Neurologic causes

A recent study found that 8% to 15% of patients referred to a dermatology clinic for chronic pruritus without skin eruption had underlying neurologic pathology.¹² Although the specific mechanisms of neuropathic itch are still poorly understood, it has been theorized that the itch emanates from neuronal damage, which can come from peripheral or central nervous system lesions.⁹

Brachioradial pruritus. There are divergent theories about the etiology of brachioradial pruritus. One hypothesis is that the condition is caused by cervical nerve-root impingement at the level of C5-C8 that leads to nerve damage²; another is that chronic exposure to sunlight causes injury to peripheral cutaneous nerves.² Brachioradial pruritus is localized to the dorsolateral forearm; it can also involve the neck, back, shoulder, upper arm, and chest, unilaterally and bilaterally. This pruritus can be intermittent and become worse upon exposure to sunlight.²

Continue to: Notalgia paresthetica

 

Notalgia paresthetica. This condition might also cause neuropathic pruritus as a consequence of nerve impingement. The itch of notalgia paresthesia is located on the skin, medial to the scapular border on the upper or mid-back.² It has been postulated that the itch is caused by nerve entrapment of the posterior rami of spinal nerves arising from T2-T6.⁹ However, another theory suggests that the itch is caused by damage to peripheral nerves.⁹ The itch of notalgia paresthetica can wax and wane.²

Poststroke pruritus. Brain lesions, most often caused by stroke, can cause neuropathic itch. One of the best-known syndromes related to poststroke itch is Wallenberg syndrome (ischemia from a lateral medullary infarction), which typically presents with itch, thermalgic hypoesthesia of the face, cerebellar dysfunction, nausea, and vomiting.⁷

Shingles. More than one-half of patients who develop postherpetic neuralgia as a consequence of a herpes zoster infection also develop neuropathic pruritus.⁹ It is thought that postherpetic pruritus shares a comparable pathophysiology with postherpetic neuralgia, in which neurons involved in itch stimuli become damaged.⁷

Diabetes mellitus. Pruritus from diabetes can be classified as systemic or neuropathic. Diabetes is one of the most common causes of small-fiber polyneuropathy, which can cause neuropathic pruritus.¹³

Multiple sclerosis. Central nervous system lesions that affect sensory pathways can lead to neuropathic itch in multiple sclerosis. Patients can have severe episodes of generalized pruritus. It has been hypothesized that the neuropathic itch in multiple sclerosis is induced by activation of artificial synapses in demyelinated areas.²

Continue to: Psychogenic pruritus

 

 

Psychogenic pruritus

Chronic pruritus can be a comorbidity of psychiatric illness. A retrospective study found that pruritus occurs in 32% to 42% of psychiatric inpatients.¹⁴ Depression, anxiety, bipolar disorders, obsessive–compulsive disorders, somatoform disorders, psychosis, and substance abuse all have a strong link to psychogenic excoriation.¹⁵ Psychogenic excoriation, which can cause secondary skin lesions, occurs in psychiatric patients who excessively pick and scratch normal skin because they perceive an itch sensation or have a delusion of infestation.² Affected skin can be marked by scattered crusted lesions (FIGURE) anywhere on the body that the patient can reach—most commonly, the extremities.²

Delusion of infestation. Patients with a delusion of infestation have a strong belief that their body is infected by some kind of insect or microorganism.¹⁶ Before a diagnosis of delusion of infestation can be made, other organic causes must be excluded, including withdrawal from such substances as cocaine, amphetamines, and alcohol.¹⁶ Patients with a delusion of infestation can have, and maintain, a symptomatic response with continuing use of an atypical antipsychotic agent, including risperidone and olanzapine.¹⁷

Evaluation and diagnostic work-up

A thorough medical history, review of systems, medication review, social history, and family history are important when evaluating a patient with chronic pruritus.¹⁸ These items can be valuable in formulating a differential diagnosis, even before a physical examination.

Physical examination. The physical exam should include detailed inspection of the entire skin and hair¹⁸; such a comprehensive physical exam can determine whether the source of the itch is cutaneous.⁷ This, in turn, can help further narrow the differential diagnosis. It is crucial that the physical exam include palpation of the liver, spleen, lymph nodes, and thyroid for organomegaly,⁸ which could indicate a serious systemic condition, such as lymphoma.

The ice-pack sign—in which an ice pack applied to the pruritic area provides immediate relief—is considered pathognomonic for brachioradial pruritus.

The ice-pack sign—in which an ice pack is applied to the pruritic area, the patient experiences immediate relief of pruritus, and the itch returns soon after the ice pack is removed—is considered pathognomonic for brachioradial pruritus.¹⁹

Continue to: Chronic pruritus with abnormal findings...

 

Chronic pruritus with abnormal findings on the physical exam should prompt an initial work-up.¹⁸ Also consider an initial work-up for a patient with chronic pruritus whose symptom has not been relieved with conservative treatment.¹⁸

Laboratory testing. The initial laboratory work-up could include any of the following evaluations: complete blood count, measurement of thyroid-stimulating hormone, comprehensive metabolic panel (liver function, renal function, and the serum glucose level) and the erythrocyte sedimentation rate (TABLE 2).¹⁸ If warranted by the evaluation and physical exam, blood work can also include serologic studies for human immunodeficiency virus infection and ­hepatitis.¹⁷

Imaging. Chest radiography should be performed if there is suspicion of malignancy, such as lymphoma.⁷ Although brachioradial pruritus and notalgia paresthetica have been postulated to be caused by impingement of spinal nerves, obtaining spinal imaging, such as magnetic resonance imaging, as part of the initial work-up is not recommended; because spinal images might not show evidence of spinal disease, obtaining spinal imaging is not a requirement before treating brachioradial pruritus and notalgia paresthetica. Do consider spinal imaging, however, for patients in whom brachioradial pruritus or notalgia paresthetica is suspected and conservative treatment has not produced a response.

Treatment: Nondrug approaches, topicals, systemic agents

Start conservatively. Treatment of pruritus should begin with behavior modification and nonpharmacotherapeutic options (TABLE 3⁸). Educate the patient that scratching might cause secondary skin lesions; empowering them with that knowledge is sometimes enough to help break the scratching cycling—especially if the patient combines behavior modification with proper skin hydration with an emollient. To prevent secondary skin lesions through involuntary scratching, consider recommending that lesions be covered with an occlusive dressing or protective clothing.¹³

Stress has been shown to make chronic itch worse; therefore, stress-reduction activities, such as exercise, meditation, and yoga, might be helpful.20 For patients in whom pruritus has a psychological component, referral to a psychiatrist or psychologist might be therapeutic.

Continue to: When a patient complains...

 

When a patient complains of severe pruritus at first presentation, consider pharmacotherapy in conjunction with nonpharmacotherapeutic options. Several of the more effective topical therapies for pruritus^a are listed in TABLE 4.²⁰ Well-known systemic agents for this purpose are reviewed below and listed in TABLE 5.⁷

Systemic treatment

Antihistamines. A staple in the treatment of pruritus for many years, antihistamines are not effective for all causes; however, they are effective in treating paraneoplastic pruritus.²⁰ First-generation antihistamines, with their sedating effect, can be useful for patients who experience generalized pruritus at night.²⁰

Anticonvulsants. Gabapentin and pregabalin are analogs of the neurotransmitter gamma-aminobutyric acid.²⁰ This drug class is helpful in neuropathic pruritus specifically caused by impingements, such as brachioradial pruritus and notalgia paresthetica.²⁰ In addition, of all systemic therapies used to treat uremic pruritus, gabapentin has, in clinical trials, most consistently been found effective for uremic pruritus.⁶ (Note: Use renal dosing of gabapentin in patients with renal failure.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs; eg, fluvoxamine, paroxetine, and sertraline) might cause itch to subside by increasing the serotonin level, which, in turn, works to decrease inflammatory substances that cause itch.⁷ SSRIs have been used to treat patients with psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.⁷

Start conservatively: Use behavior modification and nonpharmacotherapeutic options for pruritus first.

Tricyclic antidepressants (eg, amitriptyline and doxepin) lessen the itch by antagonizing histamine receptors and through anticholinergic mechanisms. Tricyclics are best used in the treatment of psychogenic and nocturnal itch.⁷

Continue to: Mirtazapine...

 

Mirtazapine, a tetracyclic antidepressant, works in patients with uremic pruritus, psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.¹

Substance P antagonist. Aprepitant, a neurokinin receptor I antagonist, is a newer agent that inhibits binding of the itch mediator substance P to the neurokinin receptor. The drug has been found helpful in patients with drug-induced, paraneoplastic, and brachioradial pruritus.⁷

Opioid-receptor agents. Naltrexone, as a mu opioid-receptor antagonist, has shown promise as a treatment for uremic pruritus and cholestatic pruritus. Nalfurafine, a kappa opioid-receptor agonist, is emerging as a possible therapy for uremic pruritus.⁷

Bile-acid sequestrants. A few small studies have shown that treatment with a bile-acid sequestrant, such as cholestyramine and ursodiol, induces moderate improvement in symptoms in patients with cholestatic pruritus.²¹

CORRESPONDENCE
Matasha Russell, MD, Department of Family and Community Medicine, The University of Texas Health Science Center at Houston, McGovern Medical School, 6431 Fannin Street, JJL 324, Houston, TX 77030; Matasha.L.Russell@uth.tmc.edu.

Pruritus, defined as a sensation that induces a desire to scratch¹ and classified as acute or chronic (lasting > 6 weeks),² is one of the most common complaints among primary care patients: Approximately 1% of ambulatory visits in the United States are linked to pruritus.³

Chronic pruritus impairs quality of life; its impact has been compared to that of chronic pain.⁴ Treatment should therefore be instituted promptly. Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition, as we describe here. When persistent pruritus is refractory to treatment, systemic causes should be fully explored.

In this article, we discuss the pathogenesis and management of pruritus without skin eruption in the adult nonpregnant patient. We also present practice recommendations to help you determine whether your patient’s pruritus is indicative of a serious systemic condition.

An incomplete understanding of the pathophysiology of pruritus

The pathophysiology of pruritus is not fully understood. It is generally recognized, however, that pruritus starts in the peripheral nerves located in the dermal–epidermal junction of the skin.⁵ The sensation is then transmitted along unmyelinated slow-conducting C fibers to the dorsal horn of the spinal cord.^5,6 There are 2 types of C fibers that transmit the itch impulse⁶: A histamine-dependent type and a non-­histamine-dependent type, which might explain why pruritus can be refractory to antihistamine treatment.⁶

Once the itch impulse has moved from the spinal cord, it travels along the spinothalamic tract up to the contralateral thalamus.¹ From there, the impulse ascends to the cerebral cortex.¹ In the cortex, the impulse triggers multiple areas of the brain, such as those responsible for sensation, motor function, reward, memory, and emotion.⁷

Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition.

Several chemical mediators have been found to be peripheral and central inducers of pruritus: histamine, endogenous opioids, substance P, and serotonin.² There are indications that certain receptors, such as mu-opioid receptors and kappa-opioid receptors, are key contributors to itch as well.²

A diverse etiology

The International Forum for the Study of Itch (IFSI) has established 6 main categories of causes of pruritus(TABLE 1)²:

• dermatologic
• systemic
• neurologic
• psychogenic
• mixed
• other.

Continue to: In this review...

 

In this review, we focus on the work-up and management of 3 of those categories: systemic, neurologic, and psychogenic causes of pruritus.

Systemic causes

Research has shown that 14% to 24% of patients who seek the care of a dermatologist for chronic itch without skin lesions have a systemic illness.⁸

Renal disease. Approximately 40% of patients with end-stage renal disease who are on hemodialysis or peritoneal dialysis have uremic pruritus.2 The itch is mostly generalized but can be pronounced on the back. For most patients, the itch is worse at night, causing a major impact on quality of life.⁶

Liver disease. In hepatic disease, there is often impairment in the secretion of bile, which can lead to cholestatic pruritus.² This condition commonly affects the hands and feet first; later, it becomes generalized.² Cholestatic pruritus can be elicited by tight-fitting clothing. Relief is not achieved by scratching.⁹ This type of itch effects 70% of patients with primary biliary cirrhosis and 15% of patients with hepatitis C infection.⁹

Hematologic disorders. Pruritus is a hallmark symptom of polycythemia rubra vera. Almost 50% of patients with this disorder report pruritus that occurs after exposure to water⁹; aquagenic pruritus can precede the formal diagnosis of polycythemia rubra vera by years.² It has been speculated that platelet aggregation in this disorder leads to release of serotonin and histamine, which, in turn, causes itch.⁹

Continue to: Endocrine disorders

 

Endocrine disorders. Approximately 4% to 11% of patients with thyrotoxicosis have pruritus.¹ It has been suggested that vasodilation, increased skin temperature, and a decreased itch threshold from untreated Graves disease might be inciting factors.

Malignancy. In generalized chronic pruritus without a known cause, strongly consider the likelihood of underlying malignancy^8,10; for 10% of these patients, their chronic pruritus is a paraneoplastic sign. Paraneoplastic pruritus is characterized as an itch that predates clinical onset, or occurs early in the course, of a malignancy.⁹ The condition is most strongly linked to cancers of the liver, gallbladder, biliary tract, hematologic system, and skin.¹¹

Palpate the liver, spleen, lymph nodes, and thyroid for organomegaly, which could indicate a serious systemic condition as the cause of pruritus.

Chronic pruritus affects 30% of patients with Hodgkin lymphoma.⁹ General pruritus can precede this diagnosis by months, even years.¹ In Hodgkin lymphoma patients who are in remission, a return of pruritic symptoms can be a harbinger of recurrence.⁹

Neurologic causes

A recent study found that 8% to 15% of patients referred to a dermatology clinic for chronic pruritus without skin eruption had underlying neurologic pathology.¹² Although the specific mechanisms of neuropathic itch are still poorly understood, it has been theorized that the itch emanates from neuronal damage, which can come from peripheral or central nervous system lesions.⁹

Brachioradial pruritus. There are divergent theories about the etiology of brachioradial pruritus. One hypothesis is that the condition is caused by cervical nerve-root impingement at the level of C5-C8 that leads to nerve damage²; another is that chronic exposure to sunlight causes injury to peripheral cutaneous nerves.² Brachioradial pruritus is localized to the dorsolateral forearm; it can also involve the neck, back, shoulder, upper arm, and chest, unilaterally and bilaterally. This pruritus can be intermittent and become worse upon exposure to sunlight.²

Continue to: Notalgia paresthetica

 

Notalgia paresthetica. This condition might also cause neuropathic pruritus as a consequence of nerve impingement. The itch of notalgia paresthesia is located on the skin, medial to the scapular border on the upper or mid-back.² It has been postulated that the itch is caused by nerve entrapment of the posterior rami of spinal nerves arising from T2-T6.⁹ However, another theory suggests that the itch is caused by damage to peripheral nerves.⁹ The itch of notalgia paresthetica can wax and wane.²

Poststroke pruritus. Brain lesions, most often caused by stroke, can cause neuropathic itch. One of the best-known syndromes related to poststroke itch is Wallenberg syndrome (ischemia from a lateral medullary infarction), which typically presents with itch, thermalgic hypoesthesia of the face, cerebellar dysfunction, nausea, and vomiting.⁷

Shingles. More than one-half of patients who develop postherpetic neuralgia as a consequence of a herpes zoster infection also develop neuropathic pruritus.⁹ It is thought that postherpetic pruritus shares a comparable pathophysiology with postherpetic neuralgia, in which neurons involved in itch stimuli become damaged.⁷

Diabetes mellitus. Pruritus from diabetes can be classified as systemic or neuropathic. Diabetes is one of the most common causes of small-fiber polyneuropathy, which can cause neuropathic pruritus.¹³

Multiple sclerosis. Central nervous system lesions that affect sensory pathways can lead to neuropathic itch in multiple sclerosis. Patients can have severe episodes of generalized pruritus. It has been hypothesized that the neuropathic itch in multiple sclerosis is induced by activation of artificial synapses in demyelinated areas.²

Continue to: Psychogenic pruritus

 

 

Psychogenic pruritus

Chronic pruritus can be a comorbidity of psychiatric illness. A retrospective study found that pruritus occurs in 32% to 42% of psychiatric inpatients.¹⁴ Depression, anxiety, bipolar disorders, obsessive–compulsive disorders, somatoform disorders, psychosis, and substance abuse all have a strong link to psychogenic excoriation.¹⁵ Psychogenic excoriation, which can cause secondary skin lesions, occurs in psychiatric patients who excessively pick and scratch normal skin because they perceive an itch sensation or have a delusion of infestation.² Affected skin can be marked by scattered crusted lesions (FIGURE) anywhere on the body that the patient can reach—most commonly, the extremities.²

Delusion of infestation. Patients with a delusion of infestation have a strong belief that their body is infected by some kind of insect or microorganism.¹⁶ Before a diagnosis of delusion of infestation can be made, other organic causes must be excluded, including withdrawal from such substances as cocaine, amphetamines, and alcohol.¹⁶ Patients with a delusion of infestation can have, and maintain, a symptomatic response with continuing use of an atypical antipsychotic agent, including risperidone and olanzapine.¹⁷

Evaluation and diagnostic work-up

A thorough medical history, review of systems, medication review, social history, and family history are important when evaluating a patient with chronic pruritus.¹⁸ These items can be valuable in formulating a differential diagnosis, even before a physical examination.

Physical examination. The physical exam should include detailed inspection of the entire skin and hair¹⁸; such a comprehensive physical exam can determine whether the source of the itch is cutaneous.⁷ This, in turn, can help further narrow the differential diagnosis. It is crucial that the physical exam include palpation of the liver, spleen, lymph nodes, and thyroid for organomegaly,⁸ which could indicate a serious systemic condition, such as lymphoma.

The ice-pack sign—in which an ice pack applied to the pruritic area provides immediate relief—is considered pathognomonic for brachioradial pruritus.

The ice-pack sign—in which an ice pack is applied to the pruritic area, the patient experiences immediate relief of pruritus, and the itch returns soon after the ice pack is removed—is considered pathognomonic for brachioradial pruritus.¹⁹

Continue to: Chronic pruritus with abnormal findings...

 

Chronic pruritus with abnormal findings on the physical exam should prompt an initial work-up.¹⁸ Also consider an initial work-up for a patient with chronic pruritus whose symptom has not been relieved with conservative treatment.¹⁸

Laboratory testing. The initial laboratory work-up could include any of the following evaluations: complete blood count, measurement of thyroid-stimulating hormone, comprehensive metabolic panel (liver function, renal function, and the serum glucose level) and the erythrocyte sedimentation rate (TABLE 2).¹⁸ If warranted by the evaluation and physical exam, blood work can also include serologic studies for human immunodeficiency virus infection and ­hepatitis.¹⁷

Imaging. Chest radiography should be performed if there is suspicion of malignancy, such as lymphoma.⁷ Although brachioradial pruritus and notalgia paresthetica have been postulated to be caused by impingement of spinal nerves, obtaining spinal imaging, such as magnetic resonance imaging, as part of the initial work-up is not recommended; because spinal images might not show evidence of spinal disease, obtaining spinal imaging is not a requirement before treating brachioradial pruritus and notalgia paresthetica. Do consider spinal imaging, however, for patients in whom brachioradial pruritus or notalgia paresthetica is suspected and conservative treatment has not produced a response.

Treatment: Nondrug approaches, topicals, systemic agents

Start conservatively. Treatment of pruritus should begin with behavior modification and nonpharmacotherapeutic options (TABLE 3⁸). Educate the patient that scratching might cause secondary skin lesions; empowering them with that knowledge is sometimes enough to help break the scratching cycling—especially if the patient combines behavior modification with proper skin hydration with an emollient. To prevent secondary skin lesions through involuntary scratching, consider recommending that lesions be covered with an occlusive dressing or protective clothing.¹³

Stress has been shown to make chronic itch worse; therefore, stress-reduction activities, such as exercise, meditation, and yoga, might be helpful.20 For patients in whom pruritus has a psychological component, referral to a psychiatrist or psychologist might be therapeutic.

Continue to: When a patient complains...

 

When a patient complains of severe pruritus at first presentation, consider pharmacotherapy in conjunction with nonpharmacotherapeutic options. Several of the more effective topical therapies for pruritus^a are listed in TABLE 4.²⁰ Well-known systemic agents for this purpose are reviewed below and listed in TABLE 5.⁷

Systemic treatment

Antihistamines. A staple in the treatment of pruritus for many years, antihistamines are not effective for all causes; however, they are effective in treating paraneoplastic pruritus.²⁰ First-generation antihistamines, with their sedating effect, can be useful for patients who experience generalized pruritus at night.²⁰

Anticonvulsants. Gabapentin and pregabalin are analogs of the neurotransmitter gamma-aminobutyric acid.²⁰ This drug class is helpful in neuropathic pruritus specifically caused by impingements, such as brachioradial pruritus and notalgia paresthetica.²⁰ In addition, of all systemic therapies used to treat uremic pruritus, gabapentin has, in clinical trials, most consistently been found effective for uremic pruritus.⁶ (Note: Use renal dosing of gabapentin in patients with renal failure.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs; eg, fluvoxamine, paroxetine, and sertraline) might cause itch to subside by increasing the serotonin level, which, in turn, works to decrease inflammatory substances that cause itch.⁷ SSRIs have been used to treat patients with psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.⁷

Start conservatively: Use behavior modification and nonpharmacotherapeutic options for pruritus first.

Tricyclic antidepressants (eg, amitriptyline and doxepin) lessen the itch by antagonizing histamine receptors and through anticholinergic mechanisms. Tricyclics are best used in the treatment of psychogenic and nocturnal itch.⁷

Continue to: Mirtazapine...

 

Mirtazapine, a tetracyclic antidepressant, works in patients with uremic pruritus, psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.¹

Substance P antagonist. Aprepitant, a neurokinin receptor I antagonist, is a newer agent that inhibits binding of the itch mediator substance P to the neurokinin receptor. The drug has been found helpful in patients with drug-induced, paraneoplastic, and brachioradial pruritus.⁷

Opioid-receptor agents. Naltrexone, as a mu opioid-receptor antagonist, has shown promise as a treatment for uremic pruritus and cholestatic pruritus. Nalfurafine, a kappa opioid-receptor agonist, is emerging as a possible therapy for uremic pruritus.⁷

Bile-acid sequestrants. A few small studies have shown that treatment with a bile-acid sequestrant, such as cholestyramine and ursodiol, induces moderate improvement in symptoms in patients with cholestatic pruritus.²¹

CORRESPONDENCE
Matasha Russell, MD, Department of Family and Community Medicine, The University of Texas Health Science Center at Houston, McGovern Medical School, 6431 Fannin Street, JJL 324, Houston, TX 77030; Matasha.L.Russell@uth.tmc.edu.

Pruritus, defined as a sensation that induces a desire to scratch¹ and classified as acute or chronic (lasting > 6 weeks),² is one of the most common complaints among primary care patients: Approximately 1% of ambulatory visits in the United States are linked to pruritus.³

Chronic pruritus impairs quality of life; its impact has been compared to that of chronic pain.⁴ Treatment should therefore be instituted promptly. Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition, as we describe here. When persistent pruritus is refractory to treatment, systemic causes should be fully explored.

In this article, we discuss the pathogenesis and management of pruritus without skin eruption in the adult nonpregnant patient. We also present practice recommendations to help you determine whether your patient’s pruritus is indicative of a serious systemic condition.

An incomplete understanding of the pathophysiology of pruritus

The pathophysiology of pruritus is not fully understood. It is generally recognized, however, that pruritus starts in the peripheral nerves located in the dermal–epidermal junction of the skin.⁵ The sensation is then transmitted along unmyelinated slow-conducting C fibers to the dorsal horn of the spinal cord.^5,6 There are 2 types of C fibers that transmit the itch impulse⁶: A histamine-dependent type and a non-­histamine-dependent type, which might explain why pruritus can be refractory to antihistamine treatment.⁶

Once the itch impulse has moved from the spinal cord, it travels along the spinothalamic tract up to the contralateral thalamus.¹ From there, the impulse ascends to the cerebral cortex.¹ In the cortex, the impulse triggers multiple areas of the brain, such as those responsible for sensation, motor function, reward, memory, and emotion.⁷

Although this condition might appear benign, chronic pruritus can be a symptom of a serious condition.

Several chemical mediators have been found to be peripheral and central inducers of pruritus: histamine, endogenous opioids, substance P, and serotonin.² There are indications that certain receptors, such as mu-opioid receptors and kappa-opioid receptors, are key contributors to itch as well.²

A diverse etiology

The International Forum for the Study of Itch (IFSI) has established 6 main categories of causes of pruritus(TABLE 1)²:

• dermatologic
• systemic
• neurologic
• psychogenic
• mixed
• other.

Continue to: In this review...

 

In this review, we focus on the work-up and management of 3 of those categories: systemic, neurologic, and psychogenic causes of pruritus.

Systemic causes

Research has shown that 14% to 24% of patients who seek the care of a dermatologist for chronic itch without skin lesions have a systemic illness.⁸

Renal disease. Approximately 40% of patients with end-stage renal disease who are on hemodialysis or peritoneal dialysis have uremic pruritus.2 The itch is mostly generalized but can be pronounced on the back. For most patients, the itch is worse at night, causing a major impact on quality of life.⁶

Liver disease. In hepatic disease, there is often impairment in the secretion of bile, which can lead to cholestatic pruritus.² This condition commonly affects the hands and feet first; later, it becomes generalized.² Cholestatic pruritus can be elicited by tight-fitting clothing. Relief is not achieved by scratching.⁹ This type of itch effects 70% of patients with primary biliary cirrhosis and 15% of patients with hepatitis C infection.⁹

Hematologic disorders. Pruritus is a hallmark symptom of polycythemia rubra vera. Almost 50% of patients with this disorder report pruritus that occurs after exposure to water⁹; aquagenic pruritus can precede the formal diagnosis of polycythemia rubra vera by years.² It has been speculated that platelet aggregation in this disorder leads to release of serotonin and histamine, which, in turn, causes itch.⁹

Continue to: Endocrine disorders

 

Endocrine disorders. Approximately 4% to 11% of patients with thyrotoxicosis have pruritus.¹ It has been suggested that vasodilation, increased skin temperature, and a decreased itch threshold from untreated Graves disease might be inciting factors.

Malignancy. In generalized chronic pruritus without a known cause, strongly consider the likelihood of underlying malignancy^8,10; for 10% of these patients, their chronic pruritus is a paraneoplastic sign. Paraneoplastic pruritus is characterized as an itch that predates clinical onset, or occurs early in the course, of a malignancy.⁹ The condition is most strongly linked to cancers of the liver, gallbladder, biliary tract, hematologic system, and skin.¹¹

Palpate the liver, spleen, lymph nodes, and thyroid for organomegaly, which could indicate a serious systemic condition as the cause of pruritus.

Chronic pruritus affects 30% of patients with Hodgkin lymphoma.⁹ General pruritus can precede this diagnosis by months, even years.¹ In Hodgkin lymphoma patients who are in remission, a return of pruritic symptoms can be a harbinger of recurrence.⁹

Neurologic causes

A recent study found that 8% to 15% of patients referred to a dermatology clinic for chronic pruritus without skin eruption had underlying neurologic pathology.¹² Although the specific mechanisms of neuropathic itch are still poorly understood, it has been theorized that the itch emanates from neuronal damage, which can come from peripheral or central nervous system lesions.⁹

Brachioradial pruritus. There are divergent theories about the etiology of brachioradial pruritus. One hypothesis is that the condition is caused by cervical nerve-root impingement at the level of C5-C8 that leads to nerve damage²; another is that chronic exposure to sunlight causes injury to peripheral cutaneous nerves.² Brachioradial pruritus is localized to the dorsolateral forearm; it can also involve the neck, back, shoulder, upper arm, and chest, unilaterally and bilaterally. This pruritus can be intermittent and become worse upon exposure to sunlight.²

Continue to: Notalgia paresthetica

 

Notalgia paresthetica. This condition might also cause neuropathic pruritus as a consequence of nerve impingement. The itch of notalgia paresthesia is located on the skin, medial to the scapular border on the upper or mid-back.² It has been postulated that the itch is caused by nerve entrapment of the posterior rami of spinal nerves arising from T2-T6.⁹ However, another theory suggests that the itch is caused by damage to peripheral nerves.⁹ The itch of notalgia paresthetica can wax and wane.²

Poststroke pruritus. Brain lesions, most often caused by stroke, can cause neuropathic itch. One of the best-known syndromes related to poststroke itch is Wallenberg syndrome (ischemia from a lateral medullary infarction), which typically presents with itch, thermalgic hypoesthesia of the face, cerebellar dysfunction, nausea, and vomiting.⁷

Shingles. More than one-half of patients who develop postherpetic neuralgia as a consequence of a herpes zoster infection also develop neuropathic pruritus.⁹ It is thought that postherpetic pruritus shares a comparable pathophysiology with postherpetic neuralgia, in which neurons involved in itch stimuli become damaged.⁷

Diabetes mellitus. Pruritus from diabetes can be classified as systemic or neuropathic. Diabetes is one of the most common causes of small-fiber polyneuropathy, which can cause neuropathic pruritus.¹³

Multiple sclerosis. Central nervous system lesions that affect sensory pathways can lead to neuropathic itch in multiple sclerosis. Patients can have severe episodes of generalized pruritus. It has been hypothesized that the neuropathic itch in multiple sclerosis is induced by activation of artificial synapses in demyelinated areas.²

Continue to: Psychogenic pruritus

 

 

Psychogenic pruritus

Chronic pruritus can be a comorbidity of psychiatric illness. A retrospective study found that pruritus occurs in 32% to 42% of psychiatric inpatients.¹⁴ Depression, anxiety, bipolar disorders, obsessive–compulsive disorders, somatoform disorders, psychosis, and substance abuse all have a strong link to psychogenic excoriation.¹⁵ Psychogenic excoriation, which can cause secondary skin lesions, occurs in psychiatric patients who excessively pick and scratch normal skin because they perceive an itch sensation or have a delusion of infestation.² Affected skin can be marked by scattered crusted lesions (FIGURE) anywhere on the body that the patient can reach—most commonly, the extremities.²

Delusion of infestation. Patients with a delusion of infestation have a strong belief that their body is infected by some kind of insect or microorganism.¹⁶ Before a diagnosis of delusion of infestation can be made, other organic causes must be excluded, including withdrawal from such substances as cocaine, amphetamines, and alcohol.¹⁶ Patients with a delusion of infestation can have, and maintain, a symptomatic response with continuing use of an atypical antipsychotic agent, including risperidone and olanzapine.¹⁷

Evaluation and diagnostic work-up

A thorough medical history, review of systems, medication review, social history, and family history are important when evaluating a patient with chronic pruritus.¹⁸ These items can be valuable in formulating a differential diagnosis, even before a physical examination.

Physical examination. The physical exam should include detailed inspection of the entire skin and hair¹⁸; such a comprehensive physical exam can determine whether the source of the itch is cutaneous.⁷ This, in turn, can help further narrow the differential diagnosis. It is crucial that the physical exam include palpation of the liver, spleen, lymph nodes, and thyroid for organomegaly,⁸ which could indicate a serious systemic condition, such as lymphoma.

The ice-pack sign—in which an ice pack applied to the pruritic area provides immediate relief—is considered pathognomonic for brachioradial pruritus.

The ice-pack sign—in which an ice pack is applied to the pruritic area, the patient experiences immediate relief of pruritus, and the itch returns soon after the ice pack is removed—is considered pathognomonic for brachioradial pruritus.¹⁹

Continue to: Chronic pruritus with abnormal findings...

 

Chronic pruritus with abnormal findings on the physical exam should prompt an initial work-up.¹⁸ Also consider an initial work-up for a patient with chronic pruritus whose symptom has not been relieved with conservative treatment.¹⁸

Laboratory testing. The initial laboratory work-up could include any of the following evaluations: complete blood count, measurement of thyroid-stimulating hormone, comprehensive metabolic panel (liver function, renal function, and the serum glucose level) and the erythrocyte sedimentation rate (TABLE 2).¹⁸ If warranted by the evaluation and physical exam, blood work can also include serologic studies for human immunodeficiency virus infection and ­hepatitis.¹⁷

Imaging. Chest radiography should be performed if there is suspicion of malignancy, such as lymphoma.⁷ Although brachioradial pruritus and notalgia paresthetica have been postulated to be caused by impingement of spinal nerves, obtaining spinal imaging, such as magnetic resonance imaging, as part of the initial work-up is not recommended; because spinal images might not show evidence of spinal disease, obtaining spinal imaging is not a requirement before treating brachioradial pruritus and notalgia paresthetica. Do consider spinal imaging, however, for patients in whom brachioradial pruritus or notalgia paresthetica is suspected and conservative treatment has not produced a response.

Treatment: Nondrug approaches, topicals, systemic agents

Start conservatively. Treatment of pruritus should begin with behavior modification and nonpharmacotherapeutic options (TABLE 3⁸). Educate the patient that scratching might cause secondary skin lesions; empowering them with that knowledge is sometimes enough to help break the scratching cycling—especially if the patient combines behavior modification with proper skin hydration with an emollient. To prevent secondary skin lesions through involuntary scratching, consider recommending that lesions be covered with an occlusive dressing or protective clothing.¹³

Stress has been shown to make chronic itch worse; therefore, stress-reduction activities, such as exercise, meditation, and yoga, might be helpful.20 For patients in whom pruritus has a psychological component, referral to a psychiatrist or psychologist might be therapeutic.

Continue to: When a patient complains...

 

When a patient complains of severe pruritus at first presentation, consider pharmacotherapy in conjunction with nonpharmacotherapeutic options. Several of the more effective topical therapies for pruritus^a are listed in TABLE 4.²⁰ Well-known systemic agents for this purpose are reviewed below and listed in TABLE 5.⁷

Systemic treatment

Antihistamines. A staple in the treatment of pruritus for many years, antihistamines are not effective for all causes; however, they are effective in treating paraneoplastic pruritus.²⁰ First-generation antihistamines, with their sedating effect, can be useful for patients who experience generalized pruritus at night.²⁰

Anticonvulsants. Gabapentin and pregabalin are analogs of the neurotransmitter gamma-aminobutyric acid.²⁰ This drug class is helpful in neuropathic pruritus specifically caused by impingements, such as brachioradial pruritus and notalgia paresthetica.²⁰ In addition, of all systemic therapies used to treat uremic pruritus, gabapentin has, in clinical trials, most consistently been found effective for uremic pruritus.⁶ (Note: Use renal dosing of gabapentin in patients with renal failure.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs; eg, fluvoxamine, paroxetine, and sertraline) might cause itch to subside by increasing the serotonin level, which, in turn, works to decrease inflammatory substances that cause itch.⁷ SSRIs have been used to treat patients with psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.⁷

Start conservatively: Use behavior modification and nonpharmacotherapeutic options for pruritus first.

Tricyclic antidepressants (eg, amitriptyline and doxepin) lessen the itch by antagonizing histamine receptors and through anticholinergic mechanisms. Tricyclics are best used in the treatment of psychogenic and nocturnal itch.⁷

Continue to: Mirtazapine...

 

Mirtazapine, a tetracyclic antidepressant, works in patients with uremic pruritus, psychogenic pruritus, cholestatic pruritus, and paraneoplastic pruritus.¹

Substance P antagonist. Aprepitant, a neurokinin receptor I antagonist, is a newer agent that inhibits binding of the itch mediator substance P to the neurokinin receptor. The drug has been found helpful in patients with drug-induced, paraneoplastic, and brachioradial pruritus.⁷

Opioid-receptor agents. Naltrexone, as a mu opioid-receptor antagonist, has shown promise as a treatment for uremic pruritus and cholestatic pruritus. Nalfurafine, a kappa opioid-receptor agonist, is emerging as a possible therapy for uremic pruritus.⁷

Bile-acid sequestrants. A few small studies have shown that treatment with a bile-acid sequestrant, such as cholestyramine and ursodiol, induces moderate improvement in symptoms in patients with cholestatic pruritus.²¹

CORRESPONDENCE
Matasha Russell, MD, Department of Family and Community Medicine, The University of Texas Health Science Center at Houston, McGovern Medical School, 6431 Fannin Street, JJL 324, Houston, TX 77030; Matasha.L.Russell@uth.tmc.edu.

 

Capillary malformation-arteriovenous malformation syndrome

Capillary Malformation-arteriovenous malformation syndrome (CM-AVM) is a rare vascular disorder characterized by the presence of capillary malformations with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.¹ CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB⁴ gene.² Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.¹

In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.³ Some CMs may be warm to touch indicating a possible underlying AVM or AVF.⁴ This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.⁴ CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.^1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.⁵ Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.³

The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.^1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.¹ This may allow for early treatment before the development of symptoms.¹ Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.¹ Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.^3,4

It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.⁴ However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.⁶ Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.¹

Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.

Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.


References

1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.

2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.

3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.

4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.

5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.

6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
 

 

Capillary malformation-arteriovenous malformation syndrome

Capillary Malformation-arteriovenous malformation syndrome (CM-AVM) is a rare vascular disorder characterized by the presence of capillary malformations with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.¹ CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB⁴ gene.² Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.¹

In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.³ Some CMs may be warm to touch indicating a possible underlying AVM or AVF.⁴ This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.⁴ CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.^1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.⁵ Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.³

The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.^1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.¹ This may allow for early treatment before the development of symptoms.¹ Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.¹ Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.^3,4

It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.⁴ However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.⁶ Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.¹

Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.

Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.


References

1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.

2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.

3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.

4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.

5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.

6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
 

 

Capillary malformation-arteriovenous malformation syndrome

Capillary Malformation-arteriovenous malformation syndrome (CM-AVM) is a rare vascular disorder characterized by the presence of capillary malformations with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.¹ CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB⁴ gene.² Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.¹

In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.³ Some CMs may be warm to touch indicating a possible underlying AVM or AVF.⁴ This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.⁴ CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.^1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.⁵ Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.³

The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.^1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.¹ This may allow for early treatment before the development of symptoms.¹ Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.¹ Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.^3,4

It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.⁴ However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.⁶ Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.¹

Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.

Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.


References

1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.

2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.

3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.

4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.

5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.

6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
 

About 70% of patients on the oral selective Janus kinase 1 inhibitor abrocitinib for moderate to severe atopic dermatitis (AD) achieved high-efficacy responses without need for any supplemental topical therapies through 48 weeks of follow-up in the JADE EXTEND study, Kristian Reich, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The head-turning outcomes achieved at the higher studied dose of 200 mg once daily as monotherapy – namely, 87% of patients had an EASI-75 response, defined as at least a 75% reduction from baseline in Eczema Area and Severity Index score, and 62% had an EASI-90 response – herald a new era in the management of atopic dermatitis, predicted Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany).

“I think we will see an evolution in the treatment goals in atopic dermatitis. It’s really good to see nearly 90% of the patients achieved EASI-75 over time. I am completely convinced that if you ultimately want to have a happy patient, you will see treatment goals moving up. We have already seen this in psoriasis. I want to see drugs that give the majority of my patients an EASI-75. And ultimately I want to see EASI-90 for my patients,” he said.

Concurrent with his presentation at the EADV congress, Pfizer announced it has filed for marketing approval of abrocitinib at 100 mg and 200 mg once daily for the treatment of moderate to severe AD. The Food and Drug Administration has granted the application priority review status, with a decision due next April. The company has also filed for marketing approval with the European Medicines Agency.

The JADE EXTEND study is an ongoing extension of the previously reported phase 3, randomized, double-blind, placebo-controlled, 12-week JADE MONO-1 and JADE MONO-2 trials. The two trials included a total of 309 patients on abrocitinib at 200 mg/day and 314 on the selective Janus kinase (JAK) 1 inhibitor at 100 mg/day, 519 of whom subsequently entered the long-term extension study on their same dose. The 70% who required no supplemental topical therapy through 48 weeks were the focus of the analysis presented by Dr. Reich.

The proportion of strong responders increased up until the week 24 or 36 assessments, then remained steady until week 48. For example, the EASI-75 rate in patients on abrocitinib at 200 mg/day rose from 82.5% at week 16, to 86.2% at week 24, 90.1% at week 36, and reached 87.2% at week 48. The EASI-90 rates at the same time points were 56.7%, 64.5%, 65.5%, and 61.6%, respectively. And the EASI-100 rates were 24%, 31.6%, 29.6%, and 24%, respectively.

Not surprisingly, the EASI-75 rates in patients on abrocitinib at 100 mg/day were less robust: 64.4% at week 16, 75.5% at week 24, 74.5% at week 36, and 68% at week 48.

An Investigator’s Global Assessment score of 0 or 1 – that is, clear or almost clear – was achieved at week 16 in 55% of patients on 200 mg/day, 64.5% at week 24, 66% at week 36, and 60.5% at week 48. In patients on the 100-mg dose, the corresponding figures were 36.5%, 46.6%, 53.3%, and 45.2%.

A hallmark of all of the JAK inhibitors under study for AD is what Dr. Reich characterized as “an amazingly fast reduction of itch,” the dominant symptom of the disease. A clinically meaningful reduction of at least 4 points in the Peak Pruritus Numerical Rating Scale – a response of 4 or greater is considered clinically important – from the mean baseline score of 7.1 was present at week 12 in 56.3% of patients on abrocitinib at 200 mg, in 74.3% at week 16, and in 72.5% at week 48. The proportion of patients achieving this endpoint on 100 mg was 41.6% at week 12, 49.4% at week 16, and 52% at week 48.

Serious treatment-emergent adverse events occurred in 6.1% of JADE EXTEND participants on abrocitinib at 100 mg and 12.8% of those on 200 mg. These events included oral herpes and elevated creatine phosphokinase levels. The sole case of pulmonary embolism that occurred during the study was deemed unrelated to treatment.

“What this is telling me here is there are no signals that we haven’t seen earlier with this drug and with other JAK inhibitors before,” the dermatologist observed. “But I want to see more data. I want to see the overall safety, not just for a year, but for 2, 3, 4, and 5 years.”

Asked by an audience member if nonresponsiveness to one JAK inhibitor predicts nonresponse to others, Dr. Reich speculated that it’s likely to be so. He noted that all three of the JAK inhibitors furthest along in the developmental pipeline for atopic dermatitis – abrocitinib, baricitinib, and upadacitinib – are inhibitors of JAK 1, although baricitinib also targets JAK 2.

“I would think that if you really are a nonresponder to any of these that it will be hard to get a good response with the others. We’re not talking about antibodies here, where there may be different epitopes. The affinity is different, and we have seen that if you have no response to a weak TNF [tumor necrosis factor] inhibitor, you can still have a response to a strong TNF inhibitor. I don’t expect the same here,” according to Dr. Reich.

He reported serving as an adviser to and paid clinical research for Pfizer, which sponsored JADE EXTEND, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

About 70% of patients on the oral selective Janus kinase 1 inhibitor abrocitinib for moderate to severe atopic dermatitis (AD) achieved high-efficacy responses without need for any supplemental topical therapies through 48 weeks of follow-up in the JADE EXTEND study, Kristian Reich, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The head-turning outcomes achieved at the higher studied dose of 200 mg once daily as monotherapy – namely, 87% of patients had an EASI-75 response, defined as at least a 75% reduction from baseline in Eczema Area and Severity Index score, and 62% had an EASI-90 response – herald a new era in the management of atopic dermatitis, predicted Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany).

“I think we will see an evolution in the treatment goals in atopic dermatitis. It’s really good to see nearly 90% of the patients achieved EASI-75 over time. I am completely convinced that if you ultimately want to have a happy patient, you will see treatment goals moving up. We have already seen this in psoriasis. I want to see drugs that give the majority of my patients an EASI-75. And ultimately I want to see EASI-90 for my patients,” he said.

Concurrent with his presentation at the EADV congress, Pfizer announced it has filed for marketing approval of abrocitinib at 100 mg and 200 mg once daily for the treatment of moderate to severe AD. The Food and Drug Administration has granted the application priority review status, with a decision due next April. The company has also filed for marketing approval with the European Medicines Agency.

The JADE EXTEND study is an ongoing extension of the previously reported phase 3, randomized, double-blind, placebo-controlled, 12-week JADE MONO-1 and JADE MONO-2 trials. The two trials included a total of 309 patients on abrocitinib at 200 mg/day and 314 on the selective Janus kinase (JAK) 1 inhibitor at 100 mg/day, 519 of whom subsequently entered the long-term extension study on their same dose. The 70% who required no supplemental topical therapy through 48 weeks were the focus of the analysis presented by Dr. Reich.

The proportion of strong responders increased up until the week 24 or 36 assessments, then remained steady until week 48. For example, the EASI-75 rate in patients on abrocitinib at 200 mg/day rose from 82.5% at week 16, to 86.2% at week 24, 90.1% at week 36, and reached 87.2% at week 48. The EASI-90 rates at the same time points were 56.7%, 64.5%, 65.5%, and 61.6%, respectively. And the EASI-100 rates were 24%, 31.6%, 29.6%, and 24%, respectively.

Not surprisingly, the EASI-75 rates in patients on abrocitinib at 100 mg/day were less robust: 64.4% at week 16, 75.5% at week 24, 74.5% at week 36, and 68% at week 48.

An Investigator’s Global Assessment score of 0 or 1 – that is, clear or almost clear – was achieved at week 16 in 55% of patients on 200 mg/day, 64.5% at week 24, 66% at week 36, and 60.5% at week 48. In patients on the 100-mg dose, the corresponding figures were 36.5%, 46.6%, 53.3%, and 45.2%.

A hallmark of all of the JAK inhibitors under study for AD is what Dr. Reich characterized as “an amazingly fast reduction of itch,” the dominant symptom of the disease. A clinically meaningful reduction of at least 4 points in the Peak Pruritus Numerical Rating Scale – a response of 4 or greater is considered clinically important – from the mean baseline score of 7.1 was present at week 12 in 56.3% of patients on abrocitinib at 200 mg, in 74.3% at week 16, and in 72.5% at week 48. The proportion of patients achieving this endpoint on 100 mg was 41.6% at week 12, 49.4% at week 16, and 52% at week 48.

Serious treatment-emergent adverse events occurred in 6.1% of JADE EXTEND participants on abrocitinib at 100 mg and 12.8% of those on 200 mg. These events included oral herpes and elevated creatine phosphokinase levels. The sole case of pulmonary embolism that occurred during the study was deemed unrelated to treatment.

“What this is telling me here is there are no signals that we haven’t seen earlier with this drug and with other JAK inhibitors before,” the dermatologist observed. “But I want to see more data. I want to see the overall safety, not just for a year, but for 2, 3, 4, and 5 years.”

Asked by an audience member if nonresponsiveness to one JAK inhibitor predicts nonresponse to others, Dr. Reich speculated that it’s likely to be so. He noted that all three of the JAK inhibitors furthest along in the developmental pipeline for atopic dermatitis – abrocitinib, baricitinib, and upadacitinib – are inhibitors of JAK 1, although baricitinib also targets JAK 2.

“I would think that if you really are a nonresponder to any of these that it will be hard to get a good response with the others. We’re not talking about antibodies here, where there may be different epitopes. The affinity is different, and we have seen that if you have no response to a weak TNF [tumor necrosis factor] inhibitor, you can still have a response to a strong TNF inhibitor. I don’t expect the same here,” according to Dr. Reich.

He reported serving as an adviser to and paid clinical research for Pfizer, which sponsored JADE EXTEND, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

About 70% of patients on the oral selective Janus kinase 1 inhibitor abrocitinib for moderate to severe atopic dermatitis (AD) achieved high-efficacy responses without need for any supplemental topical therapies through 48 weeks of follow-up in the JADE EXTEND study, Kristian Reich, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

The head-turning outcomes achieved at the higher studied dose of 200 mg once daily as monotherapy – namely, 87% of patients had an EASI-75 response, defined as at least a 75% reduction from baseline in Eczema Area and Severity Index score, and 62% had an EASI-90 response – herald a new era in the management of atopic dermatitis, predicted Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany).

“I think we will see an evolution in the treatment goals in atopic dermatitis. It’s really good to see nearly 90% of the patients achieved EASI-75 over time. I am completely convinced that if you ultimately want to have a happy patient, you will see treatment goals moving up. We have already seen this in psoriasis. I want to see drugs that give the majority of my patients an EASI-75. And ultimately I want to see EASI-90 for my patients,” he said.

Concurrent with his presentation at the EADV congress, Pfizer announced it has filed for marketing approval of abrocitinib at 100 mg and 200 mg once daily for the treatment of moderate to severe AD. The Food and Drug Administration has granted the application priority review status, with a decision due next April. The company has also filed for marketing approval with the European Medicines Agency.

The JADE EXTEND study is an ongoing extension of the previously reported phase 3, randomized, double-blind, placebo-controlled, 12-week JADE MONO-1 and JADE MONO-2 trials. The two trials included a total of 309 patients on abrocitinib at 200 mg/day and 314 on the selective Janus kinase (JAK) 1 inhibitor at 100 mg/day, 519 of whom subsequently entered the long-term extension study on their same dose. The 70% who required no supplemental topical therapy through 48 weeks were the focus of the analysis presented by Dr. Reich.

The proportion of strong responders increased up until the week 24 or 36 assessments, then remained steady until week 48. For example, the EASI-75 rate in patients on abrocitinib at 200 mg/day rose from 82.5% at week 16, to 86.2% at week 24, 90.1% at week 36, and reached 87.2% at week 48. The EASI-90 rates at the same time points were 56.7%, 64.5%, 65.5%, and 61.6%, respectively. And the EASI-100 rates were 24%, 31.6%, 29.6%, and 24%, respectively.

Not surprisingly, the EASI-75 rates in patients on abrocitinib at 100 mg/day were less robust: 64.4% at week 16, 75.5% at week 24, 74.5% at week 36, and 68% at week 48.

An Investigator’s Global Assessment score of 0 or 1 – that is, clear or almost clear – was achieved at week 16 in 55% of patients on 200 mg/day, 64.5% at week 24, 66% at week 36, and 60.5% at week 48. In patients on the 100-mg dose, the corresponding figures were 36.5%, 46.6%, 53.3%, and 45.2%.

A hallmark of all of the JAK inhibitors under study for AD is what Dr. Reich characterized as “an amazingly fast reduction of itch,” the dominant symptom of the disease. A clinically meaningful reduction of at least 4 points in the Peak Pruritus Numerical Rating Scale – a response of 4 or greater is considered clinically important – from the mean baseline score of 7.1 was present at week 12 in 56.3% of patients on abrocitinib at 200 mg, in 74.3% at week 16, and in 72.5% at week 48. The proportion of patients achieving this endpoint on 100 mg was 41.6% at week 12, 49.4% at week 16, and 52% at week 48.

Serious treatment-emergent adverse events occurred in 6.1% of JADE EXTEND participants on abrocitinib at 100 mg and 12.8% of those on 200 mg. These events included oral herpes and elevated creatine phosphokinase levels. The sole case of pulmonary embolism that occurred during the study was deemed unrelated to treatment.

“What this is telling me here is there are no signals that we haven’t seen earlier with this drug and with other JAK inhibitors before,” the dermatologist observed. “But I want to see more data. I want to see the overall safety, not just for a year, but for 2, 3, 4, and 5 years.”

Asked by an audience member if nonresponsiveness to one JAK inhibitor predicts nonresponse to others, Dr. Reich speculated that it’s likely to be so. He noted that all three of the JAK inhibitors furthest along in the developmental pipeline for atopic dermatitis – abrocitinib, baricitinib, and upadacitinib – are inhibitors of JAK 1, although baricitinib also targets JAK 2.

“I would think that if you really are a nonresponder to any of these that it will be hard to get a good response with the others. We’re not talking about antibodies here, where there may be different epitopes. The affinity is different, and we have seen that if you have no response to a weak TNF [tumor necrosis factor] inhibitor, you can still have a response to a strong TNF inhibitor. I don’t expect the same here,” according to Dr. Reich.

He reported serving as an adviser to and paid clinical research for Pfizer, which sponsored JADE EXTEND, as well as more than two dozen other pharmaceutical companies.

bjancin@mdedge.com

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

Tapinarof cream 1% applied once daily in patients with plaque psoriasis convincingly hit its primary and secondary endpoints and was well tolerated in two identical pivotal phase 3, randomized trials, Mark G. Lebwohl, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Tapinarof cream has the potential to be a first-in-class topical therapeutic aryl hydrocarbon receptor modulating agent and will provide physicians and patients with a novel nonsteroidal topical treatment option that’s effective and well tolerated,” predicted Dr. Lebwohl, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dermavant Sciences, the company developing topical tapinarof for treatment of atopic dermatitis as well as psoriasis, announced that upon completion of an ongoing long-term extension study the company plans to file for approval of the drug for psoriasis in 2021.

The two pivotal phase 3 trials, PSOARING 1 and PSOARING 2, randomized a total of 1,025 patients with plaque psoriasis to once-daily tapinarof cream 1% or its vehicle. “This was a fairly difficult group of patients,” Dr. Lebwohl said. Roughly 80% had moderate psoriasis as defined by a baseline Physician Global Assessment (PGA) score of 3, with the remainder split evenly between mild and severe disease. Participants averaged 8% body surface area involvement. Body mass index was on average greater than 31 kg/m².

The primary efficacy endpoint was a PGA score of 0 or 1 – that is, clear or almost clear – plus at least a 2-grade improvement in PGA from baseline at week 12. This was achieved in 35.4% of patients on tapinarof cream once daily in PSOARING 1 and 40.2% in PSOARING 2, compared with 6.0% and 6.3% of vehicle-treated controls, a highly significant difference (both P < .0001).

The prespecified secondary endpoint was a 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline to week 12. The PASI 75 rates were 36.1% and 47.6% with tapinarof, significantly better than the 10.2% and 6.9% rates in controls.

The most common adverse event associated with tapinarof was folliculitis, which occurred in 20.6% of treated patients in PSOARING 1 and in 15.7% in PSOARING 2. More than 98% of cases were mild or moderate. The folliculitis led to study discontinuation in only 1.8% and 0.9% of subjects in the two trials.

The other noteworthy adverse event was contact dermatitis. It occurred in 3.8% and 4.7% of tapinarof-treated patients, again with low study discontinuation rates of 1.5% and 2.2%.

During the audience discussion, Linda Stein Gold, MD, lead investigator for PSOARING 2, was asked about this folliculitis. She said the mechanism is unclear, as is the best management. She encountered it in patients, didn’t treat it, and it went away on its own. It’s not a bacterial folliculitis; when cultured it invariably proved culture negative, she noted.

The comparative efficacy of tapinarof cream versus the potent and superpotent topical corticosteroids commonly used in the treatment of psoriasis hasn’t been evaluated in head-to-head studies. Her experience and that of the other investigators has been that tapinarof’s efficacy is comparably strong, “but we don’t have the steroid side effects,” said Dr. Stein Gold, director of dermatology clinical research at Henry Ford Health System in Detroit.

In an interview, Dr. Lebwohl said tapinarof, if approved, could help meet a major unmet need for new and better topical therapies for psoriasis.

“You keep hearing about all these biologic agents and small-molecule pills coming out, but the majority of patients still only need topical therapy,” he observed.

Moreover, even when patients with more severe disease achieve a PASI 75 or PASI 90 response with systemic therapy, they usually still need supplemental topical therapy to get them closer to the goal of clear skin.

The superpotent steroids that are the current mainstay of topical therapy come with predictable side effects that dictate a 2- to 4-week limit on their approved use. Also, they’re not supposed to be applied to the face or to intertriginous sites, including the groin, axillae, and under the breasts. In contrast, tapinarof has proved safe and effective in these sensitive areas.

Asked to predict how tapinarof is likely to be used in clinical practice, Dr. Lebwohl replied: “The efficacy was equivalent to strong topical steroids, so I think it could be used first line in place of topical steroids. And in particular, in patients with psoriasis at facial and intertriginous sites, I think an argument can be made for insisting that it be first line.”

He also expects that physicians will end up utilizing tapinarof for a varied group of steroid-responsive dermatoses beyond psoriasis and atopic dermatitis.

“It clearly reduces inflammation, which is why I would expect it would work well for those,” the dermatologist said.

The mechanism of action of tapinarof has been worked out. The drug enters the cell and binds to the aryl hydrocarbon receptor, forming a complex that enters the nucleus. There it joins with the aryl hydrocarbon receptor nuclear translocator, which regulates gene expression so as to reduce production of inflammatory cytokines while promoting an increase in skin barrier proteins, which is why tapinarof is also being developed as an atopic dermatitis therapy.

Dr. Lebwohl and Dr. Stein Gold reported receiving research funds from and serving as consultants to Dermavant Sciences as well as numerous other pharmaceutical companies.

bjancin@mdedge.com

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

bjancin@mdedge.com

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

bjancin@mdedge.com

A history of prior depressive illness conferred a sevenfold increased risk of developing treatment-limiting mood symptoms in patients on isotretinoin for acne in a large Scottish observational study, Sanaa Butt, MD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

© Ocskay Bence/Fotolia.com

This was, however, the sole identifiable risk factor for treatment-limiting depressive symptoms in acne patients on isotretinoin in the study of 3,151 consecutive acne patients taking isotretinoin. There was no significant difference between those who did or did not develop depression on the oral retinoid in terms of age, gender, or daily dose of the drug at the time it was discontinued.

“Depressive symptoms occurred at any time from the date of initiation of isotretinoin up to 6 months into therapy, with no identifiable peak time period,” said Dr. Butt, a dermatologist with the U.K. National Health Service Tayside district at Ninewells Hospital, Dundee, Scotland. “Lower doses appear not to be protective,” she added.

The Tayside district has a catchment of roughly 450,000 people. The local population tends to stay put because Tayside is an economically disadvantaged and remote part of Scotland. There are very few private practice dermatologists in the area, so Dr. Butt and coinvestigators are confident their observational study of NHS patients captured the great majority of isotretinoin users in northern Scotland.

The investigators utilized software to analyze the contents of more than 8,000 digitized letters exchanged between NHS Tayside dermatologists and general practitioners during 2005-2018, zeroing in on 3,151 consecutive patients on isotretinoin for acne and 158 on the drug for other conditions, most often rosacea or folliculitis. They then drilled down further through the letters, electronically searching for key words such as suicide, depression, and anxiety. In this way, they ultimately identified 30 patients who discontinued the drug because they developed depressive symptoms. All 30 were on the drug for acne.

The annual incidence of treatment-limiting depressive mood changes was 0.96%, a figure that remained steady over the 13-year study period, even though prescribing of isotretinoin increased over time. This flat incidence rate effectively rules out the potential for confounding because of assessor bias, especially since many different NHS dermatologists were prescribing the drug, Dr. Butt said.

Half of acne patients prescribed isotretinoin were female and 50% were male. And 15 cases of treatment discontinuation caused by development of depressive symptoms occurred in females, 15 in males. A history of past depressive illness was present in 9.3% of females who started on isotretinoin and in 4.5% of the males. The relative risk of treatment-limiting depressive mood changes was increased 790% among females with a prior history of depressive illness and 440% in males with such a history.

Dr. Butt reported having no financial conflicts regarding her NHS-funded study.

bjancin@mdedge.com

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A punch biopsy of the markedly erythematous lateral edge helped to confirm this as tumid lupus erythematosus (TLE), a rare subtype of chronic cutaneous lupus erythematosus. TLE occurs in men and women of all ages. Annular or arcuate patches and plaques most often arise on the face, trunk, extremities, and V of the neck after sun exposure. However, as in this case, plaques may appear in areas covered by clothing. Plaques generally do not itch or hurt, but their presence can be alarming.

Annular and arcuate plaques raise a complex differential diagnosis including common conditions such as urticaria and tinea corporis, as well as more uncommon disorders such as erythema annulare centrifugum and lymphoma cutis. Unlike tinea corporis and erythema annulare centrifugum, there is very little, if any, scaling of the superficial epidermis. Plaques heal without scarring or changes to skin pigmentation.

Multiple punch biopsies of affected areas are key to a proper diagnosis. Patients with confirmed TLE should undergo antinuclear antibody testing to rule out systemic lupus erythematosus, although the vast majority will have normal results.

Treatment includes potent or ultrapotent topical steroids for the trunk and extremities, and mid- to low-potency steroids for intertriginous areas or the face. Systemic immunomodulators with hydroxychloroquine are used as first-line treatment for more extensive disease.

In this case, the patient had a normal antinuclear antibody titer and was treated with topical betamethasone dipropionate augmented 0.05% cream bid for 2 weeks, which led to complete clearance. She experienced a flare-up a year later and was retreated with the same results.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

“Many times, pediatricians tell parents to avoid bathing because they feel that bathing will dry out the skin,” he said. The crossover study, by showing better control of AD with frequent bathing, dispels that notion, although he is not convinced that bathing at this frequency is necessary.

“I have not advised anyone to do twice-daily bathing, with rare exceptions, on the basis on this study, but, basically, I think that whether people do daily bathing or every other day bathing, it is pretty reasonable that bathing might help as long as they are applying moisturizer immediately afterward,” he said.

Dr. Simpson reports financial relationships with AbbVie, Celgene Dermira, Genentech, GlaxoSmithKline, Incyte, Lilly, Medimmune, Pfizer, Regeneron/Sanofi, and Tioga.

This publication and Global Academy for Medical Education are owned by the same parent company.

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

“Many times, pediatricians tell parents to avoid bathing because they feel that bathing will dry out the skin,” he said. The crossover study, by showing better control of AD with frequent bathing, dispels that notion, although he is not convinced that bathing at this frequency is necessary.

“I have not advised anyone to do twice-daily bathing, with rare exceptions, on the basis on this study, but, basically, I think that whether people do daily bathing or every other day bathing, it is pretty reasonable that bathing might help as long as they are applying moisturizer immediately afterward,” he said.

Dr. Simpson reports financial relationships with AbbVie, Celgene Dermira, Genentech, GlaxoSmithKline, Incyte, Lilly, Medimmune, Pfizer, Regeneron/Sanofi, and Tioga.

This publication and Global Academy for Medical Education are owned by the same parent company.

The most effective initial step for clearing atopic dermatitis in infants and young children involves daily bathing, followed by immediate application of a moisturizer, topical steroid, or both, according to an expert speaking at the virtual annual Coastal Dermatology Symposium.

FotoDuets/iStock/Getty Images

“If they are really severe, you can do it twice-daily, but there are several studies that show there is not a huge benefit of twice-daily over once-daily,” said Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland.

He called this technique “soak-and-smear.” The “smear” is performed immediately after the bath when the skin is still damp, he said. When clearing is the goal, and the child has moderate to severe atopic dermatitis (AD), 0.1% triamcinolone or a similar medium potency topical steroid can be applied, and after clearing, the steroid can be switched for a moisturizer, according to Dr. Simpson.

Rather than restricting application to areas of greatest skin involvement, “put it all over,” he advised.

The clearing regimen should be continued “for a couple of more days” after the lesions have resolved, with a return visit in about a week to confirm clearing and reinforce the next steps for keeping patients clear, he added.

The next steps depend on severity. According to Dr. Simpson, severity is defined less by the extent of skin involvement at the baseline examination than the speed at which symptoms return.

For those with only mild symptoms after an extended period of clearing, moisturizer might be sufficient to prevent a significant relapse. For children with a more rapid relapse, it will be necessary to reintroduce topical steroid either every day, every other day, or twice per week.

Whether with moisturizer or with topical steroids, the soak-and-smear technique has now been validated in a recently published crossover randomized trial.

In the trial, children aged 6 months to 11 years, with moderate to severe AD, were randomized to a twice-daily bath, called the “wet method,” versus a twice-weekly bath, called the “dry method.” Both groups received a cleanser and moisturizer along with a low-potency topical steroid as needed.

After 2 weeks, the 40 evaluable patients were crossed over to the opposite bathing technique. The wet, or soak-and-smear approach, was associated with a highly significant reduction in the primary endpoint of SCORing Atopic Dermatitis (SCORAD) index, compared with the dry method (95% confidence interval, 14.9-27.6; P less than .0001). In a secondary analysis, this translated into a 30% relative reduction in favor of the wet method.

In addition, there was improvement in a caregiver assessment of the Atopic Dermatitis Quickscore (ADQ). These data show that “twice-daily baths with topical steroids and moisturizer can help in more moderate to severe population,” said Dr. Simpson, who noted that he has participated in open-label studies with the same soak-and-smear technique that have produced similar results.

Once children are clear, Dr. Simpson recommends a maintenance strategy individualized for severity. In many cases, this will involve moisturizers applied after the bath, supplemented intermittently, such as once or twice per week, with topical steroids. However, if parents find themselves resorting to daily steroids to maintain control, “that’s when you incorporate the TCIs [topical calcineurin inhibitors].”

TCIs “can help you stay at twice-per-week topical steroids,” Dr. Simpson said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.

TCIs also help patients avoid steroid withdrawal, a particularly common phenomenon when topical steroids are applied repeatedly to the face. He recommended a proactive approach. By applying TCIs to areas where skin lesions frequently recur, such as the eyelids, flares can often be prevented.

Repeated applications of TCIs “is perfectly safe and effective, and there are many studies that show proactive treatment is very effective and can prevent you from having to use too much topical steroids” or move to a systemic steroid, Dr. Simpson said.

These steps have been highly effective for sustained control even in challenging cases of AD, but he emphasized the importance of explaining the rationale to parents and eliciting their adherence to these treatment steps. Writing out the instructions will reduce confusion and help parents keep their children clear, he added.

Lawrence F. Eichenfield, MD, professor of pediatrics and dermatology at the University of California, San Diego, agreed that this recently published crossover trial has been helpful in counseling parents about how to manage AD in their children.

“Many times, pediatricians tell parents to avoid bathing because they feel that bathing will dry out the skin,” he said. The crossover study, by showing better control of AD with frequent bathing, dispels that notion, although he is not convinced that bathing at this frequency is necessary.

“I have not advised anyone to do twice-daily bathing, with rare exceptions, on the basis on this study, but, basically, I think that whether people do daily bathing or every other day bathing, it is pretty reasonable that bathing might help as long as they are applying moisturizer immediately afterward,” he said.

Dr. Simpson reports financial relationships with AbbVie, Celgene Dermira, Genentech, GlaxoSmithKline, Incyte, Lilly, Medimmune, Pfizer, Regeneron/Sanofi, and Tioga.

This publication and Global Academy for Medical Education are owned by the same parent company.

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”

Last month, the American College of Rheumatology joined with 11 other medical associations and disease societies asking health insurance giant UnitedHealthcare (UHC) to not proceed with its proposed copay accumulator medical benefit program.

Copay accumulators are policies adopted by insurance companies or their pharmacy benefit managers to exclude patient copayment assistance programs for high-cost drugs, which are promulgated by the drug manufacturers, from being applied to a patient’s annual deductibles or out-of-pocket maximums. The manufacturer’s copay assistance, such as in the form of coupons, is designed to minimize the patient’s out-of-pocket costs. But insurers believe manufacturers will have no pressure to lower the prices of expensive specialty drugs unless patients are unable to afford them. Copay accumulators thus are aimed at giving insurers more leverage in negotiating prices for high-cost drugs.

UHC issued its new copay accumulator protocol for commercial individual and fully insured group plans in early October, effective Jan. 1, 2021, “in order to align employer costs for specialty medications with actual member out of pocket and deductibles,” according to the company’s announcement. In other words, patients will need to pay a higher share of the costs of these medications, said rheumatologist Christopher Phillips, MD, who chairs the Insurance Subcommittee of ACR’s Rheumatologic Care Committee. The annual price of biologic therapies for rheumatologic conditions ranges from $22,000 to $44,000, according to a recent press release from ACR.

The copay accumulator will negate the benefits of manufacturers’ copayment assistance programs for the patient, shifting more of the cost to the patient. With patients being forced to pay a higher share of drug costs for expensive biologic treatments for rheumatoid arthritis, lupus, and other rheumatologic conditions, they’ll stop taking the treatments, Dr. Phillips said.

“In my solo rheumatology practice in Paducah, Kentucky, when I’ve seen this kind of program applied on the pharmacy benefit side, rather than the medical benefit side, almost uniformly patients stop taking the high-cost treatments.” That can lead to disease flares, complications, and permanent disability. The newer rheumatologic drugs can cost $500 to $1,000 per treatment, and in many cases, there’s no generic or lower-cost alternative, he says. “We see policies like this as sacrificing patients to the battle over high drug prices. It’s bad practice, bad for patient outcomes, and nobody – apart from the payer – benefits.”

In ACR’s 2020 Rheumatic Disease Patient Survey, nearly half of 1,109 online survey respondents who had rheumatic diseases reported out-of-pocket costs greater than $1,000 per year for treatment. An IQVIA report from 2016 found that one in four specialty brand prescriptions are abandoned during the deductible phase, three times the rate seen when there is no deductible.

In an Oct. 7 letter to UHC, the 12 groups acknowledged that the drugs targeted by the accumulator policy are expensive. “However, they are also vitally important for our patients.” In addition to the ACR, the organizations involved include the AIDS Institute, American Academy of Dermatology Association, American Academy of Neurology, American College of Gastroenterology, American Gastroenterological Association, American Kidney Fund, Arthritis Foundation, Association for Clinical Oncology, Cancer Support Community, Coalition of State Rheumatology Organizations, and National Multiple Sclerosis Society.

UHC did not reply to questions in time for publication.


 

 

First large-scale payer to try copay accumulator program

Under UHC’s proposed policy, providers will be required to use UHC’s portal to report payment information received from drug manufacturer copay assistance programs that are applied to patients’ cost share of these drugs through a complex, 14-step “coupon submission process” involving multiple technology interfaces. “My first oath as a physician is to do no harm to my patient. Many of us are concerned about making these reports, which could harm our patients and undermine the doctor-patient relationship,” Dr. Phillips said.

“If I don’t report, what happens? I don’t think we know the answer to that. Some of us may decide we need to part ways with UHC.” Others may decline to participate in the drug manufacturers’ coupon programs beyond simply informing patients that manufacturer assistance is available.

“We’ve watched these copay accumulator policies for several years,” he said. “Some of them are rather opaque, with names like ‘copay savings programs’ or ‘copay value programs.’ But we had not seen a large-scale payer try to do this until now. Let’s face it: If UHC’s policy goes through, you can count the days until we see it from others.”

The Department of Health & Human Services, in its May 2020 final federal “Notice of Benefit and Payment Parameters for 2021,” indicated that individual states have the responsibility to regulate copay accumulator programs. Five states have banned them or restricted their use for individual and small group health plans. Arizona, Illinois, Virginia, and West Virginia passed such laws in 2019, and Georgia did so earlier this year.

“In next year’s state legislative sessions, we’ll make it a priority to pursue similar laws in other states,” Dr. Phillips said. “I’d encourage rheumatologists to educate their patients on the issues and be active in advocating for them.”