MDedge Dermatology

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Mycophenolate mofetil, commonly used as a first-line corticosteroid-sparing agent for moderate to severe cases of the autoimmune blistering skin condition pemphigus vulgaris, has been found to be inferior to the biologic agent rituximab.

Mycophenolate mofetil is widely accepted as a first-in-line corticosteroid-sparing agent for pemphigus vulgaris, but few studies have compared the effectiveness of the two treatments for pemphigus vulgaris. The European Academy of Dermatology and Venereology recommends rituximab (Rituxan), a CD20 inhibitor, as first-line treatment for patients with new-onset cases of moderate to severe intensity or for patients who fail to achieve clinical remission with systemic corticosteroids with or without other immunosuppressive treatments.

In the current study, published online on May 19, 2021, in the New England Journal of Medicine, researchers led by Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, conducted a randomized, controlled trial of 135 patients (mean age, 48 years; 53% women) with moderate to severe pemphigus vulgaris with 67 receiving rituximab and 68 receiving mycophenolate mofetil (99% of patients in the rituximab group and 85% of patients in the mycophenolate mofetil group completed the trial).

Patients in the rituximab group received 1,000 mg of IV rituximab on days 1, 15, 168, and 182 of the study, plus twice-daily oral placebo. Intravenous methylprednisolone at 100 mg was administered before each rituximab infusion to reduce infusion-related reactions. Patients in the second group were given mycophenolate mofetil orally twice daily, starting at 1 g/day in divided doses and adjusted to 2 g/day in divided doses by week 2. They also received placebo infusions on days 1, 15, 168, and 182 of the study.

Patients in both groups received oral glucocorticoids throughout the course of the trial: an average of 3,545 mg for the rituximab treatment group and a cumulative dose of 5,140 mg for the group treated with mycophenolate mofetil, a statistically significant difference (P < .001). Outcomes based on 62 patients treated with rituximab and 63 on MMF, a modified intention-to-treat group.

By week 52, 25 patients (40%) who were treated with rituximab experienced complete sustained remission (the primary endpoint), compared with 6 patients (10%) in the mycophenolate mofetil group (95% confidence interval, 15-45, P < .001).

Only six patients in the rituximab group experienced a disease flare as compared with 44 patients in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05-0.29; P < .001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group with 3 patients in the rituximab group and 26 in the mycophenolate mofetil receiving rescue therapy.

Second to remission, the goal of treatment for pemphigus vulgaris is to reduce the use of glucocorticoids, Dr. Werth and colleagues wrote, adding: “The results of this trial showed that rituximab was superior to mycophenolate mofetil in producing sustained complete remission over 52 weeks among patients with moderate to severe pemphigus vulgaris. Rituximab had a greater glucocorticoid-sparing effect than mycophenolate mofetil, but more patients in this group had serious adverse events.”

Most adverse events in the rituximab group were limited to infusion-related reactions, but serious adverse events occurred in 15 patients (including pneumonia and upper respiratory tract infection, cellulitis and acute pyelonephritis, viral pneumonia, and skin infection). Ten patients in the mycophenolate mofetil group experienced serious adverse events (pneumonia and influenza, cellulitis and sepsis, herpes zoster, and pyelonephritis).

The current study had several limitations, primarily its small size. Plus, the authors noted a short follow-up period after glucocorticoids were stopped.

Mycophenolate mofetil, along with immunosuppressants, is approved in the United States as a treatment for organ rejection in patients who have received kidney, heart or liver transplants. But it is also used off label for pemphigus vulgaris and in rheumatology as a treatment for lupus, rheumatoid arthritis, vasculitis, inflammatory bowel disease (Crohn’s disease), inflammatory eye disease (uveitis) as well as kidney and skin disorders.

In the 2018 treatment guidelines for pemphigus by the European Dermatology Forum and the EADV, mycophenolate mofetil is recommended as a first-line corticosteroid sparing agent for pemphigus vulgaris.

Rituximab was approved in 2018 as the first biologic therapy for patients with pemphigus vulgaris and is currently recommended as a treatment for patients with pemphigus. But how well it works in comparison with the long-established mycophenolate mofetil hasn’t been extensively studied.

Other smaller studies show that mycophenolate mofetil has a treatment effect, but those studies were small. The Ritux 3 trial, published in The Lancet showed that rituximab plus glucocorticoids as opposed to glucocorticoids alone was beneficial in treating pemphigus.

“Rituximab has moved toward first-line therapy for moderate to severe pemphigus as recommended by an international panel of experts,” Dr. Werth said in an interview.

In her practice, Dr. Werth said that she has observed similar outcomes in clinical practice for patients prescribed oral mycophenolate mofetil. “Patients take a long time to get to remission and frequently end up staying on prednisone and long-term mycophenolate mofetil,” she said. She uses mycophenolate mofetil less often since rituximab has been shown to be effective for many patients, but mycophenolate mofetil “still has a place for patients who don’t want, or can’t tolerate, rituximab, or for cases in which rituximab doesn’t work.”

This study was supported by a grant from Hoffmann–La Roche. Dr. Werth disclosed having served as a consultant to Genentech on pemphigus, and that the University of Pennsylvania has received a grant/contract to perform a rituximab–mycophenolate mofetil trial for pemphigus vulgaris.

Dermatomyositis (DM) is an autoimmune condition characterized by skin and muscle inflammation with an estimated incidence of 9 cases per 1 million people. The incidence of amyopathic DM, which includes antimelanoma differentiation–associated gene 5 (anti-MDA5) DM, is approximately 2 cases per 1 million people.¹ Classic cutaneous manifestations of DM include a heliotrope rash, Gottron papules, and the shawl sign. Features of anti-MDA5 DM include cutaneous ulcerations, most commonly overlying Gottron papules on the elbows and digits, as well as painful palmar macules and papules. We describe 2 patients with anti-MDA5 DM who presented with an ulcerative heliotrope rash. Although heliotrope rash is classic for DM and cutaneous ulcerations are a hallmark of the anti-MDA5 subtype of DM, overlap of these cutaneous manifestations is not commonly reported. Furthermore, ulcerations of the lateral canthi were associated with rapidly progressive interstitial lung disease (ILD).

Case Reports

Patient 1
A woman in her 30s presented with diffuse arthralgias, bilateral eyelid edema, fatigue, and a progressive diffuse exanthem of 3 months’ duration. A review of systems was notable for the absence of myalgias. Physical examination revealed periorbital poikilodermatous patches with erythematous-to-violaceous plaques along the eyelid margins, violaceous papules on the dorsal knuckles, and edematous eroded plaques on the palmar fingertips. The patient was found to have a positive antinuclear antibody titer of 1:320 (reference range, <1:80) with a speckled pattern. A computed tomography (CT) scan of the chest showed patchy bilateral ground-glass opacities that were concerning for ILD. The cutaneous erosions, absence of myalgias, considerable proximal weakness, radiographic evidence of ILD, and positive antinuclear antibody test were clinically suggestive of anti-MDA5 DM. Further workup confirmed this diagnosis with positive reactivity to MDA5 by line immunoassay. The patient was treated with intravenous corticosteroids and was discharged after a 17-day hospitalization; however, she presented 2 months later to outpatient dermatology for progression of the cutaneous ulcerations, at which time an ulcerative heliotrope rash (Figure 1) was identified. Despite compliance with oral corticosteroids (1 mg/kg/d), she was hospitalized 1 month later for progressive respiratory insufficiency. A chest CT showed ground-glass linear opacities centrally located in all lobes of both lungs, consistent with rapidly progressive ILD. Over the course of her 5-day hospitalization, she was treated with corticosteroids, intravenous immunoglobulin (IVIG), and mycophenolate mofetil. The patient responded well to these therapies, leading to resolution of the respiratory symptoms, and she was discharged with plans to continue this regimen as an outpatient.

Patient 2
A woman in her late 30s with a history of known anti-MDA5 DM confirmed by line immunoassay 1 year prior presented to the emergency department with shortness of breath due to progressive ILD and a worsening exanthem. Dermatology was consulted to provide treatment recommendations. The treatment team was concerned for infection or anti-MDA5 DM disease progression. Physical examination revealed an ulcerative heliotrope rash (Figure 2) in addition to cutaneous findings classic for anti-MDA5 DM. Despite interventions, including high-dose corticosteroids, rituximab, IVIG, and plasma exchange, the ILD continued to progress, and the patient and her family elected to de-escalate aggressive medical care and pursue comfort care. The patient later died in in patient hospice.

Comment

Clinical Presentation of Anti-MDA5 DM
Dermatomyositis classically presents with cutaneous manifestations including a heliotropic erythematous rash and Gottron papules as well as accompanying muscle weakness.² However, a subtype known as amyopathic DM, which includes anti-MDA5 DM, usually presents without muscle involvement.³ Clinical muscle weakness has been reported in cases of anti-MDA5 DM, though it is less likely in these patients.⁴ The characteristic cutaneous phenotype of anti-MDA5 DM was described by Fiorentino et al⁵ in 2011 through a seminal retrospective study. Kurtzman and Vleugels⁶ provided validation of the clinical features of anti-MDA5 DM in their 2018 review. The classic cutaneous phenotype of anti-MDA5 DM consists of tender palmar papules and/or skin ulcerations that commonly develop over Gottron papules on the knuckles and digits, lateral nail folds, and elbows.^7-10 A meta-analysis of 1500 patients with anti-MDA5 DM found a statistically significant association with alopecia, Gottron sign or papules, mechanic’s hands, and V rash (P<.05), as well as skin ulcers, panniculitis, arthritis/arthralgia, pneumomediastinum, and rapidly progressive ILD (RP-ILD)(P≤.01).⁴ Rapidly progressive ILD is highly associated with anti-MDA5 DM.^6,11

While a heliotrope rash is classic for DM, and ulcerations are a hallmark of the anti-MDA5 DM subtype, overlap of these cutaneous manifestations is not commonly reported. In both cases presented here, ulcerations of the lateral canthi were associated with progression of ILD.

Diagnosis of Anti-MDA5 DM
Anti-MDA5 DM is defined by the presence of the anti-MDA5 antibody in the serum, named for its reactivity against the RNA helicase encoded by MDA5, within the clinical context of cutaneous signs of DM as described above.¹²

As described by Rider et al,¹³ a thorough laboratory analysis, including complete blood cell count, serum electrolytes, calcium, magnesium, phosphorus, and thyroid-stimulating hormone, is necessary to rule out conditions with similar presentations. Additionally, serum analysis for elevated muscle enzymes (creatinine phosphokinase, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) is necessary to assess for subclinical muscle involvement. Serologic evidence of myositis usually denotes an alternative diagnosis.¹³ Antinuclear antibodies and myositis-specific antibody positivity are much less frequent in the anti-MDA5 DM subtype than in other forms of DM.⁶

Anti-MDA5 antibody titer, ferritin, and IL-18 can be trended and may be useful in the evaluation of the response to treatment and ILD status in patients with anti-MDA5 DM.^14,15 Elevated alveolar-arterial gradient, serum ferritin, serum chitotriosidase, and serum chitinase-3-like protein 1 (YKL-40) have each been associated with poorer prognosis of anti-MDA5 DM. The aforementioned serologies therefore may be helpful in determination of risk stratification and treatment aggressiveness.^16-19

Because of its strong association with RP-ILD, screening for pulmonary disease is necessary in all patients with confirmed or strongly suspected anti-MDA5 DM. Screening can be performed with pulmonary function testing; however, high-resolution chest CT is the gold standard for diagnosis of ILD.²⁰

Finally, all patients with a new diagnosis of DM should be evaluated for underlying malignancy through cancer screenings, given the propensity for DM to present as a paraneoplastic process.²¹ However, reports have indicated that the anti-MDA5 DM subtype may have a reduced risk for or an inverse relationship with underlying malignancy.⁵

Treatment Options for Anti-MDA5 DM
Early and aggressive therapy should be considered in the treatment of anti-MDA5 DM because of its association with RP-ILD. No treatment protocol is well established; thus, an individualized therapeutic approach may be guided by symptom severity and the clinical, radiographic, or functional evidence of ILD.⁶ High-dose systemic corticosteroids are first line, either in combination with or as a bridge to corticosteroid-sparing agents for immunosuppression. Many steroid-sparing medications have been employed with varying success. Mycophenolate mofetil is a reasonable first-line corticosteroid-sparing immunosuppressant agent, given its added benefit of attenuating ILD progression.⁶ A combination of high-dose corticosteroids, cyclosporine, and cyclophosphamide is utilized by some initially in the treatment of anti-MDA5 with ILD.^22,23 While others have used combinations of these immunomodulatory agents with mycophenolate mofetil, IVIG, rituximab, azathioprine, tofacitinib, and polymyxin B, direct hemoperfusion has been added, leading to successful remission.^23-28

Conclusion

We present 2 patients with anti-MDA5 DM who demonstrated a rare cutaneous manifestation of an ulcerative heliotrope rash. In both cases, this cutaneous finding was associated with the development of RP-ILD. Because of the strong association with and rapid progression of ILD seen in anti-MDA5 DM, early identification and aggressive treatment of this subtype are imperative. The clinician should recognize nonacral locations of cutaneous ulcerations, including an ulcerated heliotrope rash, to optimize diagnosis and management.

Dermatomyositis (DM) is an autoimmune condition characterized by skin and muscle inflammation with an estimated incidence of 9 cases per 1 million people. The incidence of amyopathic DM, which includes antimelanoma differentiation–associated gene 5 (anti-MDA5) DM, is approximately 2 cases per 1 million people.¹ Classic cutaneous manifestations of DM include a heliotrope rash, Gottron papules, and the shawl sign. Features of anti-MDA5 DM include cutaneous ulcerations, most commonly overlying Gottron papules on the elbows and digits, as well as painful palmar macules and papules. We describe 2 patients with anti-MDA5 DM who presented with an ulcerative heliotrope rash. Although heliotrope rash is classic for DM and cutaneous ulcerations are a hallmark of the anti-MDA5 subtype of DM, overlap of these cutaneous manifestations is not commonly reported. Furthermore, ulcerations of the lateral canthi were associated with rapidly progressive interstitial lung disease (ILD).

Case Reports

Patient 1
A woman in her 30s presented with diffuse arthralgias, bilateral eyelid edema, fatigue, and a progressive diffuse exanthem of 3 months’ duration. A review of systems was notable for the absence of myalgias. Physical examination revealed periorbital poikilodermatous patches with erythematous-to-violaceous plaques along the eyelid margins, violaceous papules on the dorsal knuckles, and edematous eroded plaques on the palmar fingertips. The patient was found to have a positive antinuclear antibody titer of 1:320 (reference range, <1:80) with a speckled pattern. A computed tomography (CT) scan of the chest showed patchy bilateral ground-glass opacities that were concerning for ILD. The cutaneous erosions, absence of myalgias, considerable proximal weakness, radiographic evidence of ILD, and positive antinuclear antibody test were clinically suggestive of anti-MDA5 DM. Further workup confirmed this diagnosis with positive reactivity to MDA5 by line immunoassay. The patient was treated with intravenous corticosteroids and was discharged after a 17-day hospitalization; however, she presented 2 months later to outpatient dermatology for progression of the cutaneous ulcerations, at which time an ulcerative heliotrope rash (Figure 1) was identified. Despite compliance with oral corticosteroids (1 mg/kg/d), she was hospitalized 1 month later for progressive respiratory insufficiency. A chest CT showed ground-glass linear opacities centrally located in all lobes of both lungs, consistent with rapidly progressive ILD. Over the course of her 5-day hospitalization, she was treated with corticosteroids, intravenous immunoglobulin (IVIG), and mycophenolate mofetil. The patient responded well to these therapies, leading to resolution of the respiratory symptoms, and she was discharged with plans to continue this regimen as an outpatient.

Patient 2
A woman in her late 30s with a history of known anti-MDA5 DM confirmed by line immunoassay 1 year prior presented to the emergency department with shortness of breath due to progressive ILD and a worsening exanthem. Dermatology was consulted to provide treatment recommendations. The treatment team was concerned for infection or anti-MDA5 DM disease progression. Physical examination revealed an ulcerative heliotrope rash (Figure 2) in addition to cutaneous findings classic for anti-MDA5 DM. Despite interventions, including high-dose corticosteroids, rituximab, IVIG, and plasma exchange, the ILD continued to progress, and the patient and her family elected to de-escalate aggressive medical care and pursue comfort care. The patient later died in in patient hospice.

Comment

Clinical Presentation of Anti-MDA5 DM
Dermatomyositis classically presents with cutaneous manifestations including a heliotropic erythematous rash and Gottron papules as well as accompanying muscle weakness.² However, a subtype known as amyopathic DM, which includes anti-MDA5 DM, usually presents without muscle involvement.³ Clinical muscle weakness has been reported in cases of anti-MDA5 DM, though it is less likely in these patients.⁴ The characteristic cutaneous phenotype of anti-MDA5 DM was described by Fiorentino et al⁵ in 2011 through a seminal retrospective study. Kurtzman and Vleugels⁶ provided validation of the clinical features of anti-MDA5 DM in their 2018 review. The classic cutaneous phenotype of anti-MDA5 DM consists of tender palmar papules and/or skin ulcerations that commonly develop over Gottron papules on the knuckles and digits, lateral nail folds, and elbows.^7-10 A meta-analysis of 1500 patients with anti-MDA5 DM found a statistically significant association with alopecia, Gottron sign or papules, mechanic’s hands, and V rash (P<.05), as well as skin ulcers, panniculitis, arthritis/arthralgia, pneumomediastinum, and rapidly progressive ILD (RP-ILD)(P≤.01).⁴ Rapidly progressive ILD is highly associated with anti-MDA5 DM.^6,11

While a heliotrope rash is classic for DM, and ulcerations are a hallmark of the anti-MDA5 DM subtype, overlap of these cutaneous manifestations is not commonly reported. In both cases presented here, ulcerations of the lateral canthi were associated with progression of ILD.

Diagnosis of Anti-MDA5 DM
Anti-MDA5 DM is defined by the presence of the anti-MDA5 antibody in the serum, named for its reactivity against the RNA helicase encoded by MDA5, within the clinical context of cutaneous signs of DM as described above.¹²

As described by Rider et al,¹³ a thorough laboratory analysis, including complete blood cell count, serum electrolytes, calcium, magnesium, phosphorus, and thyroid-stimulating hormone, is necessary to rule out conditions with similar presentations. Additionally, serum analysis for elevated muscle enzymes (creatinine phosphokinase, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) is necessary to assess for subclinical muscle involvement. Serologic evidence of myositis usually denotes an alternative diagnosis.¹³ Antinuclear antibodies and myositis-specific antibody positivity are much less frequent in the anti-MDA5 DM subtype than in other forms of DM.⁶

Anti-MDA5 antibody titer, ferritin, and IL-18 can be trended and may be useful in the evaluation of the response to treatment and ILD status in patients with anti-MDA5 DM.^14,15 Elevated alveolar-arterial gradient, serum ferritin, serum chitotriosidase, and serum chitinase-3-like protein 1 (YKL-40) have each been associated with poorer prognosis of anti-MDA5 DM. The aforementioned serologies therefore may be helpful in determination of risk stratification and treatment aggressiveness.^16-19

Because of its strong association with RP-ILD, screening for pulmonary disease is necessary in all patients with confirmed or strongly suspected anti-MDA5 DM. Screening can be performed with pulmonary function testing; however, high-resolution chest CT is the gold standard for diagnosis of ILD.²⁰

Finally, all patients with a new diagnosis of DM should be evaluated for underlying malignancy through cancer screenings, given the propensity for DM to present as a paraneoplastic process.²¹ However, reports have indicated that the anti-MDA5 DM subtype may have a reduced risk for or an inverse relationship with underlying malignancy.⁵

Treatment Options for Anti-MDA5 DM
Early and aggressive therapy should be considered in the treatment of anti-MDA5 DM because of its association with RP-ILD. No treatment protocol is well established; thus, an individualized therapeutic approach may be guided by symptom severity and the clinical, radiographic, or functional evidence of ILD.⁶ High-dose systemic corticosteroids are first line, either in combination with or as a bridge to corticosteroid-sparing agents for immunosuppression. Many steroid-sparing medications have been employed with varying success. Mycophenolate mofetil is a reasonable first-line corticosteroid-sparing immunosuppressant agent, given its added benefit of attenuating ILD progression.⁶ A combination of high-dose corticosteroids, cyclosporine, and cyclophosphamide is utilized by some initially in the treatment of anti-MDA5 with ILD.^22,23 While others have used combinations of these immunomodulatory agents with mycophenolate mofetil, IVIG, rituximab, azathioprine, tofacitinib, and polymyxin B, direct hemoperfusion has been added, leading to successful remission.^23-28

Conclusion

We present 2 patients with anti-MDA5 DM who demonstrated a rare cutaneous manifestation of an ulcerative heliotrope rash. In both cases, this cutaneous finding was associated with the development of RP-ILD. Because of the strong association with and rapid progression of ILD seen in anti-MDA5 DM, early identification and aggressive treatment of this subtype are imperative. The clinician should recognize nonacral locations of cutaneous ulcerations, including an ulcerated heliotrope rash, to optimize diagnosis and management.

Dermatomyositis (DM) is an autoimmune condition characterized by skin and muscle inflammation with an estimated incidence of 9 cases per 1 million people. The incidence of amyopathic DM, which includes antimelanoma differentiation–associated gene 5 (anti-MDA5) DM, is approximately 2 cases per 1 million people.¹ Classic cutaneous manifestations of DM include a heliotrope rash, Gottron papules, and the shawl sign. Features of anti-MDA5 DM include cutaneous ulcerations, most commonly overlying Gottron papules on the elbows and digits, as well as painful palmar macules and papules. We describe 2 patients with anti-MDA5 DM who presented with an ulcerative heliotrope rash. Although heliotrope rash is classic for DM and cutaneous ulcerations are a hallmark of the anti-MDA5 subtype of DM, overlap of these cutaneous manifestations is not commonly reported. Furthermore, ulcerations of the lateral canthi were associated with rapidly progressive interstitial lung disease (ILD).

Case Reports

Patient 1
A woman in her 30s presented with diffuse arthralgias, bilateral eyelid edema, fatigue, and a progressive diffuse exanthem of 3 months’ duration. A review of systems was notable for the absence of myalgias. Physical examination revealed periorbital poikilodermatous patches with erythematous-to-violaceous plaques along the eyelid margins, violaceous papules on the dorsal knuckles, and edematous eroded plaques on the palmar fingertips. The patient was found to have a positive antinuclear antibody titer of 1:320 (reference range, <1:80) with a speckled pattern. A computed tomography (CT) scan of the chest showed patchy bilateral ground-glass opacities that were concerning for ILD. The cutaneous erosions, absence of myalgias, considerable proximal weakness, radiographic evidence of ILD, and positive antinuclear antibody test were clinically suggestive of anti-MDA5 DM. Further workup confirmed this diagnosis with positive reactivity to MDA5 by line immunoassay. The patient was treated with intravenous corticosteroids and was discharged after a 17-day hospitalization; however, she presented 2 months later to outpatient dermatology for progression of the cutaneous ulcerations, at which time an ulcerative heliotrope rash (Figure 1) was identified. Despite compliance with oral corticosteroids (1 mg/kg/d), she was hospitalized 1 month later for progressive respiratory insufficiency. A chest CT showed ground-glass linear opacities centrally located in all lobes of both lungs, consistent with rapidly progressive ILD. Over the course of her 5-day hospitalization, she was treated with corticosteroids, intravenous immunoglobulin (IVIG), and mycophenolate mofetil. The patient responded well to these therapies, leading to resolution of the respiratory symptoms, and she was discharged with plans to continue this regimen as an outpatient.

Patient 2
A woman in her late 30s with a history of known anti-MDA5 DM confirmed by line immunoassay 1 year prior presented to the emergency department with shortness of breath due to progressive ILD and a worsening exanthem. Dermatology was consulted to provide treatment recommendations. The treatment team was concerned for infection or anti-MDA5 DM disease progression. Physical examination revealed an ulcerative heliotrope rash (Figure 2) in addition to cutaneous findings classic for anti-MDA5 DM. Despite interventions, including high-dose corticosteroids, rituximab, IVIG, and plasma exchange, the ILD continued to progress, and the patient and her family elected to de-escalate aggressive medical care and pursue comfort care. The patient later died in in patient hospice.

Comment

Clinical Presentation of Anti-MDA5 DM
Dermatomyositis classically presents with cutaneous manifestations including a heliotropic erythematous rash and Gottron papules as well as accompanying muscle weakness.² However, a subtype known as amyopathic DM, which includes anti-MDA5 DM, usually presents without muscle involvement.³ Clinical muscle weakness has been reported in cases of anti-MDA5 DM, though it is less likely in these patients.⁴ The characteristic cutaneous phenotype of anti-MDA5 DM was described by Fiorentino et al⁵ in 2011 through a seminal retrospective study. Kurtzman and Vleugels⁶ provided validation of the clinical features of anti-MDA5 DM in their 2018 review. The classic cutaneous phenotype of anti-MDA5 DM consists of tender palmar papules and/or skin ulcerations that commonly develop over Gottron papules on the knuckles and digits, lateral nail folds, and elbows.^7-10 A meta-analysis of 1500 patients with anti-MDA5 DM found a statistically significant association with alopecia, Gottron sign or papules, mechanic’s hands, and V rash (P<.05), as well as skin ulcers, panniculitis, arthritis/arthralgia, pneumomediastinum, and rapidly progressive ILD (RP-ILD)(P≤.01).⁴ Rapidly progressive ILD is highly associated with anti-MDA5 DM.^6,11

While a heliotrope rash is classic for DM, and ulcerations are a hallmark of the anti-MDA5 DM subtype, overlap of these cutaneous manifestations is not commonly reported. In both cases presented here, ulcerations of the lateral canthi were associated with progression of ILD.

Diagnosis of Anti-MDA5 DM
Anti-MDA5 DM is defined by the presence of the anti-MDA5 antibody in the serum, named for its reactivity against the RNA helicase encoded by MDA5, within the clinical context of cutaneous signs of DM as described above.¹²

As described by Rider et al,¹³ a thorough laboratory analysis, including complete blood cell count, serum electrolytes, calcium, magnesium, phosphorus, and thyroid-stimulating hormone, is necessary to rule out conditions with similar presentations. Additionally, serum analysis for elevated muscle enzymes (creatinine phosphokinase, aldolase, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase) is necessary to assess for subclinical muscle involvement. Serologic evidence of myositis usually denotes an alternative diagnosis.¹³ Antinuclear antibodies and myositis-specific antibody positivity are much less frequent in the anti-MDA5 DM subtype than in other forms of DM.⁶

Anti-MDA5 antibody titer, ferritin, and IL-18 can be trended and may be useful in the evaluation of the response to treatment and ILD status in patients with anti-MDA5 DM.^14,15 Elevated alveolar-arterial gradient, serum ferritin, serum chitotriosidase, and serum chitinase-3-like protein 1 (YKL-40) have each been associated with poorer prognosis of anti-MDA5 DM. The aforementioned serologies therefore may be helpful in determination of risk stratification and treatment aggressiveness.^16-19

Because of its strong association with RP-ILD, screening for pulmonary disease is necessary in all patients with confirmed or strongly suspected anti-MDA5 DM. Screening can be performed with pulmonary function testing; however, high-resolution chest CT is the gold standard for diagnosis of ILD.²⁰

Finally, all patients with a new diagnosis of DM should be evaluated for underlying malignancy through cancer screenings, given the propensity for DM to present as a paraneoplastic process.²¹ However, reports have indicated that the anti-MDA5 DM subtype may have a reduced risk for or an inverse relationship with underlying malignancy.⁵

Treatment Options for Anti-MDA5 DM
Early and aggressive therapy should be considered in the treatment of anti-MDA5 DM because of its association with RP-ILD. No treatment protocol is well established; thus, an individualized therapeutic approach may be guided by symptom severity and the clinical, radiographic, or functional evidence of ILD.⁶ High-dose systemic corticosteroids are first line, either in combination with or as a bridge to corticosteroid-sparing agents for immunosuppression. Many steroid-sparing medications have been employed with varying success. Mycophenolate mofetil is a reasonable first-line corticosteroid-sparing immunosuppressant agent, given its added benefit of attenuating ILD progression.⁶ A combination of high-dose corticosteroids, cyclosporine, and cyclophosphamide is utilized by some initially in the treatment of anti-MDA5 with ILD.^22,23 While others have used combinations of these immunomodulatory agents with mycophenolate mofetil, IVIG, rituximab, azathioprine, tofacitinib, and polymyxin B, direct hemoperfusion has been added, leading to successful remission.^23-28

Conclusion

We present 2 patients with anti-MDA5 DM who demonstrated a rare cutaneous manifestation of an ulcerative heliotrope rash. In both cases, this cutaneous finding was associated with the development of RP-ILD. Because of the strong association with and rapid progression of ILD seen in anti-MDA5 DM, early identification and aggressive treatment of this subtype are imperative. The clinician should recognize nonacral locations of cutaneous ulcerations, including an ulcerated heliotrope rash, to optimize diagnosis and management.

As manifestations of overt racism and macroaggressions have gained increased visibility, there is a need for discussion of another expression of racism: microaggressions. Although racism classically is viewed as blatant structural, attitudinal, and behavioral prejudice, experts pose that the face of racism has evolved into a more covert insidious form. This form of racism was originally coined racial microaggressions by psychiatrist Chester M. Pierce, MD, 50 years ago.^1,2 Since that time, microaggressions have further expanded to describe “brief and commonplace daily verbal, behavioral, and environmental indignities, whether intentional or unintentional, that communicate hostile, derogatory, or negative racial, gender, sexual-orientation, and religious slights and insults to the target person or group.” ³ This article aims to define and depict examples of microaggressions in medicine, discuss the resulting harmful effects, and offer strategies to minimize and counter these negative ramifications.

What are microaggressions?

Microaggressions are behaviors that stem from implicit bias and occur at an interpersonal level. Implicit bias refers to unconscious stereotypes, assumptions, and beliefs held about an individual’s identity. One of the earliest microaggressions—invisibility—was characterized by Ralph Ellison in his novel Invisible Man. Ellison states, “I am invisible, understand, simply because people refuse to see me . . . When they approach me they see only my surroundings, themselves, or figments of their imagination—indeed, everything and anything except me.”⁴ This concept of invisibility is a primary microaggression faced by people of color.

In medicine, microaggressions and implicit bias may be encountered throughout medical training and clinical practice in interactions with colleagues, superiors, patients, and patients’ families.^5,6 Examples of microaggressions in medicine include demeaning comments, nonverbal disrespect, generalizations of social identity, assumption of nonphysician status, role- or credential-questioning behavior, explicit epithets, rejection of care, questioning or inquiries of ethnic/racial origin, and sexual harassment.⁷

An example of microaggressions in medicine was fully displayed when physician Tamika Cross described her experience of being turned away from helping an unresponsive passenger during a flight emergency.

[T]he flight attendant yells “call overhead for a physician on board.” I raised my hand to grab her attention. She said to me “oh no sweetie put [your] hand down, we are looking for actual physicians or nurses or some type of medical personnel, we don’t have time to talk to you” . . . Another “seasoned” white male approaches the row and says he is a physician as well. She says to me “thanks for your help but he can help us, and he has his credentials.”⁸

What are the effects of microaggressions?

Although microaggressions may be unconscious and unintentional by the offender, the negative ramifications are notable. Recent studies report that women and underrepresented minority (URM) medical students, residents, and physicians experience microaggressions and implicit bias at a higher prevalence and frequency compared with their male and non-URM counterparts.^7,9 Repetitive microaggressions are harmful to the health and safety of women and URM medical students, residents, physicians, other providers, and patients. The Table provides example scenarios of microaggressions in medicine categorized according to Berk.¹⁰

Microaggressions negatively impact physical, mental, and emotional well-being. Current data support that medical students and residents who experience microaggressions are more likely to report associated symptoms of burnout, depression, and suicidal thoughts.^11,12 Subjection to persistent bias can lead to minority status stress and racial battle fatigue, creating feelings of invisibility, isolation, exclusion, and loneliness for those impacted.^13,14

In the book Black Man in a White Coat: A Doctor’s Reflections on Race and Medicine, Damon Tweedy, MD, reflects on race in medicine. Tweedy notes his experience as a medical student when a professor mistakenly assumed he was a maintenance worker in the classroom. Tweedy describes how he internalized the exchange and, despite his success throughout the course of his medical training, combatted feelings of anxiety, self-doubt, and implied inferiority.¹⁵

Although microaggressions are harmful to one’s health, they also undermine the learning and teaching experience for students, residents, and faculty, and they detract from the larger goal of providing care for patients.¹¹ Frequent devaluing and questioning of an individual’s contributions, qualifications, and credentials based on identity can lower productivity and problem-solving abilities. These behaviors cultivate an unwelcome and hostile work/learning environment that is stressful and polarizing for the recipient.

Despite the heavy burden of microaggressions, most students, residents, and faculty physicians do not report incidents to their institutions and feel that training, resources, and policies to respond to bias adequately are lacking.⁷ As a result of implicit bias and microaggressions, women and URM medical students and providers are unable to focus solely on the practice of medicine. They are tasked with the additional burden of shouldering the emotional and cognitive complexities that microaggressions produce.¹⁶

What are strategies to reduce microaggressions in medicine?

To minimize the harmful effects of microaggressions, intervention strategies must be implemented that reduce the likelihood of the occurrence of microaggressions and challenge the stereotypes that undergird implicit bias. These strategies include cultivating allies, followed by demanding structural accountability. Allies are members of the majority group who collectively collaborate with members of the nonmajority group to effect change through the promotion of diversity, equity, and inclusion efforts.¹⁷ Cultivating allies involves building a network of collaboration among these groups and emphasizes education. Education is critical for allies to address microaggressions at the interpersonal level. This process of education involves personal reflection and self-awareness in exploring one’s biases, fears, and assumptions. Integral to this step is broadening one’s acceptance of different cultures, racial/ethnic groups, and identities. There must be a willingness to engage in difficult or uncomfortable conversations and a readiness to actively listen to concerns rather than perpetuating further harm through avoidance and dismissive or defensive behavior.¹⁸

Demanding structural accountability facilitates deconstruction of bias and microaggression at the larger systemic level. This strategy involves implicit bias and antiracism training, development of retention plans, and identification of mentors for women and URM providers and students. Implicit bias and microaggression training and policies should be incorporated into medical education and resident curriculums. Similarly, educational resources and training must be made available to practicing physicians, faculty, and other providers through their institutions and places of employment. Equipping students and providers with the tools needed when microaggressions are witnessed or experienced demonstrates systemic-level accountability and communicates the importance of the issue. Furthermore, the development of retention plans and identification of mentors provide a support system and foster a culture of inclusion where recipients of microaggressions feel protected and valued. Increased feelings of inclusivity and belonging help bridge the gap created through microaggressions and implicit bias.

Final Thoughts

Despite an often covert nature, the detrimental effects of microaggressions are tangible and far reaching. As providers, we must strive to understand all categories of racism and expose the many ways prejudice manifests within medical training and clinical practice. It is our obligation to undertake the challenge of “making the ‘invisible’ visible” as we confront microaggressions and implicit bias to promote a safer and more inclusive medical community and workforce.¹⁹

As manifestations of overt racism and macroaggressions have gained increased visibility, there is a need for discussion of another expression of racism: microaggressions. Although racism classically is viewed as blatant structural, attitudinal, and behavioral prejudice, experts pose that the face of racism has evolved into a more covert insidious form. This form of racism was originally coined racial microaggressions by psychiatrist Chester M. Pierce, MD, 50 years ago.^1,2 Since that time, microaggressions have further expanded to describe “brief and commonplace daily verbal, behavioral, and environmental indignities, whether intentional or unintentional, that communicate hostile, derogatory, or negative racial, gender, sexual-orientation, and religious slights and insults to the target person or group.” ³ This article aims to define and depict examples of microaggressions in medicine, discuss the resulting harmful effects, and offer strategies to minimize and counter these negative ramifications.

What are microaggressions?

Microaggressions are behaviors that stem from implicit bias and occur at an interpersonal level. Implicit bias refers to unconscious stereotypes, assumptions, and beliefs held about an individual’s identity. One of the earliest microaggressions—invisibility—was characterized by Ralph Ellison in his novel Invisible Man. Ellison states, “I am invisible, understand, simply because people refuse to see me . . . When they approach me they see only my surroundings, themselves, or figments of their imagination—indeed, everything and anything except me.”⁴ This concept of invisibility is a primary microaggression faced by people of color.

In medicine, microaggressions and implicit bias may be encountered throughout medical training and clinical practice in interactions with colleagues, superiors, patients, and patients’ families.^5,6 Examples of microaggressions in medicine include demeaning comments, nonverbal disrespect, generalizations of social identity, assumption of nonphysician status, role- or credential-questioning behavior, explicit epithets, rejection of care, questioning or inquiries of ethnic/racial origin, and sexual harassment.⁷

An example of microaggressions in medicine was fully displayed when physician Tamika Cross described her experience of being turned away from helping an unresponsive passenger during a flight emergency.

[T]he flight attendant yells “call overhead for a physician on board.” I raised my hand to grab her attention. She said to me “oh no sweetie put [your] hand down, we are looking for actual physicians or nurses or some type of medical personnel, we don’t have time to talk to you” . . . Another “seasoned” white male approaches the row and says he is a physician as well. She says to me “thanks for your help but he can help us, and he has his credentials.”⁸

What are the effects of microaggressions?

Although microaggressions may be unconscious and unintentional by the offender, the negative ramifications are notable. Recent studies report that women and underrepresented minority (URM) medical students, residents, and physicians experience microaggressions and implicit bias at a higher prevalence and frequency compared with their male and non-URM counterparts.^7,9 Repetitive microaggressions are harmful to the health and safety of women and URM medical students, residents, physicians, other providers, and patients. The Table provides example scenarios of microaggressions in medicine categorized according to Berk.¹⁰

Microaggressions negatively impact physical, mental, and emotional well-being. Current data support that medical students and residents who experience microaggressions are more likely to report associated symptoms of burnout, depression, and suicidal thoughts.^11,12 Subjection to persistent bias can lead to minority status stress and racial battle fatigue, creating feelings of invisibility, isolation, exclusion, and loneliness for those impacted.^13,14

In the book Black Man in a White Coat: A Doctor’s Reflections on Race and Medicine, Damon Tweedy, MD, reflects on race in medicine. Tweedy notes his experience as a medical student when a professor mistakenly assumed he was a maintenance worker in the classroom. Tweedy describes how he internalized the exchange and, despite his success throughout the course of his medical training, combatted feelings of anxiety, self-doubt, and implied inferiority.¹⁵

Although microaggressions are harmful to one’s health, they also undermine the learning and teaching experience for students, residents, and faculty, and they detract from the larger goal of providing care for patients.¹¹ Frequent devaluing and questioning of an individual’s contributions, qualifications, and credentials based on identity can lower productivity and problem-solving abilities. These behaviors cultivate an unwelcome and hostile work/learning environment that is stressful and polarizing for the recipient.

Despite the heavy burden of microaggressions, most students, residents, and faculty physicians do not report incidents to their institutions and feel that training, resources, and policies to respond to bias adequately are lacking.⁷ As a result of implicit bias and microaggressions, women and URM medical students and providers are unable to focus solely on the practice of medicine. They are tasked with the additional burden of shouldering the emotional and cognitive complexities that microaggressions produce.¹⁶

What are strategies to reduce microaggressions in medicine?

To minimize the harmful effects of microaggressions, intervention strategies must be implemented that reduce the likelihood of the occurrence of microaggressions and challenge the stereotypes that undergird implicit bias. These strategies include cultivating allies, followed by demanding structural accountability. Allies are members of the majority group who collectively collaborate with members of the nonmajority group to effect change through the promotion of diversity, equity, and inclusion efforts.¹⁷ Cultivating allies involves building a network of collaboration among these groups and emphasizes education. Education is critical for allies to address microaggressions at the interpersonal level. This process of education involves personal reflection and self-awareness in exploring one’s biases, fears, and assumptions. Integral to this step is broadening one’s acceptance of different cultures, racial/ethnic groups, and identities. There must be a willingness to engage in difficult or uncomfortable conversations and a readiness to actively listen to concerns rather than perpetuating further harm through avoidance and dismissive or defensive behavior.¹⁸

Demanding structural accountability facilitates deconstruction of bias and microaggression at the larger systemic level. This strategy involves implicit bias and antiracism training, development of retention plans, and identification of mentors for women and URM providers and students. Implicit bias and microaggression training and policies should be incorporated into medical education and resident curriculums. Similarly, educational resources and training must be made available to practicing physicians, faculty, and other providers through their institutions and places of employment. Equipping students and providers with the tools needed when microaggressions are witnessed or experienced demonstrates systemic-level accountability and communicates the importance of the issue. Furthermore, the development of retention plans and identification of mentors provide a support system and foster a culture of inclusion where recipients of microaggressions feel protected and valued. Increased feelings of inclusivity and belonging help bridge the gap created through microaggressions and implicit bias.

Final Thoughts

Despite an often covert nature, the detrimental effects of microaggressions are tangible and far reaching. As providers, we must strive to understand all categories of racism and expose the many ways prejudice manifests within medical training and clinical practice. It is our obligation to undertake the challenge of “making the ‘invisible’ visible” as we confront microaggressions and implicit bias to promote a safer and more inclusive medical community and workforce.¹⁹

As manifestations of overt racism and macroaggressions have gained increased visibility, there is a need for discussion of another expression of racism: microaggressions. Although racism classically is viewed as blatant structural, attitudinal, and behavioral prejudice, experts pose that the face of racism has evolved into a more covert insidious form. This form of racism was originally coined racial microaggressions by psychiatrist Chester M. Pierce, MD, 50 years ago.^1,2 Since that time, microaggressions have further expanded to describe “brief and commonplace daily verbal, behavioral, and environmental indignities, whether intentional or unintentional, that communicate hostile, derogatory, or negative racial, gender, sexual-orientation, and religious slights and insults to the target person or group.” ³ This article aims to define and depict examples of microaggressions in medicine, discuss the resulting harmful effects, and offer strategies to minimize and counter these negative ramifications.

What are microaggressions?

Microaggressions are behaviors that stem from implicit bias and occur at an interpersonal level. Implicit bias refers to unconscious stereotypes, assumptions, and beliefs held about an individual’s identity. One of the earliest microaggressions—invisibility—was characterized by Ralph Ellison in his novel Invisible Man. Ellison states, “I am invisible, understand, simply because people refuse to see me . . . When they approach me they see only my surroundings, themselves, or figments of their imagination—indeed, everything and anything except me.”⁴ This concept of invisibility is a primary microaggression faced by people of color.

In medicine, microaggressions and implicit bias may be encountered throughout medical training and clinical practice in interactions with colleagues, superiors, patients, and patients’ families.^5,6 Examples of microaggressions in medicine include demeaning comments, nonverbal disrespect, generalizations of social identity, assumption of nonphysician status, role- or credential-questioning behavior, explicit epithets, rejection of care, questioning or inquiries of ethnic/racial origin, and sexual harassment.⁷

An example of microaggressions in medicine was fully displayed when physician Tamika Cross described her experience of being turned away from helping an unresponsive passenger during a flight emergency.

[T]he flight attendant yells “call overhead for a physician on board.” I raised my hand to grab her attention. She said to me “oh no sweetie put [your] hand down, we are looking for actual physicians or nurses or some type of medical personnel, we don’t have time to talk to you” . . . Another “seasoned” white male approaches the row and says he is a physician as well. She says to me “thanks for your help but he can help us, and he has his credentials.”⁸

What are the effects of microaggressions?

Although microaggressions may be unconscious and unintentional by the offender, the negative ramifications are notable. Recent studies report that women and underrepresented minority (URM) medical students, residents, and physicians experience microaggressions and implicit bias at a higher prevalence and frequency compared with their male and non-URM counterparts.^7,9 Repetitive microaggressions are harmful to the health and safety of women and URM medical students, residents, physicians, other providers, and patients. The Table provides example scenarios of microaggressions in medicine categorized according to Berk.¹⁰

Microaggressions negatively impact physical, mental, and emotional well-being. Current data support that medical students and residents who experience microaggressions are more likely to report associated symptoms of burnout, depression, and suicidal thoughts.^11,12 Subjection to persistent bias can lead to minority status stress and racial battle fatigue, creating feelings of invisibility, isolation, exclusion, and loneliness for those impacted.^13,14

In the book Black Man in a White Coat: A Doctor’s Reflections on Race and Medicine, Damon Tweedy, MD, reflects on race in medicine. Tweedy notes his experience as a medical student when a professor mistakenly assumed he was a maintenance worker in the classroom. Tweedy describes how he internalized the exchange and, despite his success throughout the course of his medical training, combatted feelings of anxiety, self-doubt, and implied inferiority.¹⁵

Although microaggressions are harmful to one’s health, they also undermine the learning and teaching experience for students, residents, and faculty, and they detract from the larger goal of providing care for patients.¹¹ Frequent devaluing and questioning of an individual’s contributions, qualifications, and credentials based on identity can lower productivity and problem-solving abilities. These behaviors cultivate an unwelcome and hostile work/learning environment that is stressful and polarizing for the recipient.

Despite the heavy burden of microaggressions, most students, residents, and faculty physicians do not report incidents to their institutions and feel that training, resources, and policies to respond to bias adequately are lacking.⁷ As a result of implicit bias and microaggressions, women and URM medical students and providers are unable to focus solely on the practice of medicine. They are tasked with the additional burden of shouldering the emotional and cognitive complexities that microaggressions produce.¹⁶

What are strategies to reduce microaggressions in medicine?

To minimize the harmful effects of microaggressions, intervention strategies must be implemented that reduce the likelihood of the occurrence of microaggressions and challenge the stereotypes that undergird implicit bias. These strategies include cultivating allies, followed by demanding structural accountability. Allies are members of the majority group who collectively collaborate with members of the nonmajority group to effect change through the promotion of diversity, equity, and inclusion efforts.¹⁷ Cultivating allies involves building a network of collaboration among these groups and emphasizes education. Education is critical for allies to address microaggressions at the interpersonal level. This process of education involves personal reflection and self-awareness in exploring one’s biases, fears, and assumptions. Integral to this step is broadening one’s acceptance of different cultures, racial/ethnic groups, and identities. There must be a willingness to engage in difficult or uncomfortable conversations and a readiness to actively listen to concerns rather than perpetuating further harm through avoidance and dismissive or defensive behavior.¹⁸

Demanding structural accountability facilitates deconstruction of bias and microaggression at the larger systemic level. This strategy involves implicit bias and antiracism training, development of retention plans, and identification of mentors for women and URM providers and students. Implicit bias and microaggression training and policies should be incorporated into medical education and resident curriculums. Similarly, educational resources and training must be made available to practicing physicians, faculty, and other providers through their institutions and places of employment. Equipping students and providers with the tools needed when microaggressions are witnessed or experienced demonstrates systemic-level accountability and communicates the importance of the issue. Furthermore, the development of retention plans and identification of mentors provide a support system and foster a culture of inclusion where recipients of microaggressions feel protected and valued. Increased feelings of inclusivity and belonging help bridge the gap created through microaggressions and implicit bias.

Final Thoughts

Despite an often covert nature, the detrimental effects of microaggressions are tangible and far reaching. As providers, we must strive to understand all categories of racism and expose the many ways prejudice manifests within medical training and clinical practice. It is our obligation to undertake the challenge of “making the ‘invisible’ visible” as we confront microaggressions and implicit bias to promote a safer and more inclusive medical community and workforce.¹⁹

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

Adding the novel immune checkpoint inhibitor relatlimab to the more established nivolumab (Opdivo) significantly extended the progression-free survival (PFS) of patients with previously untreated advanced melanoma in comparison with nivolumab alone in the phase 3 RELATIVITY-047 trial.

Both drugs are from Bristol-Myers Squibb, which funded the study.

“Our findings demonstrate that relatlimab plus nivolumab is a potential novel treatment option for this patient population,” said lead researcher Evan J. Lipson, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore.

Relatlimab has a different mechanism of action from currently available immune checkpoint inhibitors, such as nivolumab and similar agents, which act as inhibitors of the programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1). In contrast, relatlimab acts as an antibody that targets lymphocyte-activation gene 3 (LAG-3), which inhibits T cells and thus helps cancer cells evade immune attack.

“This is the first phase 3 study to validate inhibition of the LAG-3 immune checkpoint as a therapeutic strategy for patients with cancer, and it establishes the LAG-3 pathway as the third immune checkpoint pathway in history, after CLTA-4 and PD-1, for which blockade appears to have clinical benefit,” Dr. Lipson said at a press briefing ahead of the annual meeting of the American Society of Clinical Oncology (ASCO), where this study will be presented (abstract 9503).

Commenting for ASCO, Julie R. Gralow, MD, chief medical officer and executive vice president, agreed that “these results provide validation of the LAG-3 immune checkpoint as a therapeutic target ... and they also support combination treatment with immunotherapies that act on different parts of the immune system.”

When Dr. Lipson was asked whether he would recommend the combination of relatlimab plus nivolumab as a first-line treatment for this patient population, he said that “for many patients,” the first-line treatment choice is made on a “case-by-case” basis.

“We are fortunate in melanoma that we have an ever-expanding list of seemingly effective options, and I think we’ll find at some point this will be added to that list,” he said. “Whether this is the first-line choice for any given patient really depends on a lot of factors,” he added.

Dr. Gralow added a note of caution. “The combination was clearly more toxic, and so I think there will be a lot of discussion” as to when it would be used and for which patients, she said.

In the absence of head-to-head comparisons, “I’m not sure that we have one answer” as to which treatment to choose, she added. With the ever-increasing number of options available in melanoma, the individual treatment choice is “getting more complicated,” she said.
 

Study details

The global RELATIVITY-047 study was conducted in 714 patients with previously untreated unresectable or metastatic melanoma. The participants were randomly assigned to receive either relatlimab plus nivolumab or nivolumab alone.

Dr. Lipson explained that the treatments were given as a fixed-dosed combination, meaning the preparation of relatlimab and nivolumab was given in the “same medication phial and administered as a single intravenous infusion in order to reduce preparation and infusion times and minimize the risk of administration errors.”

PFS, as determined on blinded independent central review, was significantly longer with the combination therapy than with nivolumab alone, at a median of 10.12 months vs. 4.63 months (hazard ratio, 0.75; P = .0055).

At 12 months, the PFS rate among patients given relatlimab plus nivolumab was 47.7%, versus 36.0% among those given nivolumab alone.

“This significant improvement meant that the study met its primary endpoint,” Dr. Lipson said, adding that the PFS benefit “appeared relatively early in the course of therapy.” The curves separated at 12 weeks, and benefit was “sustained” over the course of follow-up.

He added that the performance of nivolumab alone was “in the range” of that seen in previous studies, although he underlined that cross-trial comparison is difficult, given the differences in study design.

“In general, treatment-related adverse events” associated with the combination therapy were “manageable and reflected the safety profile that we typically see with immune checkpoint inhibitors,” he noted.

The results showed that 40.3% of patients who received the combination therapy experienced a grade 3-4 adverse event, compared with 33.4% of those given nivolumab alone. Grade 3-4 treatment-related adverse events leading to discontinuation occurred in 8.5% and 3.1% of patients, respectively.

Three treatment-related deaths occurred in the relatlimab and nivolumab arm. Two such deaths occurred in the nivolumab-alone group.

The study was funded by Bristol Myers Squibb. Dr. Lipson has relationships with Array BioPharma, Bristol Myers Squibb, EMD Serono, Genentech, Macrogenics, Merck, Millennium, Novartis, Sanofi/Regeneron, and Sysmex (inst). Dr. Gralow has relationships with AstraZeneca, Genentech, Sandoz, and Immunomedics.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

The Centers for Disease Control and Prevention’s latest guidance on what fully vaccinated people can do safely – including not socially distancing and not wearing a mask indoors or outdoors unless other regulations require it – has been widely misinterpreted and caused confusion, two infectious disease experts said at a briefing on May 20 hosted by the Infectious Diseases Society of America (IDSA).

The CDC did not ‘’lift” the mask mandate, but rather supplied guidance for those who are fully vaccinated. However, many questions and gray areas remain, and the experts addressed those. ‘’The CDC guidance is really directed at people who are fully vaccinated and who we know are likely to have a really solid response to the vaccine,” said Jeanne Marrazzo, MD, MPH, director of infectious diseases at the University of Alabama at Birmingham and an IDSA board member.

That message was largely lost, said Dr. Marrazzo and Jeffrey Duchin, MD, health officer of public health for Seattle and King County, Washington, and also an IDSA board member. Dr. Duchin said many people mistakenly regarded the new guidance as a message that the pandemic is over.

Among their practical tips on how to interpret the guidance:
 

To mask or not?

To make the decision, people need to think about not only the numbers of vaccinated versus unvaccinated individuals in their community but the local rates of disease, the experts said.  And they need to know that the CDC guidance doesn’t apply if regulations by federal or state authorities or businesses and workplace are in conflict.

Deciding on mask use sometimes depends on where you are going. What about going into grocery stores or large bin stores without a mask? “If you are fully vaccinated and have no other conditions that compromise your immune system, and the rates of COVID are relatively low where you live, and the vaccination rates are high, I would be 100% fine” without a mask, Dr. Marrazzo said. But it’s important to think of all these factors in calculating your risk.

“I’m still wearing a mask when I go anywhere in public,” she said, citing vaccination rates that have not yet reached 50% in her area.

If that rate reached 80%, the typical percentage talked about for herd immunity, and new cases were low, Dr. Marrazzo said she might shed the mask.

The CDC also continues to recommend masks on mass transit for all.

One population that also must be considered, and who must evaluate their risk, even if vaccinated, are the immunocompromised, Dr. Marrazzo said. While people think of the immunocompromised as those with HIV or organ transplants, the numbers are actually much larger.

“A study a couple of years ago indicated up to 3% of Americans may actually have been told by their physician they have some of level of being immunocompromised,” she said. Among the examples are those who are on dialysis, on chemotherapy, or those taking any of the medications that modify the immune system.

“Millions of people fit this bill, and we have [very] little data on whether the vaccine works in them. We think it does,” Dr. Marrazzo said.

Still, she said, it’s a reason for these people to be cautious. For some other vaccines, the dose is modified for those who are immunocompromised. What’s not known yet is whether additional doses of the COVID vaccines might boost protection for those who are immunocompromised.

Many people, even after vaccination, may choose to keep wearing a mask especially in indoor, crowded settings, Dr. Duchin said. “We need to expect, accept, and respect continued mask wearing by anyone at any time.”

In most outdoor settings, he said, “I think masks are probably not necessary, vaccinated or not, regardless of age.” One exception: close face-to-face contact, such as in certain sports.
 

How to protect toddlers and infants

With masks not practical or recommended for infants and toddlers under 2 years old, Dr. Marrazzo said adults should remember that ‘’those very little kids don’t do poorly at all [even if infected], although there is not a ton of data.”

Adults should still treat young children as vulnerable, especially newborns. Adults not yet vaccinated should wear a mask when around them, she said.
 

J & J vaccine recipients

With less ‘’real world” data on the Johnson & Johnson vaccine, should those who got it think of themselves in a different risk group than those who got Moderna or Pfizer and adjust their behavior accordingly? 

“The J&J vaccine, based on everything we know, does provide a great deal of protection,” Dr. Marrazzo said. ‘’We don’t know as much about prevention of transmission in the asymptomatic cases in the J&J.”

Most of that data, she said, is from the mRNA vaccines Pfizer and Moderna. “I think it’s an important area to study and learn about.” But all three vaccines, overall, provide a high level of protection, she said.

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

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

[email protected]

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

[email protected]

Combined reflectance confocal microscopy–optical coherence tomography is a noninvasive tool that could prove useful in the detection of squamous cell carcinoma (SCC) and distinguishing SCC in-situ and actinic keratosis (AK) from invasive SCC, results from a small prospective study demonstrated.

“A solitary scaly papule or plaque could represent an inflammatory or neoplastic process, and when neoplastic, it could be benign, premalignant, malignant in situ, or invasive malignant,” lead study author Abdullah Aleisa, MD, said in an interview during the annual conference of the American Society for Laser Medicine and Surgery. Noninvasive imaging devices, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), “have been used to help in the diagnosis of those clinically suspicious lesions, however each device has its own limitation.”

RCM images are horizontal sections of the skin with high cellular resolution but limited to 250 mcm of depth in skin, he said, while OCT images are vertical sections of the skin with low cellular resolution, but image up to 1,000-2,000 mcm of depth in skin.

“Combined RCM-OCT enables high cellular resolution and deep tissue evaluation,” said Dr. Aleisa, a micrographic surgery and dermatologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York. “The value of combined RCM-OCT has been shown in the detection and depth assessment of basal cell carcinoma, but it has never been studied in SCC. Our objective is to combine RCM and OCT simultaneously to detect SCC and assess the depth of invasion.”

Between September and December 2020, Dr. Aleisa and colleagues prospectively imaged 36 lesions suspicious of SCC, SCC in situ, or AK between September 2020 and December 2020. The mean age of the cohort was 68 years and 63% were male. Using a prototype device from Andover, Mass.–based Caliber I.D., the investigators performed handheld RCM-OCT imaging at the center of clinically suspected lesions before biopsy and to previously diagnosed lesions before Mohs micrographic surgery (to check for residual tumor) and correlated RCM-OCT findings with histopathology results. A total of 36 lesions were treated.

Dr. Aleisa reported that most common RCM-OCT feature for invasive SCC was presence of vertical blood vessels (in 89% of lesions), while for SCC in situ/AK, it was acanthosis and parakeratosis without vertical blood vessels (in 84% of lesions). For the detection of invasive SCC, RCM-OCT had a sensitivity of 82%, a specificity of 92%, a negative predictive value of 92%, and a positive predictive value of 82%. For the detection of SCC in situ/AK, RCM-OCT had a sensitivity of 86%, a specificity of 100%, a negative predictive value of 92%, and a positive predictive value of 100%. The OCT depth measurement correlated well with histopathology with a concordance correlation coefficient of r2 = 0.9.

“Using RCM’s high-resolution pictures allowed us to easily spot the vertical ‘buttonhole’ vessels associated with SCC,” Dr. Aleisa said. “However, given the depth limitation of RCM, the distinction between SCC in situ and invasive SCC could not be accomplished using RCM alone. Therefore, having simultaneous OCT live feedback to the RCM images in the combined RCM-OCT device enabled us to assess the depth of those vertical ‘buttonholes’ and distinguish between SCC in situ and invasive SCC.”

He acknowledged certain limitations of the approach, including that it requires approximately 20 minutes per imaging session, there is a steep learning curve for interpreting images, and certain anatomical sites are challenging to image, especially the nose, periocular area, and lip.

The study won a “best of session” emerging technologies abstract award from the ASLMS.

Milind Rajadhyaksha, PhD, of Memorial Sloan Kettering Cancer Center helped to develop the prototype device. Dr. Aleisa reported having no relevant financial disclosures.

[email protected]

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

No ifs, ands, or butt ventilators

Breathing, on most days, is a pretty simple task. You inhale, the oxygen goes in, fills your lungs, becomes carbon dioxide, and is exhaled. But as certain recent events have made very clear, some diseases make this task difficult, which is where ventilators come in. The issue is, some patients can’t really use ventilators.

Enter a new study from Japan, which tested the ability of mice and pigs to absorb oxygen through the rectum. Yes, breathing through the butt. It’s not actually such a far-fetched idea; several aquatic animals such as sea cucumbers and catfish absorb oxygen through their intestines, and as any drunken frat boy can tell you after a good butt chug, other chemicals can absolutely be absorbed by human intestines.

After an initial successful experiment where a group of mice had their intestines scrubbed, had pure oxygen inserted enterally, and were exposed to a hypoxic environment, the researchers decided to step up their game and avoid the exhaustive act of digestive scrubbing by enlisting the aid of something out of science fiction: perfluorocarbon. If you haven’t seen “The Abyss,” this liquid can absorb massive amounts of oxygen, so you can actually breathe it in the same way you do with air.

Robert Jones/Pixabay

Better, stronger, faster … pinker

Many people, most of whom aren’t even athletes, commit huge amounts of time, effort, and expense to improve their athletic performance. But what if there’s an easier way?

Research conducted at the University of Westminster (England) showed that participants could, with one fairly simple intervention, get on a treadmill and run 212 meters further in 30 minutes, increasing their speed by an average of 4.4%. Not only that, but “feelings of pleasure were also enhanced, meaning participants found running more enjoyable,” according to a statement from the university.

Is this amazing intervention a new wonder drug? No. Is it a super special nutritional supplement? Negatory. An energy drink that “gives you wiiings”? Nope. The latest designer steroid? Nyet.

Kristan Hutchison (Property of National Science Foundation)

Hey … I’m singing here!

Noise pollution has been linked to plenty of negative outcomes, but the latest target is the poor baby zebra finch.

Researchers at the Max Planck Institute of Ornithology in Germany say traffic noise disrupts the timing of vocal development and impairs learning in the flying finches. The noise was also shown to suppress their immune systems, because of lingering stress.

pixel2013/pixabay

Slimy soap

Remember at the beginning of the pandemic when it was almost impossible to find sufficient hand-washing supplies? Just when you thought you’d tried everything, there is soap made from snail slime.

Snail slime, surprisingly, has many beneficial properties for humans. The slime has antiaging and skin healing properties and is actually used in some Korean beauty supplies. The snails even use the slime to help fix their shells if they become damaged.

Petra Göschel/Pixabay

Of the dermatologic indications for radiofrequency microneedling (RFMN), the published evidence is strongest for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, according to results from a new systematic review.

“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”

When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.

“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”

To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.

After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.

One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”

Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”

One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”

Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”

Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
 

[email protected]

Of the dermatologic indications for radiofrequency microneedling (RFMN), the published evidence is strongest for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, according to results from a new systematic review.

“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”

When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.

“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”

To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.

After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.

One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”

Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”

One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”

Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”

Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
 

[email protected]

Of the dermatologic indications for radiofrequency microneedling (RFMN), the published evidence is strongest for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, according to results from a new systematic review.

“Most devices for aesthetic purposes induce denaturation and remodeling of collagen, elastin, and other dermal structures through tissue injury and stimulating the body’s wound-healing response,” lead study author Marcus G. Tan, MD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “Radiofrequency microneedling is no exception in this regard. RFMN creates perforations in the skin and delivers radiofrequency-generated thermal energy into the underlying tissue. However, RFMN is unique in that thermal energy is delivered in a fashion that produces a reverse temperature gradient to most ablative lasers.”

When using ablative lasers, which target water as its chromophore through selective photothermolysis, the temperature gradient is highest at the epidermis and papillary dermis, and decreases as it penetrates the deeper structures of the skin. In RFMN, radiofrequency energy is delivered directly to the target depth through the microneedle electrodes, thus creating a temperature gradient that is highest in the deep, target structures and cooler at the superficial structures. “This results in less unwanted epidermal heating and reduces the risk of postinflammatory hyperpigmentation,” explained Dr. Tan, a resident in the division of dermatology at the University of Ottawa.

“Because RFMN is unaffected by skin chromophores, it is essentially a ‘color-blind’ technology and safe for use in patients of all skin phototypes. In comparison to lasers, radiofrequency energy can also be delivered to deeper structures of the skin by increasing the length of microneedle electrodes. Despite these advantages of RFMN, this technology remains utilized less frequently compared to ablative lasers for its skin rejuvenating effects.”

To review high-quality medical literature related to RFMN, Dr. Tan and colleagues searched EMBASE and MEDLINE from inception to May 13, 2020, by using the terms “radiofrequency microneedling,” “fractional radiofrequency,” “radiofrequency needling,” or “radiofrequency percutaneous collagen induction.” They limited the analysis to dermatology-related randomized, split-body, or blinded studies with original data in humans. Of the 42 studies included in the final analysis, there were 14 studies of skin rejuvenation, 7 of acne scars, 6 of acne vulgaris, 5 each of striae and axillary hyperhidrosis, 2 of melasma, and 1 each of rosacea, cellulite, and androgenetic alopecia.

After reviewing the 42 studies, the study authors proposed that a strong recommendation for RFMN be made for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis, and a weak recommendation for the technology to be used for papulopustular rosacea, striae, and male-pattern androgenetic alopecia when used in conjunction with topical 5% minoxidil. There was insufficient evidence to make recommendations for its use in cellulite and melasma.

One finding that Dr. Tan described as “interesting” was the observation that RFMN was superior to Er:YAG fractional ablative lasers for treatment of rhytides on the lower face (i.e., the nasolabial, perioral, jawline and neck regions). “Secondly, we observed that one session of RFMN was able to achieve 37% efficacy of a surgical face-lift, but without any adverse effects,” Dr. Tan said. “Two-thirds of the patients who received surgical face-lift developed hypertrophic scarring requiring further scar management, compared to none of the patients receiving RFMN.”

Based on their review, Dr. Tan and colleagues recommend that RFMN be offered as one of the therapeutic options for patients seeking treatment for skin rejuvenation, acne vulgaris, acne scars, and axillary hyperhidrosis. “It is usually tolerable with just topical anesthesia applied 30-60 minutes before treatment, and its side effects are transient and usually resolve after 5 days,” he said. “Patients should be counseled that the benefits of RFMN may have a slower onset, compared to other treatments, but it is progressive, durable, and can be used repeatedly and safely in all skin types including darker-skin phenotypes with minimal risk of adverse events.”

One of the abstract section chairs, Fernanda H. Sakamoto, MD, PhD, said that RFMN devices have become increasingly popular in recent years. “The paper presented by Tan et al. is very relevant, as it compares clinical indications, parameters, and results in search for evidence of efficacy and appropriate settings,” said Dr. Sakamoto, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, told this news organization. “The paper provides long-needed guidelines to clinicians and helps manage patients’ expectations.”

Dr. Tan acknowledged certain limitations of the study, including the lack of head-to-head studies comparing specific RFMN devices. “There are many RFMN devices available commercially, each with different capabilities and degrees of effectiveness,” he said. “With more research and technological advancements since the first radiofrequency device was approved in 2002, RFMN has made significant improvements. In general, the newer generation devices produce markedly better results.”

Dr. Tan reported having no financial disclosures. Dr. Sakamoto disclosed that she holds intellectual property rights with Accure Acne, Massachusetts General Hospital, and Lightwater Biosciences.
 

[email protected]

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

The delivery of photobiomodulation therapy (PBMT) was found to limit the severity of acute radiodermatitis in patients undergoing treatment for head and neck cancer, according to results from the first randomized study of its kind.

“The use of light therapy-based applications for cancer therapy-related adverse events has steadily increased in the past 40 years,” lead study author Jolien Robijns, MSc, PhD, told this news organization during the annual conference of the American Society for Laser Medicine and Surgery. “The most well-known and studied indication of photobiomodulation therapy in supportive cancer care is oral mucositis,” she said, referring to a recent systematic review, which found that based on the available evidence, PBMT is an effective therapy for the prevention of oral mucositis, using well-defined PBM parameters in specific patient populations. “Various internationally well-recognized health organizations in oncology recommend PBMT to prevent and manage oral mucositis,” she added.

Based on the wound-healing and anti-inflammatory properties of PBMT, several studies have investigated its use for the prevention and management of acute radiodermatitis (ARD) since the 1990s, said Dr. Robijns, a postdoctoral researcher at Limburg Clinical Research Center in Hasselt, Belgium. Under the supervision of Jeroen Mebis, MD, PhD, at the Limburg Oncologic Laser Institute, she and her colleagues have been conducting clinical research on PBMT and ARD since 2014, with successful results. In 2020 they published a narrative review, which showed that based on nine clinical trials, PBMT could effectively reduce the incidence of severe ARD, decrease accompanying pain, and improve patients’ quality of life.

For the current study, known as the DERMISHEAD trial and published online March 9, 2021, in Radiotherapy and Oncology, investigators at Limburg Oncology Center at Jessa Hospital in Hasselt, and Hasselt University, recruited head and neck cancer patients who underwent bilateral radiotherapy with or without chemotherapy, for a total dose of 30-35 x 2 Gy . All patients received standard skin care combined with two PBMT or sham sessions twice per week during the complete course of RT, which resulted in 14 total sessions.

As described in the Radiotherapy and Oncology study, the commercially available device used for PBMT “consists of two laser diodes with different wavelengths (808-905 nm), peak powers (1.1-25 W), and emission modes (continuous and pulsed). Both diodes work simultaneously and synchronously with coincident propagation axes (average radiant power 3.3 W). The energy density (fluence) was set at 4 J/cm² based on earlier recommendations and on our clinical experience.” A blinded study nurse used Radiation Therapy Oncology Group criteria to evaluate the skin reactions.

After 303 patients were initially assessed for eligibility, 46 patients were enrolled in DERMISHEAD (18 in the placebo group and 28 in the PBMT group). At the end of radiotherapy, 77.8% of patients in the placebo group had a grade 2 or 3 skin reaction, compared with 28.6% of patients in the PBMT group (P = .001).

“The DERMISHEAD trial proved that PBMT significantly reduces the severity of ARD,” Dr. Robijns said. “Thereby, it improves the patients’ quality of life during their radiotherapy course. The trial supports the further implementation of PBM in the supportive care of cancer patients undergoing radiotherapy.”

The results are similar to those in the TRANSDERMIS trial, in which Dr. Robijns and her colleagues used PMBT to treat breast cancer patients.

“However, an interesting difference is that the percentage decrease in severe ARD was higher in the DERMISHEAD trial than in the TRANSDERMIS trial: 49% vs. 23%, respectively,” she noted. “This difference can be rationalized because in total, more control head and neck cancer patients developed grade 3 ARD than did control breast cancer patients (17% vs. 5%). A possible explanation of this finding can be related to the difference in treatment regimens and radiotherapy parameters between the two trials.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study, said that acute radiation dermatitis “can be very painful and distressing to patients, and over time, the skin changes can create long-term problems. Prevention of acute and chronic radiation dermatitis is worthwhile, particularly for patients at risk.”

This study, she added, “shows a benefit of photobiomodulation therapy as a potential preventative treatment. Notably, patients did not always follow up appropriately for the therapy, and the authors said that it is yet another thing that patients need to keep track of, in addition to their cancer therapy visits. Thus, optimally, it would be useful to have a biomarker of which patients would most benefit from treatments that prevent/potentiate radiation dermatitis.”

Dr. Robijns acknowledged certain limitations of the trial, including its small sample size and the scarcity of clinical trials on PBM and acute radiation dermatitis. “More studies are needed,” she said. “Future studies should focus on randomized controlled study designs with well-described and complete PBMT parameters in a larger and more diverse patient population. This would enable the implementation of PBM in the field of ARD and supportive cancer care, which would enhance wound care management and improve the patient’s quality of life.”

This work won a “best of clinical applications” abstract award from the ASLMS.

The research is part of the Limburg Clinical Research Center UHasselt-ZOL-Jessa, financially supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish Government, Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital. The research is also funded by Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society, Limburgs Kankerfonds, and ASA Srl. Dr. Robijns reported having no financial disclosures.

[email protected]

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.