MDedge Dermatology

A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.

This case illustrates a common problem in medicine: Noise, the chance variability in judgments that should all be identical (it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).

Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.

There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.

Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)

I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!

Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].

A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.

This case illustrates a common problem in medicine: Noise, the chance variability in judgments that should all be identical (it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).

Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.

There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.

Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)

I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!

Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].

A 26-year-old woman who reports a history of acyclovir-resistant herpes complains of a recurring, stinging rash around her mouth. Topical tacrolimus made it worse, she said. On exam, she has somewhat grouped pustules on her cutaneous lip. I mentioned her to colleagues, saying: “I’ve a patient with acyclovir-resistant herpes who isn’t improving on high-dose Valtrex.” They proffered a few alternative diagnoses and treatment recommendations. I tried several to no avail.

This case illustrates a common problem in medicine: Noise, the chance variability in judgments that should all be identical (it is after all only one condition). Nobel Prize–winning economist Daniel Kahneman, PhD, with two other authors, has written a brilliant book about this cognitive unreliability called “Noise: A Flaw in Human Judgment” (New York: Hachette Book Group, 2021).

Both bias and noise create trouble for us. Although biases get more attention, noise is both more prevalent and insidious. In a 2016 article, Dr. Kahneman and coauthors use a bathroom scale as an analogy to explain the difference. “We would say that the scale is biased if its readings are generally either too high or too low. A scale that consistently underestimates true weight by exactly 4 pounds is seriously biased but free of noise. A scale that gives two different readings when you step on it twice is noisy.” In the case presented, “measurements” by me and my colleagues were returning different “readings.” There is one true diagnosis and best treatment, yet because of noise, we waste time and resources by not getting it right the first time.

There is also evidence of bias in this case. For example, there’s probably some confirmation bias: The patient said she has a history of antiviral-resistant herpes; therefore, her rash might appear to be herpes. Also there might be salience bias: it’s easy to see how prominent pustules might be herpes simplex virus. Noise is an issue in many misdiagnoses, but trickier to see. In most instances, we don’t have the opportunity to get multiple assessments of the same case. When examined though, interrater reliability in medicine is often found to be shockingly low, an indication of how much noise there is in our clinical judgments. This leads to waste, frustration – and can even be dangerous when we’re trying to diagnose cancers such as melanoma, lung, or breast cancer.

Dr. Kahneman and colleagues have excellent recommendations on how to reduce noise, such as tips for good decision hygiene (e.g., using differential diagnoses) and using algorithms (e.g., calculating Apgar or LACE scores). I also liked their strategy of aggregating expert opinions. Fascinatingly, averaging multiple independent assessments is mathematically guaranteed to reduce noise. (God, I love economists). This is true of measurements and opinions: If you use 100 judgments for a case, you reduce noise by 90% (the noise is divided by the square root of the number of judgments averaged). So 20 colleagues’ opinions would reduce noise by almost 80%. However, those 20 opinions must be independent to avoid spurious agreement. (Again, math for the win.)

I showed photos of my patient to a few other dermatologists. They independently returned the same result: perioral dermatitis. This was the correct diagnosis and reminded me why grand rounds and tumor boards are such a great help. Multiple, independent assessments are more likely to get it right than just one opinion because we are canceling out the noise. But remember, grand rounds has to be old-school style – no looking at your coresident answers before giving yours!

Our patient cleared after restarting her topical tacrolimus and a bit of doxycycline. Credit the wisdom of the crowd. Reassuringly though, Dr. Kahneman also shows that expertise does matter in minimizing error. So that fellowship you did was still a great idea.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. He reports having no conflicts of interest. Write to him at [email protected].

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

To the Editor:

A 59-year-old man presented with a severely pruritic rash on the legs, arms, abdomen, groin, and buttocks of 3 days’ duration. He reported subjective fever and chills. Prior to the appearance of the rash, the patient and his family had eaten shiitake mushrooms daily for 3 days. He denied any new medications in the last several months or any recent upper respiratory or gastrointestinal tract illnesses. His medical history included type 2 diabetes mellitus and diabetes-induced end-stage renal disease requiring home peritoneal dialysis. His long-term medications for diabetes mellitus, hypertension, benign prostatic hyperplasia, hyperlipidemia, and insomnia included amlodipine, atorvastatin, finasteride, gabapentin, insulin glargine, linagliptin, metoprolol, and mirtazapine.

Physical examination revealed an afebrile man with medium brown skin tone and diffuse, bright red, erythematous patches on the lower legs, axillae, medial forearms, lateral trunk, lower abdomen, and groin. There were distinct flagellate, linear, red patches on the lower legs (Figure 1). In addition, small clusters of 1- to 2-mm superficial pustules were present on the right upper medial thigh and left forearm with micropapules grouped in the skin folds.

A shave biopsy specimen from a pustule on the right upper medial thigh revealed spongiotic dermatitis with neutrophilic subcorneal pustule formation and frequent eosinophils (Figure 2). The dermis contained scattered mixed inflammatory cells including neutrophils, eosinophils, lymphocytes, and histiocytes (Figure 3). These histologic findings were consistent with acute generalized exanthematous pustulosis (AGEP). No biopsy was performed on the flagellate patches due to its clinically distinct presentation and well-established association with shiitake mushroom ingestion.

The patient was treated with triamcinolone ointment and systemic corticosteroids to reduce pruritus and quickly clear the lesions due to his comorbidities. He recovered completely within 1 week and had no evidence of postinflammatory hyperpigmentation from the flagellate dermatitis.

Flagellate dermatitis is an intensely pruritic dermatitis characterized by 1-mm, disseminated, erythematous papules in a linear grouped arrangement secondary to koebnerization due to the patient scratching. It was first described in 1977 by Nakamura.¹ Although it rarely is seen outside of China and Japan, there are well-established associations of flagellate dermatitis with bleomycin and shiitake mushroom (Lentinula edodes) ingestion. One key clinical difference between the two causes is that postinflammatory hyperpigmentation changes usually are seen with bleomycin-induced flagellate dermatitis and typically are not present with shiitake mushroom–induced flagellate dermatitis.² Following ingestion of shiitake mushrooms, the median time of onset of presentation typically is 24 hours but ranges from 12 hours to 5 days. Most patients completely recover by 3 weeks, with or without treatment.³ Although the pathogenesis of shiitake mushroom–induced flagellate dermatitis is not clear, the most common theory is a toxic reaction to lentinan, a polysaccharide isolated from shiitake mushrooms. However, type I and IV allergic hypersensitivities also have been supported by the time of onset, clearance, severe pruritus, benefit from steroids and antihistamines, and lack of grouped outbreaks in people exposed to shared meals containing shiitake mushrooms.^3,4 Furthermore, there is a case of patch test–confirmed allergic contact dermatitis to shiitake mushrooms, demonstrating a 1+ reaction at 96 hours to the cap of a shiitake mushroom but a negative pin-prick test at 20 minutes, suggesting type IV hypersensitivity.⁵ An additional case revealed a positive skin-prick test with formation of a 4-mm wheal and subsequent pruritic papules and vesicles appearing 48 to 72 hours later at the prick site.⁶ Subsequent cases have been reported in association with consumption of raw shiitake mushrooms, but cases have been reported after consumption of fully cooked mushrooms, which does not support a toxin-mediated theory, as cooking the mushroom before consumption likely would denature or change the structure of the suspected toxin.²

Acute generalized exanthematous pustulosis is a rare eruption that occurs due to ingestion of a causative agent, usually an antibiotic, and is characterized by the presence of fever and disseminated, erythematous, pinpoint, sterile pustules on the skin and mucous membranes. It affects 1 to 5 persons per million per year, with more than 90% of cases attributed to drug ingestion.⁷ Spontaneous resolution can be expected within 15 days of its onset; however, there is a mortality rate of up to 5% that occurs most often in those with severe comorbidities or in older patients, for whom systemic corticosteroid therapy may be justified.^7,8 A multinational case-control study conducted to evaluate the risk of AGEP associated with certain drugs revealed macrolides (namely pristinamycin); β-lactam antibiotics including penicillin, aminopenicillin, and cephalosporin; quinolones; hydroxychloroquine; anti-infective sulfonamides; terbinafine; and diltiazem as the most strongly associated culprits.⁹ Our patient’s flagellate dermatitis was unique in that it also showed histologic features of AGEP. The pathogenesis of drug-induced AGEP has been partially elucidated and involves activation of drug-specific CD4⁺ and CD8⁺ T cells that migrate to the skin and participate in apoptotic signaling of keratinocytes and recruitment of neutrophils and eosinophils, which form subcorneal sterile pustules.⁷ In a study of severe cutaneous adverse drug reactions, 50% (7/14) of patients with AGEP had positive patch tests to the causative agent.¹⁰ This T cell–dependent response explains why the condition responds to systemic corticosteroids. Additionally, our case report of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP suggests that the pathogenesis of flagellate dermatitis may be a T cell–mediated type IV hypersensitivity reaction. The time of onset, lack of grouped outbreaks in those sharing shiitake mushroom–containing meals, severe pruritus, lack of cases demonstrating an anaphylactic or wheal and flare response, benefit of steroids, and a case with histologic features of AGEP all lend support to this theory.

We report a case of shiitake mushroom–induced flagellate dermatitis with histologic features of AGEP. The time course, histologic features of AGEP, absence of new medications, and resolution with discontinuation of shiitake mushrooms lends support of the hypothesis that the pathogenesis of shiitake mushroom–induced flagellate dermatitis is similar to AGEP’s type IV hypersensitivity reaction. To further elucidate its pathogenesis, skin prick testing and patch testing with shiitake mushrooms in patients exhibiting shiitake mushroom–induced flagellate dermatitis may prove to be beneficial.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

To the Editor:

PTEN hamartoma tumor syndrome (PHTS) encompasses a spectrum of disorders that most commonly are caused by autosomal-dominant germline mutations in the phosphatase and tensin homolog, PTEN, tumor suppressor gene on chromosome 10q23. We describe a patient who presented with clinical features of PHTS and Birt-Hogg-Dubé syndrome (BHDS). Because the genetic mutations associated with both PHTS and BHDS result in altered mammalian target of rapamycin (mTOR) signaling, patients may have overlapping phenotypic features.

A 51-year-old man with a history of multiple carcinomas presented for evaluation of flesh-colored papules on the cheeks, nose, tongue, and hands, in addition to numerous skin tags on the neck, axillae, and lower abdomen bilaterally. His medical history was notable for several nasal and gastrointestinal tract polyps, chromophobe renal cell carcinoma, cutaneous lipomas, atypical carcinoid syndrome of the right lung, and a multinodular thyroid. His family history was notable for small cell lung cancer in his father, breast cancer and pancreatic cancer in his maternal aunt, esophageal cancer in his maternal grandfather, and celiac disease in his daughter.

Clinical examination revealed flesh-colored, dome-shaped papules measuring 1 to 2 mm in diameter on the nose and cheeks (Figure 1). He had hyperkeratotic papules on the dorsal fingers, consistent with acral keratoses. Additionally, multiple flesh-colored papules with a cobblestonelike appearance were noted on the oral mucosa (Figure 2). Other findings included pedunculated papules on the neck, axillae, and lower abdomen bilaterally, consistent with fibroepithelial polyps, as well as hyperpigmented velvety plaques on the axillae, characteristic of acanthosis nigricans (Figure 3). A shave biopsy of a papule on the right cheek revealed a proliferation of plump stellate fibroblasts, small blood vessels, and thick collagen bundles, characteristic of a fibrous papule (Figure 4).

Differential diagnoses for our patient included BHDS and Cowden syndrome (CS). Due to the combination of extensive family history of multiorgan cancers as well as the clinical findings, he was referred to a geneticist for further evaluation. Genetic analysis was positive for a heterozygous mutation variant of uncertain significance in the PTEN gene.

The PHTS disorders include CS, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Proteus syndrome, and Proteus-like syndrome (Table).^1-9 Our patient’s clinical findings were indicative of CS, a rare genodermatosis characterized by multiple hamartomas and neoplasms of ectodermal, mesodermal, and endodermal origin.¹ Most CS patients develop trichilemmomas of the central face, mucocutaneous papillomatous papules, and acral and plantar keratoses by the third decade of life.¹ Importantly, CS patients have an increased risk for breast, thyroid, renal, endometrial, and colorectal cancers, as well as melanoma, with estimated lifetime risks of 85%, 35%, 33%, 28%, 9%, and 6%, respectively.^2,10

Regarding the pathophysiology of PHTS disorders, PTEN encodes a phosphatase that inhibits phosphoinositide 3-kinase/Akt and mTOR signaling pathways, thereby controlling cell proliferation, cell-cycle progression, and apoptosis.^2,3 Loss of PTEN function, as seen in CS patients, results in an increased risk for cancer.² Other genetic diseases, including juvenile polyposis syndrome, Proteus syndrome, tuberous sclerosis, and Peutz-Jeghers syndrome, have phenotypic similarities to PHTS.³ Specifically, loss-of-function mutations of TSC1 and TSC2, tumor suppressor genes associated with tuberous sclerosis, similarly result in dysregulation of mTOR signaling.

Our patient also had some clinical features characteristic of BHDS, such as flesh-colored facial papules, acrochordonlike lesions, and chromophobe renal cell carcinoma.¹¹ Birt-Hogg-Dubé syndrome most often is caused by an autosomal-dominant germline mutation in FLCN, a tumor suppressor gene.¹¹ Interestingly, FLCN interacts with AMP-activated protein kinase to help regulate mTOR signaling, which may explain phenotypic similarities seen in CS and BHDS.¹²

Because the PHTS disorders and BHDS result in similar functional consequences on the mTOR signaling pathway, patients can present with overlapping clinical features that may be diagnostically challenging. Management includes patient education regarding cancer risk, surveillance for early detection of malignancy, and genetic counseling for family members.² It is important for clinicians to appreciate phenotypic similarities between PHTS and other disorders affecting mTOR signaling to prevent delays in diagnosis.

To the Editor:

PTEN hamartoma tumor syndrome (PHTS) encompasses a spectrum of disorders that most commonly are caused by autosomal-dominant germline mutations in the phosphatase and tensin homolog, PTEN, tumor suppressor gene on chromosome 10q23. We describe a patient who presented with clinical features of PHTS and Birt-Hogg-Dubé syndrome (BHDS). Because the genetic mutations associated with both PHTS and BHDS result in altered mammalian target of rapamycin (mTOR) signaling, patients may have overlapping phenotypic features.

A 51-year-old man with a history of multiple carcinomas presented for evaluation of flesh-colored papules on the cheeks, nose, tongue, and hands, in addition to numerous skin tags on the neck, axillae, and lower abdomen bilaterally. His medical history was notable for several nasal and gastrointestinal tract polyps, chromophobe renal cell carcinoma, cutaneous lipomas, atypical carcinoid syndrome of the right lung, and a multinodular thyroid. His family history was notable for small cell lung cancer in his father, breast cancer and pancreatic cancer in his maternal aunt, esophageal cancer in his maternal grandfather, and celiac disease in his daughter.

Clinical examination revealed flesh-colored, dome-shaped papules measuring 1 to 2 mm in diameter on the nose and cheeks (Figure 1). He had hyperkeratotic papules on the dorsal fingers, consistent with acral keratoses. Additionally, multiple flesh-colored papules with a cobblestonelike appearance were noted on the oral mucosa (Figure 2). Other findings included pedunculated papules on the neck, axillae, and lower abdomen bilaterally, consistent with fibroepithelial polyps, as well as hyperpigmented velvety plaques on the axillae, characteristic of acanthosis nigricans (Figure 3). A shave biopsy of a papule on the right cheek revealed a proliferation of plump stellate fibroblasts, small blood vessels, and thick collagen bundles, characteristic of a fibrous papule (Figure 4).

Differential diagnoses for our patient included BHDS and Cowden syndrome (CS). Due to the combination of extensive family history of multiorgan cancers as well as the clinical findings, he was referred to a geneticist for further evaluation. Genetic analysis was positive for a heterozygous mutation variant of uncertain significance in the PTEN gene.

The PHTS disorders include CS, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Proteus syndrome, and Proteus-like syndrome (Table).^1-9 Our patient’s clinical findings were indicative of CS, a rare genodermatosis characterized by multiple hamartomas and neoplasms of ectodermal, mesodermal, and endodermal origin.¹ Most CS patients develop trichilemmomas of the central face, mucocutaneous papillomatous papules, and acral and plantar keratoses by the third decade of life.¹ Importantly, CS patients have an increased risk for breast, thyroid, renal, endometrial, and colorectal cancers, as well as melanoma, with estimated lifetime risks of 85%, 35%, 33%, 28%, 9%, and 6%, respectively.^2,10

Regarding the pathophysiology of PHTS disorders, PTEN encodes a phosphatase that inhibits phosphoinositide 3-kinase/Akt and mTOR signaling pathways, thereby controlling cell proliferation, cell-cycle progression, and apoptosis.^2,3 Loss of PTEN function, as seen in CS patients, results in an increased risk for cancer.² Other genetic diseases, including juvenile polyposis syndrome, Proteus syndrome, tuberous sclerosis, and Peutz-Jeghers syndrome, have phenotypic similarities to PHTS.³ Specifically, loss-of-function mutations of TSC1 and TSC2, tumor suppressor genes associated with tuberous sclerosis, similarly result in dysregulation of mTOR signaling.

Our patient also had some clinical features characteristic of BHDS, such as flesh-colored facial papules, acrochordonlike lesions, and chromophobe renal cell carcinoma.¹¹ Birt-Hogg-Dubé syndrome most often is caused by an autosomal-dominant germline mutation in FLCN, a tumor suppressor gene.¹¹ Interestingly, FLCN interacts with AMP-activated protein kinase to help regulate mTOR signaling, which may explain phenotypic similarities seen in CS and BHDS.¹²

Because the PHTS disorders and BHDS result in similar functional consequences on the mTOR signaling pathway, patients can present with overlapping clinical features that may be diagnostically challenging. Management includes patient education regarding cancer risk, surveillance for early detection of malignancy, and genetic counseling for family members.² It is important for clinicians to appreciate phenotypic similarities between PHTS and other disorders affecting mTOR signaling to prevent delays in diagnosis.

To the Editor:

PTEN hamartoma tumor syndrome (PHTS) encompasses a spectrum of disorders that most commonly are caused by autosomal-dominant germline mutations in the phosphatase and tensin homolog, PTEN, tumor suppressor gene on chromosome 10q23. We describe a patient who presented with clinical features of PHTS and Birt-Hogg-Dubé syndrome (BHDS). Because the genetic mutations associated with both PHTS and BHDS result in altered mammalian target of rapamycin (mTOR) signaling, patients may have overlapping phenotypic features.

A 51-year-old man with a history of multiple carcinomas presented for evaluation of flesh-colored papules on the cheeks, nose, tongue, and hands, in addition to numerous skin tags on the neck, axillae, and lower abdomen bilaterally. His medical history was notable for several nasal and gastrointestinal tract polyps, chromophobe renal cell carcinoma, cutaneous lipomas, atypical carcinoid syndrome of the right lung, and a multinodular thyroid. His family history was notable for small cell lung cancer in his father, breast cancer and pancreatic cancer in his maternal aunt, esophageal cancer in his maternal grandfather, and celiac disease in his daughter.

Clinical examination revealed flesh-colored, dome-shaped papules measuring 1 to 2 mm in diameter on the nose and cheeks (Figure 1). He had hyperkeratotic papules on the dorsal fingers, consistent with acral keratoses. Additionally, multiple flesh-colored papules with a cobblestonelike appearance were noted on the oral mucosa (Figure 2). Other findings included pedunculated papules on the neck, axillae, and lower abdomen bilaterally, consistent with fibroepithelial polyps, as well as hyperpigmented velvety plaques on the axillae, characteristic of acanthosis nigricans (Figure 3). A shave biopsy of a papule on the right cheek revealed a proliferation of plump stellate fibroblasts, small blood vessels, and thick collagen bundles, characteristic of a fibrous papule (Figure 4).

Differential diagnoses for our patient included BHDS and Cowden syndrome (CS). Due to the combination of extensive family history of multiorgan cancers as well as the clinical findings, he was referred to a geneticist for further evaluation. Genetic analysis was positive for a heterozygous mutation variant of uncertain significance in the PTEN gene.

The PHTS disorders include CS, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Proteus syndrome, and Proteus-like syndrome (Table).^1-9 Our patient’s clinical findings were indicative of CS, a rare genodermatosis characterized by multiple hamartomas and neoplasms of ectodermal, mesodermal, and endodermal origin.¹ Most CS patients develop trichilemmomas of the central face, mucocutaneous papillomatous papules, and acral and plantar keratoses by the third decade of life.¹ Importantly, CS patients have an increased risk for breast, thyroid, renal, endometrial, and colorectal cancers, as well as melanoma, with estimated lifetime risks of 85%, 35%, 33%, 28%, 9%, and 6%, respectively.^2,10

Regarding the pathophysiology of PHTS disorders, PTEN encodes a phosphatase that inhibits phosphoinositide 3-kinase/Akt and mTOR signaling pathways, thereby controlling cell proliferation, cell-cycle progression, and apoptosis.^2,3 Loss of PTEN function, as seen in CS patients, results in an increased risk for cancer.² Other genetic diseases, including juvenile polyposis syndrome, Proteus syndrome, tuberous sclerosis, and Peutz-Jeghers syndrome, have phenotypic similarities to PHTS.³ Specifically, loss-of-function mutations of TSC1 and TSC2, tumor suppressor genes associated with tuberous sclerosis, similarly result in dysregulation of mTOR signaling.

Our patient also had some clinical features characteristic of BHDS, such as flesh-colored facial papules, acrochordonlike lesions, and chromophobe renal cell carcinoma.¹¹ Birt-Hogg-Dubé syndrome most often is caused by an autosomal-dominant germline mutation in FLCN, a tumor suppressor gene.¹¹ Interestingly, FLCN interacts with AMP-activated protein kinase to help regulate mTOR signaling, which may explain phenotypic similarities seen in CS and BHDS.¹²

Because the PHTS disorders and BHDS result in similar functional consequences on the mTOR signaling pathway, patients can present with overlapping clinical features that may be diagnostically challenging. Management includes patient education regarding cancer risk, surveillance for early detection of malignancy, and genetic counseling for family members.² It is important for clinicians to appreciate phenotypic similarities between PHTS and other disorders affecting mTOR signaling to prevent delays in diagnosis.

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

Medicare reimbursement for a group of 46 common dermatologic procedures dropped by a mean of 4.8% from 2007 to 2021, after adjusting for inflation, according to a new analysis.

Large increases in mean reimbursement for skin biopsies (+30.3%) and shave removal (+24.6%) were not enough to offset lower rates for procedures such as simple repair (–38.7%), premalignant destruction (–19.6%), Mohs micrographic surgery (–14.4%), and flap repair (–14.1%), Rishabh S. Mazmudar, BS, of Case Western Reserve University, Cleveland, and associates said.

“Given Medicare’s contribution to a large proportion of health care expenditures, changes in Medicare reimbursement rates may result in parallel changes in private insurance reimbursement,” they wrote in JAMA Dermatology.

A recently published study showed that Medicare reimbursement for 20 dermatologic service codes had fallen by 10% between the two comparison years, 2000 and 2020. The current study expanded the number of procedures to 46 (divided into nine categories) and used historical Medicare fee schedules to examine annual trends over a 15-year period, Mr. Mazmudar and associates explained.

Other specialties have seen reimbursement fall by more than 4.8%, including emergency medicine (–21.2% from 2000 to 2020) and general surgery (–24.4% from 2000 to 2018), but “these comparisons are likely skewed by the disproportionate increase in reimbursement rates for biopsies and shave removals during this time period,” the investigators said.

If those two procedure categories were excluded from the analysis, the mean change in overall reimbursement for the remaining dermatologic procedures would be −9.6%, they noted.

Detailed payment information provided for 15 of the 46 procedures shows that only intermediate repair (+4.5%) and benign destruction (+2.3%) joined biopsies and shave excisions with increased reimbursement from 2007 to 2021. The smallest drop among the other procedures was –1.9% for malignant destruction, the research team reported.

The inflation-adjusted, year-by-year analysis showed that reimbursement for the nine procedure categories has gradually declined since peaking in 2011, with the most notable exceptions being biopsies and shave excisions. Both had been following the trend until 2013, when reimbursement for shave removals jumped by almost 30 percentage points, and 2019, when rates for biopsies soared by more than 30 percentage points, according to the investigators.

The increase for skin biopsies followed the split of the original CPT code into three categories, but “the jump in reimbursement for shave removals in 2013 requires further investigation,” Mr. Mazmudar and associates wrote.

The investigators did not disclose any conflicts of interest.

[email protected]

Medicare reimbursement for a group of 46 common dermatologic procedures dropped by a mean of 4.8% from 2007 to 2021, after adjusting for inflation, according to a new analysis.

Large increases in mean reimbursement for skin biopsies (+30.3%) and shave removal (+24.6%) were not enough to offset lower rates for procedures such as simple repair (–38.7%), premalignant destruction (–19.6%), Mohs micrographic surgery (–14.4%), and flap repair (–14.1%), Rishabh S. Mazmudar, BS, of Case Western Reserve University, Cleveland, and associates said.

“Given Medicare’s contribution to a large proportion of health care expenditures, changes in Medicare reimbursement rates may result in parallel changes in private insurance reimbursement,” they wrote in JAMA Dermatology.

A recently published study showed that Medicare reimbursement for 20 dermatologic service codes had fallen by 10% between the two comparison years, 2000 and 2020. The current study expanded the number of procedures to 46 (divided into nine categories) and used historical Medicare fee schedules to examine annual trends over a 15-year period, Mr. Mazmudar and associates explained.

Other specialties have seen reimbursement fall by more than 4.8%, including emergency medicine (–21.2% from 2000 to 2020) and general surgery (–24.4% from 2000 to 2018), but “these comparisons are likely skewed by the disproportionate increase in reimbursement rates for biopsies and shave removals during this time period,” the investigators said.

If those two procedure categories were excluded from the analysis, the mean change in overall reimbursement for the remaining dermatologic procedures would be −9.6%, they noted.

Detailed payment information provided for 15 of the 46 procedures shows that only intermediate repair (+4.5%) and benign destruction (+2.3%) joined biopsies and shave excisions with increased reimbursement from 2007 to 2021. The smallest drop among the other procedures was –1.9% for malignant destruction, the research team reported.

The inflation-adjusted, year-by-year analysis showed that reimbursement for the nine procedure categories has gradually declined since peaking in 2011, with the most notable exceptions being biopsies and shave excisions. Both had been following the trend until 2013, when reimbursement for shave removals jumped by almost 30 percentage points, and 2019, when rates for biopsies soared by more than 30 percentage points, according to the investigators.

The increase for skin biopsies followed the split of the original CPT code into three categories, but “the jump in reimbursement for shave removals in 2013 requires further investigation,” Mr. Mazmudar and associates wrote.

The investigators did not disclose any conflicts of interest.

[email protected]

Medicare reimbursement for a group of 46 common dermatologic procedures dropped by a mean of 4.8% from 2007 to 2021, after adjusting for inflation, according to a new analysis.

Large increases in mean reimbursement for skin biopsies (+30.3%) and shave removal (+24.6%) were not enough to offset lower rates for procedures such as simple repair (–38.7%), premalignant destruction (–19.6%), Mohs micrographic surgery (–14.4%), and flap repair (–14.1%), Rishabh S. Mazmudar, BS, of Case Western Reserve University, Cleveland, and associates said.

“Given Medicare’s contribution to a large proportion of health care expenditures, changes in Medicare reimbursement rates may result in parallel changes in private insurance reimbursement,” they wrote in JAMA Dermatology.

A recently published study showed that Medicare reimbursement for 20 dermatologic service codes had fallen by 10% between the two comparison years, 2000 and 2020. The current study expanded the number of procedures to 46 (divided into nine categories) and used historical Medicare fee schedules to examine annual trends over a 15-year period, Mr. Mazmudar and associates explained.

Other specialties have seen reimbursement fall by more than 4.8%, including emergency medicine (–21.2% from 2000 to 2020) and general surgery (–24.4% from 2000 to 2018), but “these comparisons are likely skewed by the disproportionate increase in reimbursement rates for biopsies and shave removals during this time period,” the investigators said.

If those two procedure categories were excluded from the analysis, the mean change in overall reimbursement for the remaining dermatologic procedures would be −9.6%, they noted.

Detailed payment information provided for 15 of the 46 procedures shows that only intermediate repair (+4.5%) and benign destruction (+2.3%) joined biopsies and shave excisions with increased reimbursement from 2007 to 2021. The smallest drop among the other procedures was –1.9% for malignant destruction, the research team reported.

The inflation-adjusted, year-by-year analysis showed that reimbursement for the nine procedure categories has gradually declined since peaking in 2011, with the most notable exceptions being biopsies and shave excisions. Both had been following the trend until 2013, when reimbursement for shave removals jumped by almost 30 percentage points, and 2019, when rates for biopsies soared by more than 30 percentage points, according to the investigators.

The increase for skin biopsies followed the split of the original CPT code into three categories, but “the jump in reimbursement for shave removals in 2013 requires further investigation,” Mr. Mazmudar and associates wrote.

The investigators did not disclose any conflicts of interest.

[email protected]

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

More than one-quarter of patients undergoing dermatologic surgery said they would prefer not to take an oral antibiotic, even if it could eliminate the risk of a surgical-site infection (SSI) and had negligible side effects, in a prospective multicenter study.

In addition, a similar proportion of patients preferred to take an antibiotic if there was no SSI reduction and a high risk of adverse events.

Those are two key findings from the study aimed at understanding patient preferences for prophylactic oral antibiotic use following dermatologic surgery, which was published in Dermatologic Surgery.

“Patient risk-benefit thresholds for using antibiotics vary considerably,” the study’s corresponding author, Jeremy R. Etzkorn, MD, MS, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, told this news organization. “Physicians should appreciate and consider the variation between patients before deciding to send in a prescription after skin surgery.”

To investigate patient preferences about taking antibiotics to prevent SSI relative to antibiotic efficacy and antibiotic-associated adverse drug reactions, Dr. Etzkorn and colleagues at six U.S. medical centers prospectively administered a web-based survey and discrete choice experiment to 388 adults including dermatologic surgery patients and their family members, as well as health care workers (defined as dermatologic surgery patients who work in health care, individuals who work in health care and are accompanying patients to their surgery, or staff in the dermatology clinic.) “A lot has been published about physician preferences and practice patterns with respect to antibiotic prescribing after dermatologic surgery,” Dr. Etzkorn noted. “This is the first study to evaluate patient preferences in a rigorous way.”

He and his coinvestigators used a technique from marketing and product research (conjoint analysis/discrete choice experiments) to quantify what patients think about using antibiotics and what trade-offs they are – or are not – willing to make to reduce their risk of infection.

Nearly half of the respondents (47%) were patients, 29% were family members of patients, 19% were health care workers, and the rest were described as patient caregivers or “other.” More than half (59%) were female, the mean age at surgery was 59 years, and 69% had college or postgraduate degrees.

More than half of respondents (55%) would choose to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (defined as a 1% risk gastrointestinal upset, 0.5% risk itchy skin rash, and 0.01% risk ED visit). Even if an antibiotic could eliminate SSI risk entirely and had a low adverse drug reaction profile, 27% of respondents preferred not to take prophylactic oral antibiotics.

A subgroup analysis revealed that only 21% of health care workers would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 41% of those who do not work in health care. Respondent age also drove treatment choice. For example, only 33% of respondents younger than age 65 would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 45% of those aged 65 years and older.

“We knew patients would likely trade some antibiotic efficacy for some side effects, just as one would trade price for features when shopping for a car,” Dr. Etzkorn said. “We were shocked to see that over a quarter – 27% – of respondents preferred to not take antibiotics even if they were able to prevent all infections and had minimal side effects.”

“It’s interesting that between 27% [and] 55% of patients preferred no operative antibiotic prophylaxis despite a theoretical 100% cure rate for surgical-site infections,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study results.

“I think this mirrors dermatologist’s preferences, as a majority also prefer not to prescribe postoperative antibiotic therapy, unless operating in an area of or a patient with a high risk for infection. It would also be interesting to see if a less educated population would also have similar preferences.”

Dr. Etzkorn acknowledged certain limitations of the study, including that while it evaluated patient reported preferences, it did not include all possible risks and benefits, and “it does not measure actual patient behaviors.”

The researchers reported having no relevant financial disclosures. Dr. Etzkorn disclosed that he serves as a data safety monitoring board member for a clinical trial of Replimmune. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

[email protected]

More than one-quarter of patients undergoing dermatologic surgery said they would prefer not to take an oral antibiotic, even if it could eliminate the risk of a surgical-site infection (SSI) and had negligible side effects, in a prospective multicenter study.

In addition, a similar proportion of patients preferred to take an antibiotic if there was no SSI reduction and a high risk of adverse events.

Those are two key findings from the study aimed at understanding patient preferences for prophylactic oral antibiotic use following dermatologic surgery, which was published in Dermatologic Surgery.

“Patient risk-benefit thresholds for using antibiotics vary considerably,” the study’s corresponding author, Jeremy R. Etzkorn, MD, MS, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, told this news organization. “Physicians should appreciate and consider the variation between patients before deciding to send in a prescription after skin surgery.”

To investigate patient preferences about taking antibiotics to prevent SSI relative to antibiotic efficacy and antibiotic-associated adverse drug reactions, Dr. Etzkorn and colleagues at six U.S. medical centers prospectively administered a web-based survey and discrete choice experiment to 388 adults including dermatologic surgery patients and their family members, as well as health care workers (defined as dermatologic surgery patients who work in health care, individuals who work in health care and are accompanying patients to their surgery, or staff in the dermatology clinic.) “A lot has been published about physician preferences and practice patterns with respect to antibiotic prescribing after dermatologic surgery,” Dr. Etzkorn noted. “This is the first study to evaluate patient preferences in a rigorous way.”

He and his coinvestigators used a technique from marketing and product research (conjoint analysis/discrete choice experiments) to quantify what patients think about using antibiotics and what trade-offs they are – or are not – willing to make to reduce their risk of infection.

Nearly half of the respondents (47%) were patients, 29% were family members of patients, 19% were health care workers, and the rest were described as patient caregivers or “other.” More than half (59%) were female, the mean age at surgery was 59 years, and 69% had college or postgraduate degrees.

More than half of respondents (55%) would choose to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (defined as a 1% risk gastrointestinal upset, 0.5% risk itchy skin rash, and 0.01% risk ED visit). Even if an antibiotic could eliminate SSI risk entirely and had a low adverse drug reaction profile, 27% of respondents preferred not to take prophylactic oral antibiotics.

A subgroup analysis revealed that only 21% of health care workers would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 41% of those who do not work in health care. Respondent age also drove treatment choice. For example, only 33% of respondents younger than age 65 would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 45% of those aged 65 years and older.

“We knew patients would likely trade some antibiotic efficacy for some side effects, just as one would trade price for features when shopping for a car,” Dr. Etzkorn said. “We were shocked to see that over a quarter – 27% – of respondents preferred to not take antibiotics even if they were able to prevent all infections and had minimal side effects.”

“It’s interesting that between 27% [and] 55% of patients preferred no operative antibiotic prophylaxis despite a theoretical 100% cure rate for surgical-site infections,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study results.

“I think this mirrors dermatologist’s preferences, as a majority also prefer not to prescribe postoperative antibiotic therapy, unless operating in an area of or a patient with a high risk for infection. It would also be interesting to see if a less educated population would also have similar preferences.”

Dr. Etzkorn acknowledged certain limitations of the study, including that while it evaluated patient reported preferences, it did not include all possible risks and benefits, and “it does not measure actual patient behaviors.”

The researchers reported having no relevant financial disclosures. Dr. Etzkorn disclosed that he serves as a data safety monitoring board member for a clinical trial of Replimmune. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

[email protected]

More than one-quarter of patients undergoing dermatologic surgery said they would prefer not to take an oral antibiotic, even if it could eliminate the risk of a surgical-site infection (SSI) and had negligible side effects, in a prospective multicenter study.

In addition, a similar proportion of patients preferred to take an antibiotic if there was no SSI reduction and a high risk of adverse events.

Those are two key findings from the study aimed at understanding patient preferences for prophylactic oral antibiotic use following dermatologic surgery, which was published in Dermatologic Surgery.

“Patient risk-benefit thresholds for using antibiotics vary considerably,” the study’s corresponding author, Jeremy R. Etzkorn, MD, MS, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, told this news organization. “Physicians should appreciate and consider the variation between patients before deciding to send in a prescription after skin surgery.”

To investigate patient preferences about taking antibiotics to prevent SSI relative to antibiotic efficacy and antibiotic-associated adverse drug reactions, Dr. Etzkorn and colleagues at six U.S. medical centers prospectively administered a web-based survey and discrete choice experiment to 388 adults including dermatologic surgery patients and their family members, as well as health care workers (defined as dermatologic surgery patients who work in health care, individuals who work in health care and are accompanying patients to their surgery, or staff in the dermatology clinic.) “A lot has been published about physician preferences and practice patterns with respect to antibiotic prescribing after dermatologic surgery,” Dr. Etzkorn noted. “This is the first study to evaluate patient preferences in a rigorous way.”

He and his coinvestigators used a technique from marketing and product research (conjoint analysis/discrete choice experiments) to quantify what patients think about using antibiotics and what trade-offs they are – or are not – willing to make to reduce their risk of infection.

Nearly half of the respondents (47%) were patients, 29% were family members of patients, 19% were health care workers, and the rest were described as patient caregivers or “other.” More than half (59%) were female, the mean age at surgery was 59 years, and 69% had college or postgraduate degrees.

More than half of respondents (55%) would choose to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (defined as a 1% risk gastrointestinal upset, 0.5% risk itchy skin rash, and 0.01% risk ED visit). Even if an antibiotic could eliminate SSI risk entirely and had a low adverse drug reaction profile, 27% of respondents preferred not to take prophylactic oral antibiotics.

A subgroup analysis revealed that only 21% of health care workers would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 41% of those who do not work in health care. Respondent age also drove treatment choice. For example, only 33% of respondents younger than age 65 would choose a moderate efficacy antibiotic (2.5% SSI risk) with a high adverse effect profile, compared with 45% of those aged 65 years and older.

“We knew patients would likely trade some antibiotic efficacy for some side effects, just as one would trade price for features when shopping for a car,” Dr. Etzkorn said. “We were shocked to see that over a quarter – 27% – of respondents preferred to not take antibiotics even if they were able to prevent all infections and had minimal side effects.”

“It’s interesting that between 27% [and] 55% of patients preferred no operative antibiotic prophylaxis despite a theoretical 100% cure rate for surgical-site infections,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study results.

“I think this mirrors dermatologist’s preferences, as a majority also prefer not to prescribe postoperative antibiotic therapy, unless operating in an area of or a patient with a high risk for infection. It would also be interesting to see if a less educated population would also have similar preferences.”

Dr. Etzkorn acknowledged certain limitations of the study, including that while it evaluated patient reported preferences, it did not include all possible risks and benefits, and “it does not measure actual patient behaviors.”

The researchers reported having no relevant financial disclosures. Dr. Etzkorn disclosed that he serves as a data safety monitoring board member for a clinical trial of Replimmune. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.

[email protected]

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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