MDedge Dermatology

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.

The Diagnosis: Hypertrophic Lichen Planus

Two biopsies from the left lateral foot revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis, and a bandlike lymphocytic infiltrate in the superficial dermis with a classic sawtooth pattern of the rete ridges (Figure 1). Based on the clinical findings and histopathology, the patient was diagnosed with hypertrophic lichen planus (LP) and was treated with clobetasol ointment 0.05%, which resulted in progression of the symptoms. She experienced notable improvement 3 months after adding methotrexate 12.5 mg weekly (Figure 2).

Lichen planus is an idiopathic chronic inflammatory condition of the skin and mucous membranes that classically manifests as pruritic violaceous papules and plaques, which commonly are found on the wrists, lower back, and ankles.¹ The most common variants of LP are hypertrophic, linear, mucosal, actinic, follicular, pigmented, annular, atrophic, and guttate.² The clinical presentation and biopsy results in our patient were consistent with the hypertrophic variant of LP, which is a chronic condition that most often manifests on the lower legs, especially around the ankles, as hyperkeratotic papules, plaques, and nodules.^2,3 The exact pathophysiology of hypertrophic LP is unknown, but there is evidence that the immune system plays a role in its development and that the Koebner phenomenon may contribute to its exacerbation.⁴ There is a well-known association between LP and hepatitis. Patients with chronic LP may develop squamous cell carcinoma.⁴ The variants of LP can overlap and do not exist independent of one another. Recognizing the overlap in these variants allows for earlier diagnosis and therapeutic intervention of the disease process to limit disease progression and patient clinic visits and to improve patient quality of life.

The differential diagnosis for hyperkeratotic plaques of the feet and ankles can be broad and may include keratosis lichenoides chronica, palmoplantar keratoderma, palmoplantar psoriasis, or lichen amyloidosis. These conditions are classified based on various criteria that include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis.⁵ Keratosis lichenoides chronica is a rare dermatosis that presents as a distinctive seborrheic dermatitis–like facial eruption. The facial eruption is accompanied by violaceous papular and nodular lesions that appear on the extremities and trunk, typically arranged in a linear or reticular pattern.⁶ Palmoplantar keratoderma represents a group of acquired and hereditary conditions that are characterized by excessive thickening of the palms and soles.⁵ Palmoplantar psoriasis is a variant of psoriasis that affects the palms and soles and can manifest as hyperkeratosis, pustular, or mixed morphology.⁷ Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis that manifests as multiple pruritic, firm, hyperpigmented, hyperkeratotic papules on the shins that later coalesce in a rippled pattern.^8,9

The first-line treatment for hypertrophic LP is topical corticosteroids. Alternative therapies include mycophenolate mofetil, acitretin, and intralesional corticosteroid injections.⁴ Treatment is similar for all of the LP variants.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

TOPLINE:

Despite a high frequency of atypical features, longitudinal melanonychia (LM) in children is associated with an exceedingly low rate of malignancy.

METHODOLOGY:

• LM — a pigmented band in the nail plate caused by increased melanin deposition — occurs in children and adults, resulting from melanocytic activation or proliferation in response to infection, systemic disease, medication, trauma, and other factors.
• Clinical features of LM in children mimic red-flag signs of subungual melanoma in adults although rarely is subungual melanoma.
• A biopsy can confirm the diagnosis, but other considerations include the scar, cost and stress of a procedure, and possibly pain or deformity.
• The researchers conducted a systematic review and meta-analysis of the prevalence of clinical and dermoscopic features in 1391 pediatric patients with LM (diagnosed at a mean age of 5-13 years) from 24 studies published between 1996 and 2023.

TAKEAWAY:

• Of 731 lesions in which a diagnosis was provided, benign nail matrix nevus accounted for 86% of cases.
• Only eight cases of subungual melanoma in situ were diagnosed, with no cases of invasive melanoma identified.
• Most lesions occurred on the fingernails (76%), particularly in the first digits (45%), and the most frequent clinical features included dark-colored bands (70%), multicolored bands (48%), broad bandwidth (41%), and pseudo-Hutchinson sign (41%).
• During a median follow-up of 1-5.5 years, 30% of lesions continued to evolve with changes in width or color, while 23% remained stable and 20% underwent spontaneous regression.

IN PRACTICE:

“In the pivotal clinical decision of whether to biopsy a child with longitudinal melanonychia, perhaps with features that would require a prompt biopsy in an adult, this study provides data to support the option of clinical monitoring,” the authors wrote.

SOURCE:

The meta-analysis, led by Serena Yun-Chen Tsai, MD, in the Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, was published online in Pediatric Dermatology.

LIMITATIONS:

Most studies were conducted in Asia, and data stratified by skin type were limited. Inconsistent reporting and missing critical features could affect data quality. Also, certain features displayed high heterogeneity.

DISCLOSURES:

This meta-analysis was supported by the Pediatric Dermatology Research Alliance Career Bridge Research Grant. One co-author disclosed relationships with UpToDate (author, reviewer), Skin Analytics (consultant), and DermTech (research materials).

A version of this article appeared on Medscape.com.

TOPLINE:

Despite a high frequency of atypical features, longitudinal melanonychia (LM) in children is associated with an exceedingly low rate of malignancy.

METHODOLOGY:

• LM — a pigmented band in the nail plate caused by increased melanin deposition — occurs in children and adults, resulting from melanocytic activation or proliferation in response to infection, systemic disease, medication, trauma, and other factors.
• Clinical features of LM in children mimic red-flag signs of subungual melanoma in adults although rarely is subungual melanoma.
• A biopsy can confirm the diagnosis, but other considerations include the scar, cost and stress of a procedure, and possibly pain or deformity.
• The researchers conducted a systematic review and meta-analysis of the prevalence of clinical and dermoscopic features in 1391 pediatric patients with LM (diagnosed at a mean age of 5-13 years) from 24 studies published between 1996 and 2023.

TAKEAWAY:

• Of 731 lesions in which a diagnosis was provided, benign nail matrix nevus accounted for 86% of cases.
• Only eight cases of subungual melanoma in situ were diagnosed, with no cases of invasive melanoma identified.
• Most lesions occurred on the fingernails (76%), particularly in the first digits (45%), and the most frequent clinical features included dark-colored bands (70%), multicolored bands (48%), broad bandwidth (41%), and pseudo-Hutchinson sign (41%).
• During a median follow-up of 1-5.5 years, 30% of lesions continued to evolve with changes in width or color, while 23% remained stable and 20% underwent spontaneous regression.

IN PRACTICE:

“In the pivotal clinical decision of whether to biopsy a child with longitudinal melanonychia, perhaps with features that would require a prompt biopsy in an adult, this study provides data to support the option of clinical monitoring,” the authors wrote.

SOURCE:

The meta-analysis, led by Serena Yun-Chen Tsai, MD, in the Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, was published online in Pediatric Dermatology.

LIMITATIONS:

Most studies were conducted in Asia, and data stratified by skin type were limited. Inconsistent reporting and missing critical features could affect data quality. Also, certain features displayed high heterogeneity.

DISCLOSURES:

This meta-analysis was supported by the Pediatric Dermatology Research Alliance Career Bridge Research Grant. One co-author disclosed relationships with UpToDate (author, reviewer), Skin Analytics (consultant), and DermTech (research materials).

A version of this article appeared on Medscape.com.

TOPLINE:

Despite a high frequency of atypical features, longitudinal melanonychia (LM) in children is associated with an exceedingly low rate of malignancy.

METHODOLOGY:

• LM — a pigmented band in the nail plate caused by increased melanin deposition — occurs in children and adults, resulting from melanocytic activation or proliferation in response to infection, systemic disease, medication, trauma, and other factors.
• Clinical features of LM in children mimic red-flag signs of subungual melanoma in adults although rarely is subungual melanoma.
• A biopsy can confirm the diagnosis, but other considerations include the scar, cost and stress of a procedure, and possibly pain or deformity.
• The researchers conducted a systematic review and meta-analysis of the prevalence of clinical and dermoscopic features in 1391 pediatric patients with LM (diagnosed at a mean age of 5-13 years) from 24 studies published between 1996 and 2023.

TAKEAWAY:

• Of 731 lesions in which a diagnosis was provided, benign nail matrix nevus accounted for 86% of cases.
• Only eight cases of subungual melanoma in situ were diagnosed, with no cases of invasive melanoma identified.
• Most lesions occurred on the fingernails (76%), particularly in the first digits (45%), and the most frequent clinical features included dark-colored bands (70%), multicolored bands (48%), broad bandwidth (41%), and pseudo-Hutchinson sign (41%).
• During a median follow-up of 1-5.5 years, 30% of lesions continued to evolve with changes in width or color, while 23% remained stable and 20% underwent spontaneous regression.

IN PRACTICE:

“In the pivotal clinical decision of whether to biopsy a child with longitudinal melanonychia, perhaps with features that would require a prompt biopsy in an adult, this study provides data to support the option of clinical monitoring,” the authors wrote.

SOURCE:

The meta-analysis, led by Serena Yun-Chen Tsai, MD, in the Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, was published online in Pediatric Dermatology.

LIMITATIONS:

Most studies were conducted in Asia, and data stratified by skin type were limited. Inconsistent reporting and missing critical features could affect data quality. Also, certain features displayed high heterogeneity.

DISCLOSURES:

This meta-analysis was supported by the Pediatric Dermatology Research Alliance Career Bridge Research Grant. One co-author disclosed relationships with UpToDate (author, reviewer), Skin Analytics (consultant), and DermTech (research materials).

A version of this article appeared on Medscape.com.

TOPLINE:

Hypoplastic pitted amelogenesis imperfecta may affect patients with the rare genetic disorder Kindler epidermolysis bullosa (KEB).

METHODOLOGY:

• KEB or Kindler syndrome, a genetic skin-blistering disease associated with pathogenic variants in FERMT1, is the rarest type of EB. Early detection and preventive measures can minimize complications, such as gum disease and other oral health issues, that have been reported in patients with KEB.
• Amelogenesis imperfecta is a group of rare genetic developmental conditions characterized by tooth enamel defects and can be associated with hypersensitivity and eruption disturbances in teeth, as well as periodontal conditions.
• Researchers conducted a longitudinal study on 36 patients with KEB (age, 2 weeks to 70 years; 42% female) from two clinics in Germany and Chile from 2003 to 2023, with follow-up times of 1-24 years.
• The primary outcomes were presence of orofacial features, including amelogenesis imperfecta, intraoral wounds,  and periodontal disease, and oral squamous cell carcinoma.

TAKEAWAY:

• All 11 patients with information on enamel structure in their records had pitted enamel anomalies (pitted amelogenesis imperfecta), with variable severity.
• Of patients whose enamel could not be analyzed, three had all teeth crowned in their 20s, suggesting enamel defects, and two had all teeth extracted in their teens or 20s, indicating severe periodontal disease.
• The most common orofacial features were periodontal disease (27 of 36 patients), intraoral lesions (16 of 22 patients), angular cheilitis (24 of 33 patients), and cheilitis (22 of 34 patients), gingival overgrowth (17 of 26 patients), microstomia (14 of 25 patients), and vestibular obliteration (8 of 16 patients).
• Oral squamous cell carcinoma was diagnosed at the site of chronic lip lesions in two patients, with lethal outcomes.

IN PRACTICE:

These findings highlight the extent and severity of oral manifestations in KEB, the authors concluded, adding that “oral care is mandatory” in patients with KEB.

SOURCE:

This report, led by Susanne Krämer, DDS, MSc, of Medical Faculty and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany, was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and the retrospective nature of the study could limit its generalizability.

DISCLOSURES:

The authors did not disclose any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypoplastic pitted amelogenesis imperfecta may affect patients with the rare genetic disorder Kindler epidermolysis bullosa (KEB).

METHODOLOGY:

• KEB or Kindler syndrome, a genetic skin-blistering disease associated with pathogenic variants in FERMT1, is the rarest type of EB. Early detection and preventive measures can minimize complications, such as gum disease and other oral health issues, that have been reported in patients with KEB.
• Amelogenesis imperfecta is a group of rare genetic developmental conditions characterized by tooth enamel defects and can be associated with hypersensitivity and eruption disturbances in teeth, as well as periodontal conditions.
• Researchers conducted a longitudinal study on 36 patients with KEB (age, 2 weeks to 70 years; 42% female) from two clinics in Germany and Chile from 2003 to 2023, with follow-up times of 1-24 years.
• The primary outcomes were presence of orofacial features, including amelogenesis imperfecta, intraoral wounds,  and periodontal disease, and oral squamous cell carcinoma.

TAKEAWAY:

• All 11 patients with information on enamel structure in their records had pitted enamel anomalies (pitted amelogenesis imperfecta), with variable severity.
• Of patients whose enamel could not be analyzed, three had all teeth crowned in their 20s, suggesting enamel defects, and two had all teeth extracted in their teens or 20s, indicating severe periodontal disease.
• The most common orofacial features were periodontal disease (27 of 36 patients), intraoral lesions (16 of 22 patients), angular cheilitis (24 of 33 patients), and cheilitis (22 of 34 patients), gingival overgrowth (17 of 26 patients), microstomia (14 of 25 patients), and vestibular obliteration (8 of 16 patients).
• Oral squamous cell carcinoma was diagnosed at the site of chronic lip lesions in two patients, with lethal outcomes.

IN PRACTICE:

These findings highlight the extent and severity of oral manifestations in KEB, the authors concluded, adding that “oral care is mandatory” in patients with KEB.

SOURCE:

This report, led by Susanne Krämer, DDS, MSc, of Medical Faculty and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany, was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and the retrospective nature of the study could limit its generalizability.

DISCLOSURES:

The authors did not disclose any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypoplastic pitted amelogenesis imperfecta may affect patients with the rare genetic disorder Kindler epidermolysis bullosa (KEB).

METHODOLOGY:

• KEB or Kindler syndrome, a genetic skin-blistering disease associated with pathogenic variants in FERMT1, is the rarest type of EB. Early detection and preventive measures can minimize complications, such as gum disease and other oral health issues, that have been reported in patients with KEB.
• Amelogenesis imperfecta is a group of rare genetic developmental conditions characterized by tooth enamel defects and can be associated with hypersensitivity and eruption disturbances in teeth, as well as periodontal conditions.
• Researchers conducted a longitudinal study on 36 patients with KEB (age, 2 weeks to 70 years; 42% female) from two clinics in Germany and Chile from 2003 to 2023, with follow-up times of 1-24 years.
• The primary outcomes were presence of orofacial features, including amelogenesis imperfecta, intraoral wounds,  and periodontal disease, and oral squamous cell carcinoma.

TAKEAWAY:

• All 11 patients with information on enamel structure in their records had pitted enamel anomalies (pitted amelogenesis imperfecta), with variable severity.
• Of patients whose enamel could not be analyzed, three had all teeth crowned in their 20s, suggesting enamel defects, and two had all teeth extracted in their teens or 20s, indicating severe periodontal disease.
• The most common orofacial features were periodontal disease (27 of 36 patients), intraoral lesions (16 of 22 patients), angular cheilitis (24 of 33 patients), and cheilitis (22 of 34 patients), gingival overgrowth (17 of 26 patients), microstomia (14 of 25 patients), and vestibular obliteration (8 of 16 patients).
• Oral squamous cell carcinoma was diagnosed at the site of chronic lip lesions in two patients, with lethal outcomes.

IN PRACTICE:

These findings highlight the extent and severity of oral manifestations in KEB, the authors concluded, adding that “oral care is mandatory” in patients with KEB.

SOURCE:

This report, led by Susanne Krämer, DDS, MSc, of Medical Faculty and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany, was published online in JAMA Dermatology.

LIMITATIONS:

The small sample size and the retrospective nature of the study could limit its generalizability.

DISCLOSURES:

The authors did not disclose any source of funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.¹ Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).¹ The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.² These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.³ The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.²

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.¹ Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.³ Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.¹

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.⁴ Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.⁴ The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.⁴

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.⁶ Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.⁷ Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.⁶ Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.⁸

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.⁹ Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.³

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.¹⁰ Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.¹¹ The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).¹² The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.¹¹ An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.¹²

The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.¹ Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).¹ The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.² These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.³ The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.²

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.¹ Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.³ Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.¹

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.⁴ Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.⁴ The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.⁴

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.⁶ Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.⁷ Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.⁶ Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.⁸

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.⁹ Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.³

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.¹⁰ Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.¹¹ The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).¹² The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.¹¹ An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.¹²

The Diagnosis: Lymphoepithelioma-like Carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.¹ Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).¹ The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.² These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.³ The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.²

The usual treatment of LELC is wide local excision or Mohs micrographic surgery.¹ Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.³ Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.¹

Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.⁴ Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.⁴ The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.⁴

Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.⁶ Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.⁷ Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.⁶ Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.⁸

Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.⁹ Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.³

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.¹⁰ Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.¹¹ The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).¹² The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.¹¹ An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.¹²

Plant Parts and Nomenclature

Ficus carica (common fig) is a deciduous shrub or small tree with smooth gray bark that can grow up to 10 m in height (Figure 1). It is characterized by many spreading branches, but the trunk rarely grows beyond a diameter of 7 in. Its hairy leaves are coarse on the upper side and soft underneath with 3 to 7 deep lobes that can extend up to 25 cm in length or width; the leaves grow individually, alternating along the sides of the branches. Fig trees often can be seen adorning yards, gardens, and parks, especially in tropical and subtropical climates. Ficus carica should not be confused with Ficus benjamina (weeping fig), a common ornamental tree that also is used to provide shade in hot climates, though both can cause phototoxic skin eruptions.

The common fig tree originated in the Mediterranean and western Asia¹ and has been cultivated by humans since the second and third millennia bc for its fruit, which commonly is used to sweeten cookies, cakes, and jams.² Figs are the most commonly mentioned food plant in the Bible, with at least 56 references in the Old and New Testaments.³ The “fruit” technically is a syconium—a hollow fleshy receptacle with a small opening at the apex partly closed by small scales. It can be obovoid, turbinate, or pear shaped; can be 1 to 4 inches long; and can vary in color from yellowish green to coppery, bronze, or dark purple (Figure 2).

Ficus carica is a member of the Moraceae family (derived from the Latin name for the mulberry tree), which includes 53 genera and approximately 1400 species, of which about 850 belong to the genus Ficus (the Latin name for a fig tree). The term carica likely comes from the Latin word carricare (to load) to describe a tree loaded with figs. Family members include trees, shrubs, lianas, and herbs that usually contain laticifers with a milky latex.

Traditional Uses

For centuries, components of the fig tree have been used in herbal teas and pastes to treat ailments ranging from sore throats to diarrhea, though there is no evidence to support their efficacy.⁴ Ancient Indians and Egyptians used plants such as the common fig tree containing furocoumarins to induce hyperpigmentation in vitiligo.⁵

Phototoxic Components

The leaves and sap of the common fig tree contain psoralens, which are members of the furocoumarin group of chemical compounds and are the source of its phototoxicity. The fruit does not contain psoralens.^6-9 The tree also produces proteolytic enzymes such as protease, amylase, ficin, triterpenoids, and lipodiastase that enhance its phototoxic effects.⁸ Exposure to UV light between 320 and 400 nm following contact with these phototoxic components triggers a reaction in the skin over the course of 1 to 3 days.⁵ The psoralens bind in epidermal cells, cross-link the DNA, and cause cell-membrane destruction, leading to edema and necrosis.¹⁰ The delay in symptoms may be attributed to the time needed to synthesize acute-phase reaction proteins such as tumor necrosis factor α and IL-1.¹¹ In spring and summer months, an increased concentration of psoralens in the leaves and sap contribute to an increased incidence of phytophotodermatitis.⁹ Humidity and sweat also increase the percutaneous absorption of psoralens.^12,13

Allergens

Fig trees produce a latex protein that can cause cross-reactive hypersensitivity reactions in those allergic to F benjamina latex and rubber latex.⁶ The latex proteins in fig trees can act as airborne respiratory allergens. Ingestion of figs can produce anaphylactic reactions in those sensitized to rubber latex and F benjamina latex.⁷ Other plant families associated with phototoxic reactions include Rutaceae (lemon, lime, bitter orange), Apiaceae (formerly Umbelliferae)(carrot, parsnip, parsley, dill, celery, hogweed), and Fabaceae (prairie turnip).

 

 

Cutaneous Manifestations

Most cases of fig phytophotodermatitis begin with burning, pain, and/or itching within hours of sunlight exposure in areas of the skin that encountered components of the fig tree, often in a linear pattern. The affected areas become erythematous and edematous with formation of bullae and unilocular vesicles over the course of 1 to 3 days.^12,14,15 Lesions may extend beyond the region of contact with the fig tree as they spread across the skin due to sweat or friction, and pain may linger even after the lesions resolve.^12,13,16 Adults who handle fig trees (eg, pruning) are susceptible to phototoxic reactions, especially those using chain saws or other mechanisms that result in spray exposure, as the photosensitizing sap permeates the wood and bark of the entire tree.¹⁷ Similarly, children who handle fig leaves or sap during outdoor play can develop bullous eruptions. Severe cases have resulted in hospital admission after prolonged exposure.¹⁶ Additionally, irritant dermatitis may arise from contact with the trichomes or “hairs” on various parts of the plant.

Image provided with permission by Scott Norton, MD, MPH, MSc (Washington, DC).

Patients who use natural remedies containing components of the fig tree without the supervision of a medical provider put themselves at risk for unsafe or unwanted adverse effects, such as phytophotodermatitis.^12,15,16,18 An entire family presented with burns after they applied fig leaf extract to the skin prior to tanning outside in the sun.¹⁹ A 42-year-old woman acquired a severe burn covering 81% of the body surface after topically applying fig leaf tea to the skin as a tanning agent.²⁰ A subset of patients ingesting or applying fig tree components for conditions such as vitiligo, dermatitis, onychomycosis, and motor retardation developed similar cutaneous reactions.^13,14,21,22 Lesions resembling finger marks can raise concerns for potential abuse or neglect in children.²²

The differential diagnosis for fig phytophotodermatitis includes sunburn, chemical burns, drug-related photosensitivity, infectious lesions (eg, herpes simplex, bullous impetigo, Lyme disease, superficial lymphangitis), connective tissue disease (eg, systemic lupus erythematosus), contact dermatitis, and nonaccidental trauma.^12,15,18 Compared to sunburn, phytophotodermatitis tends to increase in severity over days following exposure and heals with dramatic hyperpigmentation, which also prompts visits to dermatology.¹²

Treatment

Treatment of fig phytophotodermatitis chiefly is symptomatic, including analgesia, appropriate wound care, and infection prophylaxis. Topical and systemic corticosteroids may aid in the resolution of moderate to severe reactions.^15,23,24 Even severe injuries over small areas or mild injuries to a high percentage of the total body surface area may require treatment in a burn unit. Patients should be encouraged to use mineral-based sunscreens on the affected areas to reduce the risk for hyperpigmentation. Individuals who regularly handle fig trees should use contact barriers including gloves and protective clothing (eg, long-sleeved shirts, long pants).

Plant Parts and Nomenclature

Ficus carica (common fig) is a deciduous shrub or small tree with smooth gray bark that can grow up to 10 m in height (Figure 1). It is characterized by many spreading branches, but the trunk rarely grows beyond a diameter of 7 in. Its hairy leaves are coarse on the upper side and soft underneath with 3 to 7 deep lobes that can extend up to 25 cm in length or width; the leaves grow individually, alternating along the sides of the branches. Fig trees often can be seen adorning yards, gardens, and parks, especially in tropical and subtropical climates. Ficus carica should not be confused with Ficus benjamina (weeping fig), a common ornamental tree that also is used to provide shade in hot climates, though both can cause phototoxic skin eruptions.

The common fig tree originated in the Mediterranean and western Asia¹ and has been cultivated by humans since the second and third millennia bc for its fruit, which commonly is used to sweeten cookies, cakes, and jams.² Figs are the most commonly mentioned food plant in the Bible, with at least 56 references in the Old and New Testaments.³ The “fruit” technically is a syconium—a hollow fleshy receptacle with a small opening at the apex partly closed by small scales. It can be obovoid, turbinate, or pear shaped; can be 1 to 4 inches long; and can vary in color from yellowish green to coppery, bronze, or dark purple (Figure 2).

Ficus carica is a member of the Moraceae family (derived from the Latin name for the mulberry tree), which includes 53 genera and approximately 1400 species, of which about 850 belong to the genus Ficus (the Latin name for a fig tree). The term carica likely comes from the Latin word carricare (to load) to describe a tree loaded with figs. Family members include trees, shrubs, lianas, and herbs that usually contain laticifers with a milky latex.

Traditional Uses

For centuries, components of the fig tree have been used in herbal teas and pastes to treat ailments ranging from sore throats to diarrhea, though there is no evidence to support their efficacy.⁴ Ancient Indians and Egyptians used plants such as the common fig tree containing furocoumarins to induce hyperpigmentation in vitiligo.⁵

Phototoxic Components

The leaves and sap of the common fig tree contain psoralens, which are members of the furocoumarin group of chemical compounds and are the source of its phototoxicity. The fruit does not contain psoralens.^6-9 The tree also produces proteolytic enzymes such as protease, amylase, ficin, triterpenoids, and lipodiastase that enhance its phototoxic effects.⁸ Exposure to UV light between 320 and 400 nm following contact with these phototoxic components triggers a reaction in the skin over the course of 1 to 3 days.⁵ The psoralens bind in epidermal cells, cross-link the DNA, and cause cell-membrane destruction, leading to edema and necrosis.¹⁰ The delay in symptoms may be attributed to the time needed to synthesize acute-phase reaction proteins such as tumor necrosis factor α and IL-1.¹¹ In spring and summer months, an increased concentration of psoralens in the leaves and sap contribute to an increased incidence of phytophotodermatitis.⁹ Humidity and sweat also increase the percutaneous absorption of psoralens.^12,13

Allergens

Fig trees produce a latex protein that can cause cross-reactive hypersensitivity reactions in those allergic to F benjamina latex and rubber latex.⁶ The latex proteins in fig trees can act as airborne respiratory allergens. Ingestion of figs can produce anaphylactic reactions in those sensitized to rubber latex and F benjamina latex.⁷ Other plant families associated with phototoxic reactions include Rutaceae (lemon, lime, bitter orange), Apiaceae (formerly Umbelliferae)(carrot, parsnip, parsley, dill, celery, hogweed), and Fabaceae (prairie turnip).

 

 

Cutaneous Manifestations

Most cases of fig phytophotodermatitis begin with burning, pain, and/or itching within hours of sunlight exposure in areas of the skin that encountered components of the fig tree, often in a linear pattern. The affected areas become erythematous and edematous with formation of bullae and unilocular vesicles over the course of 1 to 3 days.^12,14,15 Lesions may extend beyond the region of contact with the fig tree as they spread across the skin due to sweat or friction, and pain may linger even after the lesions resolve.^12,13,16 Adults who handle fig trees (eg, pruning) are susceptible to phototoxic reactions, especially those using chain saws or other mechanisms that result in spray exposure, as the photosensitizing sap permeates the wood and bark of the entire tree.¹⁷ Similarly, children who handle fig leaves or sap during outdoor play can develop bullous eruptions. Severe cases have resulted in hospital admission after prolonged exposure.¹⁶ Additionally, irritant dermatitis may arise from contact with the trichomes or “hairs” on various parts of the plant.

Image provided with permission by Scott Norton, MD, MPH, MSc (Washington, DC).

Patients who use natural remedies containing components of the fig tree without the supervision of a medical provider put themselves at risk for unsafe or unwanted adverse effects, such as phytophotodermatitis.^12,15,16,18 An entire family presented with burns after they applied fig leaf extract to the skin prior to tanning outside in the sun.¹⁹ A 42-year-old woman acquired a severe burn covering 81% of the body surface after topically applying fig leaf tea to the skin as a tanning agent.²⁰ A subset of patients ingesting or applying fig tree components for conditions such as vitiligo, dermatitis, onychomycosis, and motor retardation developed similar cutaneous reactions.^13,14,21,22 Lesions resembling finger marks can raise concerns for potential abuse or neglect in children.²²

The differential diagnosis for fig phytophotodermatitis includes sunburn, chemical burns, drug-related photosensitivity, infectious lesions (eg, herpes simplex, bullous impetigo, Lyme disease, superficial lymphangitis), connective tissue disease (eg, systemic lupus erythematosus), contact dermatitis, and nonaccidental trauma.^12,15,18 Compared to sunburn, phytophotodermatitis tends to increase in severity over days following exposure and heals with dramatic hyperpigmentation, which also prompts visits to dermatology.¹²

Treatment

Treatment of fig phytophotodermatitis chiefly is symptomatic, including analgesia, appropriate wound care, and infection prophylaxis. Topical and systemic corticosteroids may aid in the resolution of moderate to severe reactions.^15,23,24 Even severe injuries over small areas or mild injuries to a high percentage of the total body surface area may require treatment in a burn unit. Patients should be encouraged to use mineral-based sunscreens on the affected areas to reduce the risk for hyperpigmentation. Individuals who regularly handle fig trees should use contact barriers including gloves and protective clothing (eg, long-sleeved shirts, long pants).

Plant Parts and Nomenclature

Ficus carica (common fig) is a deciduous shrub or small tree with smooth gray bark that can grow up to 10 m in height (Figure 1). It is characterized by many spreading branches, but the trunk rarely grows beyond a diameter of 7 in. Its hairy leaves are coarse on the upper side and soft underneath with 3 to 7 deep lobes that can extend up to 25 cm in length or width; the leaves grow individually, alternating along the sides of the branches. Fig trees often can be seen adorning yards, gardens, and parks, especially in tropical and subtropical climates. Ficus carica should not be confused with Ficus benjamina (weeping fig), a common ornamental tree that also is used to provide shade in hot climates, though both can cause phototoxic skin eruptions.

The common fig tree originated in the Mediterranean and western Asia¹ and has been cultivated by humans since the second and third millennia bc for its fruit, which commonly is used to sweeten cookies, cakes, and jams.² Figs are the most commonly mentioned food plant in the Bible, with at least 56 references in the Old and New Testaments.³ The “fruit” technically is a syconium—a hollow fleshy receptacle with a small opening at the apex partly closed by small scales. It can be obovoid, turbinate, or pear shaped; can be 1 to 4 inches long; and can vary in color from yellowish green to coppery, bronze, or dark purple (Figure 2).

Ficus carica is a member of the Moraceae family (derived from the Latin name for the mulberry tree), which includes 53 genera and approximately 1400 species, of which about 850 belong to the genus Ficus (the Latin name for a fig tree). The term carica likely comes from the Latin word carricare (to load) to describe a tree loaded with figs. Family members include trees, shrubs, lianas, and herbs that usually contain laticifers with a milky latex.

Traditional Uses

For centuries, components of the fig tree have been used in herbal teas and pastes to treat ailments ranging from sore throats to diarrhea, though there is no evidence to support their efficacy.⁴ Ancient Indians and Egyptians used plants such as the common fig tree containing furocoumarins to induce hyperpigmentation in vitiligo.⁵

Phototoxic Components

The leaves and sap of the common fig tree contain psoralens, which are members of the furocoumarin group of chemical compounds and are the source of its phototoxicity. The fruit does not contain psoralens.^6-9 The tree also produces proteolytic enzymes such as protease, amylase, ficin, triterpenoids, and lipodiastase that enhance its phototoxic effects.⁸ Exposure to UV light between 320 and 400 nm following contact with these phototoxic components triggers a reaction in the skin over the course of 1 to 3 days.⁵ The psoralens bind in epidermal cells, cross-link the DNA, and cause cell-membrane destruction, leading to edema and necrosis.¹⁰ The delay in symptoms may be attributed to the time needed to synthesize acute-phase reaction proteins such as tumor necrosis factor α and IL-1.¹¹ In spring and summer months, an increased concentration of psoralens in the leaves and sap contribute to an increased incidence of phytophotodermatitis.⁹ Humidity and sweat also increase the percutaneous absorption of psoralens.^12,13

Allergens

Fig trees produce a latex protein that can cause cross-reactive hypersensitivity reactions in those allergic to F benjamina latex and rubber latex.⁶ The latex proteins in fig trees can act as airborne respiratory allergens. Ingestion of figs can produce anaphylactic reactions in those sensitized to rubber latex and F benjamina latex.⁷ Other plant families associated with phototoxic reactions include Rutaceae (lemon, lime, bitter orange), Apiaceae (formerly Umbelliferae)(carrot, parsnip, parsley, dill, celery, hogweed), and Fabaceae (prairie turnip).

 

 

Cutaneous Manifestations

Most cases of fig phytophotodermatitis begin with burning, pain, and/or itching within hours of sunlight exposure in areas of the skin that encountered components of the fig tree, often in a linear pattern. The affected areas become erythematous and edematous with formation of bullae and unilocular vesicles over the course of 1 to 3 days.^12,14,15 Lesions may extend beyond the region of contact with the fig tree as they spread across the skin due to sweat or friction, and pain may linger even after the lesions resolve.^12,13,16 Adults who handle fig trees (eg, pruning) are susceptible to phototoxic reactions, especially those using chain saws or other mechanisms that result in spray exposure, as the photosensitizing sap permeates the wood and bark of the entire tree.¹⁷ Similarly, children who handle fig leaves or sap during outdoor play can develop bullous eruptions. Severe cases have resulted in hospital admission after prolonged exposure.¹⁶ Additionally, irritant dermatitis may arise from contact with the trichomes or “hairs” on various parts of the plant.

Image provided with permission by Scott Norton, MD, MPH, MSc (Washington, DC).

Patients who use natural remedies containing components of the fig tree without the supervision of a medical provider put themselves at risk for unsafe or unwanted adverse effects, such as phytophotodermatitis.^12,15,16,18 An entire family presented with burns after they applied fig leaf extract to the skin prior to tanning outside in the sun.¹⁹ A 42-year-old woman acquired a severe burn covering 81% of the body surface after topically applying fig leaf tea to the skin as a tanning agent.²⁰ A subset of patients ingesting or applying fig tree components for conditions such as vitiligo, dermatitis, onychomycosis, and motor retardation developed similar cutaneous reactions.^13,14,21,22 Lesions resembling finger marks can raise concerns for potential abuse or neglect in children.²²

The differential diagnosis for fig phytophotodermatitis includes sunburn, chemical burns, drug-related photosensitivity, infectious lesions (eg, herpes simplex, bullous impetigo, Lyme disease, superficial lymphangitis), connective tissue disease (eg, systemic lupus erythematosus), contact dermatitis, and nonaccidental trauma.^12,15,18 Compared to sunburn, phytophotodermatitis tends to increase in severity over days following exposure and heals with dramatic hyperpigmentation, which also prompts visits to dermatology.¹²

Treatment

Treatment of fig phytophotodermatitis chiefly is symptomatic, including analgesia, appropriate wound care, and infection prophylaxis. Topical and systemic corticosteroids may aid in the resolution of moderate to severe reactions.^15,23,24 Even severe injuries over small areas or mild injuries to a high percentage of the total body surface area may require treatment in a burn unit. Patients should be encouraged to use mineral-based sunscreens on the affected areas to reduce the risk for hyperpigmentation. Individuals who regularly handle fig trees should use contact barriers including gloves and protective clothing (eg, long-sleeved shirts, long pants).