MDedge Dermatology

To the Editor:

Granular parakeratosis is a rare condition with an unclear etiology that results from a myriad of factors, including exposure to irritants, friction, moisture, and heat. The diagnosis is made based on a distinct histologic reaction pattern that may be protective against the triggers. We present a case of isolated scrotal granular parakeratosis in a patient with compensatory hyperhidrosis after endoscopic thoracic sympathectomy.

A 52-year-old man presented with a 5-year history of a recurrent rash affecting the scrotum. He experienced monthly flares that were exacerbated by inguinal hyperhidrosis. His symptoms included a burning sensation and pruritus followed by superficial desquamation, with gradual yet temporary improvement. His medical history was remarkable for primary axillary and palmoplantar hyperhidrosis, with compensatory inguinal hyperhidrosis after endoscopic thoracic sympathectomy 8 years prior to presentation.

Physical examination revealed a well-demarcated, scaly, erythematous plaque affecting the scrotal skin with sparing of the median raphe, penis, and inguinal folds (Figure 1). There were no other lesions noted in the axillary region or other skin folds.

Murine models have postulated that granular parakeratosis may result from a deficiency in caspase 14, a protease vital to the formation of a well-functioning skin barrier.⁹ A cornified envelope often is noted in granular parakeratotic cells with no defects in desmosomes and cell membranes, suggesting that the pathogenesis lies within processing of profilaggrin to filaggrin, resulting in a failure to degrade keratohyalin granules and aggregation of keratin filaments.¹⁰ Granular parakeratosis is not known to be associated with other medical conditions, but it has been observed in patients receiving chemotherapy for breast¹¹ and ovarian¹² carcinomas. In infants with atopic dermatitis, granular parakeratosis was reported in 5 out of 7 cases.⁶ In our patient with secondary inguinal hyperhidrosis after thoracic sympathectomy, granular parakeratosis may be reactive to excess sweating and friction in the scrotal area.

Granular parakeratosis follows a waxing and waning pattern that may spontaneously resolve without any treatment; it also can follow a protracted course, as in a case with associated facial papules that persisted for 20 years.¹³ Topical corticosteroids alone or in combination with topical antifungal agents have been used for the treatment of granular parakeratosis with the goal of accelerating resolution.^2,14 However, the efficacy of these therapeutic interventions is limited, and no controlled trials are underway. Topical vitamin D analogues^15,16 and topical retinoids¹⁷ also have been reported with successful outcomes. Spontaneous resolution also has been observed in 2 different cases after previously being unresponsive to topical treatment.^18,19 Treatment with Clostridium botulinum toxin A resulted in complete remission of the disease observed at 6-month follow-up. The pharmacologic action of the neurotoxin disrupts the stimulation of eccrine sweat glands, resulting in decreased sweating, a known exacerbating factor of granular parakeratosis.²⁰

In summary, our case represents a unique clinical presentation of granular parakeratosis with classic histopathologic features. A high index of suspicion and a biopsy are vital to arriving at the correct diagnosis.

To the Editor:

Granular parakeratosis is a rare condition with an unclear etiology that results from a myriad of factors, including exposure to irritants, friction, moisture, and heat. The diagnosis is made based on a distinct histologic reaction pattern that may be protective against the triggers. We present a case of isolated scrotal granular parakeratosis in a patient with compensatory hyperhidrosis after endoscopic thoracic sympathectomy.

A 52-year-old man presented with a 5-year history of a recurrent rash affecting the scrotum. He experienced monthly flares that were exacerbated by inguinal hyperhidrosis. His symptoms included a burning sensation and pruritus followed by superficial desquamation, with gradual yet temporary improvement. His medical history was remarkable for primary axillary and palmoplantar hyperhidrosis, with compensatory inguinal hyperhidrosis after endoscopic thoracic sympathectomy 8 years prior to presentation.

Physical examination revealed a well-demarcated, scaly, erythematous plaque affecting the scrotal skin with sparing of the median raphe, penis, and inguinal folds (Figure 1). There were no other lesions noted in the axillary region or other skin folds.

Murine models have postulated that granular parakeratosis may result from a deficiency in caspase 14, a protease vital to the formation of a well-functioning skin barrier.⁹ A cornified envelope often is noted in granular parakeratotic cells with no defects in desmosomes and cell membranes, suggesting that the pathogenesis lies within processing of profilaggrin to filaggrin, resulting in a failure to degrade keratohyalin granules and aggregation of keratin filaments.¹⁰ Granular parakeratosis is not known to be associated with other medical conditions, but it has been observed in patients receiving chemotherapy for breast¹¹ and ovarian¹² carcinomas. In infants with atopic dermatitis, granular parakeratosis was reported in 5 out of 7 cases.⁶ In our patient with secondary inguinal hyperhidrosis after thoracic sympathectomy, granular parakeratosis may be reactive to excess sweating and friction in the scrotal area.

Granular parakeratosis follows a waxing and waning pattern that may spontaneously resolve without any treatment; it also can follow a protracted course, as in a case with associated facial papules that persisted for 20 years.¹³ Topical corticosteroids alone or in combination with topical antifungal agents have been used for the treatment of granular parakeratosis with the goal of accelerating resolution.^2,14 However, the efficacy of these therapeutic interventions is limited, and no controlled trials are underway. Topical vitamin D analogues^15,16 and topical retinoids¹⁷ also have been reported with successful outcomes. Spontaneous resolution also has been observed in 2 different cases after previously being unresponsive to topical treatment.^18,19 Treatment with Clostridium botulinum toxin A resulted in complete remission of the disease observed at 6-month follow-up. The pharmacologic action of the neurotoxin disrupts the stimulation of eccrine sweat glands, resulting in decreased sweating, a known exacerbating factor of granular parakeratosis.²⁰

In summary, our case represents a unique clinical presentation of granular parakeratosis with classic histopathologic features. A high index of suspicion and a biopsy are vital to arriving at the correct diagnosis.

To the Editor:

Granular parakeratosis is a rare condition with an unclear etiology that results from a myriad of factors, including exposure to irritants, friction, moisture, and heat. The diagnosis is made based on a distinct histologic reaction pattern that may be protective against the triggers. We present a case of isolated scrotal granular parakeratosis in a patient with compensatory hyperhidrosis after endoscopic thoracic sympathectomy.

A 52-year-old man presented with a 5-year history of a recurrent rash affecting the scrotum. He experienced monthly flares that were exacerbated by inguinal hyperhidrosis. His symptoms included a burning sensation and pruritus followed by superficial desquamation, with gradual yet temporary improvement. His medical history was remarkable for primary axillary and palmoplantar hyperhidrosis, with compensatory inguinal hyperhidrosis after endoscopic thoracic sympathectomy 8 years prior to presentation.

Physical examination revealed a well-demarcated, scaly, erythematous plaque affecting the scrotal skin with sparing of the median raphe, penis, and inguinal folds (Figure 1). There were no other lesions noted in the axillary region or other skin folds.

Murine models have postulated that granular parakeratosis may result from a deficiency in caspase 14, a protease vital to the formation of a well-functioning skin barrier.⁹ A cornified envelope often is noted in granular parakeratotic cells with no defects in desmosomes and cell membranes, suggesting that the pathogenesis lies within processing of profilaggrin to filaggrin, resulting in a failure to degrade keratohyalin granules and aggregation of keratin filaments.¹⁰ Granular parakeratosis is not known to be associated with other medical conditions, but it has been observed in patients receiving chemotherapy for breast¹¹ and ovarian¹² carcinomas. In infants with atopic dermatitis, granular parakeratosis was reported in 5 out of 7 cases.⁶ In our patient with secondary inguinal hyperhidrosis after thoracic sympathectomy, granular parakeratosis may be reactive to excess sweating and friction in the scrotal area.

Granular parakeratosis follows a waxing and waning pattern that may spontaneously resolve without any treatment; it also can follow a protracted course, as in a case with associated facial papules that persisted for 20 years.¹³ Topical corticosteroids alone or in combination with topical antifungal agents have been used for the treatment of granular parakeratosis with the goal of accelerating resolution.^2,14 However, the efficacy of these therapeutic interventions is limited, and no controlled trials are underway. Topical vitamin D analogues^15,16 and topical retinoids¹⁷ also have been reported with successful outcomes. Spontaneous resolution also has been observed in 2 different cases after previously being unresponsive to topical treatment.^18,19 Treatment with Clostridium botulinum toxin A resulted in complete remission of the disease observed at 6-month follow-up. The pharmacologic action of the neurotoxin disrupts the stimulation of eccrine sweat glands, resulting in decreased sweating, a known exacerbating factor of granular parakeratosis.²⁰

In summary, our case represents a unique clinical presentation of granular parakeratosis with classic histopathologic features. A high index of suspicion and a biopsy are vital to arriving at the correct diagnosis.

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

To the Editor:

A range of dermatologic manifestations of COVID-19 have been reported, including nonspecific maculopapular exanthems, urticaria, and varicellalike eruptions.¹ Additionally, there have been sporadic accounts of cutaneous vasculopathic signs such as perniolike lesions, acro-ischemia, livedo reticularis, and retiform purpura.² We describe exuberant hemorrhagic bullae occurring on the extremities of 2 critically ill patients with COVID-19. We hypothesized that the bullae were vasculopathic in nature and possibly exacerbated by peripheral intravenous (IV)–related injury.

A 62-year-old woman with a history of diabetes mellitus and chronic obstructive pulmonary disease was admitted to the intensive care unit for acute hypoxemic respiratory failure secondary to COVID-19 infection. Dermatology was consulted for evaluation of blisters on the right arm. A new peripheral IV line was inserted into the patient’s right forearm for treatment of secondary methicillin-resistant Staphylococcus aureus pneumonia. The peripheral IV was inserted into the right proximal forearm for 2 days prior to development of ecchymosis and blisters. Intravenous medications included vancomycin, cefepime, methylprednisolone, and famotidine, as well as maintenance fluids (normal saline). Physical examination revealed extensive confluent ecchymoses with overlying tense bullae (Figure 1). Notable laboratory findings included an elevated D-dimer (peak of 8.67 μg/mL fibrinogen-equivalent units [FEUs], reference range <0.5 μg/mL FEU) and fibrinogen (789 mg/dL, reference range 200–400 mg/dL) levels. Three days later she developed worsening edema of the right arm, accompanied by more extensive bullae formation (Figure 2). Computed tomography of the right arm showed extensive subcutaneous stranding and subcutaneous edema. An orthopedic consultation determined that there was no compartment syndrome, and surgical intervention was not recommended. The patient’s course was complicated by multiorgan failure, and she died 18 days after admission.

Extravasation injury results from unintentional administration of potentially vesicant substances into tissues surrounding the intended vascular channel.⁴ The mechanism of action of these injuries is postulated to arise from direct tissue injury from cytotoxic substances, elevated osmotic pressure, and reduced blood supply if vasoconstrictive substances are infused.⁵ In our patients, these injuries also may have promoted vascular occlusion leading to the brisk reaction observed. Although ecchymoses typically are associated with hypocoagulable states, both of our patients were noted to have normal platelet levels throughout hospitalization. Additionally, findings of elevated D-dimer and fibrinogen levels point to a hypercoagulable state. However, there is a possibility of platelet dysfunction leading to the observed cutaneous findings of ecchymoses. Thrombocytopenia is a common finding in patients with COVID-19 and is found to be associated with increased in-hospital mortality.⁶ Additional study of these reactions is needed given the propensity for multiorgan failure and death in patients with COVID-19 from suspected diffuse microvascular damage.³

To the Editor:

A range of dermatologic manifestations of COVID-19 have been reported, including nonspecific maculopapular exanthems, urticaria, and varicellalike eruptions.¹ Additionally, there have been sporadic accounts of cutaneous vasculopathic signs such as perniolike lesions, acro-ischemia, livedo reticularis, and retiform purpura.² We describe exuberant hemorrhagic bullae occurring on the extremities of 2 critically ill patients with COVID-19. We hypothesized that the bullae were vasculopathic in nature and possibly exacerbated by peripheral intravenous (IV)–related injury.

A 62-year-old woman with a history of diabetes mellitus and chronic obstructive pulmonary disease was admitted to the intensive care unit for acute hypoxemic respiratory failure secondary to COVID-19 infection. Dermatology was consulted for evaluation of blisters on the right arm. A new peripheral IV line was inserted into the patient’s right forearm for treatment of secondary methicillin-resistant Staphylococcus aureus pneumonia. The peripheral IV was inserted into the right proximal forearm for 2 days prior to development of ecchymosis and blisters. Intravenous medications included vancomycin, cefepime, methylprednisolone, and famotidine, as well as maintenance fluids (normal saline). Physical examination revealed extensive confluent ecchymoses with overlying tense bullae (Figure 1). Notable laboratory findings included an elevated D-dimer (peak of 8.67 μg/mL fibrinogen-equivalent units [FEUs], reference range <0.5 μg/mL FEU) and fibrinogen (789 mg/dL, reference range 200–400 mg/dL) levels. Three days later she developed worsening edema of the right arm, accompanied by more extensive bullae formation (Figure 2). Computed tomography of the right arm showed extensive subcutaneous stranding and subcutaneous edema. An orthopedic consultation determined that there was no compartment syndrome, and surgical intervention was not recommended. The patient’s course was complicated by multiorgan failure, and she died 18 days after admission.

Extravasation injury results from unintentional administration of potentially vesicant substances into tissues surrounding the intended vascular channel.⁴ The mechanism of action of these injuries is postulated to arise from direct tissue injury from cytotoxic substances, elevated osmotic pressure, and reduced blood supply if vasoconstrictive substances are infused.⁵ In our patients, these injuries also may have promoted vascular occlusion leading to the brisk reaction observed. Although ecchymoses typically are associated with hypocoagulable states, both of our patients were noted to have normal platelet levels throughout hospitalization. Additionally, findings of elevated D-dimer and fibrinogen levels point to a hypercoagulable state. However, there is a possibility of platelet dysfunction leading to the observed cutaneous findings of ecchymoses. Thrombocytopenia is a common finding in patients with COVID-19 and is found to be associated with increased in-hospital mortality.⁶ Additional study of these reactions is needed given the propensity for multiorgan failure and death in patients with COVID-19 from suspected diffuse microvascular damage.³

To the Editor:

A range of dermatologic manifestations of COVID-19 have been reported, including nonspecific maculopapular exanthems, urticaria, and varicellalike eruptions.¹ Additionally, there have been sporadic accounts of cutaneous vasculopathic signs such as perniolike lesions, acro-ischemia, livedo reticularis, and retiform purpura.² We describe exuberant hemorrhagic bullae occurring on the extremities of 2 critically ill patients with COVID-19. We hypothesized that the bullae were vasculopathic in nature and possibly exacerbated by peripheral intravenous (IV)–related injury.

A 62-year-old woman with a history of diabetes mellitus and chronic obstructive pulmonary disease was admitted to the intensive care unit for acute hypoxemic respiratory failure secondary to COVID-19 infection. Dermatology was consulted for evaluation of blisters on the right arm. A new peripheral IV line was inserted into the patient’s right forearm for treatment of secondary methicillin-resistant Staphylococcus aureus pneumonia. The peripheral IV was inserted into the right proximal forearm for 2 days prior to development of ecchymosis and blisters. Intravenous medications included vancomycin, cefepime, methylprednisolone, and famotidine, as well as maintenance fluids (normal saline). Physical examination revealed extensive confluent ecchymoses with overlying tense bullae (Figure 1). Notable laboratory findings included an elevated D-dimer (peak of 8.67 μg/mL fibrinogen-equivalent units [FEUs], reference range <0.5 μg/mL FEU) and fibrinogen (789 mg/dL, reference range 200–400 mg/dL) levels. Three days later she developed worsening edema of the right arm, accompanied by more extensive bullae formation (Figure 2). Computed tomography of the right arm showed extensive subcutaneous stranding and subcutaneous edema. An orthopedic consultation determined that there was no compartment syndrome, and surgical intervention was not recommended. The patient’s course was complicated by multiorgan failure, and she died 18 days after admission.

Extravasation injury results from unintentional administration of potentially vesicant substances into tissues surrounding the intended vascular channel.⁴ The mechanism of action of these injuries is postulated to arise from direct tissue injury from cytotoxic substances, elevated osmotic pressure, and reduced blood supply if vasoconstrictive substances are infused.⁵ In our patients, these injuries also may have promoted vascular occlusion leading to the brisk reaction observed. Although ecchymoses typically are associated with hypocoagulable states, both of our patients were noted to have normal platelet levels throughout hospitalization. Additionally, findings of elevated D-dimer and fibrinogen levels point to a hypercoagulable state. However, there is a possibility of platelet dysfunction leading to the observed cutaneous findings of ecchymoses. Thrombocytopenia is a common finding in patients with COVID-19 and is found to be associated with increased in-hospital mortality.⁶ Additional study of these reactions is needed given the propensity for multiorgan failure and death in patients with COVID-19 from suspected diffuse microvascular damage.³

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

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

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

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

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

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

To the Editor:

A 62-year-old woman with a history of dermatomyositis (DM) presented to dermatology clinic for evaluation of multiple subcutaneous nodules. Two years prior to the current presentation, the patient was diagnosed by her primary care physician with DM based on clinical presentation. She initially developed body aches, muscle pain, and weakness of the upper extremities, specifically around the shoulders, and later the lower extremities, specifically around the thighs. The initial physical examination revealed pain with movement, tenderness to palpation, and proximal extremity weakness. The patient also noted a 50-lb weight loss. Over the next year, she noted dysphagia and developed multiple subcutaneous nodules on the right arm, chest, and left axilla. Subsequently, she developed a violaceous, hyperpigmented, periorbital rash and erythema of the anterior chest. She did not experience hair loss, oral ulcers, photosensitivity, or joint pain.

Laboratory testing in the months following the initial presentation revealed a creatine phosphokinase level of 436 U/L (reference range, 20–200 U/L), an erythrocyte sedimentation rate of 60 mm/h (reference range, <31 mm/h), and an aldolase level of 10.4 U/L (reference range, 1.0–8.0 U/L). Lactate dehydrogenase and thyroid function tests were within normal limits. Antinuclear antibodies, anti–double-stranded DNA, anti-Smith antibodies, anti-ribonucleoprotein, anti–Jo-1 antibodies, and anti–smooth muscle antibodies all were negative. Total blood complement levels were elevated, but complement C3 and C4 were within normal limits. Imaging demonstrated normal chest radiographs, and a modified barium swallow confirmed swallowing dysfunction. A right quadricep muscle biopsy confirmed the diagnosis of DM. A malignancy work-up including mammography, colonoscopy, and computed tomography of the chest, abdomen, and pelvis was negative aside from nodular opacities in the chest. She was treated with prednisone (60 mg, 0.9 mg/kg) daily and methotrexate (15–20 mg) weekly for several months. While the treatment attenuated the rash and improved weakness, the nodules persisted, prompting a referral to dermatology.

Physical examination at the dermatology clinic demonstrated the persistent subcutaneous nodules were indurated and bilaterally located on the arms, axillae, chest, abdomen, buttocks, and thighs with no pain or erythema (Figure). Laboratory tests demonstrated a normal creatine phosphokinase level, elevated erythrocyte sedimentation rate (70 mm/h), and elevated aldolase level (9.3 U/L). Complement levels were elevated, though complement C3 and C4 remained within normal limits. Histopathology of nodules from the medial right upper arm and left thigh showed lobular panniculitis with fat necrosis, calcification, and interface changes. The patient was treated for several months with daily mycophenolate mofetil (1 g increased to 3 g) and daily hydroxychloroquine (200 mg) without any effect on the nodules.

A majority of the reported panniculitis cases in DM have responded to treatment with prednisone; however, treatment with prednisone has been more recalcitrant in other cases. Reports of successful additional therapies include methotrexate, cyclosporine, azathioprine, hydroxychloroquine, intravenous immunoglobulin, mepacrine, or a combination of these entities.^19,22 In most cases, improvement of the panniculitis and other DM symptoms occurred simultaneously.²⁵ It is noteworthy that the muscular symptoms often resolved more rapidly than cutaneous manifestations.³³ Few reported cases (6 including the current case) found a persistent panniculitis despite improvement and remission of the myositis.^3,5,10,11,30

Our patient was treated with both prednisone and methotrexate for several months, leading to remission of muscular symptoms (along with return to baseline of creatine phosphokinase), yet the panniculitis did not improve. The subcutaneous nodules also did not respond to treatment with mycophenolate mofetil and hydroxychloroquine.

Recent immunohistochemical studies have suggested that panniculitic lesions show better outcomes with immunosuppressive therapy when compared with other DM-related skin lesions.⁴⁰ However, this was not the case for our patient, who after months of immunosuppressive therapy showed complete resolution of the periorbital and chest rashes with persistence of multiple indurated subcutaneous nodules.

Our case adds to a number of reports of DM presenting with panniculitis. Our patient fit the classic demographic of previously reported cases, as she was an adult woman without evidence of underlying malignancy; however, our case remains an example of the therapeutic challenge that exists when encountering a persistent, treatment-resistant panniculitis despite resolution of all other features of DM.

TABLE IS AVAILABLE IN THE PDF OF THIS ARTICLE

To the Editor:

A 62-year-old woman with a history of dermatomyositis (DM) presented to dermatology clinic for evaluation of multiple subcutaneous nodules. Two years prior to the current presentation, the patient was diagnosed by her primary care physician with DM based on clinical presentation. She initially developed body aches, muscle pain, and weakness of the upper extremities, specifically around the shoulders, and later the lower extremities, specifically around the thighs. The initial physical examination revealed pain with movement, tenderness to palpation, and proximal extremity weakness. The patient also noted a 50-lb weight loss. Over the next year, she noted dysphagia and developed multiple subcutaneous nodules on the right arm, chest, and left axilla. Subsequently, she developed a violaceous, hyperpigmented, periorbital rash and erythema of the anterior chest. She did not experience hair loss, oral ulcers, photosensitivity, or joint pain.

Laboratory testing in the months following the initial presentation revealed a creatine phosphokinase level of 436 U/L (reference range, 20–200 U/L), an erythrocyte sedimentation rate of 60 mm/h (reference range, <31 mm/h), and an aldolase level of 10.4 U/L (reference range, 1.0–8.0 U/L). Lactate dehydrogenase and thyroid function tests were within normal limits. Antinuclear antibodies, anti–double-stranded DNA, anti-Smith antibodies, anti-ribonucleoprotein, anti–Jo-1 antibodies, and anti–smooth muscle antibodies all were negative. Total blood complement levels were elevated, but complement C3 and C4 were within normal limits. Imaging demonstrated normal chest radiographs, and a modified barium swallow confirmed swallowing dysfunction. A right quadricep muscle biopsy confirmed the diagnosis of DM. A malignancy work-up including mammography, colonoscopy, and computed tomography of the chest, abdomen, and pelvis was negative aside from nodular opacities in the chest. She was treated with prednisone (60 mg, 0.9 mg/kg) daily and methotrexate (15–20 mg) weekly for several months. While the treatment attenuated the rash and improved weakness, the nodules persisted, prompting a referral to dermatology.

Physical examination at the dermatology clinic demonstrated the persistent subcutaneous nodules were indurated and bilaterally located on the arms, axillae, chest, abdomen, buttocks, and thighs with no pain or erythema (Figure). Laboratory tests demonstrated a normal creatine phosphokinase level, elevated erythrocyte sedimentation rate (70 mm/h), and elevated aldolase level (9.3 U/L). Complement levels were elevated, though complement C3 and C4 remained within normal limits. Histopathology of nodules from the medial right upper arm and left thigh showed lobular panniculitis with fat necrosis, calcification, and interface changes. The patient was treated for several months with daily mycophenolate mofetil (1 g increased to 3 g) and daily hydroxychloroquine (200 mg) without any effect on the nodules.

A majority of the reported panniculitis cases in DM have responded to treatment with prednisone; however, treatment with prednisone has been more recalcitrant in other cases. Reports of successful additional therapies include methotrexate, cyclosporine, azathioprine, hydroxychloroquine, intravenous immunoglobulin, mepacrine, or a combination of these entities.^19,22 In most cases, improvement of the panniculitis and other DM symptoms occurred simultaneously.²⁵ It is noteworthy that the muscular symptoms often resolved more rapidly than cutaneous manifestations.³³ Few reported cases (6 including the current case) found a persistent panniculitis despite improvement and remission of the myositis.^3,5,10,11,30

Our patient was treated with both prednisone and methotrexate for several months, leading to remission of muscular symptoms (along with return to baseline of creatine phosphokinase), yet the panniculitis did not improve. The subcutaneous nodules also did not respond to treatment with mycophenolate mofetil and hydroxychloroquine.

Recent immunohistochemical studies have suggested that panniculitic lesions show better outcomes with immunosuppressive therapy when compared with other DM-related skin lesions.⁴⁰ However, this was not the case for our patient, who after months of immunosuppressive therapy showed complete resolution of the periorbital and chest rashes with persistence of multiple indurated subcutaneous nodules.

Our case adds to a number of reports of DM presenting with panniculitis. Our patient fit the classic demographic of previously reported cases, as she was an adult woman without evidence of underlying malignancy; however, our case remains an example of the therapeutic challenge that exists when encountering a persistent, treatment-resistant panniculitis despite resolution of all other features of DM.

TABLE IS AVAILABLE IN THE PDF OF THIS ARTICLE

To the Editor:

A 62-year-old woman with a history of dermatomyositis (DM) presented to dermatology clinic for evaluation of multiple subcutaneous nodules. Two years prior to the current presentation, the patient was diagnosed by her primary care physician with DM based on clinical presentation. She initially developed body aches, muscle pain, and weakness of the upper extremities, specifically around the shoulders, and later the lower extremities, specifically around the thighs. The initial physical examination revealed pain with movement, tenderness to palpation, and proximal extremity weakness. The patient also noted a 50-lb weight loss. Over the next year, she noted dysphagia and developed multiple subcutaneous nodules on the right arm, chest, and left axilla. Subsequently, she developed a violaceous, hyperpigmented, periorbital rash and erythema of the anterior chest. She did not experience hair loss, oral ulcers, photosensitivity, or joint pain.

Laboratory testing in the months following the initial presentation revealed a creatine phosphokinase level of 436 U/L (reference range, 20–200 U/L), an erythrocyte sedimentation rate of 60 mm/h (reference range, <31 mm/h), and an aldolase level of 10.4 U/L (reference range, 1.0–8.0 U/L). Lactate dehydrogenase and thyroid function tests were within normal limits. Antinuclear antibodies, anti–double-stranded DNA, anti-Smith antibodies, anti-ribonucleoprotein, anti–Jo-1 antibodies, and anti–smooth muscle antibodies all were negative. Total blood complement levels were elevated, but complement C3 and C4 were within normal limits. Imaging demonstrated normal chest radiographs, and a modified barium swallow confirmed swallowing dysfunction. A right quadricep muscle biopsy confirmed the diagnosis of DM. A malignancy work-up including mammography, colonoscopy, and computed tomography of the chest, abdomen, and pelvis was negative aside from nodular opacities in the chest. She was treated with prednisone (60 mg, 0.9 mg/kg) daily and methotrexate (15–20 mg) weekly for several months. While the treatment attenuated the rash and improved weakness, the nodules persisted, prompting a referral to dermatology.

Physical examination at the dermatology clinic demonstrated the persistent subcutaneous nodules were indurated and bilaterally located on the arms, axillae, chest, abdomen, buttocks, and thighs with no pain or erythema (Figure). Laboratory tests demonstrated a normal creatine phosphokinase level, elevated erythrocyte sedimentation rate (70 mm/h), and elevated aldolase level (9.3 U/L). Complement levels were elevated, though complement C3 and C4 remained within normal limits. Histopathology of nodules from the medial right upper arm and left thigh showed lobular panniculitis with fat necrosis, calcification, and interface changes. The patient was treated for several months with daily mycophenolate mofetil (1 g increased to 3 g) and daily hydroxychloroquine (200 mg) without any effect on the nodules.

A majority of the reported panniculitis cases in DM have responded to treatment with prednisone; however, treatment with prednisone has been more recalcitrant in other cases. Reports of successful additional therapies include methotrexate, cyclosporine, azathioprine, hydroxychloroquine, intravenous immunoglobulin, mepacrine, or a combination of these entities.^19,22 In most cases, improvement of the panniculitis and other DM symptoms occurred simultaneously.²⁵ It is noteworthy that the muscular symptoms often resolved more rapidly than cutaneous manifestations.³³ Few reported cases (6 including the current case) found a persistent panniculitis despite improvement and remission of the myositis.^3,5,10,11,30

Our patient was treated with both prednisone and methotrexate for several months, leading to remission of muscular symptoms (along with return to baseline of creatine phosphokinase), yet the panniculitis did not improve. The subcutaneous nodules also did not respond to treatment with mycophenolate mofetil and hydroxychloroquine.

Recent immunohistochemical studies have suggested that panniculitic lesions show better outcomes with immunosuppressive therapy when compared with other DM-related skin lesions.⁴⁰ However, this was not the case for our patient, who after months of immunosuppressive therapy showed complete resolution of the periorbital and chest rashes with persistence of multiple indurated subcutaneous nodules.

Our case adds to a number of reports of DM presenting with panniculitis. Our patient fit the classic demographic of previously reported cases, as she was an adult woman without evidence of underlying malignancy; however, our case remains an example of the therapeutic challenge that exists when encountering a persistent, treatment-resistant panniculitis despite resolution of all other features of DM.

TABLE IS AVAILABLE IN THE PDF OF THIS ARTICLE

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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

Since the U.S. Food and Drug Administration established its accelerated drug approval pathway 28 years ago, more than 2 in 5 drugs granted fast-track approval have not been confirmed clinically effective as required, an in-depth investigation published in The BMJ has determined.

“Despite the pathway’s good intentions to accelerate ‘the availability of drugs that treat serious diseases,’ experts are concerned that it is now being exploited – to the detriment of patients, who may be prescribed a drug that offers little benefit and possible harm, and to taxpayers,” writes Elisabeth Mahase, clinical reporter at The BMJ, who carried out the analysis.

The FDA’s accelerated approval pathway is intended to provide earlier access to drugs for serious diseases when there is lingering uncertainty at the time of approval regarding the drug’s ultimate clinical benefit.
 

Required studies rarely completed

As part of this fast-track pathway, drug manufacturers must conduct postapproval, phase 4 confirmatory trials to verify the anticipated clinical benefit. If these trials indicate no benefit, FDA approval can be withdrawn.

However, the analysis of FDA data shows once they are approved drugs are rarely taken off the market.

The BMJ investigation that analyzed data up to the end of 2020 shows that 112 of the 253 (44%) medications granted accelerated approval have not been confirmed to be effective.

In addition, 24 (21%) of these questionable drugs have been on the market for more than 5 years and some have been on the market for more than 20 years – often with a hefty price tag.

Furthermore, only 16 drugs approved through the accelerated approval process have ever been withdrawn, and most were shown to be ineffective, but in some cases the confirmatory trials were never done, Ms. Mahase reports.

For example, the COX-2 inhibitor celecoxib (Celebrex), which was granted accelerated approval in 1999 for the treatment of familial adenomatous polyposis, was on the market for 12 years before the FDA finally asked Pfizer to voluntarily withdraw it for this indication because efficacy trials were never completed.

As part of The BMJ’s investigation, Ms. Mahase asked manufacturers of the 24 drugs that have remained on the market for more than 5 years whether they had conducted the required phase 4 confirmatory trials. Six of the drugs had been withdrawn, approved, or postponed.

Of the remaining 18 drugs, the manufacturers provided the relevant trial information for only six. Only four drugmakers had started to recruit patients; two said they were still in discussion with the FDA over the final trial design.

“These products routinely have side effects, but the benefit information is a lot less certain. That’s what we’re concerned about – that we may have drugs on the market that don’t have any benefits, but certainly predictably have harms associated with them,” Huseyin Naci, PhD, MHS, with the London School of Economics, comments in the report.
 

Call for reform

As reported by this news organization, a 2015 report by the General Accountability Office (GAO) concluded that the FDA does not do an effective job of tracking the clinical efficacy or the safety of drugs with expedited approval after they hit the market.

In April of this year, the Institute for Clinical and Economic Review (ICER) cited a lack of “credible threats” to withdraw approval if companies don’t do confirmatory trials – meaning drugmakers have little incentive to do the trials.

“There are some instances where the companies really do seem to be taking advantage of the accelerated approval pathway and are using it in a way that makes it harder to get at the truth about whether these products really are safe and effective,” Rachel Sachs, JD, MPH, Washington University, St. Louis, said in The BMJ article.

In addition, the authors of a recent viewpoint article in JAMA Internal Medicine assert the recent approval of the controversial anti-amyloid drug aducanumab (Aduhelm, Biogen) shows that the accelerated approval pathway needs to be reformed.

Despite the concerns, Ms. Mahase said all experts who spoke to The BMJ believe the accelerated approval pathway is still useful and can be beneficial to patients, although some changes are needed.

One effective reform might be to have confirmatory trials designed, and even started, as part of accelerated approval.

“One important piece of the puzzle is for the FDA itself to be tougher on these companies, to hold them to the bargain that they have agreed to, and to take action when the company has not met their obligations,” Ms. Sachs told the journal.

An FDA spokesperson told the BMJ that the agency is “committed to working with sponsors to ensure that confirmatory studies are completed in a timely manner.”

“We expect sponsors to commit all resources needed to move trials forward as effectively as possible, with the aim of completing trials as soon as is feasible, while assuring the quality of the data and the robustness of the results,” the agency said.

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