Dermatology

This woman’s palpable purpura with edema in her lower extremities was consistent with cutaneous leukocytoclastic vasculitis (LCV).

LCV is characterized by the circulation of immune complexes that promote activation of complement, leading to endothelial injury and palpable purpura. Pain, arthralgia, cutaneous ulceration, and constitutional symptoms may be observed. About 50% of LCV cases are idiopathic. Identified causes include infection (including syphilis infection), drugs, malignancy, and connective tissue disease.

Systemic involvement must be ruled out in any patient with cutaneous LCV. The work-up is based on the individual patient assessment and may include a complete blood count with differential, complete metabolic panel, inflammatory markers, urinalysis, hepatitis panel, anti-nuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, cryoglobulins, serum protein electrophoresis, and serum complement. A cutaneous punch biopsy for both hematoxylin and eosin (H&E) and direct immunofluorescence (DIF) confirms the diagnosis of LCV.

For uncomplicated LCV cases without systemic involvement, treatment is generally supportive. Any identified underlying cause should be addressed. Analgesics may be considered for pain. Systemic therapy is indicated for patients with cutaneous ulceration, systemic vasculitis, or recurrent cases; this therapy may include colchicine, dapsone, corticosteroids, mycophenolate mofetil, and methotrexate.

In this patient’s case, a punch biopsy of the left lower extremity showed findings consistent with cutaneous LCV. She denied a history of intravenous drug use or initiation of new medications. Labs were notable for an elevated erythrocyte sedimentation rate, c-reactive protein, and elevated creatinine.

Incidentally, she was found to be 32-weeks pregnant, went into pre-term labor while admitted, and delivered her baby without complication.

She had a reactive treponemal antibody, with rapid plasma reagin titer of 1:128, which confirmed a diagnosis of syphilis. She was treated with 1 dose of intra-muscular penicillin G while an inpatient. Her arthralgias improved during her hospitalization without initiation of steroids or other immunomodulatory therapy. Outpatient follow-up was expected to consist of completion of 3 total doses of IM penicillin, as well as renal studies, given her elevated creatinine.

‌

Photo courtesy of Cyrelle R. Fermin, MD, and text courtesy of Cyrelle R. Fermin, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This woman’s palpable purpura with edema in her lower extremities was consistent with cutaneous leukocytoclastic vasculitis (LCV).

LCV is characterized by the circulation of immune complexes that promote activation of complement, leading to endothelial injury and palpable purpura. Pain, arthralgia, cutaneous ulceration, and constitutional symptoms may be observed. About 50% of LCV cases are idiopathic. Identified causes include infection (including syphilis infection), drugs, malignancy, and connective tissue disease.

Systemic involvement must be ruled out in any patient with cutaneous LCV. The work-up is based on the individual patient assessment and may include a complete blood count with differential, complete metabolic panel, inflammatory markers, urinalysis, hepatitis panel, anti-nuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, cryoglobulins, serum protein electrophoresis, and serum complement. A cutaneous punch biopsy for both hematoxylin and eosin (H&E) and direct immunofluorescence (DIF) confirms the diagnosis of LCV.

For uncomplicated LCV cases without systemic involvement, treatment is generally supportive. Any identified underlying cause should be addressed. Analgesics may be considered for pain. Systemic therapy is indicated for patients with cutaneous ulceration, systemic vasculitis, or recurrent cases; this therapy may include colchicine, dapsone, corticosteroids, mycophenolate mofetil, and methotrexate.

In this patient’s case, a punch biopsy of the left lower extremity showed findings consistent with cutaneous LCV. She denied a history of intravenous drug use or initiation of new medications. Labs were notable for an elevated erythrocyte sedimentation rate, c-reactive protein, and elevated creatinine.

Incidentally, she was found to be 32-weeks pregnant, went into pre-term labor while admitted, and delivered her baby without complication.

She had a reactive treponemal antibody, with rapid plasma reagin titer of 1:128, which confirmed a diagnosis of syphilis. She was treated with 1 dose of intra-muscular penicillin G while an inpatient. Her arthralgias improved during her hospitalization without initiation of steroids or other immunomodulatory therapy. Outpatient follow-up was expected to consist of completion of 3 total doses of IM penicillin, as well as renal studies, given her elevated creatinine.

‌

Photo courtesy of Cyrelle R. Fermin, MD, and text courtesy of Cyrelle R. Fermin, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This woman’s palpable purpura with edema in her lower extremities was consistent with cutaneous leukocytoclastic vasculitis (LCV).

LCV is characterized by the circulation of immune complexes that promote activation of complement, leading to endothelial injury and palpable purpura. Pain, arthralgia, cutaneous ulceration, and constitutional symptoms may be observed. About 50% of LCV cases are idiopathic. Identified causes include infection (including syphilis infection), drugs, malignancy, and connective tissue disease.

Systemic involvement must be ruled out in any patient with cutaneous LCV. The work-up is based on the individual patient assessment and may include a complete blood count with differential, complete metabolic panel, inflammatory markers, urinalysis, hepatitis panel, anti-nuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, cryoglobulins, serum protein electrophoresis, and serum complement. A cutaneous punch biopsy for both hematoxylin and eosin (H&E) and direct immunofluorescence (DIF) confirms the diagnosis of LCV.

For uncomplicated LCV cases without systemic involvement, treatment is generally supportive. Any identified underlying cause should be addressed. Analgesics may be considered for pain. Systemic therapy is indicated for patients with cutaneous ulceration, systemic vasculitis, or recurrent cases; this therapy may include colchicine, dapsone, corticosteroids, mycophenolate mofetil, and methotrexate.

In this patient’s case, a punch biopsy of the left lower extremity showed findings consistent with cutaneous LCV. She denied a history of intravenous drug use or initiation of new medications. Labs were notable for an elevated erythrocyte sedimentation rate, c-reactive protein, and elevated creatinine.

Incidentally, she was found to be 32-weeks pregnant, went into pre-term labor while admitted, and delivered her baby without complication.

She had a reactive treponemal antibody, with rapid plasma reagin titer of 1:128, which confirmed a diagnosis of syphilis. She was treated with 1 dose of intra-muscular penicillin G while an inpatient. Her arthralgias improved during her hospitalization without initiation of steroids or other immunomodulatory therapy. Outpatient follow-up was expected to consist of completion of 3 total doses of IM penicillin, as well as renal studies, given her elevated creatinine.

‌

Photo courtesy of Cyrelle R. Fermin, MD, and text courtesy of Cyrelle R. Fermin, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This man has pitted keratolysis (PK), characterized by multiple small pits on the soles of the feet. PK is often associated with hyperhidrosis and significant odor. The lesions usually have a punched-out appearance and are flesh-colored. The dark color of these lesions was due to the patient’s footwear.

PK is caused by bacterial overgrowth in the stratum corneum. Corynebacterium is the most common bacterial culprit, but Kytococcus, Actinomyces, and Dermatophilus have also been implicated. The bacterial infection is thought to be secondary to hyperhidrosis or as a result of hygiene, footwear, or other conditions that retain moisture and promote maceration of the soles of the feet. Therefore, treatment includes a 2-pronged approach: Resolve the bacterial infection and reduce excess moisture. Effective antibacterials include topical clindamycin, erythromycin, fusidic acid, and benzoyl peroxide. Oral antibiotics are not often required.

Hyperhidrosis can be treated with prescription strength 20% aluminum chloride antiperspirant applied to the feet in a tapering schedule, first daily and then 2 or 3 times weekly. Aluminum chloride is frequently not covered by insurance companies, but over-the-counter (OTC) 12% formulations (Certain DRI) usually suffice. Additionally, changing socks and using moisture-wicking shoes or socks are helpful measures to keep feet dry.

One study treated PK with topical erythromycin 3% gel twice daily, without the use of aluminum chloride antiperspirants, and found that the hyperhidrosis greatly improved. The authors theorized that the gram-positive bacterial infection upregulated eccrine sweat glands causing hyperhidrosis as a secondary, rather than the primary, cause of PK.

This patient was prescribed topical erythromycin gel twice daily for the soles of his feet. For his hyperhidrosis, he was advised to purchase OTC aluminum chloride antiperspirants to apply to his feet daily for the first week and to then decrease to 2 or 3 times per week. He was counseled to take an extra pair of socks for changing midway through his workday and to return for reevaluation if his skin did not improve.

‌

Image courtesy of Sarah Friedberg, MD, and text courtesy of Daniel Stulberg, MD, FAAFP, and Sarah Friedberg, MD, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

ANSWER

The correct answer is Grover disease (choice “c”).

DISCUSSION

Grover disease—also known as transient acantholytic dermatosis—was first described in 1975 by Ralph Grover, MD, and is now recognized as a relatively common condition, especially in White men older than 40. Its appearance on darker skin is unusual. The morphologic presentation seen in this case is fairly typical, though most patients complain more about itching than this patient did.

The actual cause of Grover disease is unknown. Heat, sweat, and sunlight are suspected triggers. Its appearance can be associated with certain medications, recent treatment with ionizing radiation, or end-stage renal failure.

Biopsy is the key to diagnosis of Grover disease, especially in the context of the clinical presentation. This method also serves to rule out the other items in the differential.

Tinea corporis (choice “a”) was ruled out by the KOH as well as the rash’s appearance. Darier disease (choice “b”)—otherwise known as keratosis follicularis—is an inherited dermatosis that presents with multiple findings on skin, nails, and mucous membranes; however, the papulosquamous rash would be far more coarse than what manifests in Grover disease, and it would have manifested at a much earlier age. While folliculitis (choice “d”) was a possibility in this patient, the biopsy ruled it out.

TREATMENT

Grover disease is notoriously difficult to treat. Although it is described as a “transient” dermatosis, it can last months to years despite all therapeutic efforts.

This patient was treated with a stronger topical steroid (0.05% betamethasone cream) twice a day and minocycline (100 mg/d) for 2 months. These cleared his rash.

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Activated circulating basophils appear to play a key role in mediating the underappreciated phenomenon of acute-on-chronic itch flares in atopic dermatitis, Brian S. Kim, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

Recent years have brought enormous progress in understanding how chronic itch in patients with atopic dermatitis (AD) is mediated by type 2 cytokines, including interleukin-13, IL-4, and IL-31, as well as by Janus kinase (JAK) signaling. This has led to development of potent therapies targeting these mediators, including dupilumab (Dupixent) and the investigational agents tralokinumab, lebrikizumab, abrocitinib, upadacitinib, baricitinib, and the IL-31 inhibitor nemolizumab.

“This is now one of the most active areas in the field of dermatology,” observed Dr. Kim, a dermatologist and codirector of the Center for the Study of Itch and Sensory Disorders at Washington University in St. Louis.

He has figured prominently in this effort. He and his coinvestigators conducted translational studies in mouse models which unraveled key mechanisms by which the immune system responsible for skin inflammation in AD communicates with the nervous system to trigger the neural sensation of itch. He also led a phase 2 randomized trial in 307 patients with AD, which demonstrated that the investigational JAK1/JAK2 inhibitor ruxolitinib cream markedly improved itch within 36 hours, well before subsequent improvement in skin inflammation – and the topical JAK inhibitor did so with minimal systemic absorption.

Compared with chronic itch, much less research attention has been devoted to the phenomenon of acute itch flares superimposed upon the chronic itch of AD. These acute-on-chronic itch flares are a common feature of the disease. In a soon-to-be-published study of 159 AD patients in the placebo arm of a clinical trial, Dr. Kim and coinvestigators found that 26% exhibited a pattern of acute itch flares during the course of a single month. During the next month, 3.1% of patients under study went from an acute-on-chronic itch pattern in month 1 to a nonflare pattern, 20% went from a nonflare pattern in month 1 to acute itch flares in month 2, and 23% of the overall study population retained their pattern of acute itch flares through both months.

“This does not seem to be just a static phenotype, but rather these patients can evolve over time. And we think that this can be driven by allergen-specific IgE,” according to Dr. Kim.

Indeed, the investigators found that patients with allergen-specific IgE in their serum were roughly twice as likely to exhibit the acute-on-chronic itch flare pattern than those without allergen-specific IgE.

The classical thinking has been that IgE binds to its receptors on mast cells, causing mast cell degranulation and release of histamine and other itch-inducing molecules. Yet antihistamines have proven notoriously ineffective for the treatment of AD.

Circulating basophils capable of working their way into inflamed skin also have IgE receptors. Dr. Kim and colleagues have shown that allergen-specific IgE in mice binds to those receptors, causing the basophils to degenerate, releasing itch-promoting chemicals. They have subsequently carried over this work into the clinical arena.

“We’ve found that patients with atopic dermatitis have significantly higher expression of receptors for IgE in their basophils than in the basophils of healthy controls, indicating perhaps that the basophils in patients with atopic dermatitis are much more prone to stimulation by allergen by way of IgE. This is a new concept that we’re exploring,” Dr. Kim said.

“We haven’t really known before what IgE does in atopic dermatitis, but it turns out that it may actually play a very important role in triggering acute flares of itch,” the dermatologist explained. “What’s been surprising is that the IgE activity is not mediated so much by mast cells, which are tissue-resident; the predominant means appears to be that IgE acts on basophils. That then creates release not of histamine, but of leukotriene C4, which is a very potent pruritogen. This may be responsible for those acute itch flares.”

Asked during an audience Q&A how allergen-specific IgE–mediated basophil activation might be targeted therapeutically in order to prevent acute-on-chronic itch flares in patients with AD, Dr. Kim mentioned two possibilities. One is treatment with potent anti-IgE agents, which to date have not been adequately tested for their antipruritic prowess in AD.

“Also, there’s another molecule that seems to be relatively basophil-selective and -specific that’s just been discovered by my colleague Xinzhong Dong at Johns Hopkins University [in Baltimore] – called MRGPRX2 – that may actually be a potentially viable way to go after basophils, maybe even by depleting them if you had an antibody against that,” Dr. Kim said. He was a coinvestigator in Dr. Dong’s recent study characterizing MRGPRX2, the mast-cell-expressed Mas-related G-protein–coupled receptor activator.

Dr. Kim reported receiving research funding from Cara Therapeutics and LEO Pharma, holding a patent for the use of JAK inhibitors in chronic itch, and serving as a consultant to numerous pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

A novel proprietary topical combination of microencapsulated 3% benzoyl peroxide and microencapsulated 0.1% tretinoin achieved its efficacy and safety endpoints in two large pivotal phase 3 clinical acne trials, James Del Rosso, MD, reported at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

olavs/Thinkstock

Sol-Gel Technologies, the Israeli company developing the fixed-dose cream, called Twyneo, has applied to the Food and Drug Administration for marketing approval.

The product combines two workhorse topical agents for the treatment of acne, which are ordinarily incompatible, since benzoyl peroxide degrades tretinoin and reduces its effectiveness. The company’s silica-based microencapsulation technology overcomes that obstacle, explained Dr. Del Rosso, a dermatologist at JDR Research in Las Vegas.

The two identical phase 3, randomized, double-blind, vehicle-controlled clinical trials included a total of 858 patients ages 9 years and older with moderate to severe acne enrolled at 63 U.S. sites. Participants were randomized 2:1 to once-daily application of Twyneo or its vehicle cream for 12 weeks.

In one trial, the coprimary endpoint of at least a two-grade reduction and clear or almost clear skin at week 12 on a 5-point Investigator Global Assessment (IGA) scale was achieved in 38.5% of patients on Twyneo and 11.5% of controls. In the other trial, the IGA success rates were 25.4% and 14.7%. In both trials, the between-group difference was statistically significant.

The other coprimary endpoints were the absolute change from baseline in inflammatory and noninflammatory lesion counts. Inflammatory lesions were reduced by 21.6% and 16.2% in the active treatment arms of the two trials, compared with 14.8% and 14.1% reductions in the control groups. Noninflammatory lesion counts fell by 29.7% and 24.2% in patients on active treatment, versus 19.8% and 17.4% reductions in controls. The between-group differences were statistically significant.

Skin tolerability of Twyneo was “very good” and similar to vehicle, according to Dr. Del Rosso.

He reported receiving research funding from Sol-Gel, the studies’ sponsor.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

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

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

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

[email protected]

The dramatic advances in targeted therapies for late-stage melanoma capture the headlines, but a recent Australian study quietly concluded that the most cost-effective way to lower both the incidence of melanoma and deaths caused by the malignancy over the long haul is through primary prevention in the form of daily sunscreen use, according to Laura Korb Ferris, MD, PhD, a dermatologist and director of clinical trials in the department of dermatology at the University of Pittsburgh.

Wavebreakmedia Ltd/Thinkstock

“I think it’s really important that we recognize the importance of preventing skin cancer, and not just early detection, not just treatment of late disease,” Dr. Ferris said at a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education.

She highlighted the Australian cost-effectiveness analysis, which used Markov modeling of data from two published population-based, randomized controlled trials carried out in Queensland, Australia.

The cost-effectiveness study compared the estimated long-term impact of three different approaches to control of melanoma: a primary prevention strategy, which basically consisted of promoting daily sunscreen use and other forms of sun protection; early detection through annual whole-body skin examinations by physicians starting at age 50; and no intervention. The analysis provided estimates of the number of cases of melanoma, deaths caused by melanoma, nonmelanoma skin cancers, and quality of life outcomes over the course of 30 years starting in 50-year-old men and women.

Primary prevention through sun protection was the clear winner, as shown by the results:

• A 44% reduction in the incidence of melanoma, compared with early detection via annual physician skin examinations.
• A 39% reduction in projected melanoma deaths compared with early detection, which in turn achieved only a 2% reduction when compared with no intervention.
• 27% fewer keratinocyte cancers excised than with annual skin examinations.
• A 21.7% reduction in societal costs, compared with an early-detection program.

Daily sunscreen use for primary prevention was also associated with a modest 0.1% increase in quality-adjusted life-years. “Prevention is low cost, low risk, and effective,” Dr. Ferris observed.

The investigators noted that, while residents of the Australian state of Queensland are mainly fair-skinned and confront high UV radiation levels throughout the year, somewhat limiting the generalizability of the study findings, the relationships between the costs of interventional strategies and their outcomes should be proportional in other countries.

True enough, but a strategy of annual skin examinations starting at age 50 years as modeled in the Australian study is not the most productive way to conduct a melanoma early-detection program, Dr. Ferris said. She noted that data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program show that the median age at diagnosis of melanoma in the United States is 65 years, while the median age at death caused by the malignancy is 71 years. That information is helpful in formulating strategies to improve early detection through more focused, higher-yield screening.

UPMC

Case in point: European investigators have estimated that, by screening everyone age 50 years and older, 475 people need to be screened and an average of 19.6 lesions must be biopsied in order to detect one melanoma. But by reserving screening for those age 50 years and up who have any one of three risk factors – a personal history of melanoma, atypical nevi, or at least 40 common nevi – those numbers drop dramatically: 98 people need to be screened and 13.5 lesions biopsied to detect one melanoma. And by further narrowing the screened population to those age 65 years or older with any of the three risk factors, 63 seniors would need to be screened and 9.2 lesions excised to find one melanoma.

Total-body skin examinations are time-consuming for dermatologists. In a recent U.S. study, investigators determined that the additional face-to-face time required per skin cancer detected by doing a total-body skin exam in adults who present to a dermatologist for another reason is 4.5 hours. And that’s just the time involved in detecting any type of skin cancer.

“To get that number for melanoma, multiply by 15 to 20,” Dr. Ferris said.

The investigators also determined that, for each decade of advancing age and increment in lighter skin phototype, the number-needed-to-examine in order to identify one skin cancer of any type decreased.

“By focusing on patients who are older and have fair skin types we can get that time down to about 1 hour,” commented Dr. Ferris, who penned an editorial perspective on the study.

While many dermatologists recommend that people with a high common nevus count undergo frequent screening for melanoma because they are at particularly high risk for invasive disease, a couple of recent studies challenge that notion, she pointed out. One was a retrospective study of 326 consecutive new melanoma patients which found that patients with a higher nevus count had thinner melanomas and a greater likelihood of in situ melanoma. Patients who presented with invasive melanoma had a mean total nevus count of 31.5 lesions, while those with in situ melanoma averaged 57.2 nevi. Each additional nevus was associated with a 4% reduction in the likelihood of invasive melanoma, independent of age and sex.

The other study included 566 newly diagnosed melanoma patients in two U.S. centers. Among the 56% of patients who were younger than 60 years, those who had more than 50 total nevi were 68% less likely to have a thick melanoma in a logistic regression analysis that controlled for demographic factors, as well as anatomic location of the melanoma, histologic subtype, and skin cancer screening frequency. In contrast, younger patients with more than 5 atypical nevi were 2.43-fold more likely to have thicker melanomas than were those with no such lesions. The lesson, according to the investigators, is that total nevus count isn’t a reliable determinant of a patient’s risk status or the need for skin examinations.

Dr. Ferris reported no financial conflicts of interest regarding her presentation.

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

[email protected]

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.

The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.

“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.

Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.

“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”

European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.

“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.

The full IPC report was published in the Journal of the American Academy of Dermatology.

The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

“We’ll have a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
 

Mild or moderate psoriasis

Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.

Pediatric studies

A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.

“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.

Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.

Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.

“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.

Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.

One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
 

Topical PDE-4 inhibitor shows promise

Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.

“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.

The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.

A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.

The phase 3 program is now recruiting participants.

Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]