Atopic Dermatitis

To the Editor:

We read with interest the case reported by Yanovsky et al¹ (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.

First, Yanovsky et al¹ reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai² to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai² did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.³ We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.

Second, the case report indicated that AD lesions improved with the biologic dupilumab,¹ which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.⁴ It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.⁵ In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.

Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.⁶

Fourth, Yanovsky et al¹ reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,⁷ unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.

Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.⁸ This has been reported,⁸ but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.

Yanovsky et al¹ described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.

Author’s Response

Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.

Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.

To the Editor:

We read with interest the case reported by Yanovsky et al¹ (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.

First, Yanovsky et al¹ reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai² to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai² did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.³ We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.

Second, the case report indicated that AD lesions improved with the biologic dupilumab,¹ which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.⁴ It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.⁵ In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.

Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.⁶

Fourth, Yanovsky et al¹ reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,⁷ unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.

Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.⁸ This has been reported,⁸ but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.

Yanovsky et al¹ described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.

Author’s Response

Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.

Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.

To the Editor:

We read with interest the case reported by Yanovsky et al¹ (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.

First, Yanovsky et al¹ reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai² to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai² did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.³ We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.

Second, the case report indicated that AD lesions improved with the biologic dupilumab,¹ which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.⁴ It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.⁵ In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.

Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.⁶

Fourth, Yanovsky et al¹ reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,⁷ unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.

Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.⁸ This has been reported,⁸ but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.

Yanovsky et al¹ described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.

Author’s Response

Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.

Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.

There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.^1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.^3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).

However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.⁵

Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,⁶ and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.⁷ One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.⁸ These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.

Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.⁹ Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.⁹

Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.

For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al⁸ specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.⁸

Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.¹⁰ These are deep-seated problems in the United States; while they may be surmountable in certain geo­graphic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.

A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.¹¹ A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.¹² As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.¹³ The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.¹³

Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.

There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.^1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.^3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).

However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.⁵

Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,⁶ and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.⁷ One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.⁸ These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.

Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.⁹ Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.⁹

Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.

For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al⁸ specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.⁸

Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.¹⁰ These are deep-seated problems in the United States; while they may be surmountable in certain geo­graphic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.

A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.¹¹ A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.¹² As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.¹³ The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.¹³

Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.

There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.^1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.^3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).

However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.⁵

Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,⁶ and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.⁷ One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.⁸ These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.

Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.⁹ Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.⁹

Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.

For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al⁸ specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.⁸

Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.¹⁰ These are deep-seated problems in the United States; while they may be surmountable in certain geo­graphic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.

A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.¹¹ A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.¹² As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.¹³ The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.¹³

Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

On August 13, 2024, the Food and Drug Administration (FDA) approved nemolizumab for the treatment of adults with prurigo nodularis (PN).

A first-in-class monoclonal antibody specifically designed to inhibit interleukin (IL)–31 signaling, nemolizumab, will be available in a prefilled pen for subcutaneous injection and will be marketed as Nemluvio. It is currently under FDA review for treating atopic dermatitis in adolescents and adults. 

Approval for PN is based on data from the phase 3 OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in 560 patients with PN, according to a press release from Galderma, the manufacturer.

According to the press release, in OLYMPIA 1 and OLYMPIA 2, 58% and 56% of patients, respectively, achieved at least a 4-point reduction in itch intensity at week 16 as measured by the Peak Pruritus Numerical Rating Scale, compared with 16% in both placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the Investigator Global Assessment score at week 16, compared with 7% and 11% in the placebo groups (P < .0001).

According to the company press release, the most common side effects of nemolizumab are headache and rashes in the form of eczema, atopic dermatitis, and nummular eczema. 

“By inhibiting the signaling of IL-31, Nemluvio addresses a key driver of prurigo nodularis, safely and effectively improving itch as well as skin nodules,” Shawn G. Kwatra, MD, PhD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, and lead investigator of the OLYMPIA program, stated in the press release.

The regulatory submission of nemolizumab in atopic dermatitis is based on data from the phase 3 ARCADIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in adolescents and adults with moderate to severe atopic dermatitis. A decision on approval for this indication from the FDA is expected in December 2024.

In September 2022, dupilumab became the first FDA-approved treatment for PN in the United States.

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

TORONTO — Reading a storybook about embracing differences can reduce anxiety and boost self-esteem in children with a visible skin condition, the early results of an ongoing study suggested.

So far, “the study demonstrates that these books have value to patients and families,” one of the study authors, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital Kansas City, Kansas City, Missouri, said in an interview.

“There are tools to help kids cope with their skin conditions, but we’re underutilizing them,” she added. “And part of the reason we’re underutilizing storybooks is that we just don’t know what’s out there.” For the study, the researchers received funding to purchase 18 “creative and thoughtful” storybooks related to pediatric skin conditions, reviewed by at least two pediatric dermatologists before being selected, which are just a sample of related books that are available.

The study results were presented as a poster at the annual meeting of the Society for Pediatric Dermatology.

Children with visible skin conditions, which can include port-wine stains, capillary malformations, and congenital moles, may be subjected to teasing or bullying at school, and the conditions can also affect their quality of life.
 

Beauty and the Birthmark

The books include one titled “Beauty with a Birthmark” and another, “My Hair Went on Vacation.” An illustrated book, “Just Ask: Be Different, Be Brave, Be You,” by US Supreme Court Justice Sonia Sotomayor, offers tips on how to answer common questions about someone’s appearance.

Dr. Havele said that Justice Sotomayor’s book “empowers kids, their siblings, their classmates ... to ask questions, and it teaches patients not to be afraid of those questions, and to really lean into educating their peers, and their family members.”

“Kids are really just curious,” she added. “They’ll make comments like: ‘Hey, what’s that spot on your face?’ Or, they’ll ask about vitiligo because they’ve never seen somebody with it before.”

To evaluate the psychosocial impact of these types of books for children with visible skin conditions, Dr. Havele and colleagues designed a study that includes patients aged 2-12 years dealing with issues related to self-esteem, acceptance, coping, or bullying. Parents are provided with a relevant storybook to read at home with their child in a “safe and comfortable space” and “at their own pace and their own time,” said Dr. Havele.

Inside the book is a QR code to access the validated Children’s Dermatology Life Quality Index (CDLQI). Families complete the survey at baseline and provide feedback after reading the book. Researchers collect information about demographics, age, gender, and skin conditions, which included atopic dermatitis, alopecia areata, vitiligo, hemangioma, and port-wine stain.

The response rate so far is 34%, and close to 80 parents have completed the survey with their child, Dr. Havele said.

At baseline, many of the children were either moderately or severely affected in terms of their quality of life (45% scored ≥ 6 on the CDLQI).

After reading the book, about 80% of parents reported it had a positive impact, and about 20% said it had a somewhat positive impact on their child’s self-image or confidence. Almost 80% agreed, and the remainder somewhat agreed it encouraged their child to embrace differences.

Most respondents also said the book helped the parent and child cope with the child’s condition. “So really, it was overall a positive response,” said Dr. Havele. “We are able to demonstrate that these books have value in a more scientific or objective way.”

This may not be surprising. Dr. Havele referred to more formal bibliotherapy (book therapy), which has been studied in other pediatric populations, including patients with cancer and those who have experienced trauma.
 

Awesome Space

Pediatric dermatologists are perfectly positioned to play a role in improving the lives of their patients with skin issues. “We see the impact of visible skin disease on children all the time,” said Dr. Havele. “The dermatology visit is an awesome space and opportunity to introduce these books to families and potentially help them talk about the skin condition with their child.”

In addition to prescribing therapies, “we’re also with these kids through an emotional journey, and I think giving them tools for that emotional journey is very helpful,” she added.

Such books would have been a great help to Dr. Havele herself. Growing up, she had severe atopic dermatitis covering much of her body. “Having such a resource would have helped me better cope with my reality of being different than everyone else.”

She hopes a database will be established to house these resources so other providers can refer patients to the list of books. Other books include “The Itchy-saurus: The Dino with an itch that can’t be scratched,” “Hair in My Brush,” and “I am Unique!”

Dr. Havele had no relevant disclosures.

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

TORONTO — Reading a storybook about embracing differences can reduce anxiety and boost self-esteem in children with a visible skin condition, the early results of an ongoing study suggested.

So far, “the study demonstrates that these books have value to patients and families,” one of the study authors, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital Kansas City, Kansas City, Missouri, said in an interview.

“There are tools to help kids cope with their skin conditions, but we’re underutilizing them,” she added. “And part of the reason we’re underutilizing storybooks is that we just don’t know what’s out there.” For the study, the researchers received funding to purchase 18 “creative and thoughtful” storybooks related to pediatric skin conditions, reviewed by at least two pediatric dermatologists before being selected, which are just a sample of related books that are available.

The study results were presented as a poster at the annual meeting of the Society for Pediatric Dermatology.

Children with visible skin conditions, which can include port-wine stains, capillary malformations, and congenital moles, may be subjected to teasing or bullying at school, and the conditions can also affect their quality of life.
 

Beauty and the Birthmark

The books include one titled “Beauty with a Birthmark” and another, “My Hair Went on Vacation.” An illustrated book, “Just Ask: Be Different, Be Brave, Be You,” by US Supreme Court Justice Sonia Sotomayor, offers tips on how to answer common questions about someone’s appearance.

Dr. Havele said that Justice Sotomayor’s book “empowers kids, their siblings, their classmates ... to ask questions, and it teaches patients not to be afraid of those questions, and to really lean into educating their peers, and their family members.”

“Kids are really just curious,” she added. “They’ll make comments like: ‘Hey, what’s that spot on your face?’ Or, they’ll ask about vitiligo because they’ve never seen somebody with it before.”

To evaluate the psychosocial impact of these types of books for children with visible skin conditions, Dr. Havele and colleagues designed a study that includes patients aged 2-12 years dealing with issues related to self-esteem, acceptance, coping, or bullying. Parents are provided with a relevant storybook to read at home with their child in a “safe and comfortable space” and “at their own pace and their own time,” said Dr. Havele.

Inside the book is a QR code to access the validated Children’s Dermatology Life Quality Index (CDLQI). Families complete the survey at baseline and provide feedback after reading the book. Researchers collect information about demographics, age, gender, and skin conditions, which included atopic dermatitis, alopecia areata, vitiligo, hemangioma, and port-wine stain.

The response rate so far is 34%, and close to 80 parents have completed the survey with their child, Dr. Havele said.

At baseline, many of the children were either moderately or severely affected in terms of their quality of life (45% scored ≥ 6 on the CDLQI).

After reading the book, about 80% of parents reported it had a positive impact, and about 20% said it had a somewhat positive impact on their child’s self-image or confidence. Almost 80% agreed, and the remainder somewhat agreed it encouraged their child to embrace differences.

Most respondents also said the book helped the parent and child cope with the child’s condition. “So really, it was overall a positive response,” said Dr. Havele. “We are able to demonstrate that these books have value in a more scientific or objective way.”

This may not be surprising. Dr. Havele referred to more formal bibliotherapy (book therapy), which has been studied in other pediatric populations, including patients with cancer and those who have experienced trauma.
 

Awesome Space

Pediatric dermatologists are perfectly positioned to play a role in improving the lives of their patients with skin issues. “We see the impact of visible skin disease on children all the time,” said Dr. Havele. “The dermatology visit is an awesome space and opportunity to introduce these books to families and potentially help them talk about the skin condition with their child.”

In addition to prescribing therapies, “we’re also with these kids through an emotional journey, and I think giving them tools for that emotional journey is very helpful,” she added.

Such books would have been a great help to Dr. Havele herself. Growing up, she had severe atopic dermatitis covering much of her body. “Having such a resource would have helped me better cope with my reality of being different than everyone else.”

She hopes a database will be established to house these resources so other providers can refer patients to the list of books. Other books include “The Itchy-saurus: The Dino with an itch that can’t be scratched,” “Hair in My Brush,” and “I am Unique!”

Dr. Havele had no relevant disclosures.

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

TORONTO — Reading a storybook about embracing differences can reduce anxiety and boost self-esteem in children with a visible skin condition, the early results of an ongoing study suggested.

So far, “the study demonstrates that these books have value to patients and families,” one of the study authors, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital Kansas City, Kansas City, Missouri, said in an interview.

“There are tools to help kids cope with their skin conditions, but we’re underutilizing them,” she added. “And part of the reason we’re underutilizing storybooks is that we just don’t know what’s out there.” For the study, the researchers received funding to purchase 18 “creative and thoughtful” storybooks related to pediatric skin conditions, reviewed by at least two pediatric dermatologists before being selected, which are just a sample of related books that are available.

The study results were presented as a poster at the annual meeting of the Society for Pediatric Dermatology.

Children with visible skin conditions, which can include port-wine stains, capillary malformations, and congenital moles, may be subjected to teasing or bullying at school, and the conditions can also affect their quality of life.
 

Beauty and the Birthmark

The books include one titled “Beauty with a Birthmark” and another, “My Hair Went on Vacation.” An illustrated book, “Just Ask: Be Different, Be Brave, Be You,” by US Supreme Court Justice Sonia Sotomayor, offers tips on how to answer common questions about someone’s appearance.

Dr. Havele said that Justice Sotomayor’s book “empowers kids, their siblings, their classmates ... to ask questions, and it teaches patients not to be afraid of those questions, and to really lean into educating their peers, and their family members.”

“Kids are really just curious,” she added. “They’ll make comments like: ‘Hey, what’s that spot on your face?’ Or, they’ll ask about vitiligo because they’ve never seen somebody with it before.”

To evaluate the psychosocial impact of these types of books for children with visible skin conditions, Dr. Havele and colleagues designed a study that includes patients aged 2-12 years dealing with issues related to self-esteem, acceptance, coping, or bullying. Parents are provided with a relevant storybook to read at home with their child in a “safe and comfortable space” and “at their own pace and their own time,” said Dr. Havele.

Inside the book is a QR code to access the validated Children’s Dermatology Life Quality Index (CDLQI). Families complete the survey at baseline and provide feedback after reading the book. Researchers collect information about demographics, age, gender, and skin conditions, which included atopic dermatitis, alopecia areata, vitiligo, hemangioma, and port-wine stain.

The response rate so far is 34%, and close to 80 parents have completed the survey with their child, Dr. Havele said.

At baseline, many of the children were either moderately or severely affected in terms of their quality of life (45% scored ≥ 6 on the CDLQI).

After reading the book, about 80% of parents reported it had a positive impact, and about 20% said it had a somewhat positive impact on their child’s self-image or confidence. Almost 80% agreed, and the remainder somewhat agreed it encouraged their child to embrace differences.

Most respondents also said the book helped the parent and child cope with the child’s condition. “So really, it was overall a positive response,” said Dr. Havele. “We are able to demonstrate that these books have value in a more scientific or objective way.”

This may not be surprising. Dr. Havele referred to more formal bibliotherapy (book therapy), which has been studied in other pediatric populations, including patients with cancer and those who have experienced trauma.
 

Awesome Space

Pediatric dermatologists are perfectly positioned to play a role in improving the lives of their patients with skin issues. “We see the impact of visible skin disease on children all the time,” said Dr. Havele. “The dermatology visit is an awesome space and opportunity to introduce these books to families and potentially help them talk about the skin condition with their child.”

In addition to prescribing therapies, “we’re also with these kids through an emotional journey, and I think giving them tools for that emotional journey is very helpful,” she added.

Such books would have been a great help to Dr. Havele herself. Growing up, she had severe atopic dermatitis covering much of her body. “Having such a resource would have helped me better cope with my reality of being different than everyone else.”

She hopes a database will be established to house these resources so other providers can refer patients to the list of books. Other books include “The Itchy-saurus: The Dino with an itch that can’t be scratched,” “Hair in My Brush,” and “I am Unique!”

Dr. Havele had no relevant disclosures.

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

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Nemolizumab, an interleukin 31 receptor antagonist, was well tolerated and significantly improved inflammation and pruritus in patients with moderate to severe atopic dermatitis (AD).

METHODOLOGY:

• The researchers conducted two 48-week randomized, double-blind, placebo-controlled phase 3 trials, ARCADIA 1 (n = 941; 47% women) and ARCADIA 2 (n = 787; 52% women), involving patients aged 12 and older with moderate to severe AD.
• Participants were randomly assigned in a 2:1 ratio to receive either 30 mg nemolizumab (with a 60-mg loading dose) or placebo, along with background topical corticosteroids with or without topical calcineurin inhibitors. The mean age range was 33.3-35.2 years.
• The coprimary endpoints were Investigator’s Global Assessment (IGA) success (score of 0 or 1 with at least a two-point improvement from baseline) and at least a 75% improvement in the Eczema Area and Severity Index (EASI-75) at week 16.

TAKEAWAY:

• At week 16, significantly more patients receiving nemolizumab vs placebo achieved IGA success in both the ARCADIA 1 (36% vs 25%; P = .0003) and ARCADIA 2 (38% vs 26%; P = .0006) trials.
• EASI-75 response rates were also significantly higher in the nemolizumab group than in the placebo group in both trials: ARCADIA 1 (44% vs 29%; P < .0001) and 2 (42% vs 30%; P = .0006).
• Significant improvements in pruritus were observed as early as week 1, with a greater proportion of participants in the nemolizumab vs placebo group achieving at least a four-point reduction in the Peak Pruritus Numerical Rating Scale score in both trials.
• Rates of adverse events were similar between the nemolizumab and placebo groups, with severe treatment-emergent adverse events occurring in 2%-4% of patients.

IN PRACTICE:

“Nemolizumab showed statistically and clinically significant improvements in inflammation and pruritus in adults and adolescents with moderate to severe atopic dermatitis and a rapid effect in reducing pruritus, as one of the primary complaints of patients. As such, nemolizumab might offer a valuable extension of the therapeutic armament if approved,” the authors concluded.

SOURCE:

The study was led by Jonathan Silverberg, MD, PhD, from the Department of Dermatology, George Washington University, Washington, DC. It was published online in The Lancet.

LIMITATIONS:

The study’s limitations included the absence of longer-term safety data. Additionally, the predominantly White population of the trials may limit the generalizability of the findings to other racial and ethnic groups. The use of concomitant topical therapy might have influenced the placebo response.

DISCLOSURES:

This study was funded by Galderma. Dr. Silverberg received honoraria from pharmaceutical companies, including Galderma, and his institution also received grants from Galderma, Incyte, and Pfizer. Four authors were employees of Galderma. Other authors also declared having ties with pharmaceutical companies, including Galderma, outside this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

Potentially life-threatening cutaneous adverse drug reactions (cADRs) are associated with commonly prescribed oral antibiotics, according to a large, population-based, nested case-control study of older adults, spanning two decades.

The findings, published online in JAMA, “underscore the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate,” noted senior author David Juurlink, MD, PhD, professor of medicine; pediatrics; and health policy, management and evaluation at the University of Toronto, and head of the Clinical Pharmacology and Toxicology Division at Sunnybrook Health Sciences Centre, also in Toronto, Ontario, Canada, and coauthors.

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in an interview. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”

Serious cADRs are “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs,” the authors wrote. “Typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) — the most severe cADR, which has a reported mortality of 20%-40%,” they noted.

Speculation Without Data

Although it has been speculated that some oral antibiotics are more likely than others to be associated with serious cADRs, there have been no population-based studies examining this, they added.

The study included adults aged 66 years or older and used administrative health databases in Ontario, spanning from April 1, 2002, to March 31, 2022. Data on antibiotic use were taken from the Ontario Drug Benefit database. The Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System was used to obtain data on emergency department (ED) visits for cADRs, while the CIHI Discharge Abstract Database was used to identify hospitalizations for cADRs. Finally, demographic information and outpatient healthcare utilization data were obtained from the Registered Persons Database and the Ontario Health Insurance Plan database, respectively.

A cohort of 21,758 older adults (median age, 75 years; 64.1% women) who had an ED visit or hospitalization for serious cADRs within 60 days of receiving antibiotic therapy was matched by age and sex with 87,025 antibiotic-treated controls who did not have a cutaneous reaction.

The median duration of antibiotic prescription was 7 days among cases and controls, and among the cases, the median latency period between antibiotic prescriptions and hospital visits for cADRs was 14 days. Most of the case patients went to the ED only (86.9%), and the rest were hospitalized.

The most commonly prescribed antibiotic class was penicillins (28.9%), followed by cephalosporins (18.2%), fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%). Less commonly used antibiotics (“other” antibiotics) accounted for 6.9%.

Macrolide antibiotics were used as the reference because they are rarely associated with serious cADRs, noted the authors, and the multivariable analysis, adjusted for risk factors associated with serious cADRs, including malignancy, chronic liver disease, chronic kidney disease, and HIV.

After multivariable adjustment, relative to macrolides, sulfonamides were most strongly associated with serious cADRs (adjusted odds ratio [aOR], 2.9) but so were all other antibiotic classes, including cephalosporins (aOR, 2.6), “other” antibiotics (aOR, 2.3), nitrofurantoin (aOR, 2.2), penicillins (aOR, 1.4), and fluoroquinolones (aOR,1.3).

In the secondary analysis, the crude rate of ED visits or hospitalizations for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions), followed by sulfonamides (3.22 per 1000 prescriptions). Among hospitalized patients, the median length of stay was 6 days, with 9.6% requiring transfer to a critical care unit and 5.3% dying in the hospital.
 

Hospitalizations, ED Visits Not Studied Previously

“Notably, the rate of antibiotic-associated serious cADRs leading to an ED visit or hospitalization has not been previously studied,” noted the authors. “We found that at least two hospital encounters for serious cADRs ensued for every 1000 antibiotic prescriptions. This rate is considerably higher than suggested by studies that examine only SJS/TEN and drug reaction with eosinophilia and systemic symptoms.”

Dr. Lee also emphasized the previously unreported findings about nitrofurantoin. “It is surprising to find that nitrofurantoin, a commonly prescribed antibiotic for urinary tract infection, is also associated with an increased risk of severe drug rash,” she said in an interview.

“This finding highlights a potential novel risk at a population-based level and should be further explored in other populations to verify this association,” the authors wrote.

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, Maryland, and a spokesperson for the Infectious Diseases Society of America, who was not involved in the study, agreed that the nitrofurantoin finding was surprising, but he was not surprised that sulfonamides were high on the list.

“The study reinforces that antibiotics are not benign medications to be dispensed injudiciously,” he said in an interview. “Antibiotics have risks, including serious skin reactions, as well as the fostering of antibiotic resistance. Clinicians should always first ask themselves if their patient actually merits an antibiotic and then assess what is the safest antibiotic for the purpose, bearing in mind that certain antibiotics are more likely to result in adverse reactions than others.”

The study was supported by the Canadian Institutes of Health Research. The study was conducted at ICES, which is funded in part by an annual grant from the Ontario Ministry of Health and Long-Term Care. One coauthor reported receiving compensation from the British Journal of Dermatology as reviewer and section editor, the American Academy of Dermatology as guidelines writer, Canadian Dermatology Today as manuscript writer, and the National Eczema Association and the Canadian Agency for Drugs and Technologies in Health as consultant; as well as receiving research grants to the coauthor’s institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes of Health Research, US National Institutes of Health, and PSI Foundation. Another coauthor reported receiving grants from AbbVie, Bausch Health, Celgene, Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, Amgen, and Boehringer Ingelheim; receiving payment or honoraria for speaking from Sanofi China; participating on advisory boards for LEO Pharma, Novartis, Sanofi, and Union Therapeutics; and receiving equipment donation from L’Oréal. Dr. Adalja reported no relevant disclosures.

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

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

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

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

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

WASHINGTON — Immunoglobulin E (IgE) and eosinophils appeared to be reliable biomarkers of type 2 inflammation in chronic pruritus of unknown origin (CPUO) and predictors of a positive response to immunomodulatory therapies, Shawn G. Kwatra, MD, said at the ElderDerm conference on dermatology in older patients hosted by the GW School of Medicine & Health Sciences.

“We found a few years ago that eosinophils seem to differentiate this group, and now we’re finding that IgE and CBC [complete blood count] differential can help you get a little better sense of who has an immune-driven itch vs something more neuropathic,” said Dr. Kwatra, professor and chair of dermatology at the University of Maryland, Baltimore, who founded and directed the Johns Hopkins Itch Center before coming to the University of Maryland in 2023. Not all patients with immune-driven itch will have these biomarkers, “but it’s a helpful tool,” he said.

Dr. Kwatra

CPUO is the term that is increasingly being used, he said, to describe intense, chronic pruritus without primary skin lesions or rashes and without any known systemic cause. It becomes more common as people get older and is sometimes debilitating. The initial evaluation should be kept “simple and straightforward,” he advised, with heightened concern for underlying malignancy in those who present with an itch of less than 12 months’ duration.
 

Biologics, JAK Inhibitors: Case Reports, Ongoing Research 

Research conducted by Dr. Kwatra and Jaya Manjunath, a fourth-year medical student at The George Washington University, Washington, documented higher levels of Th2-associated cytokines and inflammatory markers in patients with CPUO who had elevated IgE or eosinophil levels, or both than in patients with itch who had low IgE and eosinophil levels. The patients with higher levels also had a greater response to off-label treatment with immunomodulatory therapy.

“Multiple Th2-related inflammatory markers, like IL [interleukin]-5 and eotaxin-3, were reduced after dupilumab” in patients who responded to the therapy, said Ms. Manjunath, who co-presented the meeting session on chronic itch with Dr. Kwatra. Other changes in the plasma cytokine profile included a reduction in the serum level of thymus and activation-regulated chemokine, which is a biomarker for atopic dermatitis. The research is under review for publication.

Meanwhile, a phase 3 trial (LIBERTY-CPUO-CHIC) of dupilumab for CPUO is currently underway, Dr. Kwatra noted. Investigators are randomizing patients with severe pruritus (Worst Itch Numeric Rating Scale [WI-NRS] ≥ 7) to dupilumab or placebo for 12 or 24 weeks.

In one of several cases shared by Dr. Kwatra and Ms. Manjunath, a 71-year-old Black woman with a 6-month history of generalized itch (WI-NRS = 10) and a history of type 2 diabetes, hypertension, and chronic kidney disease was found to have elevated eosinophil levels and a negative malignancy workup. Previous therapies included antihistamines and topical steroids. She was started on a 600-mg loading dose of subcutaneous dupilumab followed by 300 mg every 14 days. At the 2-month follow-up, her WI-NRS score was 0.

Because “dupilumab is off label right now for this form of itch, oftentimes our first line is methotrexate,” Dr. Kwatra said. Patients “can have a good response with this therapeutic.”

He also described the case of a 72-year-old Black woman with total body itch for 2 years (WI-NRS = 10) and a history of seasonal allergies, thyroid disease, and hypertension. Previous therapies included prednisone, antihistamines, topical steroids, and gabapentin. The patient was found to have high IgE (447 kU/L) and eosinophil levels (4.9%), was started on methotrexate, and had an itch score of 0 at the 8-month follow-up.

JAK inhibitors may also have a role in the management of CPUO. A phase 2 nonrandomized controlled trial of abrocitinib for adults with prurigo nodularis (PN) or CPUO, recently published in JAMA Dermatology, showed itch scores decreased by 53.7% in the CPUO group (and 78.3% in the PN group) after 12 weeks of treatment with oral abrocitinib 200 mg daily. Patients had significant improvements in quality of life and no serious adverse events, said Dr. Kwatra, the lead author of the paper.

One of these patients was a 73-year-old White man who had experienced total body itch for 1.5 years (predominantly affecting his upper extremities; WI-NRS = 10) and a history of ascending aortic aneurysm, hypertension, and hyperlipidemia. Previous failed therapies included dupilumab (> 6 months), topical steroids, tacrolimus, and antihistamines. Labs showed elevated IgE (456 kU/L) and eosinophil levels (11.7%). After 12 weeks of treatment with abrocitinib, the WI-NRS decreased to 2.
 

PD-1 Inhibitors As a Trigger

Chronic pruritus caused by the anticancer PD-1 inhibitors is becoming more common as the utilization of these immune checkpoint inhibitors increases, Dr. Kwatra noted. “You don’t see much in the skin, but [these patients have] very high IgE and eosinophils,” he said. “We’ve been seeing more reports recently of utilizing agents that target type 2 inflammation off label for PD-1 inhibitor–related skin manifestations.”

One such patient with PD-1 inhibitor–induced pruritus was a 65-year-old White man with metastatic melanoma who reported a 6-month history of itching that began 3 weeks after the start of treatment with the PD-1 inhibitor pembrolizumab. His WI-NRS score was 10 despite treatment with topical steroids and antihistamines. He had a history of psoriasis. Labs showed elevated IgE (1350 kU/L) and eosinophil levels (4.5%). At a 4-month follow-up after treatment with off-label dupilumab (a 600-mg subcutaneous loading dose followed by 300 mg every 14 days), his WI-NRS score was 0.

In a paper recently published in JAAD International, Dr. Kwatra, Ms. Manjunath, and coinvestigators reported on a series of 15 patients who developed chronic pruritus following an immune stimulus exposure, including immunotherapy and vaccination (2024 Apr 7:16:97-102. doi: 10.1016/j.jdin.2024.03.022). Most immunotherapy-treated patients experienced pruritus during treatment or after 21-60 days of receiving treatment, and the patients with vaccine-stimulated pruritus (after Tdap and messenger RNA COVID-19 vaccination) developed pruritus within a week of vaccination.

In addition to the elevated levels of IgE and eosinophils, plasma cytokine analysis showed elevated levels of IL-5, thymic stromal lymphopoietin, and other Th2-related cytokines and inflammatory markers in patients with immune-stimulated pruritus compared with healthy controls, Ms. Manjunath said at the meeting.

When a Malignancy Workup Becomes Important

The initial part of any diagnostic workup for CPUO should include CBC with differential, liver function tests, renal function tests, and thyroid function testing, said Kwatra, referring to a diagnostic algorithm he developed, which was published as part of a CME review in the Journal of the American Academy of Dermatology in 2022.

Then, as indicated by risk factors in the history and physical, one could order other tests such as HIV serology, hepatitis B/C serologies, bullous pemphigoid testing, chest x-rays, evaluation for gammopathies, stool examination for ova and parasites, or heavy metal testing. “Do you do everything at once? We like to keep it straightforward,” Dr. Kwatra said. “Depending on the patient’s risk factors, you could order more or less.”

A malignancy workup should be strongly considered in patients whose itch duration is less than 12 months — and especially if the duration is less than 3 months — with an emphasis on cancers more frequently associated with itch: Hematologic and hepatobiliary cancers. This is “when concern should be heightened ... when there should be a lower threshold for workup,” he said.

The 12-month recommendation stems from a Danish cohort study published in 2014 that demonstrated a twofold increased incidence of cancer among patients with pruritus in the first 3 months after the diagnosis of pruritus. The 1-year absolute cancer risk was 1.63%.

Other risk factors for underlying malignancy or malignancy development in patients with CPUO include age older than 60 years, male sex, liver disease, and current or prior smoking, according to another study, noted Dr. Kwatra.

Dr. Kwatra disclosed that he is an advisory board member/consultant for Pfizer, Regeneron, Sanofi, and other companies and an investigator for Galderma, Incyte, Pfizer, and Sanofi. Manjunath served as the codirector of the ElderDerm conference.
 

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

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

TORONTO — With rates of childhood obesity increasing to the point of becoming a public health concern, related skin conditions are also on the rise in the pediatric population, results of new research show.

The retrospective cohort study found markedly higher rates of skin infections, atopic dermatitis (AD), and acanthosis nigricans among children with overweight, compared with children with average weight.

“Many conditions associated with obesity are strong predictors of cardiovascular mortality as these children age, so doctors can play a key role in advocating for weight loss strategies in this population,” lead study author Samantha Epstein, third-year medical student at Case Western Reserve University, Cleveland, Ohio, said in an interview. The findings were presented at the annual meeting of the Society for Pediatric Dermatology.

Previous research has linked obesity, a chronic inflammatory condition, to psoriasis, AD, hidradenitis suppurativa (HS), acne vulgaris, infections, and rosacea in adults. However, there’s scant research exploring the connection between obesity and cutaneous conditions in children.

According to the Cleveland Clinic, childhood obesity is defined as a body mass index, which is weight in kg divided by the square of height in m², at or above the 95th percentile for age and sex in children aged 2 years or older.

For the study, Ms. Epstein and coauthor Sonal D. Shah, MD, associate professor, Department of Dermatology, Case Western Reserve University, and a board-certified pediatric dermatologist accessed a large national research database and used diagnostic codes to identify over 1 million children (mean age, 8.5 years). Most (about 44%) were White; about one-quarter were Black. The groups were propensity matched, so there were about equal numbers of youngsters with and without obesity and of boys and girls.

They collected data on AD, HS, rosacea, psoriasis, and acanthosis nigricans (a thickened purplish discoloration typically found in body folds around the armpits, groin, and neck). They also gathered information on comorbidities.

Acanthosis nigricans, which is linked to metabolic syndrome, type 2 diabetes, and insulin resistance , was more prevalent among children with obesity (20,885 cases in the with-obesity group and 336 in the without-obesity group, for a relative risk [RR] of 62.16 and an odds ratio [OR] of 64.38).

Skin and subcutaneous tissue infections were also more common among those with obesity (14,795 cases) vs 4720 cases among those without obesity (RR, 3.14; OR, 3.2). As for AD, there were 11,892 cases in the with-obesity group and 2983 in the without-obesity group (RR, 3.99; OR, 4.06). There were 1166 cases of psoriasis among those with obesity and 408 among those without obesity (RR, 2.86; OR, 2.88).

HS (587 cases in the with-obesity group and 70 in the without-obesity group; RR, 8.39; OR, 8.39) and rosacea (351 in the with-obesity group and 138 in the without-obesity group; RR, 2.54; OR, 2.55) were the least common skin conditions.

Higher Comorbidity Rates

Compared with their average-weight counterparts, the children with obesity had higher rates of comorbidities, including type 2 diabetes. Ms. Epstein noted that children with diabetes and obesity had increased risks for every skin condition except for infections of the skin and subcutaneous tissue when compared with children without obesity. 

Such infections were the most common skin conditions among children without obesity. “This was expected just due to the fact that children are outside, they’re playing in the grass and the dirt, and they get infected,” said Ms. Epstein. Still, these infections were three times more common in youngsters with obesity.

Although acanthosis nigricans is “highly correlated” with type 2 diabetes, “not as many children as we would expect in this population have developed type 2 diabetes,” said Ms. Epstein. This might make some sense, though, because these children are still quite young. “When dermatologists recognize this skin condition, they can advocate for weight loss management to try to prevent it.”

Other conditions seen more often in the overweight children with overweight included: hypertension, hyperlipidemia, obstructive sleep apnea, polycystic ovarian syndrome, attention-deficit/hyperactivity disorder, major depressive disorder, depressive episodes, and anxiety (all P < .001).

Commenting on the results, Sonia Havele, MD, a pediatrician and dermatology resident at Children’s Mercy Hospital, Kansas City, Missouri, said in an interview that the study reflects trends that she and her colleagues see in clinic: There are more common skin conditions in their patients with obesity.

She agreed that it offers an opening for education. “The results of this study highlight the opportunity we have as pediatric dermatologists to provide additional counseling on obesity and offer referrals to our colleagues in endocrinology, gastroenterology, and nutrition if needed.”

No conflicts of interest were reported.

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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

WASHINGTON — The chronic, excessive fragility of aging and sun-damaged skin has a name in the medical literature: dermatoporosis. This identification is helpful because it validates patients’ suffering and conveys the skin’s vulnerability to serious medical complications, said Adam Friedman, MD, at the ElderDerm conference on dermatology in the older patient.

Key features of dermatoporosis include atrophic skin, solar purpura, white pseudoscars, easily acquired skin lacerations and tears, bruises, and delayed healing. “We’re going to see more of this, and it will more and more be a chief complaint of patients,” said Dr. Friedman, professor and chair of dermatology at George Washington University (GWU) in Washington, and co-chair of the meeting. GWU hosted the conference, describing it as a first-of-its-kind meeting dedicated to improving dermatologic care for older adults.

Likely Pathophysiology

Advancing age and chronic ultraviolet (UV) radiation exposure are the chief drivers of dermatoporosis. In addition to UVA and UVB light, other secondary drivers include genetic susceptibility, topical and systematic corticosteroid use, and anticoagulant treatment.

Its pathogenesis is not well described in the literature but is easy to envision, Dr. Friedman said. For one, both advancing age and exposure to UV light lead to a reduction in hygroscopic glycosaminoglycans, including hyaluronate (HA), and the impact of this diminishment is believed to go “beyond [the loss of] buoyancy,” he noted. Researchers have “been showing these are not just water-loving molecules, they also have some biologic properties” relating to keratinocyte production and epidermal turnover that appear to be intricately linked to the pathogenesis of dermatoporosis. 

HAs have been shown to interact with the cell surface receptor CD44 to stimulate keratinocyte proliferation, and low levels of CD44 have been reported in skin with dermatoporosis compared with a younger control population. (A newly characterized organelle, the hyaluronosome, serves as an HA factory and contains CD44 and heparin-binding epidermal growth factor, Dr. Friedman noted. Inadequate functioning may be involved in skin atrophy.) 

Advancing age also brings an increase in matrix metalloproteinases (MMPs)–1, –2, and –3, which are “the demolition workers of the skin,” and downregulation of a tissue inhibitor of MMPs, he said. 

Adding insult to injury, dermis-penetrating UVA also activates MMPs, “obliterating collagen and elastin.” UVB generates DNA photoproducts, including oxidative stress and damaging skin cell DNA. “That UV light induces breakdown [of the skin] through different mechanisms and inhibits buildup is a simple concept I think our patients can understand,” Dr. Friedman said.
 

Multifaceted Treatment

For an older adult, “there is never a wrong time to start sun-protective measures” to prevent or try to halt the progression of dermatoporosis, Dr. Friedman said, noting that “UV radiation is an immunosuppressant, so there are many good reasons to start” if the adult is not already taking measures on a regular basis.

Potential treatments for the syndrome of dermatoporosis are backed by few clinical studies, but dermatologists are skilled at translating the use of products from one disease state to another based on understandings of pathophysiology and mechanistic pathways, Dr. Friedman commented in an interview after the meeting. 

For instance, “from decades of research, we know what retinoids will do to the skin,” he said in the interview. “We know they will turn on collagen-1 and -3 genes in the skin, and that they will increase the production of glycosaminoglycans ... By understanding the biology, we can translate this to dermatoporosis.” These changes were demonstrated, for instance, in a small study of topical retinol in older adults.

Studies of topical alpha hydroxy acid (AHA), moreover, have demonstrated epidermal thickening and firmness, and “some studies show they can limit steroid-induced atrophy,” Dr. Friedman said at the meeting. “And things like lactic acid and urea are super accessible.”

Topical dehydroepiandrosterone is backed by even less data than retinoids or AHAs are, “but it’s still something to consider” as part of a multimechanistic approach to dermatoporosis, Dr. Friedman shared, noting that a small study demonstrated beneficial effects on epidermal atrophy in aging skin. 

The use of vitamin D analogues such as calcipotriene, which is approved for the treatment of psoriasis, may also be promising. “One concept is that [vitamin D analogues] increase calcium concentrations in the epidermis, and calcium is so central to keratinocyte differentiation” and epidermal function that calcipotriene in combination with topical steroid therapy has been shown to limit skin atrophy, he noted.

Nutritionally, low protein intake is a known problem in the older population and is associated with increased skin fragility and poorer healing. From a prevention and treatment standpoint, therefore, patients can be counseled to be attentive to their diets, Dr. Friedman said. Experts have recommended a higher protein intake for older adults than for younger adults; in 2013, an international group recommended a protein intake of 1-1.5 g/kg/d for healthy older adults and more for those with acute or chronic illness.

“Patients love talking about diet and skin disease ... and they love over-the-counter nutraceuticals as well because they want something natural,” Dr. Friedman said. “I like using bioflavonoids in combination with vitamin C, which can be effective especially for solar purpura.”

Courtesy Dr. Adam Friedman

Skin Injury and Wound Prevention

In addition to recommending gentle skin cleansers and daily moisturizing, dermatologists should talk to their older patients with dermatoporosis about their home environments. “What is it like? Is there furniture with sharp edges?” Dr. Friedman advised. If so, could they use sleeves or protectors on their arms or legs “to protect against injury?”

In a later meeting session about lower-extremity wounds on geriatric patients, Michael Stempel, DPM, assistant professor of medicine and surgery and chief of podiatry at GWU, said that he was happy to hear the term dermatoporosis being used because like diabetes, it’s a risk factor for developing lower-extremity wounds and poor wound healing. 

He shared the case of an older woman with dermatoporosis who “tripped and skinned her knee against a step and then self-treated it for over a month by pouring hydrogen peroxide over it and letting air get to it.” The wound developed into “full-thickness tissue loss,” said Dr. Stempel, also medical director of the Wound Healing and Limb Preservation Center at GWU Hospital. 

Misperceptions are common among older patients about how a simple wound should be managed; for instance, the adage “just let it get air” is not uncommon. This makes anticipatory guidance about basic wound care — such as the importance of a moist and occlusive environment and the safe use of hydrogen peroxide — especially important for patients with dermatoporosis, Dr. Friedman commented after the meeting.

Dermatoporosis is quantifiable, Dr. Friedman said during the meeting, with a scoring system having been developed by the researchers in Switzerland who originally coined the term. Its use in practice is unnecessary, but its existence is “nice to share with patients who feel bothered because oftentimes, patients feel it’s been dismissed by other providers,” he said. “Telling your patients there’s an actual name for their problem, and that there are ways to quantify and measure changes over time, is validating.” 

Its recognition as a medical condition, Dr. Friedman added, also enables the dermatologist to bring it up and counsel appropriately — without a patient feeling shame — when it is identified in the context of a skin excision, treatment of a primary inflammatory skin disease, or management of another dermatologic problem.

Dr. Friedman disclosed that he is a consultant/advisory board member for L’Oréal, La Roche-Posay, Galderma, and other companies; a speaker for Regeneron/Sanofi, Incyte, BMD, and Janssen; and has grants from Pfizer, Lilly, Incyte, and other companies. Dr. Stempel reported no disclosures.

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