Dermatology

NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

NEW YORK – Many inflammatory diseases, such as psoriasis and atopic dermatitis (AD), can present differently in patients with darker skin types, but it is the pigmentary changes themselves that are often a dominant concern for parents, according to pediatric dermatologist Candrice R. Heath, MD.

Skin diseases pose a greater risk of both hyper- and hypopigmentation in patients with darker skin types, but the fear and concern that this raises for permanent disfigurement is not limited to Blacks, Dr. Heath, assistant professor of pediatric dermatology at Temple University, Philadelphia, said at the Skin of Color Update 2023.

“Culturally, pigmentation changes can be huge. For people of Indian descent, for example, pigmentary changes like light spots on the skin might be an obstacle to marriage, so it can really be life changing,” she added.

In patients with darker skin tones presenting with an inflammatory skin disease, such as AD or psoriasis, Dr. Heath advised asking specifically about change in skin tone even if it is not readily apparent. In pediatric patients, it is also appropriate to include parents in this conversation.
 

Consider the parent’s perspective

“When you are taking care of a child or adolescent, the patient is likely to be concerned about changes in pigmentation, but it is important to remember that the adult in the room might have had their own journey with brown skin and has dealt with the burden of pigment changes,” Dr. Heath said.

For the parent, the pigmentation changes, rather than the inflammation, might be the governing issue and the reason that he or she brought the child to the clinician. Dr. Heath suggested that it is important for caregivers to explicitly recognize their concern, explain that addressing the pigmentary changes is part of the treatment plan, and to create realistic expectations about how long pigmentary changes will take to resolve.

As an example, Dr. Heath recounted a difficult case of a Black infant with disseminated hyperpigmentation and features that did not preclude pathology other than AD. Dr. Heath created a multifaceted treatment plan to address the inflammation in distinct areas of the body that included low-strength topical steroids for the face, stronger steroids for the body, and advice on scalp and skin care.

“I thought this was a great treatment plan out of the gate – I was covering all of the things on my differential list – I thought that the mom would be thinking, this doctor is amazing,” Dr. Heath said.
 

Pigmentary changes are a priority

However, that was not what the patient’s mother was thinking. Having failed to explicitly recognize her concern about the pigmentation changes and how the treatment would address this issue, the mother was disappointed.

“She had one question: Will my baby ever be one color? That was her main concern,” said Dr. Heath, indicating that other clinicians seeing inflammatory diseases in children with darker skin types can learn from her experience.

“Really, you have to acknowledge that the condition you are treating is causing the pigmentation change, and we do see that and that we have a treatment plan in place,” she said.

Because of differences in how inflammatory skin diseases present in darker skin types, there is plenty of room for a delayed diagnosis for clinicians who do not see many of these patients, according to Dr. Heath. Follicular eczema, which is common in skin of color, often presents with pruritus but differences in the appearance of the underlying disease can threaten a delay in diagnosis.

In cases of follicular eczema with itch in darker skin, the bumps look and feel like goose bumps, which “means that the eczema is really active and inflamed,” Dr. Heath said. When the skin becomes smooth and the itch dissipates, “you know that they are under great control.”

Psoriasis is often missed in children with darker skin types based on the misperception that it is rare. Although it is true that it is less common in Blacks than Whites, it is not rare, according to Dr. Heath. In inspecting the telltale erythematous plaque–like lesions, clinicians might start to consider alternative diagnoses when they do not detect the same erythematous appearance, but the reddish tone is often concealed in darker skin.

She said that predominant involvement in the head and neck and diaper area is often more common in children of color and that nail or scalp involvement, when present, is often a clue that psoriasis is the diagnosis.

Again, because many clinicians do not think immediately of psoriasis in darker skin children with lesions in the scalp, Dr. Heath advised this is another reason to include psoriasis in the differential diagnosis.

“If you have a child that has failed multiple courses of treatment for tinea capitis and they have well-demarcated plaques, it’s time to really start to think about pediatric psoriasis,” she said.
 

Restoring skin tone can be the priority

Asked to comment on Dr. Heath’s advice about the importance of acknowledging pigmentary changes associated with inflammatory skin diseases in patients of color, Jenna Lester, MD, the founding director of the Skin of Color Clinic at the University of California, San Francisco, called it an “often unspoken concern of patients.”

“Pigmentary changes that occur secondary to an inflammatory condition should be addressed and treated alongside the inciting condition,” she agreed.

Even if changes in skin color or skin tone are not a specific complaint of the patients, Dr. Lester also urged clinicians to raise the topic. If change in skin pigmentation is part of the clinical picture, this should be targeted in the treatment plan.

“In acne, for example, often times I find that patients are as worried about postinflammatory hyperpigmentation as they are about their acne,” she said, reiterating the advice provided by Dr. Heath.

Dr. Heath has financial relationships with Arcutis, Janssen, Johnson & Johnson, Lilly, and Regeneron. Dr. Lester reported no potential conflicts of interest.

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

The patient was given a diagnosis of sialadenosis (also known as sialosis), a noninflammatory, non-neoplastic enlargement of the parotid glands. It can often manifest as fatty degeneration of the parotid glands, which may be associated with underlying conditions such as hypertriglyceridemia, diabetes, and metabolic syndrome.^1-3

Ultrasonography and a subsequent computed tomography with contrast demonstrated fatty hypertrophy of the parotid glands without any concerning parotid mass or enlarged cervical lymph nodes. No abnormalities of the ductal system (eg, stricture or obstruction with stone) were noted, so sialography and sialendoscopy were not indicated.

Evaluation for inflammatory, autoimmune, and granulomatous diseases was negative, including negative anti-Ro/SSA and anti-La/SSB antibodies and negative HIV screen. However, our patient had an elevated serum triglyceride level of 589 mg/dL (reference range, < 150 mg/dL), while serum total cholesterol was within the reference range (< 200 mg/dL). (Interestingly, his triglycerides were normal a year earlier.) The patient’s A1c level was normal.

The differential diagnosis for this patient included Sjögren syndrome, abscess, viral infection (eg, mumps, HIV sialopathy), Kimura disease, sarcoidosis, masseter hypertrophy, and tumors of the parotid gland (eg, Warthin tumor and pleomorphic adenoma). Drug-induced sialadenitis was another possibility, as several drugs may be associated with salivary gland enlargement.⁴ However, no association was found for our patient.

Primary management is focused on treating the underlying disorder. The application of heat, massage, and sialagogues (eg, pilocarpine 5 mg orally tid) can be used to stimulate salivation, which may help reduce the swelling. Bilateral parotid gland swelling in patients with increased triglyceride levels often resolves after treatment of hypertriglyceridemia.^3,5 Less common modalities include botulinum neurotoxin injection, tympanic neurectomy, and parotidectomy.⁶

The treatment plan for this patient included aggressive dietary modification and increasing his current dosage of atorvastatin from 20 mg to 80 mg at bedtime. Increasing the dosage of statin was preferred over adding another agent (such as fibrates) to decrease the risk of myopathy. Fine-needle aspiration biopsy may be considered if the swelling does not resolve after correction of lipid abnormalities, which can take between 6 months and 3 years.³

‌

Photo courtesy of Faryal Tahir, MD. Text courtesy of Faryal Tahir, MD, Assistant Professor, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University, Homer Stryker, MD School of Medicine, Kalamazoo.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

The European Commission has approved lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged 12 years and older who have failed topical therapies, according to a press release from the manufacturer.

Lebrikizumab, which selectively targets interleukin-13 and inhibits its signaling pathway, will first be available in Germany, with a rollout in other European countries expected through 2024, according to Almirall, the manufacturer.

The European approval of lebrikizumab (Ebglyss) was based on data from a trio of pivotal phase 3 studies including ADvocate1 and ADvocate2, which evaluated lebrikizumab as monotherapy, and ADhere, which evaluated lebrikizumab in combination with topical corticosteroids. All three trials included adult and adolescent patients aged 12 years and older with moderate-to-severe AD.

In the two ADvocate studies, published in the New England Journal of Medicine, participants were randomized to a 250-mg injection of lebrikizumab or placebo every 2 weeks. The primary outcome was a score of clear or almost clear skin based on the Investigator’s Global Assessment with at least a 2-point reduction from baseline to 16 weeks. 

Compared with placebo, lebrikizumab showed significant clinical efficacy in both studies. In study 1, 43.1% of 283 patients treated with lebrikizumab versus 12.7% of 141 patients on placebo met the primary endpoint (P < .001), as did 33.2% of the 281 patients on lebrikizumab and 10.8% of 146 patients on placebo in study 2 (P < .001). In addition, 58.8% and 52.1% of patients on lebrikizumab in studies 1 and 2, respectively, met the secondary endpoint of a 75% reduction in the Eczema Area and Severity Index score (EASI-75), versus 16.2% and 18.1% of patients on placebo in study 1 and 2, respectively (P < .001 for both).

In the ADhere study, published in JAMA Dermatology, 41.2% of patients receiving a lebrikizumab/corticosteroid combination and 22.1% of those randomized to a placebo/corticosteroid combination met the primary endpoint of IGA scores of 0 or 1 at 16 weeks, and nearly 70% patients treated with a combination of lebrikizumab and topical corticosteroids achieved EASI-75, compared with 42% of those on the combination.

Nearly 80% of patients who responded at 16 weeks and continued treatment with lebrikizumab as monotherapy or combination therapy showed sustained results up to 52 weeks with maintenance monthly dosing, according to the Almirall press release.

Most adverse events across the studies were mild or moderate and were not associated with treatment discontinuation. The most common adverse reactions were conjunctivitis, injection site reactions, allergic conjunctivitis, and dry eye.

Further research has shown showed clinical efficacy and safety in patients who used lebrikizumab for up to 2 years, either as monotherapy or in combination with topical corticosteroids, according to the manufacturer.

Lebrikizumab remains under review in the United States after the Food and Drug Administration issued a complete response letter in October regarding findings made during an inspection of a third-party contract manufacturer that included the “monoclonal antibody drug substance” for lebrikizumab, although no concerns about clinical data or safety were raised, Eli Lilly announced in October. Eli Lilly has the rights to develop lebrikizumab in the United States and the rest of the world excluding Europe.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

A 40-year-old women is evaluated for liver abnormalities. She had elevated transaminases and alkaline phosphatase. A liver ultrasound showed multiple lesions. She underwent liver biopsy, which showed granulomas. What test results, if abnormal, would be most suggestive of sarcoidosis?

A. Erythrocyte sedimentation rate

B. C-reactive protein

C. Lymphocyte count

D. Antinuclear antibodies

The correct answer here is lymphocyte count. Sarcoidosis is in just about every differential diagnosis, as it can involve every organ system. I will share with you a few pearls I have learned over 30 years of taking care of patients with sarcoidosis. Lymphocyte counts drop with active sarcoidosis. Sarcoidosis should always be part of the differential when you see lymphopenia. El Jammal et al. studied 90 patients referred for possible granulomatous hepatitis.¹ Seventy-three patients had a final diagnosis of granulomatous hepatitis, and 38 of those patients had sarcoidosis. Lymphopenia had a high specificity (85.7%) for the diagnosis of sarcoidosis, with a specificity of 100% in the patients under 50 years old.

Morell and colleagues looked at whether low lymphocyte counts and low lymphocyte percentage were markers of active sarcoidosis.² Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. A low lymphocyte count and a low lymphocyte percentage (< 20%) were detected more frequently in patients with active sarcoidosis than in the patients with asymptomatic sarcoidosis (P < .02 and P < .0001).

Jones et al. looked at lymphopenia as a marker of sarcoidosis in patients presenting with uveitis.³ The study was a retrospective case-control study (112 patients with sarcoidosis-associated uveitis and 398 controls with other forms of uveitis). The mean lymphocyte count for patients with sarcoidosis was 1.43 vs. 2.04 for other causes of uveitis (P ≤ .0001).

Patients with sarcoidosis are at risk of hypercalciuria, hypercalcemia, and kidney stones. These are common in patients with sarcoidosis, with up to 50% of such patients having hypercalciuria. This is because in sarcoidosis patients 25(OH) vitamin D is converted in granulomas by activated macrophages to 1,25(OH)₂ vitamin D, which is the active form of vitamin D.

Several studies have looked at the diagnostic utility of 1,25(OH)₂ vitamin D levels in patients with suspected sarcoidosis. Rohmer and colleagues looked at whether 1,25(OH)₂ vitamin D levels could help with the diagnosis of sarcoidosis as the cause of uveitis.⁴ They found that the level of 25(OH) vitamin D in sarcoidosis patients with uveitis was lower than in patients with uveitis without sarcoidosis, 34 vs. 43 nmol/mL (P < .02), whereas the 1,25(OH)₂ vitamin D level was higher in patients with sarcoidosis than in those with uveitis without sarcoidosis, 132 vs. 108 pmol/L (P = .02). They looked at the 1,25(OH)₂D/25(OH)D ratio; a ratio > 3.5 was strongly associated with an abnormal chest CT-scan (OR = 5.7, P = .003) and granulomas on bronchial biopsy (OR = 14.7, P = .007).

Kavathia et al. looked at whether elevated 1,25(OH)₂ vitamin D levels predicted chronicity of sarcoidosis.⁵ A total of 59 sarcoidosis patients were recruited for the study. Higher serum 1,25(OH)₂ vitamin D levels were associated with patients requiring repeated systemic immunosuppressive therapy or > 1 year of therapy. Increasing quartiles of serum 1,25(OH)₂ vitamin D level were associated with increased odds of patients having chronic sarcoidosis (OR = 1.82; 95% CI, 1.11-2.99, P = .019).

Because of the higher activated vitamin D levels in sarcoidosis patients, they are at risk for problems with vitamin D supplementation. I have seen two patients develop large numbers of kidney stones after receiving high-dose vitamin D. Sodhi and Aldrich reported on a cohort of 196 sarcoidosis patients who had received vitamin D and compared them with 196 control patients with sarcoidosis who were not receiving vitamin D.⁶ Hypercalcemia was more frequent in the group that received vitamin D (42.3%) than in the group that did not (18.3%, P < .0001). In this study, only a minority (23%) of patients receiving vitamin D had their 1,25(OH)₂ vitamin D level checked.


Pearl: Lymphocyte count and 1,25(OH)₂ vitamin D levels can be helpful tests in assessing sarcoidosis activity. Patients with sarcoidosis who receive vitamin D should have their 1.25(OH)₂ vitamin D levels monitored.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. El Jammal et al. Sarcoidosis Vasc Diffuse Lung Dis. 2023 Sep 13;40(3):e2023031.

2. Morell F et al. Chest. 2002 Apr;121(4):1239-44.

3. Jones NP et al. Br J Ophthalmol. 2016 Oct;100(10):1393-6.

4. Rohmer J et al. Ocul Immunol Inflamm. 2020 Apr 2;28(3):341-7.

5. Kavathia D et al. Respir Med. 2010 Apr;104(4):564–70.

6. Sodhi A and Aldrich T. Am J Med Sci. 2016 Sep;352(3):252-7.

TOPLINE:

Lower-extremity (LE) lymphedema increases the risk for all types of skin cancer on the lower extremities.

METHODOLOGY:

• In the retrospective cohort study, researchers reviewed reports at Mayo Clinic for all patients who had LE lymphedema, limiting the review to those who had an ICD code for lymphedema.
• 4,437 patients with the ICD code from 2000 to 2020 were compared with 4,437 matched controls.
• The records of patients with skin cancer diagnoses were reviewed manually to determine whether the skin cancer, its management, or both were a cause of lymphedema; cancers that caused secondary lymphedema were excluded.
• This is the first large-scale study evaluating the association between LE lymphedema and LE skin cancer.

TAKEAWAY:

• 211 patients (4.6%) in the LE lymphedema group had any ICD code for LE skin cancer, compared with 89 (2%) in the control group.
• Among those with LE lymphedema, the risk for skin cancer was 1.98 times greater compared with those without lymphedema (95% confidence interval, 1.43-2.74; P < .001). Cases included all types of skin cancer.
• Nineteen of 24 patients with unilateral LE lymphedema had a history of immunosuppression.
• In the group of 24 patients with unilateral LE lymphedema, the lymphedematous LE was more likely to have one or more skin cancers than were the unaffected LE (87.5% vs. 33.3%; P < .05), and skin cancer was 2.65 times more likely to develop on the affected LE than in the unaffected LE (95% CI, 1.17-5.99; P = .02).

IN PRACTICE:

“Our findings suggest the need for a relatively high degree of suspicion of skin cancer at sites with lymphedema,” senior author, Afsaneh Alavi, MD, professor of dermatology at the Mayo Clinic, said in a Mayo Clinic press release reporting the results.

SOURCE:

The study was conducted by researchers at the Mayo Clinic and Meharry Medical College, Nashville. It was published in the November 2023 Mayo Clinic Proceedings.

LIMITATIONS:

This was a single-center retrospective study, and patients with LE lymphedema may be overdiagnosed with LE skin cancer because they have a greater number of examinations.

DISCLOSURES:

Dr. Alavi reports having been a consultant for AbbVie, Boehringer Ingelheim, InflaRx, Novartis, and UCB SA and an investigator for Processa Pharmaceuticals and Boehringer Ingelheim. The other authors had no disclosures.

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

TOPLINE:

Lower-extremity (LE) lymphedema increases the risk for all types of skin cancer on the lower extremities.

METHODOLOGY:

• In the retrospective cohort study, researchers reviewed reports at Mayo Clinic for all patients who had LE lymphedema, limiting the review to those who had an ICD code for lymphedema.
• 4,437 patients with the ICD code from 2000 to 2020 were compared with 4,437 matched controls.
• The records of patients with skin cancer diagnoses were reviewed manually to determine whether the skin cancer, its management, or both were a cause of lymphedema; cancers that caused secondary lymphedema were excluded.
• This is the first large-scale study evaluating the association between LE lymphedema and LE skin cancer.

TAKEAWAY:

• 211 patients (4.6%) in the LE lymphedema group had any ICD code for LE skin cancer, compared with 89 (2%) in the control group.
• Among those with LE lymphedema, the risk for skin cancer was 1.98 times greater compared with those without lymphedema (95% confidence interval, 1.43-2.74; P < .001). Cases included all types of skin cancer.
• Nineteen of 24 patients with unilateral LE lymphedema had a history of immunosuppression.
• In the group of 24 patients with unilateral LE lymphedema, the lymphedematous LE was more likely to have one or more skin cancers than were the unaffected LE (87.5% vs. 33.3%; P < .05), and skin cancer was 2.65 times more likely to develop on the affected LE than in the unaffected LE (95% CI, 1.17-5.99; P = .02).

IN PRACTICE:

“Our findings suggest the need for a relatively high degree of suspicion of skin cancer at sites with lymphedema,” senior author, Afsaneh Alavi, MD, professor of dermatology at the Mayo Clinic, said in a Mayo Clinic press release reporting the results.

SOURCE:

The study was conducted by researchers at the Mayo Clinic and Meharry Medical College, Nashville. It was published in the November 2023 Mayo Clinic Proceedings.

LIMITATIONS:

This was a single-center retrospective study, and patients with LE lymphedema may be overdiagnosed with LE skin cancer because they have a greater number of examinations.

DISCLOSURES:

Dr. Alavi reports having been a consultant for AbbVie, Boehringer Ingelheim, InflaRx, Novartis, and UCB SA and an investigator for Processa Pharmaceuticals and Boehringer Ingelheim. The other authors had no disclosures.

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

TOPLINE:

Lower-extremity (LE) lymphedema increases the risk for all types of skin cancer on the lower extremities.

METHODOLOGY:

• In the retrospective cohort study, researchers reviewed reports at Mayo Clinic for all patients who had LE lymphedema, limiting the review to those who had an ICD code for lymphedema.
• 4,437 patients with the ICD code from 2000 to 2020 were compared with 4,437 matched controls.
• The records of patients with skin cancer diagnoses were reviewed manually to determine whether the skin cancer, its management, or both were a cause of lymphedema; cancers that caused secondary lymphedema were excluded.
• This is the first large-scale study evaluating the association between LE lymphedema and LE skin cancer.

TAKEAWAY:

• 211 patients (4.6%) in the LE lymphedema group had any ICD code for LE skin cancer, compared with 89 (2%) in the control group.
• Among those with LE lymphedema, the risk for skin cancer was 1.98 times greater compared with those without lymphedema (95% confidence interval, 1.43-2.74; P < .001). Cases included all types of skin cancer.
• Nineteen of 24 patients with unilateral LE lymphedema had a history of immunosuppression.
• In the group of 24 patients with unilateral LE lymphedema, the lymphedematous LE was more likely to have one or more skin cancers than were the unaffected LE (87.5% vs. 33.3%; P < .05), and skin cancer was 2.65 times more likely to develop on the affected LE than in the unaffected LE (95% CI, 1.17-5.99; P = .02).

IN PRACTICE:

“Our findings suggest the need for a relatively high degree of suspicion of skin cancer at sites with lymphedema,” senior author, Afsaneh Alavi, MD, professor of dermatology at the Mayo Clinic, said in a Mayo Clinic press release reporting the results.

SOURCE:

The study was conducted by researchers at the Mayo Clinic and Meharry Medical College, Nashville. It was published in the November 2023 Mayo Clinic Proceedings.

LIMITATIONS:

This was a single-center retrospective study, and patients with LE lymphedema may be overdiagnosed with LE skin cancer because they have a greater number of examinations.

DISCLOSURES:

Dr. Alavi reports having been a consultant for AbbVie, Boehringer Ingelheim, InflaRx, Novartis, and UCB SA and an investigator for Processa Pharmaceuticals and Boehringer Ingelheim. The other authors had no disclosures.

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

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

SAN DIEGO – Continuing a tumor necrosis factor inhibitor (TNFi) during pregnancy does not increase risk of worse fetal or obstetric outcomes, according to new research presented at the annual meeting of the American College of Rheumatology.

Patients who continued a TNFi also had fewer severe infections requiring hospitalization, compared with those who stopped taking the medication during their pregnancy.

Lucy Hicks/Medscape Medical News

“The main message is that patients continuing were not doing worse than the patients stopping. It’s an important clinical message for rheumatologists who are not really confident in dealing with these drugs during pregnancy,” said Anna Moltó, MD, PhD, a rheumatologist at Cochin Hospital, Paris, who led the research. “It adds to the data that it seems to be safe,” she added in an interview.

Previous research, largely from pregnant patients with inflammatory bowel disease, suggests that taking a TNFi during pregnancy is safe, and 2020 ACR guidelines conditionally recommend continuing therapy prior to and during pregnancy; however, many people still stop taking the drugs during pregnancy for fear of potentially harming the fetus.

To better understand how TNFi use affected pregnancy outcomes, Dr. Moltó and colleagues analyzed data from a French nationwide health insurance database to identify adult women with chronic rheumatic inflammatory disease. All women included in the cohort had a singleton pregnancy between 2008 and 2017 and were taking a TNFi upon pregnancy diagnosis.

Patients who restarted TNFi after initially pausing because of pregnancy were included in the continuation group.

Researchers identified more than 2,000 pregnancies, including 1,503 in individuals with spondyloarthritis and 579 individuals with rheumatoid arthritis. Patients were, on average, 31 years old and were diagnosed with a rheumatic disease 4 years prior to their pregnancy.

About 72% (n = 1,497) discontinued TNFi after learning they were pregnant, and 584 individuals continued treatment. Dr. Moltó noted that data from more recent years might have captured lower discontinuation rates among pregnant individuals, but those data were not available for the study.

There was no difference in unfavorable obstetrical or infant outcomes, including spontaneous abortion, preeclampsia, gestational diabetes, major congenital malformation, and severe infection of the infant requiring hospitalization. Somewhat surprisingly, the data showed that women who discontinued a TNFi were more likely to be hospitalized for infection either during their pregnancy or up to 6 weeks after delivery, compared with those who continued therapy (1.3% vs. 0.2%, respectively).

Dr. Moltó is currently looking into what could be behind this counterintuitive result, but she hypothesizes that patients who had stopped TNFi may have been taking more glucocorticoids.

“At our institution, there is generally a comfort level with continuing TNF inhibitors during pregnancy, at least until about 36 weeks,” said Sara K. Tedeschi, MD, MPH, a rheumatologist at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Sometimes, there is concern for risk of infection to the infant, depending on the type of TNFi being used, she added during a press conference.

“I think that these are really informative and supportive data to let women know that they probably have a really good chance of doing very well during the pregnancy if they continue” their TNFi, said Dr. Tedeschi, who was not involved with the study.
 

TNF discontinuation on the decline

In a related study, researchers at McGill University, Montreal, found that TNFi discontinuation prior to pregnancy had decreased over time in individuals with chronic inflammatory diseases.

Using a database of U.S. insurance claims, they identified 3,372 women with RA, ankylosing spondylitis (AS), psoriasis/psoriatic arthritis (PsA), and/or inflammatory bowel disease (IBD) who previously used a TNFi and gave birth between 2011 and 2019. A patient was considered to have used a TNFi if she had filled a prescription or had an infusion procedure insurance claim within 12 weeks before the gestational period or anytime during pregnancy. Researchers did not have time-specific data to account for women who stopped treatment at pregnancy diagnosis.

Nearly half (47%) of all identified pregnancies were in individuals with IBD, and the rest included patients with RA (24%), psoriasis or PsA (16%), AS (3%), or more than one diagnosis (10%).

In total, 14% of women discontinued TNFi use in the 12 weeks before becoming pregnant and did not restart. From 2011 to 2013, 19% of patients stopped their TNFi, but this proportion decreased overtime, with 10% of patients stopping therapy from 2017 to 2019 (P < .0001).

Lucy Hicks/Medscape Medical News

This decline “possibly reflects the increase in real-world evidence about the safety of TNFi in pregnancy. That research, in turn, led to new guidelines recommending the continuation of TNFi during pregnancy,” first author Leah Flatman, a PhD candidate in epidemiology at McGill, said in an interview. “I think we can see this potentially as good news.”

More patients with RA, psoriasis/PsA, and AS discontinued TNFi therapy prior to conception (23%-25%), compared with those with IBD (5%).

Ms. Flatman noted that her study and Moltó’s study complement each other by providing data on individuals stopping TNFi prior to conception versus those stopping treatment after pregnancy diagnosis.

“These findings demonstrate that continuing TNFi during pregnancy appears not to be associated with an increase in adverse obstetrical or infant outcomes,” Ms. Flatman said of Dr. Moltó’s study. “As guidelines currently recommend continuing TNFi, studies like this help demonstrate that the guideline changes do not appear to be associated with an increase in adverse events.”

Dr. Moltó and Ms. Flatman disclosed no relevant financial relationships. Dr. Tedeschi has worked as a consultant for Novartis.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

These skin findings were the latest manifestation of a condition that the patient had been diagnosed with at age 32: basal cell nevus syndrome (BCNS), also called Gorlin syndrome. This syndrome is characterized by multiple biopsy-proven BCCs, palmar pitting, frontal bossing, scoliosis, and gum cysts. This patient had had gum cysts since she was 8 years old; her sister and mother had similar gum cysts and her mother had at least 1 BCC. BCNS is caused by an inheritable defect in the Patched 1 (PTCH1) gene, leading to various findings—including numerous BCCs at a young age.¹

The Oncology team started the patient on the oral small-molecule chemotherapy agent vismodegib, 150 mg/d. The patient was also referred to Medical Genetics and Wound Care. Although her diagnosis had been made clinically years earlier, genetic testing was performed and confirmed a defect in the PTCH1 gene. This helped with surveillance plans. A computed tomography scan of the head revealed a nasal dermoid cyst of the ethmoid sinus that the Ear, Nose, & Throat and Neurology teams felt safe to observe.

After 3 months of therapy with vismodegib, the patient had significant improvement of facial lesions and significant re-epithelialization of the crown.

Patients on vismodegib often deal with adverse effects, but adjusted dosing regimens have proved to improve tolerability. This patient had substantial adverse effects including fatigue, hair loss, loss of taste, and weight loss (26 lbs). Because of these adverse effects, her regimen was adjusted to 1 month of every other day active treatment and 2 months off treatment, cycled continuously. With this regimen, her weight returned to normal and her sense of taste returned for most days in the treatment cycle.

She has been tolerating this regimen for 3 years with continued control of BCCs.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.

When topical treatment does not control atopic dermatitis (AD) in adults, a range of advanced treatments may improve outcomes and can be considered, according to new evidence-based guidelines from the American Academy of Dermatology (AAD)..

The guidelines cover approved and off-label uses of systemic therapies and phototherapy, including new treatments that have become available since the last guidelines were published almost a decade ago. These include biologics and oral Janus kinase (JAK) inhibitors, as well as older oral or injectable immunomodulators and antimetabolites, oral antibiotics, antihistamines, and phosphodiesterase-4 inhibitors. The guidelines rate the existing evidence as “strong” for dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. They also conditionally recommend phototherapy, as well as cyclosporine, methotrexate, azathioprine, and mycophenolate, but recommend against the use of systemic corticosteroids.

The guidelines update the AAD’s 2014 recommendations for managing AD in adults with phototherapy and systemic therapies. “At that time, prednisone – universally agreed to be the least appropriate chronic therapy for AD – was the only Food and Drug Administration–approved agent,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the guidelines, told this news organization. “This was the driver.”

The latest guidelines were published online in the Journal of the American Academy of Dermatology.
 

Broad evidence review

Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at the Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic evidence review of phototherapy such as narrowband and broadband UVB and systemic therapies, including biologics such as dupilumab and tralokinumab, JAK inhibitors such as upadacitinib and abrocitinib, and immunosuppressants such as methotrexate and azathioprine.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

Recommendations, future studies

Of the 11 evidence-based recommendations of therapies for adults with AD refractory to topical medications, the work group ranks 5 as “strong” based on the evidence and the rest as “conditional.” “Strong” implies the benefits clearly outweigh risks and burdens, they apply to most patients in most circumstances, and they fall under good clinical practice. “Conditional” means the benefits and risks are closely balanced for most patients, “but the appropriate action may different depending on the patient or other stakeholder values,” the authors wrote.

In their remarks about phototherapy, the work group noted that most published literature on the topic “reports on the efficacy and safety of narrow band UVB. Wherever possible, use a light source that minimizes the potential for harm under the supervision of a qualified clinician.”

In their remarks about cyclosporine, they noted that evidence suggests an initial dose of 3 mg/kg per day to 5 mg/kg per day is effective, but that the Food and Drug Administration has not approved cyclosporine for use in AD. “The FDA has approved limited-term use (up to 1 year) in psoriasis,” they wrote. “Comorbidities or drug interactions that may exacerbate toxicity make this intervention inappropriate for select patients.” The work group noted that significant research gaps remain in phototherapy, especially trials that compare different phototherapy modalities and those that compare phototherapy with other AD treatment strategies.

“Larger clinical trials would also be helpful for cyclosporine, methotrexate, azathioprine, and mycophenolate to improve the certainty of evidence for those medications,” they added. “Furthermore, formal cost-effectiveness analyses comparing older to newer treatments are needed.”

They recommended the inclusion of active comparator arms in randomized, controlled trials as new systemic therapies continue to be developed and tested.

The work group ranked the level of evidence they reviewed for the therapies from very low to moderate. No therapy was judged to have high evidence. They also cited the short duration of most randomized controlled trials of phototherapy.

Using the guidelines in clinical care

According to Dr. Davis, the topic of which agent if any should be considered “first line” generated robust discussion among the work group members.

“When there are not robust head-to-head trials – and there are not – it is often opinion that governs this decision, and opinion should not, when possible, govern a guideline,” Dr. Davis said. “Accordingly, we determined based upon the evidence agents – plural – that deserve to be considered ‘first line’ but not a single agent.”

In her opinion, the top three considerations regarding use of systemic therapy for AD relate to patient selection and shared decision making. One, standard therapy has failed. Two, diagnosis is assured. And three, “steroid phobia should be considered,” and patients should be “fully informed of risks and benefits of both treating and not treating,” she said.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Micreos. Dr. Davis reported having no relevant disclosures. Other work group members reported having financial disclosures with many pharmaceutical companies. The study was supported by internal funds from the American Academy of Dermatology.