Dermatology

Examination revealed diffusely bordered periumbilical pink to violet scaly plaques consistent with nickel allergic contact dermatitis (Ni-ACD). The patient was wearing a belt with a buckle containing nickel, which had begun dispersing nickel. Her earlobes were also pierced and had similar scale and erythema around the metal earring studs

Ni-ACD is the most common, delayed-type hypersensitivity reaction worldwide. It affects 10% of people in the United States with a strong female predominance and a 4-fold increase in the last 30 years.¹ The induction of nickel delayed-type hypersensitivity has been well-studied and includes nickel corrosion dissolving into a solution and exceeding an immunogenic threshold. Piercing practices, sweat, and friction facilitate this process.

Gold jewelry that’s less than 24 karat, “white gold,” and stainless steel all contain nickel and may cause allergy in sensitized individuals. It’s wise to assume that any shiny metal fashion accessory contains nickel, unless proven otherwise. Items can be tested for the presence of nickel with an inexpensive kit containing dimethylglyoxime.

Symptoms of Ni-ACD may range from mild erythema to thickened and weepy lichenified plaques. Distribution is often present at the site of exposure but may also be seen on the eyelids or hands from nickel transfer. A systematized reaction or id reaction is uncommon but can occur. Allergic contact dermatitis can be distinguished from psoriasis by a fading border rather than a sharp, well-demarcated border.

The patient in this case switched to a nonmetallic belt and earrings with plastic studs. She was prescribed topical triamcinolone cream 0.1% bid for 3 weeks, which led to clearance of her rash.

‌

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

Examination revealed diffusely bordered periumbilical pink to violet scaly plaques consistent with nickel allergic contact dermatitis (Ni-ACD). The patient was wearing a belt with a buckle containing nickel, which had begun dispersing nickel. Her earlobes were also pierced and had similar scale and erythema around the metal earring studs

Ni-ACD is the most common, delayed-type hypersensitivity reaction worldwide. It affects 10% of people in the United States with a strong female predominance and a 4-fold increase in the last 30 years.¹ The induction of nickel delayed-type hypersensitivity has been well-studied and includes nickel corrosion dissolving into a solution and exceeding an immunogenic threshold. Piercing practices, sweat, and friction facilitate this process.

Gold jewelry that’s less than 24 karat, “white gold,” and stainless steel all contain nickel and may cause allergy in sensitized individuals. It’s wise to assume that any shiny metal fashion accessory contains nickel, unless proven otherwise. Items can be tested for the presence of nickel with an inexpensive kit containing dimethylglyoxime.

Symptoms of Ni-ACD may range from mild erythema to thickened and weepy lichenified plaques. Distribution is often present at the site of exposure but may also be seen on the eyelids or hands from nickel transfer. A systematized reaction or id reaction is uncommon but can occur. Allergic contact dermatitis can be distinguished from psoriasis by a fading border rather than a sharp, well-demarcated border.

The patient in this case switched to a nonmetallic belt and earrings with plastic studs. She was prescribed topical triamcinolone cream 0.1% bid for 3 weeks, which led to clearance of her rash.

‌

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

Examination revealed diffusely bordered periumbilical pink to violet scaly plaques consistent with nickel allergic contact dermatitis (Ni-ACD). The patient was wearing a belt with a buckle containing nickel, which had begun dispersing nickel. Her earlobes were also pierced and had similar scale and erythema around the metal earring studs

Ni-ACD is the most common, delayed-type hypersensitivity reaction worldwide. It affects 10% of people in the United States with a strong female predominance and a 4-fold increase in the last 30 years.¹ The induction of nickel delayed-type hypersensitivity has been well-studied and includes nickel corrosion dissolving into a solution and exceeding an immunogenic threshold. Piercing practices, sweat, and friction facilitate this process.

Gold jewelry that’s less than 24 karat, “white gold,” and stainless steel all contain nickel and may cause allergy in sensitized individuals. It’s wise to assume that any shiny metal fashion accessory contains nickel, unless proven otherwise. Items can be tested for the presence of nickel with an inexpensive kit containing dimethylglyoxime.

Symptoms of Ni-ACD may range from mild erythema to thickened and weepy lichenified plaques. Distribution is often present at the site of exposure but may also be seen on the eyelids or hands from nickel transfer. A systematized reaction or id reaction is uncommon but can occur. Allergic contact dermatitis can be distinguished from psoriasis by a fading border rather than a sharp, well-demarcated border.

The patient in this case switched to a nonmetallic belt and earrings with plastic studs. She was prescribed topical triamcinolone cream 0.1% bid for 3 weeks, which led to clearance of her rash.

‌

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

Additional history from the family revealed that they were cleaning the wound with copious amounts of hydrogen peroxide twice a week—a practice that impedes wound healing and was ultimately the cause of this patient’s wound closure delay.

A nonhealing wound should be carefully evaluated to rule out malignancy, infection, or an inflammatory disorder such as pyoderma gangrenosum (PG). In this case, punch biopsies were performed to exclude PG and malignancy, particularly squamous cell carcinoma. Additionally, punch biopsies were performed for bacterial and fungal tissue culture. A complete blood count with differential was obtained to evaluate for signs of infection or hematologic malignancy. All work-ups and biopsies were consistent with a noninfected surgical wound.

Widely available over the counter in 3% to 5% solutions, hydrogen peroxide is used as a low-cost antiseptic for minor cuts and wounds. Data are mixed as to whether hydrogen peroxide improves or impedes wound healing when used outside of initial first aid or postoperatively.¹ At higher concentrations, it uniformly causes skin necrosis. Owing to its debriding effect, it is FDA approved to treat seborrheic keratoses as an alternative to cryotherapy or electrodessication and curettage.

At the time of this work-up, and in the absence of other signs of infection, the patient and family were told to stop using hydrogen peroxide. Care instructions were changed to daily topical petroleum jelly and wound occlusion. Four weeks after wound care changes were made, the wound had re-epithelialized completely and reduced in size by two-thirds.

‌

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

Additional history from the family revealed that they were cleaning the wound with copious amounts of hydrogen peroxide twice a week—a practice that impedes wound healing and was ultimately the cause of this patient’s wound closure delay.

A nonhealing wound should be carefully evaluated to rule out malignancy, infection, or an inflammatory disorder such as pyoderma gangrenosum (PG). In this case, punch biopsies were performed to exclude PG and malignancy, particularly squamous cell carcinoma. Additionally, punch biopsies were performed for bacterial and fungal tissue culture. A complete blood count with differential was obtained to evaluate for signs of infection or hematologic malignancy. All work-ups and biopsies were consistent with a noninfected surgical wound.

Widely available over the counter in 3% to 5% solutions, hydrogen peroxide is used as a low-cost antiseptic for minor cuts and wounds. Data are mixed as to whether hydrogen peroxide improves or impedes wound healing when used outside of initial first aid or postoperatively.¹ At higher concentrations, it uniformly causes skin necrosis. Owing to its debriding effect, it is FDA approved to treat seborrheic keratoses as an alternative to cryotherapy or electrodessication and curettage.

At the time of this work-up, and in the absence of other signs of infection, the patient and family were told to stop using hydrogen peroxide. Care instructions were changed to daily topical petroleum jelly and wound occlusion. Four weeks after wound care changes were made, the wound had re-epithelialized completely and reduced in size by two-thirds.

‌

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

Additional history from the family revealed that they were cleaning the wound with copious amounts of hydrogen peroxide twice a week—a practice that impedes wound healing and was ultimately the cause of this patient’s wound closure delay.

A nonhealing wound should be carefully evaluated to rule out malignancy, infection, or an inflammatory disorder such as pyoderma gangrenosum (PG). In this case, punch biopsies were performed to exclude PG and malignancy, particularly squamous cell carcinoma. Additionally, punch biopsies were performed for bacterial and fungal tissue culture. A complete blood count with differential was obtained to evaluate for signs of infection or hematologic malignancy. All work-ups and biopsies were consistent with a noninfected surgical wound.

Widely available over the counter in 3% to 5% solutions, hydrogen peroxide is used as a low-cost antiseptic for minor cuts and wounds. Data are mixed as to whether hydrogen peroxide improves or impedes wound healing when used outside of initial first aid or postoperatively.¹ At higher concentrations, it uniformly causes skin necrosis. Owing to its debriding effect, it is FDA approved to treat seborrheic keratoses as an alternative to cryotherapy or electrodessication and curettage.

At the time of this work-up, and in the absence of other signs of infection, the patient and family were told to stop using hydrogen peroxide. Care instructions were changed to daily topical petroleum jelly and wound occlusion. Four weeks after wound care changes were made, the wound had re-epithelialized completely and reduced in size by two-thirds.

‌

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

A 17-year-old high school baseball player presented to a sports medicine clinic for left anterior knee pain. During the exam, a hyperpigmented lesion was incidentally noted on his left palm. The patient, who also played basketball and football, was unsure of how long he’d had the lesion, and he did not recall having any prior lesions on his hand. He denied any discomfort or significant past medical history. There was no known family history of skin cancers, but the patient did report that his brother, also an athlete, had a similar lesion on his hand.

On closer examination, scattered black dots were noted within a 2 × 1–cm thickened keratotic plaque at the hypothenar eminence of the patient’s left hand (Figure). There was no tenderness, erythema, warmth, or disruption of normal skin architecture or drainage.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Posttraumatic tache noir (also known as talon noir on the volar aspect of the feet) is a subcorneal hematoma. The diagnosis is made clinically.

Identifying “pebbles on a ridge” or “satellite globules” during dermoscopic evaluation can differentiate benign from malignant sources of this type of lesion.

Our patient was a competitive baseball player, and he noted that the knob of his baseball bat rubbed the hypothenar eminence of his nondominant hand when he took a swing. The sheer force of the knob led to the subcorneal hematoma. Tache noir was high on the differential due to the author’s clinical experience with similar cases.

Tache noir occurs predominantly in people ages 12 to 24 years, without regard to gender.¹ The condition is commonly found in athletes who participate in baseball, cricket, racquet sports, weightlifting, and rock climbing.^1-3 Talon noir occurs most commonly in athletes who are frequently jumping, turning, and pivoting, as in football, basketball, tennis, and lacrosse. One should have a high index of suspicion for this diagnosis in patients who participate in any sport that might lead to shearing forces involving the volar aspect of the hands or feet.

Confirmation is obtained through a simple procedure. Dermoscopic evaluation of tache/talon noir will reveal “pebbles on a ridge” or “satellite globules.” Confirmation of tache/talon noir can be made by paring the corneum with a #15 blade, which will reveal blood in the shavings and punctate lesions.⁴

Other lesions may havea similar appearance

Tache noir can be differentiated from other conditions by the presence of preserved architecture of the skin surface and punctate capillaries beneath the stratum corneum. The differential diagnosis includes verruca vulgaris, acral melanoma, and a traumatic tattoo.

Continue to: Verruca vulgaris

Verruca vulgaris similarly contains puncta but typically appears as a raised lesion with a disruption of the stratum corneum.⁵

Acral melanoma can be distinguished from tache/talon noir by dermoscopic evaluation and/or paring of the corneum. On dermoscopic evaluation, both acral melanoma and tache/talon noir will reveal parallel ridge patterns; this finding has an 86% sensitivity and 96% specificity for early acral melanoma.⁶ What differentiates the 2 is the “satellite globules” or “pebbles on a ridge” that are seen with a subcorneal hematoma. Furthermore, paring the corneum would demonstrate an absence of blood within the ridges of the skin shavings, pointing away from tache/talon noir as the diagnosis.^1-3,5-7

Traumatic tattoo can also mimic tache/talon noir, due to foreign-material deposits in the skin (gunpowder, carbon, lead, dirt, and asphalt). A history of penetrating trauma should help to narrow the differential. Attempts at paring with traumatic tattoo may or may not help with differentiation.¹

In this case, time does heal all wounds

Talon/tache noir are benign conditions that do not require treatment and do not affect sports performance. The lesion will usually self-resolve within a matter of weeks from onset or can even be gently scraped with a sterile needle or blade, which can partially or completely remove the pigmentation from within the parallel ridges.^3,5,8

Our patient was advised that the lesion would resolve on its own. His knee pain was determined to be a simple case of patellofemoral syndrome or “runner’s knee” and he opted to complete a home exercise program to obtain relief.

A 17-year-old high school baseball player presented to a sports medicine clinic for left anterior knee pain. During the exam, a hyperpigmented lesion was incidentally noted on his left palm. The patient, who also played basketball and football, was unsure of how long he’d had the lesion, and he did not recall having any prior lesions on his hand. He denied any discomfort or significant past medical history. There was no known family history of skin cancers, but the patient did report that his brother, also an athlete, had a similar lesion on his hand.

On closer examination, scattered black dots were noted within a 2 × 1–cm thickened keratotic plaque at the hypothenar eminence of the patient’s left hand (Figure). There was no tenderness, erythema, warmth, or disruption of normal skin architecture or drainage.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Posttraumatic tache noir (also known as talon noir on the volar aspect of the feet) is a subcorneal hematoma. The diagnosis is made clinically.

Identifying “pebbles on a ridge” or “satellite globules” during dermoscopic evaluation can differentiate benign from malignant sources of this type of lesion.

Our patient was a competitive baseball player, and he noted that the knob of his baseball bat rubbed the hypothenar eminence of his nondominant hand when he took a swing. The sheer force of the knob led to the subcorneal hematoma. Tache noir was high on the differential due to the author’s clinical experience with similar cases.

Tache noir occurs predominantly in people ages 12 to 24 years, without regard to gender.¹ The condition is commonly found in athletes who participate in baseball, cricket, racquet sports, weightlifting, and rock climbing.^1-3 Talon noir occurs most commonly in athletes who are frequently jumping, turning, and pivoting, as in football, basketball, tennis, and lacrosse. One should have a high index of suspicion for this diagnosis in patients who participate in any sport that might lead to shearing forces involving the volar aspect of the hands or feet.

Confirmation is obtained through a simple procedure. Dermoscopic evaluation of tache/talon noir will reveal “pebbles on a ridge” or “satellite globules.” Confirmation of tache/talon noir can be made by paring the corneum with a #15 blade, which will reveal blood in the shavings and punctate lesions.⁴

Other lesions may havea similar appearance

Tache noir can be differentiated from other conditions by the presence of preserved architecture of the skin surface and punctate capillaries beneath the stratum corneum. The differential diagnosis includes verruca vulgaris, acral melanoma, and a traumatic tattoo.

Continue to: Verruca vulgaris

Verruca vulgaris similarly contains puncta but typically appears as a raised lesion with a disruption of the stratum corneum.⁵

Acral melanoma can be distinguished from tache/talon noir by dermoscopic evaluation and/or paring of the corneum. On dermoscopic evaluation, both acral melanoma and tache/talon noir will reveal parallel ridge patterns; this finding has an 86% sensitivity and 96% specificity for early acral melanoma.⁶ What differentiates the 2 is the “satellite globules” or “pebbles on a ridge” that are seen with a subcorneal hematoma. Furthermore, paring the corneum would demonstrate an absence of blood within the ridges of the skin shavings, pointing away from tache/talon noir as the diagnosis.^1-3,5-7

Traumatic tattoo can also mimic tache/talon noir, due to foreign-material deposits in the skin (gunpowder, carbon, lead, dirt, and asphalt). A history of penetrating trauma should help to narrow the differential. Attempts at paring with traumatic tattoo may or may not help with differentiation.¹

In this case, time does heal all wounds

Talon/tache noir are benign conditions that do not require treatment and do not affect sports performance. The lesion will usually self-resolve within a matter of weeks from onset or can even be gently scraped with a sterile needle or blade, which can partially or completely remove the pigmentation from within the parallel ridges.^3,5,8

Our patient was advised that the lesion would resolve on its own. His knee pain was determined to be a simple case of patellofemoral syndrome or “runner’s knee” and he opted to complete a home exercise program to obtain relief.

A 17-year-old high school baseball player presented to a sports medicine clinic for left anterior knee pain. During the exam, a hyperpigmented lesion was incidentally noted on his left palm. The patient, who also played basketball and football, was unsure of how long he’d had the lesion, and he did not recall having any prior lesions on his hand. He denied any discomfort or significant past medical history. There was no known family history of skin cancers, but the patient did report that his brother, also an athlete, had a similar lesion on his hand.

On closer examination, scattered black dots were noted within a 2 × 1–cm thickened keratotic plaque at the hypothenar eminence of the patient’s left hand (Figure). There was no tenderness, erythema, warmth, or disruption of normal skin architecture or drainage.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Posttraumatic tache noir (also known as talon noir on the volar aspect of the feet) is a subcorneal hematoma. The diagnosis is made clinically.

Identifying “pebbles on a ridge” or “satellite globules” during dermoscopic evaluation can differentiate benign from malignant sources of this type of lesion.

Our patient was a competitive baseball player, and he noted that the knob of his baseball bat rubbed the hypothenar eminence of his nondominant hand when he took a swing. The sheer force of the knob led to the subcorneal hematoma. Tache noir was high on the differential due to the author’s clinical experience with similar cases.

Tache noir occurs predominantly in people ages 12 to 24 years, without regard to gender.¹ The condition is commonly found in athletes who participate in baseball, cricket, racquet sports, weightlifting, and rock climbing.^1-3 Talon noir occurs most commonly in athletes who are frequently jumping, turning, and pivoting, as in football, basketball, tennis, and lacrosse. One should have a high index of suspicion for this diagnosis in patients who participate in any sport that might lead to shearing forces involving the volar aspect of the hands or feet.

Confirmation is obtained through a simple procedure. Dermoscopic evaluation of tache/talon noir will reveal “pebbles on a ridge” or “satellite globules.” Confirmation of tache/talon noir can be made by paring the corneum with a #15 blade, which will reveal blood in the shavings and punctate lesions.⁴

Other lesions may havea similar appearance

Tache noir can be differentiated from other conditions by the presence of preserved architecture of the skin surface and punctate capillaries beneath the stratum corneum. The differential diagnosis includes verruca vulgaris, acral melanoma, and a traumatic tattoo.

Continue to: Verruca vulgaris

Verruca vulgaris similarly contains puncta but typically appears as a raised lesion with a disruption of the stratum corneum.⁵

Acral melanoma can be distinguished from tache/talon noir by dermoscopic evaluation and/or paring of the corneum. On dermoscopic evaluation, both acral melanoma and tache/talon noir will reveal parallel ridge patterns; this finding has an 86% sensitivity and 96% specificity for early acral melanoma.⁶ What differentiates the 2 is the “satellite globules” or “pebbles on a ridge” that are seen with a subcorneal hematoma. Furthermore, paring the corneum would demonstrate an absence of blood within the ridges of the skin shavings, pointing away from tache/talon noir as the diagnosis.^1-3,5-7

Traumatic tattoo can also mimic tache/talon noir, due to foreign-material deposits in the skin (gunpowder, carbon, lead, dirt, and asphalt). A history of penetrating trauma should help to narrow the differential. Attempts at paring with traumatic tattoo may or may not help with differentiation.¹

In this case, time does heal all wounds

Talon/tache noir are benign conditions that do not require treatment and do not affect sports performance. The lesion will usually self-resolve within a matter of weeks from onset or can even be gently scraped with a sterile needle or blade, which can partially or completely remove the pigmentation from within the parallel ridges.^3,5,8

Our patient was advised that the lesion would resolve on its own. His knee pain was determined to be a simple case of patellofemoral syndrome or “runner’s knee” and he opted to complete a home exercise program to obtain relief.

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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

Among patients with the recently defined severe autoinflammatory syndrome VEXAS, those who are transfusion dependent or have a specific amino acid substitution are at highest risk for death, whereas those with ear chondritis are at significantly lower risk, a multinational team of investigators has found.

Courtesy Dr. Marcela Ferrada

Their study of mortality and predictors of survival among patients with genetically confirmed VEXAS showed that patients with a VEXAS variant resulting in an amino acid substitution of a methionine for a valine had a 3.5-fold higher risk for death, compared with patients with either a methionine-to-threonine substitution or a methionine-to-leucine swap.

Transfusion dependence was an independent predictor of mortality. Patients who became dependent on transfusions after symptom onset had a nearly threefold higher risk for death, reported Marcela A. Ferrada, MD, a clinical fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

“These findings should inform risk assessment and clinical management in patients with VEXAS syndrome,” she said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.

“These genetic findings have proven right now to be not only diagnostic, but we have shown that they’re also prognostic, and we hope that this is going to help us identify patients who could have more aggressive treatment,” Dr. Ferrada said.

She also discussed her findings in a media briefing held 2 days prior to her plenary presentation. At that briefing, this news organization asked participating clinicians whether they had patients who they suspected may have had undiagnosed VEXAS.

“My answer to that is interesting,” replied moderator Vaneet Sandhu, MD, from Loma Linda (Calif.) University and Riverside University Health System.

“In the last couple of days, I’ve been reading about VEXAS, and actually texted one of my colleagues yesterday and said, ‘Hey, you know these patients we’ve been seeing who have these strange rashes and chondritis and have maybe a diagnosis of leukocytoclastic vasculitis or something else – are we not diagnosing these patients?’ ” she said.

“I think we are looking at every patient with chondritis and reexamining their phenotype. We had dismissed certain symptoms because they didn’t fit the archetype for relapsing polychondritis, for example, but it could be VEXAS,” said Alfred Kim, MD, PhD, of Washington University in St. Louis, who also presented data during the briefing.

Three variants

VEXAS is caused by somatic mutations in UBA1, a gene that initiates cytoplasmic ubiquitylation, a process by which misfolded proteins are tagged for degradation.

The syndrome’s name is an acronym descriptive of the major features:

• Vacuoles in bone marrow cells.
• E-1 activating enzyme that UBA1 encodes for.
• X-linked.
• Autoinflammatory.
• Somatic mutation featuring hematologic mosaicism.

VEXAS results in rheumatologic, dermatologic, and hematologic symptoms that are often misdiagnosed as being caused by treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, giant cell arteritis, or myelodysplastic syndrome (MDS).

VEXAS was identified as a distinct syndrome within the past year by Dr. Ferrada and other investigators at NIAMS, the National Human Genome Research Institute, and other institutions.

In the study reported at ACR 2021, Dr. Ferrada and colleagues assessed 83 men who had been referred for genetic testing for VEXAS at the National Institutes of Health, in Bethesda, Md., and at Leeds (England) Teaching Hospitals NHS Trust.

All patients were confirmed to have VEXAS-defining genetic mutations in UBA1 by Sanger sequencing of peripheral blood samples. Only those patients with mutations at codon p.Met41 were included in the investigators’ analysis. Mutations at that site account for nearly all cases of VEXAS that have been identified to date.

The most common clinical manifestation of VEXAS was skin involvement, which occurred in all but one of the 83 patients. Other common manifestations included arthritis (58 patients), pulmonary infiltrates (57 patients), and ear chondritis (54 patients).

Fifteen patients were found to have the leucine variant, 18 had the valine variant, and 50 had the threonine variant. The median age at disease onset was 66 years in the leucine and threonine variant groups and 65 in the valine variant group.

The clinical diagnosis differed according to genotype: 4 of 18 patients (22%) with the valine variant were diagnosed with relapsing polychondritis, compared with 8 of 15 (53%) with the leucine variant and 31 of 50 (62%) with the threonine variant (P = .01).

In contrast, 55% of patients with valine genotype were diagnosed with undifferentiated fever, compared with 6% of those with the leucine and 16% with the threonine genotypes (P = .001). More patients with the leucine variant (60%) were diagnosed with Sweet syndrome, compared with 11% and 14% of patients with the valine and threonine variants, respectively (P = .001).

There was no significant difference among the three genotypes in the percentage of patients diagnosed with MDS.

The follow-up period ranged from 1 to 18 years (median, 4.7 years). The median survival time from disease onset for all patients was 10 years.

Among patients with the valine variant, median survival was 9 years, which was significantly less than among patients with the other two variants (P = .01).

In univariable analysis, independent predictors of mortality were ear chondritis (hazard ratio, 0.26; P = .005), transfusion dependence, a time-dependent variable (HR, 2.59; P = .03), and the valine variant (HR, 3.5; P = .008).

The association between VEXAS genotype and phenotype could be explained by the finding that, among patients with the valine variant, there was significantly less translation of the catalytically proficient UBA1b isoform than in patients with the other two variants, Dr. Ferrada said.

Therapeutic options

Dr. Ferrada noted that to date no drugs have been shown to provide consistent therapeutic benefits for patients with VEXAS, but evidence as to the etiology of the syndrome points to possible treatment approaches.

“All of these findings I think are extremely important to help us guide management of these patients, as we know that the mutation is located in the stem cells in the bone marrow. So we suspect that doing a bone marrow transplant in these patients is going to be curative,” Dr. Ferrada said during the briefing.

Investigators are planning a phase 2 trial of allogeneic hematopoietic stem cell transplant for patients with VEXAS.

The study was supported by the National Institutes of Health. Dr. Ferrada, Dr. Sandhu, and Dr. Kim have disclosed no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Exposure to arsenic and other metals in utero is associated with an elevated risk for atopic dermatitis in children, researchers report in a study published Oct. 27, 2021, in JAMA Network Open.

In this multicenter cohort study, led by epidemiologist Shu-Li Wang, PhD, of the National Institute of Environmental Health Sciences, in Taiwan, each twofold increase in prenatal arsenic level correlated with a 2.4-fold higher rate of atopic dermatitis in 4-year-olds.

Atopic diseases have been on the rise. Eczema (atopic dermatitis) is the first stage of the so-called atopic march, followed by food allergies, allergic rhinitis, and asthma later in childhood. Previous research has linked heavy metal exposure to allergic diseases in adults. In another study by Dr. Wang and colleagues that was published in 2021, prenatal and early-life arsenic exposure was found to correlate with higher rates of allergic rhinitis and asthma in children. In that study, the participants were followed every 2-3 years through the age of 14 as part of the Taiwan Maternal and Infant Cohort Study.

The new study included 370 mother and child pairs who were enrolled in that birth cohort study between October 2012 and May 2015. During their third trimester of pregnancy, women completed questionnaires about their lifestyle, diet, and living environment. In addition, their height, weight, and blood pressure were recorded, and urine samples were taken. In follow-up interviews 3-4 years later, the mothers were asked whether their child had ever been diagnosed with atopic dermatitis.

The researchers used an inductively coupled plasma mass spectrometer to analyze the participants’ urine samples. They assessed for exposures in utero to eight metals: arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc.

Each unit increase of an index that estimates the combined exposure to these metals during pregnancy was associated with 63% higher odds of atopic dermatitis in the children by age 4. The researchers adjusted for parental allergies (yes or no), mother’s educational level (<12 years, 13-16 years, or >16 years), geographic area (central or eastern Taiwan), exposure to tobacco smoke during pregnancy, and the child’s gender. Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal coexposure index.

A wealth of previous research links arsenic exposure during adulthood to skin disease and immune dysfunction. Early-life arsenic exposure has been linked with elevated risk for various adult disorders, including cancer, diabetes, and heart disease, years later. In light of such research, “the findings in this paper are not surprising,” J. Christopher States, PhD, director of the Center for Integrative Environmental Health Science at the University of Louisville (Ky.), told this news organization. “Low-level arsenic exposure does not cause disease immediately, but it does appear to have long-lasting effects, making individuals susceptible to ‘second hits’ with another environmental agent.”

Research into the molecular mechanisms for these links has shown that arsenic and cadmium exposure can promote allergic phenotypes in immune cells. “We think the toxic metals activate the alarmin pathway, thus inducing innate lymphoid cells, then activating T-helper 2 cells, which drive immunoglobulin E production and breakdown of the epithelium and promotion of allergies,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford University. Dr. Nadeau led that study, published in 2017 in PLOS One, along with epidemiologist Margaret Karagas, PhD, of Geisel School of Medicine at Dartmouth, Hanover, N.H.

As for what pregnant women can do to minimize their exposure to heavy metals, “that is a difficult problem and primarily a function of where one lives,” said Dr. States.

Drinking water and food are major sources of arsenic exposure. Groundwater is naturally contaminated with arsenic deposits that seep in from bedrock, said Dr. States. The U.S. Environmental Protection Agency regulates arsenic levels in public drinking water that is supplied to more than a few thousand people. However, small water supplies and private wells are unregulated, he said, and having these water sources tested for arsenic or fitted with systems to reduce arsenic can be very expensive.

Among foods, rice can have high concentrations of arsenic, Dr. Karagas told this news organization. To minimize arsenic exposure through the diet, women can limit rice-based foods, according to a web-based tool developed by her and coworkers.

In addition, tobacco smoke is a major source of cadmium exposure and a moderate source of arsenic exposure, Dr. States noted. Women can reduce their exposure to these metals by avoiding tobacco and secondhand smoke.

The study was supported by grants from the National Health Research Institutes, Chung Shan Medical University Hospital, Taiwan Ministry of Science and Technology, and the Taiwan Environmental Protection Administration. The authors and quoted experts report no relevant financial relationships.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Four years after new infant feeding guidelines were issued to prevent allergies to peanut and other foods, 70% of surveyed parents and caregivers in the United States said they had never heard about the new recommendation.

Food allergies in developed countries have doubled in each of the last decades and now affect 7.6% of U.S. children. About 1 in 50 are allergic to peanut. Data from the 2015 LEAP study and other research has convincingly shown that early, sustained feeding of peanuts, eggs, and other allergens can prevent babies from developing allergies to these foods.

Based on those findings, the National Institute of Allergy and Infectious Diseases (NIAID) updated its feeding guidelines in 2017, urging parents to introduce these foods to babies around 4-6 months of age rather than wait until 1-3 years of age, as previously recommended. The American Academy of Pediatrics approved those guidelines too, and in 2019 changed its own feeding recommendations.

To assess awareness of this new guidance and to what extent these recommendations are being translated into clinical practice, researchers surveyed a demographically representative U.S. sample of 3,062 parents and caregivers with children between 7 months and 3½ years old. The survey was conducted in English and Spanish over the web or by phone.

More than one-third reported that their child’s primary care physician never discussed when to start feeding peanut-containing foods. And among those whose doctors did offer guidance, fewer than 1 in 4 specifically recommended introducing peanut by 6 months of age.

These data show that “despite strong evidence that early introduction of peanut within the first year of life can prevent the development of peanut allergy, this evidence is simply not making its way to parents of infants,” said Christopher Warren, PhD, assistant professor of preventive medicine at the Northwestern University Feinberg School of Medicine, Chicago. Dr. Warren led the study and presented the findings on a poster at this year’s American College of Allergy, Asthma & Immunology annual meeting in New Orleans.

In addition to caregivers, the Northwestern team surveyed U.S. allergists and pediatricians about the new feeding guidelines. Uptake was fairly good among allergists, with 65% reporting full implementation. On the other hand, while most pediatricians seemed familiar with the 2017 recommendations, fewer than one-third said they were following them.

“What’s unique about this challenge is that it’s not just a guideline change – it’s a guideline reversal,” said Wendy Sue Swanson, MD, chief medical officer for SpoonfulONE, a company that makes mix-ins and other products for multi-allergen feeding. After telling families for years to avoid these allergens in early life because food allergies were rising, “it’s harder advice to say, actually, we were wrong. Not only should you not wait, you should get peanut in while your baby’s immune system has this critical moment to learn and develop, and you should keep getting it in,” Dr. Swanson said in an interview.

Making matters worse, pediatricians are time pressed. Typically, at 4- to 6-month-old well-check visits, “they’re talking about sleep and development and feeding and milestones,” said Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern Feinberg, who led the allergist and pediatrician analyses.

Another challenge: Guidelines differ depending on the child’s level of food allergy risk, so it’s hard to explain them clearly and quickly. Babies at highest risk – as judged by having severe eczema, egg allergy, or both – should get peanut IgE blood testing and, if negative, begin regular consumption of peanut by 4-6 months. Intermediate-risk babies who have mild-to-moderate eczema are recommended to start peanut-containing foods by 6 months. And for low-risk babies with no eczema or known food allergies, the guidance is simply to introduce peanut-containing foods “in accordance with family preferences and cultural practices.”

As for pediatricians who say it’s hard to distinguish mild-to-moderate from severe eczema, “any eczema puts you at some risk,” Dr. Gupta told this news organization. “If they’ve required steroid creams to clear up their skin, or if you look at their skin, and you think it’s severe, don’t hesitate. Go ahead and draw the IgE and send them to an allergist.”

Australia, which has the highest rate of confirmed food allergy, has had more success implementing early feeding guidelines, said Dr. Swanson. Unlike the United States’ tiered approach, she said, they “had a national guideline that very crisply, years ago, told parents what to do.” Australia also has nurse educators that follow up with new moms to make sure they understand and follow the recommendations.

Dr. Gupta receives research support from the National Institutes of Health, Food Allergy Research and Education, the Melchiorre Family Foundation, the Sunshine Charitable Foundation, the Walder Foundation, the UnitedHealth Group, Thermo Fisher Scientific, and Genentech. She serves as a medical consultant/advisor for Genentech, Novartis, and Food Allergy Research and Education. Dr. Swanson serves as chief medical officer for SpoonfulONE.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.

Courtesy Charlotte E. LaSenna and Dr. Andrea Maderal, University of Miami

At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.

“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.

“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.

A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”

“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.

Randomized trial

Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.

In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m² or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.

The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.

The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).

In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.

However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.

There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).

The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.

Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.

Convincing results

“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.

“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.

He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.

Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.

“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.

The study results were previously published in the Lancet Rheumatology.

The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.

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

Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.

After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.

“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.

“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.

The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
 

Significant psychological impact

Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.

However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).

Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.

Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).

Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.

The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.

The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
 

Dual intervention

After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.

When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.

The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.

Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.

“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.

“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.

“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
 

No cause and effect

Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”

“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.

She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.

At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.

The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.

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

Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.

After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.

“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.

“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.

The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
 

Significant psychological impact

Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.

However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).

Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.

Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).

Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.

The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.

The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
 

Dual intervention

After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.

When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.

The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.

Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.

“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.

“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.

“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
 

No cause and effect

Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”

“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.

She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.

At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.

The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.

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

Alopecia areata (AA) has been linked to a significantly increased risk for dementia, new research shows.

After controlling for an array of potential confounders, investigators found a threefold higher risk of developing any form of dementia and a fourfold higher risk of developing Alzheimer’s disease (AD) in those with AA versus the controls.

“AA shares a similar inflammatory signature with dementia and has great psychological impacts that lead to poor social engagement,” lead author Cheng-Yuan Li, MD, MSc, of the department of dermatology, Taipei (Taiwan) Veterans General Hospital.

“Poor social engagement and shared inflammatory cytokines might both be important links between AA and dementia,” said Dr. Li, who is also affiliated with the School of Medicine and the Institute of Brain Science at National Yang Ming Chiao Tung University, Taipei.

The study was published online Oct. 26, 2021, in the Journal of Clinical Psychiatry (doi: 10.4088/JCP.21m13931).
 

Significant psychological impact

Patients with AA often experience anxiety and depression, possibly caused by the negative emotional and psychological impact of the hair loss and partial or even complete baldness associated with the disease, the authors noted.

However, AA is also associated with an array of other atopic and autoimmune diseases, including psoriasis and systemic lupus erythematosus (SLE).

Epidemiologic research has suggested a link between dementia and autoimmune diseases such as psoriasis and SLE, with some evidence suggesting that autoimmune and inflammatory mechanisms may “play a role” in the development of AD.

Dementia in general and AD in particular, “have been shown to include an inflammatory component” that may share some of the same mediators seen in AA (eg, IL-1 beta, IL-6, and tumor necrosis factor–alpha).

Moreover, “the great negative psychosocial impact of AA might result in poor social engagement, a typical risk factor for dementia,” said Dr. Li. The investigators sought to investigate whether patients with AA actually do have a higher dementia risk than individuals without AA.

The researchers used data from the Taiwan National Health Insurance Research Database, comparing 2,534 patients with AA against 25,340 controls matched for age, sex, residence, income, dementia-related comorbidities, systemic steroid use, and annual outpatient visits. Participants were enrolled between 1998 and 2011 and followed to the end of 2013.

The mean age of the cohort was 53.9 years, and a little over half (57.6%) were female. The most common comorbidity was hypertension (32.3%), followed by dyslipidemia (27%) and diabetes (15.4%).
 

Dual intervention

After adjusting for potential confounders, those with AA were more likely to develop dementia, AD, and unspecified dementia, compared with controls. They also had a numerically higher risk for vascular dementia, compared with controls, but it was not statistically significant.

When participants were stratified by age, investigators found a significant association between AA and higher risk for any dementia as well as unspecified dementia in individuals of all ages and an increased risk for AD in patients with dementia age at onset of 65 years and older.

The mean age of dementia diagnosis was considerably younger in patients with AA versus controls (73.4 vs. 78.9 years, P = .002). The risk for any dementia and unspecified dementia was higher in patients of both sexes, but the risk for AD was higher only in male patients.

Sensitivity analyses that excluded the first year or first 3 years of observation yielded similar and consistent findings.

“Intervention targeting poor social engagement and inflammatory cytokines may be beneficial to AA-associated dementia,” said Dr. Li.

“Physicians should be more aware of this possible association, help reduce disease discrimination among the public, and encourage more social engagement for AA patients,” he said.

“Further studies are needed to elucidate the underlying pathophysiology between AA and dementia risk,” he added.
 

No cause and effect

Commenting on the study, Heather M. Snyder, PhD, vice president of medical and scientific affairs, Alzheimer’s Association, said, “We continue to learn about and better understand factors that may increase or decrease a person’s risk of dementia.”

“While we know the immune system plays a role in Alzheimer’s and other dementia, we are still investigating links between, and impact of, autoimmune diseases – like alopecia areata, rheumatoid arthritis, and others – on our overall health and our brains, [which] may eventually give us important information on risk reduction strategies as well,” said Dr. Snyder, who was not involved in the research.

She cautioned that although the study did show a correlation between AA and dementia risk, this does not equate to a demonstration of cause and effect.

At present, “the message for clinicians is that when a patient comes to your office with complaints about their memory, they should, No. 1, be taken seriously; and, No. 2, receive a thorough evaluation that takes into account the many factors that may lead to cognitive decline,” Dr. Snyder said.

The study was supported by a grant from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. Dr. Li, coauthors, and Dr. Snyder disclosed no relevant financial relationships.

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

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

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

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

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

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

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

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.