Napping and AFib risk: The long and the short of it

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Napping for more than half an hour during the day was associated with a 90% increased risk of atrial fibrillation (AFib), but shorter naps were linked to a reduced risk, based on data from more than 20,000 individuals.

“Short daytime napping is a common, healthy habit, especially in Mediterranean countries,” Jesus Diaz-Gutierrez, MD, of Juan Ramon Jimenez University Hospital, Huelva, Spain, said in a presentation at the annual congress of the European Association of Preventive Cardiology (EAPC).

Judith Shidlowsky/Pixabay

Previous studies have shown a potential link between sleep patterns and AFib risk, but the association between specific duration of daytime naps and AFib risk has not been explored, he said.

Dr. Diaz-Gutierrez and colleagues used data from the University of Navarra Follow-up (SUN) Project, a prospective cohort of Spanish university graduates, to explore the possible link between naps and AFib. The study population included 20,348 individuals without AFib at baseline who were followed for a median of 13.8 years. The average age of participants at baseline was 38 years; 61% were women.

Daytime napping patterns were assessed at baseline, and participants were divided into nap groups of short nappers (defined as less than 30 minutes per day), and longer nappers (30 minutes or more per day), and those who reported no napping.

The researchers identified 131 incident cases of AFib during the follow-up period. Overall, the relative risk of incident AFib was significantly higher for the long nappers (adjusted hazard ratio 1.90) compared with short nappers in a multivariate analysis, while no significant risk appeared among non-nappers compared to short nappers (aHR 1.26).

The researchers then excluded the non-nappers in a secondary analysis to explore the impact of more specific daily nap duration on AFib risk. In a multivariate analysis, they found a 42% reduced risk of AF among those who napped for less than 15 minutes, and a 56% reduced risk for those who napped for 15-30 minutes, compared with those who napped for more than 30 minutes (aHR 0.56 and 0.42, respectively).

Potential explanations for the associations include the role of circadian rhythms, Dr. Diaz-Gutierrez said in a press release accompanying the presentation at the meeting. “Long daytime naps may disrupt the body’s internal clock (circadian rhythm), leading to shorter nighttime sleep, more nocturnal awakening, and reduced physical activity. In contrast, short daytime napping may improve circadian rhythm, lower blood pressure levels, and reduce stress.” More research is needed to validate the findings and the optimum nap duration, and whether a short nap is more advantageous than not napping in terms of AFib risk reduction, he said.

The study results suggest that naps of 15-30 minutes represent “a potential novel healthy lifestyle habit in the primary prevention of AFib,” Dr. Diaz-Gutierrez said in his presentation. However, the results also suggest that daily naps be limited to less than 30 minutes, he concluded.
 

Sleep habits may serve as red flag

“As we age, most if not all of us will develop sleep disturbances, such as insomnia, obstructive sleep apnea (OSA), and other sleep issues,” Lawrence S. Rosenthal, MD, of the University of Massachusetts, Worcester, said in an interview.

Therefore, “this study is near and dear to most people, and most would agree that poor sleeping habits affect our health.” In particular, OSA has been linked to AFib, although that was not measured in the current study, he added.

Dr. Rosenthal said he was not surprised by the current study findings. “It seems that a quick recharge of your ‘battery’ during the day is healthier than a long, deep sleep daytime nap,” he said. In addition, “Longer naps may be a marker of OSA,” he noted.

For clinicians, the take-home message of the current study is the need to consider underlying medical conditions in patients who regularly take long afternoon naps, and to consider these longer naps as a potential marker for AFib, said Dr. Rosenthal.

Looking ahead, a “deeper dive into the makeup of the populations studied” would be useful as a foundation for additional research, he said.

The SUN Project disclosed funding from the Spanish Government-Instituto de Salud Carlos III and the European Regional Development Fund (FEDER), the Navarra Regional Government, Plan Nacional Sobre Drogas, the University of Navarra, and the European Research Council. The researchers, and Dr. Rosenthal, had no financial conflicts to disclose.

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Napping for more than half an hour during the day was associated with a 90% increased risk of atrial fibrillation (AFib), but shorter naps were linked to a reduced risk, based on data from more than 20,000 individuals.

“Short daytime napping is a common, healthy habit, especially in Mediterranean countries,” Jesus Diaz-Gutierrez, MD, of Juan Ramon Jimenez University Hospital, Huelva, Spain, said in a presentation at the annual congress of the European Association of Preventive Cardiology (EAPC).

Judith Shidlowsky/Pixabay

Previous studies have shown a potential link between sleep patterns and AFib risk, but the association between specific duration of daytime naps and AFib risk has not been explored, he said.

Dr. Diaz-Gutierrez and colleagues used data from the University of Navarra Follow-up (SUN) Project, a prospective cohort of Spanish university graduates, to explore the possible link between naps and AFib. The study population included 20,348 individuals without AFib at baseline who were followed for a median of 13.8 years. The average age of participants at baseline was 38 years; 61% were women.

Daytime napping patterns were assessed at baseline, and participants were divided into nap groups of short nappers (defined as less than 30 minutes per day), and longer nappers (30 minutes or more per day), and those who reported no napping.

The researchers identified 131 incident cases of AFib during the follow-up period. Overall, the relative risk of incident AFib was significantly higher for the long nappers (adjusted hazard ratio 1.90) compared with short nappers in a multivariate analysis, while no significant risk appeared among non-nappers compared to short nappers (aHR 1.26).

The researchers then excluded the non-nappers in a secondary analysis to explore the impact of more specific daily nap duration on AFib risk. In a multivariate analysis, they found a 42% reduced risk of AF among those who napped for less than 15 minutes, and a 56% reduced risk for those who napped for 15-30 minutes, compared with those who napped for more than 30 minutes (aHR 0.56 and 0.42, respectively).

Potential explanations for the associations include the role of circadian rhythms, Dr. Diaz-Gutierrez said in a press release accompanying the presentation at the meeting. “Long daytime naps may disrupt the body’s internal clock (circadian rhythm), leading to shorter nighttime sleep, more nocturnal awakening, and reduced physical activity. In contrast, short daytime napping may improve circadian rhythm, lower blood pressure levels, and reduce stress.” More research is needed to validate the findings and the optimum nap duration, and whether a short nap is more advantageous than not napping in terms of AFib risk reduction, he said.

The study results suggest that naps of 15-30 minutes represent “a potential novel healthy lifestyle habit in the primary prevention of AFib,” Dr. Diaz-Gutierrez said in his presentation. However, the results also suggest that daily naps be limited to less than 30 minutes, he concluded.
 

Sleep habits may serve as red flag

“As we age, most if not all of us will develop sleep disturbances, such as insomnia, obstructive sleep apnea (OSA), and other sleep issues,” Lawrence S. Rosenthal, MD, of the University of Massachusetts, Worcester, said in an interview.

Therefore, “this study is near and dear to most people, and most would agree that poor sleeping habits affect our health.” In particular, OSA has been linked to AFib, although that was not measured in the current study, he added.

Dr. Rosenthal said he was not surprised by the current study findings. “It seems that a quick recharge of your ‘battery’ during the day is healthier than a long, deep sleep daytime nap,” he said. In addition, “Longer naps may be a marker of OSA,” he noted.

For clinicians, the take-home message of the current study is the need to consider underlying medical conditions in patients who regularly take long afternoon naps, and to consider these longer naps as a potential marker for AFib, said Dr. Rosenthal.

Looking ahead, a “deeper dive into the makeup of the populations studied” would be useful as a foundation for additional research, he said.

The SUN Project disclosed funding from the Spanish Government-Instituto de Salud Carlos III and the European Regional Development Fund (FEDER), the Navarra Regional Government, Plan Nacional Sobre Drogas, the University of Navarra, and the European Research Council. The researchers, and Dr. Rosenthal, had no financial conflicts to disclose.

Napping for more than half an hour during the day was associated with a 90% increased risk of atrial fibrillation (AFib), but shorter naps were linked to a reduced risk, based on data from more than 20,000 individuals.

“Short daytime napping is a common, healthy habit, especially in Mediterranean countries,” Jesus Diaz-Gutierrez, MD, of Juan Ramon Jimenez University Hospital, Huelva, Spain, said in a presentation at the annual congress of the European Association of Preventive Cardiology (EAPC).

Judith Shidlowsky/Pixabay

Previous studies have shown a potential link between sleep patterns and AFib risk, but the association between specific duration of daytime naps and AFib risk has not been explored, he said.

Dr. Diaz-Gutierrez and colleagues used data from the University of Navarra Follow-up (SUN) Project, a prospective cohort of Spanish university graduates, to explore the possible link between naps and AFib. The study population included 20,348 individuals without AFib at baseline who were followed for a median of 13.8 years. The average age of participants at baseline was 38 years; 61% were women.

Daytime napping patterns were assessed at baseline, and participants were divided into nap groups of short nappers (defined as less than 30 minutes per day), and longer nappers (30 minutes or more per day), and those who reported no napping.

The researchers identified 131 incident cases of AFib during the follow-up period. Overall, the relative risk of incident AFib was significantly higher for the long nappers (adjusted hazard ratio 1.90) compared with short nappers in a multivariate analysis, while no significant risk appeared among non-nappers compared to short nappers (aHR 1.26).

The researchers then excluded the non-nappers in a secondary analysis to explore the impact of more specific daily nap duration on AFib risk. In a multivariate analysis, they found a 42% reduced risk of AF among those who napped for less than 15 minutes, and a 56% reduced risk for those who napped for 15-30 minutes, compared with those who napped for more than 30 minutes (aHR 0.56 and 0.42, respectively).

Potential explanations for the associations include the role of circadian rhythms, Dr. Diaz-Gutierrez said in a press release accompanying the presentation at the meeting. “Long daytime naps may disrupt the body’s internal clock (circadian rhythm), leading to shorter nighttime sleep, more nocturnal awakening, and reduced physical activity. In contrast, short daytime napping may improve circadian rhythm, lower blood pressure levels, and reduce stress.” More research is needed to validate the findings and the optimum nap duration, and whether a short nap is more advantageous than not napping in terms of AFib risk reduction, he said.

The study results suggest that naps of 15-30 minutes represent “a potential novel healthy lifestyle habit in the primary prevention of AFib,” Dr. Diaz-Gutierrez said in his presentation. However, the results also suggest that daily naps be limited to less than 30 minutes, he concluded.
 

Sleep habits may serve as red flag

“As we age, most if not all of us will develop sleep disturbances, such as insomnia, obstructive sleep apnea (OSA), and other sleep issues,” Lawrence S. Rosenthal, MD, of the University of Massachusetts, Worcester, said in an interview.

Therefore, “this study is near and dear to most people, and most would agree that poor sleeping habits affect our health.” In particular, OSA has been linked to AFib, although that was not measured in the current study, he added.

Dr. Rosenthal said he was not surprised by the current study findings. “It seems that a quick recharge of your ‘battery’ during the day is healthier than a long, deep sleep daytime nap,” he said. In addition, “Longer naps may be a marker of OSA,” he noted.

For clinicians, the take-home message of the current study is the need to consider underlying medical conditions in patients who regularly take long afternoon naps, and to consider these longer naps as a potential marker for AFib, said Dr. Rosenthal.

Looking ahead, a “deeper dive into the makeup of the populations studied” would be useful as a foundation for additional research, he said.

The SUN Project disclosed funding from the Spanish Government-Instituto de Salud Carlos III and the European Regional Development Fund (FEDER), the Navarra Regional Government, Plan Nacional Sobre Drogas, the University of Navarra, and the European Research Council. The researchers, and Dr. Rosenthal, had no financial conflicts to disclose.

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FROM ESC PREVENTIVE CARDIOLOGY 2023

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Most adults, more than one in three children take dietary supplements: Report

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More than one in three children and nearly three in five adults take dietary supplements in the United States, a new report shows.

The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.

The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.

The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.

More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.

The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.

The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”

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

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More than one in three children and nearly three in five adults take dietary supplements in the United States, a new report shows.

The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.

The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.

The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.

More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.

The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.

The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”

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

More than one in three children and nearly three in five adults take dietary supplements in the United States, a new report shows.

The new figures continue a 15-year trend of small, steady increases in how many people in the United States use the products that can deliver essential nutrients, but their usage includes a risk of getting more nutrients than recommended. In 2007, 48% of adults took supplements, and that figure has reached nearly 59% in this latest count.

The new report looked at whether people took a multivitamin, as well as other more specific supplements. Among children and adolescents aged 19 and under, 23.5% took a multivitamin, while 31.5% of adults reported taking one. The most common specialized supplement that people took was vitamin D.

The report, released by the CDC’s National Center for Health Statistics, compiled survey data from 2017 through 2020 in which 15,548 people reported their household’s usage of dietary supplements. Dietary supplements include vitamins, minerals, herbs, or other botanicals that are taken by mouth in pill, capsule, tablet, or liquid form. The researchers said the vitamin and supplement market is large and growing, totaling $55.7 billion in sales in 2020.

More than one-third of adults (36%) reported taking more than one supplement, and one in four people aged 60 and older said they took four or more.

The data showed demographic trends in who uses dietary supplements. Women and girls were more likely to take supplements than men and boys, although there were similar usage levels for both genders among 1- to 2-year-olds. People with higher education or income levels were more likely to use supplements. Asian people and White people were more likely to take supplements, compared with Hispanic people and Black people.

The authors wrote that monitoring trends in supplement use is important because the products “contribute substantially to nutrient intake as well as increase the risk of excessive intake of certain micronutrients.”

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

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Scattered Red-Brown, Centrally Violaceous, Blanching Papules on an Infant

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Scattered Red-Brown, Centrally Violaceous, Blanching Papules on an Infant

The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)

The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.

A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).
A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).

Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4

Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5

Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4

In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.

References
  1. Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
  2. Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
  3. Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
  4. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
  5. Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
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Ms. Rivin is from and Dr. Flood was from the University of Cincinnati, Ohio. Ms. Rivin is from the College of Medicine, and Dr. Flood was from the Department of Dermatology. Dr. Flood currently is from the Department of Dermatology, Northwestern University, Evanston, Illinois. Dr. Marathe is from the Department of Dermatology, Cincinnati Children’s Hospital Medical Center.

Ms. Rivin and Dr. Marathe report no conflict of interest. Dr. Flood previously received fellowship funding paid directly to her institution from the National Psoriasis Foundation; AbbVie; and Janssen Pharmaceuticals, Inc.

Correspondence: Gabrielle Marie Rivin, BA, 231 Albert Sabin Way, Cincinnati, OH 45220 ([email protected]).

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Ms. Rivin is from and Dr. Flood was from the University of Cincinnati, Ohio. Ms. Rivin is from the College of Medicine, and Dr. Flood was from the Department of Dermatology. Dr. Flood currently is from the Department of Dermatology, Northwestern University, Evanston, Illinois. Dr. Marathe is from the Department of Dermatology, Cincinnati Children’s Hospital Medical Center.

Ms. Rivin and Dr. Marathe report no conflict of interest. Dr. Flood previously received fellowship funding paid directly to her institution from the National Psoriasis Foundation; AbbVie; and Janssen Pharmaceuticals, Inc.

Correspondence: Gabrielle Marie Rivin, BA, 231 Albert Sabin Way, Cincinnati, OH 45220 ([email protected]).

Author and Disclosure Information

Ms. Rivin is from and Dr. Flood was from the University of Cincinnati, Ohio. Ms. Rivin is from the College of Medicine, and Dr. Flood was from the Department of Dermatology. Dr. Flood currently is from the Department of Dermatology, Northwestern University, Evanston, Illinois. Dr. Marathe is from the Department of Dermatology, Cincinnati Children’s Hospital Medical Center.

Ms. Rivin and Dr. Marathe report no conflict of interest. Dr. Flood previously received fellowship funding paid directly to her institution from the National Psoriasis Foundation; AbbVie; and Janssen Pharmaceuticals, Inc.

Correspondence: Gabrielle Marie Rivin, BA, 231 Albert Sabin Way, Cincinnati, OH 45220 ([email protected]).

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The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)

The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.

A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).
A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).

Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4

Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5

Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4

In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.

The Diagnosis: Neonatal-Onset Multisystem Inflammatory Disorder (NOMID)

The punch biopsy demonstrated a predominantly deep but somewhat superficial, periadnexal, neutrophilic and eosinophilic infiltrate (Figure). The eruption resolved 3 days later with supportive treatment, including appropriate wound care. Genetic analysis revealed an autosomal-dominant NLR family pyrin domain containing 3 gene, NLRP3, de novo variant associated with neonatal-onset multisystem inflammatory disorder (NOMID). Additional workup to characterize our patient’s inflammatory profile revealed elevated IL-18, CD3, CD4, S100A12, and S100A8/A9 levels. On day 48 of life, she was started on anakinra, an IL-1 inhibitor, at a dose of 1 mg/kg subcutaneously, which eventually was titrated to 10 mg/kg at hospital discharge. Hearing screenings were within normal limits.

A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).
A punch biopsy demonstrated a periadnexal infiltrate with eosinophils (mature and immature), neutrophils, and macrophages in the deep dermis (H&E, original magnification ×200).

Cryopyrin-associated periodic syndromes (CAPS) consist of 3 rare, IL-1–associated, autoinflammatory disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID (also known as chronic infantile neurologic cutaneous and articular syndrome). These conditions result from a sporadic or autosomal-dominant gain-of-function mutations in a single gene, NLRP3, on chromosome 1q44. NLRP3 encodes for cryopyrin, an important component of an IL-1 and IL-18 activating inflammasome.1 The most severe manifestation of CAPS is NOMID, which typically presents at birth as a migratory urticarial eruption, growth failure, myalgia, fever, and abnormal facial features, including frontal bossing, saddle-shaped nose, and protruding eyes.2 The illness also can manifest with hepatosplenomegaly, lymphadenopathy, uveitis, sensorineural hearing loss, cerebral atrophy, and other neurologic manifestations.3 A diagnosis of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome was less likely given that our patient remained afebrile and did not show signs of lipodystrophy and persistent violaceous eyelid swelling. Both FCAS and MWS are less severe forms of CAPS when compared to NOMID. Familial cold autoinflammatory syndrome was less likely given the absence of the typical periodic fever pattern associated with the condition and severity of our patient’s symptoms. Muckle-Wells syndrome typically presents in adolescence with symptoms of FCAS, painful urticarial plaques, and progressive sensorinueral hearing loss. Tumor necrosis factor receptor–associated periodic fever (TRAPS) usually is associated with episodic fevers, abdominal pain, periorbital edema, migratory erythema, and arthralgia.1,3,4

Diagnostic criteria for CAPS include elevated inflammatory markers and serum amyloid, plus at least 2 of the typical CAPS symptoms: urticarial rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis, and skeletal abnormalities.4 The sensitivity and specificity of these diagnostic criteria are 84% and 91%, respectively. Additional findings that can be seen but are not part of the diagnostic criteria include intermittent fever, transient joint swelling, bony overgrowths, uveitis, optic disc edema, impaired growth, and hepatosplenomegaly.5 Laboratory findings may reveal leukocytosis, eosinophilia, anemia, and/or thrombocytopenia.3,5

Genetic testing, skin biopsies, ophthalmic examinations, neuroimaging, joint radiography, cerebrospinal fluid tests, and hearing examinations can be performed for confirmation of diagnosis and evaluation of systemic complications.4 A skin biopsy may reveal a neutrophilic infiltrate. Ophthalmic examination can demonstrate uveitis and optic disk edema. Neuroimaging may reveal cerebral atrophy or ventricular dilation. Lastly, joint radiography can be used to evaluate for the presence of premature long bone ossification or osseous overgrowth.4

In summary, NOMID is a multisystemic disorder with cutaneous manifestations. Early recognition of this entity is important given the severe sequelae and available efficacious therapy. Dermatologists should be aware of these manifestations, as dermatologic consultation and a skin biopsy may aid in diagnosis.

References
  1. Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
  2. Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
  3. Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
  4. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
  5. Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
References
  1. Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol. 2017;31:596-609. doi:10.1016/j.berh.2017.12.001
  2. Hull KM, Shoham N, Jin Chae J, et al. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15:61-69. doi:10.1097/00002281-200301000-00011
  3. Ahmadi N, Brewer CC, Zalewski C, et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol Head Neck Surg. 2011;145:295-302. doi:10.1177/0194599811402296
  4. Kuemmerle-Deschner JB, Ozen S, Tyrrell PN, et al. Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Ann Rheum Dis. 2017;76:942-947. doi:10.1136/annrheumdis-2016-209686
  5. Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrinassociated autoinflammatory diseases. Arthritis Rheum. 2002; 46:3340-3348. doi:10.1002/art.10688
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Scattered Red-Brown, Centrally Violaceous, Blanching Papules on an Infant
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A 2-week-old infant girl was transferred to a specialty pediatric hospital where dermatology was consulted for evaluation of a diffuse eruption triggered by cold that was similar to an eruption present at birth. She was born at 31 weeks and 2 days’ gestation at an outside hospital via caesarean delivery. Early delivery was prompted by superimposed pre-eclampsia with severe hypertension after administration of antenatal steroids. At birth, the infant was cyanotic and apneic and had a documented skin eruption, according to the medical record. She had thrombocytopenia, elevated C-reactive protein, and an elevated temperature without fever. Extensive septic workup, including blood, urine, and cerebrospinal fluid cultures; herpes simplex virus and cytomegalovirus screening; and Toxoplasma polymerase chain reaction were negative. Magnetic resonance imaging of the brain revealed no evidence of intracranial congenital infection. Ampicillinsulbactam was initiated for presumed culture-negative sepsis. On day 2 of hospitalization, she developed conjunctival icterus, hepatomegaly, and jaundice. Direct hyperbilirubinemia; anemia; and elevated triglycerides, ferritin, and ammonia all were present. Coagulation studies were normal. Subsequent workup, including abdominal ultrasonography and hepatobiliary iminodiacetic acid scan, was concerning for biliary atresia. Despite appropriate treatment, her condition did not improve and she was transferred. Repeat abdominal ultrasonography on day 24 of life confirmed hepatomegaly but did not demonstrate other findings of biliary atresia. At the current presentation, physical examination revealed many scattered, redbrown and centrally violaceous, blanching papules measuring a few millimeters involving the trunk, arms, buttocks, and legs. A punch biopsy was obtained.

Scattered red-brown, centrally violaceous, blanching papules on an infant

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Cleansing balms

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A skin care trend, particularly in the Korean beauty product market and now worldwide, cleansing balms are a soft, yet solid variation of an oil-based cleanser. The solid oily component is combined with a surfactant or emulsifier. The cream balm texture melts into more of an oil texture once warmed with fingertips and applied to facial skin. The oils are effective at breaking down or attracting skin care products, oil, and grime on the skin surface. Once warm water is added, the oil emulsifies, and after it is wiped or rinsed off, what’s left behind is clean, hydrated skin.

Dr. Naissan O. Wesley

Unlike surfactant-based liquid cleansers that typically produce foam, cleansing balms are thicker in consistency and do not foam. These products are often packaged in a jar as a thick creamy cleanser or a solid stick. They don’t tend to compromise the moisture barrier or disrupt skin pH, thus, resulting in less dry skin and have less potential to cause irritation. These products are particularly useful during drier, colder months, or in dry climates, and for those who have dry skin or eczema.

The popularity of cleansing balms has largely been based on their ability to remove makeup, similar to an oil cleanser, without the need to necessarily “double cleanse” with a regular cleanser afterward.



Alternatives to remove makeup besides cleansing balms, oil cleansers, and regular liquid water-based cleansers include micellar water (oil in water), chemical makeup removing cloths, and nonchemical makeup removing pads used with water. Micellar water is also gentle on the skin; it requires a cotton pad, tip, or cloth to remove makeup, without the need for water or washing. Both are effective, but it may be easier to remove makeup with cleansing balms, without the need for rubbing dry skin, than with micellar water. A study published in 2020 of 20 individuals reported that waterproof sunscreen was more effectively removed with a cleansing oil than a non–oil-based cleanser, with less irritation and dryness. Both were effective at removing non-waterproof sunscreen.

Both cleansing balms and oil-based cleansers need to be kept at room temperature (not in the refrigerator), since they may separate or solidify at low temperatures.

Jose A. Bernat Bacete/Getty Images

Most cleansing balms can be applied to dry skin, massaged, and rinsed off with warm water, but they are sometimes easier to remove with a wet cloth (typically either cotton or muslin). Many are nonirritating to the eyes, which is important when used to remove eye makeup and mascara on delicate skin. While many cleansing balms are noncomedogenic, residue from balms that are too thick or not rinsed off properly can contribute to comedones or milia. If residue is present after use, then “double-cleansing” with a water-based cleanser is reasonable, but not necessary for most users.

Did the development of Ponds cold cream mark the beginning of this trend? Yes and no. The creation of the first cold cream prototype has been attributed to the Greek physician, Galen (who lived in Rome), a combination of rose water, beeswax, and olive oil in 150 CE. While Ponds also has manufactured a cleansing balm, the original cold cream is a 50% moisturizer in a cleanser. So while similar in containing an oil, water, emulsifier, and thickener, and effective, it is more of a moisturizer and less of a solid oil/balm in its consistency.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She had no relevant disclosures.

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A skin care trend, particularly in the Korean beauty product market and now worldwide, cleansing balms are a soft, yet solid variation of an oil-based cleanser. The solid oily component is combined with a surfactant or emulsifier. The cream balm texture melts into more of an oil texture once warmed with fingertips and applied to facial skin. The oils are effective at breaking down or attracting skin care products, oil, and grime on the skin surface. Once warm water is added, the oil emulsifies, and after it is wiped or rinsed off, what’s left behind is clean, hydrated skin.

Dr. Naissan O. Wesley

Unlike surfactant-based liquid cleansers that typically produce foam, cleansing balms are thicker in consistency and do not foam. These products are often packaged in a jar as a thick creamy cleanser or a solid stick. They don’t tend to compromise the moisture barrier or disrupt skin pH, thus, resulting in less dry skin and have less potential to cause irritation. These products are particularly useful during drier, colder months, or in dry climates, and for those who have dry skin or eczema.

The popularity of cleansing balms has largely been based on their ability to remove makeup, similar to an oil cleanser, without the need to necessarily “double cleanse” with a regular cleanser afterward.



Alternatives to remove makeup besides cleansing balms, oil cleansers, and regular liquid water-based cleansers include micellar water (oil in water), chemical makeup removing cloths, and nonchemical makeup removing pads used with water. Micellar water is also gentle on the skin; it requires a cotton pad, tip, or cloth to remove makeup, without the need for water or washing. Both are effective, but it may be easier to remove makeup with cleansing balms, without the need for rubbing dry skin, than with micellar water. A study published in 2020 of 20 individuals reported that waterproof sunscreen was more effectively removed with a cleansing oil than a non–oil-based cleanser, with less irritation and dryness. Both were effective at removing non-waterproof sunscreen.

Both cleansing balms and oil-based cleansers need to be kept at room temperature (not in the refrigerator), since they may separate or solidify at low temperatures.

Jose A. Bernat Bacete/Getty Images

Most cleansing balms can be applied to dry skin, massaged, and rinsed off with warm water, but they are sometimes easier to remove with a wet cloth (typically either cotton or muslin). Many are nonirritating to the eyes, which is important when used to remove eye makeup and mascara on delicate skin. While many cleansing balms are noncomedogenic, residue from balms that are too thick or not rinsed off properly can contribute to comedones or milia. If residue is present after use, then “double-cleansing” with a water-based cleanser is reasonable, but not necessary for most users.

Did the development of Ponds cold cream mark the beginning of this trend? Yes and no. The creation of the first cold cream prototype has been attributed to the Greek physician, Galen (who lived in Rome), a combination of rose water, beeswax, and olive oil in 150 CE. While Ponds also has manufactured a cleansing balm, the original cold cream is a 50% moisturizer in a cleanser. So while similar in containing an oil, water, emulsifier, and thickener, and effective, it is more of a moisturizer and less of a solid oil/balm in its consistency.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She had no relevant disclosures.

A skin care trend, particularly in the Korean beauty product market and now worldwide, cleansing balms are a soft, yet solid variation of an oil-based cleanser. The solid oily component is combined with a surfactant or emulsifier. The cream balm texture melts into more of an oil texture once warmed with fingertips and applied to facial skin. The oils are effective at breaking down or attracting skin care products, oil, and grime on the skin surface. Once warm water is added, the oil emulsifies, and after it is wiped or rinsed off, what’s left behind is clean, hydrated skin.

Dr. Naissan O. Wesley

Unlike surfactant-based liquid cleansers that typically produce foam, cleansing balms are thicker in consistency and do not foam. These products are often packaged in a jar as a thick creamy cleanser or a solid stick. They don’t tend to compromise the moisture barrier or disrupt skin pH, thus, resulting in less dry skin and have less potential to cause irritation. These products are particularly useful during drier, colder months, or in dry climates, and for those who have dry skin or eczema.

The popularity of cleansing balms has largely been based on their ability to remove makeup, similar to an oil cleanser, without the need to necessarily “double cleanse” with a regular cleanser afterward.



Alternatives to remove makeup besides cleansing balms, oil cleansers, and regular liquid water-based cleansers include micellar water (oil in water), chemical makeup removing cloths, and nonchemical makeup removing pads used with water. Micellar water is also gentle on the skin; it requires a cotton pad, tip, or cloth to remove makeup, without the need for water or washing. Both are effective, but it may be easier to remove makeup with cleansing balms, without the need for rubbing dry skin, than with micellar water. A study published in 2020 of 20 individuals reported that waterproof sunscreen was more effectively removed with a cleansing oil than a non–oil-based cleanser, with less irritation and dryness. Both were effective at removing non-waterproof sunscreen.

Both cleansing balms and oil-based cleansers need to be kept at room temperature (not in the refrigerator), since they may separate or solidify at low temperatures.

Jose A. Bernat Bacete/Getty Images

Most cleansing balms can be applied to dry skin, massaged, and rinsed off with warm water, but they are sometimes easier to remove with a wet cloth (typically either cotton or muslin). Many are nonirritating to the eyes, which is important when used to remove eye makeup and mascara on delicate skin. While many cleansing balms are noncomedogenic, residue from balms that are too thick or not rinsed off properly can contribute to comedones or milia. If residue is present after use, then “double-cleansing” with a water-based cleanser is reasonable, but not necessary for most users.

Did the development of Ponds cold cream mark the beginning of this trend? Yes and no. The creation of the first cold cream prototype has been attributed to the Greek physician, Galen (who lived in Rome), a combination of rose water, beeswax, and olive oil in 150 CE. While Ponds also has manufactured a cleansing balm, the original cold cream is a 50% moisturizer in a cleanser. So while similar in containing an oil, water, emulsifier, and thickener, and effective, it is more of a moisturizer and less of a solid oil/balm in its consistency.

Dr. Wesley practices dermatology in Beverly Hills, Calif. Write to her at [email protected]. She had no relevant disclosures.

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Thirty years of epilepsy therapy: ‘Plus ça change, plus c’est la même chose’?

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Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

Dr. Jacqueline A. French

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

 

 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

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Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

Dr. Jacqueline A. French

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

 

 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

Although the past 30 years have stirred up a whirlwind of neurological research that has dramatically expanded therapeutic options for patients with epilepsy, historical pioneers in the field might be disappointed at the fact that treatment response has remained stubbornly stagnant. “Plus ça change, plus c’est la même chose,” they might say: The more things change, the more they stay the same. In fact, since 1993, despite an explosion of third-generation drugs, an abundance of new surgical approaches, and a whole new category of treatment in the form of neurostimulation devices, response rates in epilepsy have not budged, with roughly two-thirds of patients achieving seizure freedom and a third still struggling with treatment resistance.

Dr. Jacqueline A. French

But if you widen the lens and look towards the horizon, things are “on the cusp and going like a rocket,” said Jacqueline A. French, MD, professor of neurology in the Comprehensive Epilepsy Center at NYU Langone Health, New York. While treatment response rates may be stuck, adverse effects of those treatments have plummeted, and even treatment-resistant patients dealing with residual seizures live a much freer life with far fewer and less serious episodes.
 

Simpler times

In the late 1980s, just as Dr. French was finishing her second epilepsy fellowship at Yale, it was “almost laughable that things were so simple,” she recalls. “There were a few major centers that were doing epilepsy surgery … and in the world of medication, there were just five major drugs: phenobarbital, primidone, carbamazepine, phenytoin, and valproate.” That all changed as she was settling in to her first academic position at the University of Pennsylvania, with the “explosive” introduction of felbamate, a new antiseizure drug whose precipitous rise and fall from favor cast a sobering shadow which set the course for future drug development in the field.

“The felbamate story has a lot to do with what came after, but it was a drug that was much more advantageous in regards to a lot of the things that we didn’t like about antiseizure medicines or antiepileptic drugs as we called them at that time,” she said. The older drugs affected the cerebellum, making people sleepy and unable to concentrate. They also came with the risk of serious adverse effects such as hepatic enzyme induction and teratogenicity. Not only was felbamate nonsedating, “it actually was a little bit alerting,” said Dr. French. “People felt so different and so great on it, and it was effective for some seizure types that we didn’t really have good drugs for.” Very quickly, felbamate became a first-line therapy. Within its first year on the market, 150,000 newly diagnosed patients were started on it, “which is unthinkable now,” she said.

Sure enough, it all came crashing down a year later, on Aug. 1, 1994, when the drug was urgently withdrawn by the U.S. Food and Drug Administration after being linked to the development of aplastic anemia. “There was a day that anybody who was there at the time will remember when we all got the news, that everybody had to be taken off the drug,” Dr. French recalled. “We spent the weekend in the chart room, looking chart by chart by chart, for who was on felbamate.”

Until then, Dr. French had been straddling the line between her interests in pharmacologic versus surgical treatments for epilepsy. In fact, during her second epilepsy fellowship, which was dedicated to surgery, she published “Characteristics of medial temporal lobe epilepsy” in Annals of Neurology, one of the most-cited papers of her career. “Epilepsy from the temporal lobe is the biggest and best shot on goal when you’re talking about sending somebody to epilepsy surgery and rendering them completely seizure free,” she said. “Early in my career at the University of Pennsylvania, it was all about identifying those patients. And you know, there is nothing more gratifying than taking somebody whose life has been devastated by frequent seizures, who is injuring themselves and not able to be independent, and doing a surgery, which is very safe, and then all the seizures are gone – which is probably why I was so excited by surgery at the time.”

For a while, in the early 1990s, temporal lobectomy eclipsed many of the other avenues in epilepsy treatment, but it too has given way to a much wider variety of more complex techniques, which may be less curative but more palliative.
 

 

 

More drug options

Meanwhile, the felbamate story had ignited debate in the field about safer drug development – pushing Dr. French into establishing what was then known as the Antiepileptic Drug Trials conference, later renamed the Epilepsy Therapies & Diagnostics Development Symposium – a forum that encouraged safer, but also swifter movement of drugs through the pipeline and onto the market. “After felbamate, came gabapentin, and then came to topiramate and lamotrigine, and very quickly there were many, many, many choices,” she explained. “But once stung, twice shy. Felbamate really gave us a new perspective on which patients we put on the new drugs. Now we have a process of starting them in people with treatment-resistant epilepsy first. The risk-benefit equation is more reasonable because they have lots of risks. And then we work our way back to people with newly diagnosed epilepsy.”

Disease-modifying therapies

Today, the medications used to treat epilepsy are referred to as antiseizure rather than antiepileptic drugs because they simply suppress seizure symptoms and do not address the cause. But the rocket that Dr. French is watching gain speed and momentum is the disease-modifying gene therapies – true antiepileptics that may significantly move the needle on the number and type of patients who can reach seizure freedom. “We spent the last 25 years not even thinking we would ever have antiepileptic therapies, and now in the last 5 years or so, we were pretty sure we will,” she said. “We have gene therapies that can intervene now – none yet that have actually reached approval, these are all currently in trials – but we certainly have high expectations that they will very soon be available.”

Improving patients’ lives

While gene therapy rockets ahead, new device developments are already improving life for patients, even despite ongoing seizures. A drug-delivering pump is still in trials, but could make a big difference to daily medication adherence, and wearable or implantable devices are being developed to track seizures. More accurate tracking has also revealed that many people’s seizures are actually quite predictable, with regular cycles allowing for the possibility of prophylactic medication when increased seizure activity is expected.

Despite 30 years of no change in the proportion of epilepsy patients experiencing treatment resistance, Dr. French said that drugs, devices, and surgeries have improved the lives of all patients – both treatment resistant and treatment sensitive. “The difference between almost seizure free and completely seizure free is a big one because it means you can’t drive, you may have difficulty with your employment, but being able to take a pill every day and feel otherwise completely normal? We’ve come a long way.”

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Get action! – Teddy Roosevelt

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“Papa! Where donut?” asks my 2½ year-old sitting with her legs dangling and hands folded in a bustling Starbucks. We’ve been waiting for 8 minutes and we’ve reached her limit of tolerance. She’s unimpressed by the queued customers who compliment her curly blonde hair, many of whom have come and gone since we’ve been waiting. I agree – how long does it take to pour a kiddie milk and grab a donut? We can both see it in the case right there!

No one likes to wait. Truly, one of the great benefits of the modern world is that wait times are now incredibly short. Many Starbucks customers, unlike my daughter, ordered their drink ahead and waited exactly 0 minutes to get their drink. What about Amazon? I ordered a bird feeder this morning and it’s already hanging in the yard. It’s still daylight. Feel like Himalayan Momo Dumplings tonight? Your food could arrive in 37 minutes. The modern wait standard has been set impossibly high for us.

Yes, medicine is no doubt at the top of the list of “Worst Wait Times.” We make patients wait for appointments (sometimes months), wait to be seen, wait for biopsy results, wait for follow-up surgery, wait for those second results, even wait for PET scans and treatment plans for some. We created a whole room just for waiting. Airlines call theirs “The Platinum Executive Lounge.” Ours is “The waiting room.”

Excess waiting is a significant reason why health care gets beat up in reviews. We’re unable to keep up with the new expectations. Waiting is also a significant cause of distress. Many patients report the most difficult part of their cancer diagnosis was the waiting for results, not the treatment. It’s because when under stress, we are hardwired to take action. Binding patients into inaction while they wait is very uncomfortable.



Fortunately, the psychology of waiting is well understood and there are best practices that can help. First, anxiety makes waiting much worse. Conveying confidence and reassuring patients they are in the right place and that everything will be OK makes the wait time feel shorter for them. Uncertainty also compounds their apprehension. If you believe the diagnosis will be melanoma, tell them that at the time of the biopsy and tell them what you expect next. This is better than saying, “Well, that could be cancer. We’ll see.”

Knowing a wait time is also much better than not. Have your staff advise patients on how much longer they can expect before seeing you (telling them they’re next isn’t as effective). Advise that test results should be back by the end of next week. Of course, under promise and over deliver. When the results are back on Tuesday, you’ve got a pleased patient.

Explaining that you had to add in an urgent patient helps. Even if it’s not your fault, it’s still better to apologize. For example, the 78 highway, the left anterior descending artery to our office, has been closed because of a sinkhole this month (not kidding). I’ve been apologizing to a lot of patients saying that all our patients are arriving late, which is putting us behind. As they can envision the linear parking lot that used to be a highway, it helps.

Lastly, as any child can tell you, waiting has to not only be, but to also appear, fair. The only thing worse than waiting for an appointment, or donut, is seeing someone who came in after you get their donut before you do. If you’re pulling both Mohs and cosmetics patients from the same waiting area, then your surgery patients will see a lot of patients come and go while they are sitting. Demarcating one sitting area for Mohs and one for clinics might help. So does ordering ahead. I’d show my daughter how to use the app so we don’t have to wait so long next week, but she’s 2 and I’m quite sure she already knows.

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. Write to him at [email protected].

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“Papa! Where donut?” asks my 2½ year-old sitting with her legs dangling and hands folded in a bustling Starbucks. We’ve been waiting for 8 minutes and we’ve reached her limit of tolerance. She’s unimpressed by the queued customers who compliment her curly blonde hair, many of whom have come and gone since we’ve been waiting. I agree – how long does it take to pour a kiddie milk and grab a donut? We can both see it in the case right there!

No one likes to wait. Truly, one of the great benefits of the modern world is that wait times are now incredibly short. Many Starbucks customers, unlike my daughter, ordered their drink ahead and waited exactly 0 minutes to get their drink. What about Amazon? I ordered a bird feeder this morning and it’s already hanging in the yard. It’s still daylight. Feel like Himalayan Momo Dumplings tonight? Your food could arrive in 37 minutes. The modern wait standard has been set impossibly high for us.

Yes, medicine is no doubt at the top of the list of “Worst Wait Times.” We make patients wait for appointments (sometimes months), wait to be seen, wait for biopsy results, wait for follow-up surgery, wait for those second results, even wait for PET scans and treatment plans for some. We created a whole room just for waiting. Airlines call theirs “The Platinum Executive Lounge.” Ours is “The waiting room.”

Excess waiting is a significant reason why health care gets beat up in reviews. We’re unable to keep up with the new expectations. Waiting is also a significant cause of distress. Many patients report the most difficult part of their cancer diagnosis was the waiting for results, not the treatment. It’s because when under stress, we are hardwired to take action. Binding patients into inaction while they wait is very uncomfortable.



Fortunately, the psychology of waiting is well understood and there are best practices that can help. First, anxiety makes waiting much worse. Conveying confidence and reassuring patients they are in the right place and that everything will be OK makes the wait time feel shorter for them. Uncertainty also compounds their apprehension. If you believe the diagnosis will be melanoma, tell them that at the time of the biopsy and tell them what you expect next. This is better than saying, “Well, that could be cancer. We’ll see.”

Knowing a wait time is also much better than not. Have your staff advise patients on how much longer they can expect before seeing you (telling them they’re next isn’t as effective). Advise that test results should be back by the end of next week. Of course, under promise and over deliver. When the results are back on Tuesday, you’ve got a pleased patient.

Explaining that you had to add in an urgent patient helps. Even if it’s not your fault, it’s still better to apologize. For example, the 78 highway, the left anterior descending artery to our office, has been closed because of a sinkhole this month (not kidding). I’ve been apologizing to a lot of patients saying that all our patients are arriving late, which is putting us behind. As they can envision the linear parking lot that used to be a highway, it helps.

Lastly, as any child can tell you, waiting has to not only be, but to also appear, fair. The only thing worse than waiting for an appointment, or donut, is seeing someone who came in after you get their donut before you do. If you’re pulling both Mohs and cosmetics patients from the same waiting area, then your surgery patients will see a lot of patients come and go while they are sitting. Demarcating one sitting area for Mohs and one for clinics might help. So does ordering ahead. I’d show my daughter how to use the app so we don’t have to wait so long next week, but she’s 2 and I’m quite sure she already knows.

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. Write to him at [email protected].

“Papa! Where donut?” asks my 2½ year-old sitting with her legs dangling and hands folded in a bustling Starbucks. We’ve been waiting for 8 minutes and we’ve reached her limit of tolerance. She’s unimpressed by the queued customers who compliment her curly blonde hair, many of whom have come and gone since we’ve been waiting. I agree – how long does it take to pour a kiddie milk and grab a donut? We can both see it in the case right there!

No one likes to wait. Truly, one of the great benefits of the modern world is that wait times are now incredibly short. Many Starbucks customers, unlike my daughter, ordered their drink ahead and waited exactly 0 minutes to get their drink. What about Amazon? I ordered a bird feeder this morning and it’s already hanging in the yard. It’s still daylight. Feel like Himalayan Momo Dumplings tonight? Your food could arrive in 37 minutes. The modern wait standard has been set impossibly high for us.

Yes, medicine is no doubt at the top of the list of “Worst Wait Times.” We make patients wait for appointments (sometimes months), wait to be seen, wait for biopsy results, wait for follow-up surgery, wait for those second results, even wait for PET scans and treatment plans for some. We created a whole room just for waiting. Airlines call theirs “The Platinum Executive Lounge.” Ours is “The waiting room.”

Excess waiting is a significant reason why health care gets beat up in reviews. We’re unable to keep up with the new expectations. Waiting is also a significant cause of distress. Many patients report the most difficult part of their cancer diagnosis was the waiting for results, not the treatment. It’s because when under stress, we are hardwired to take action. Binding patients into inaction while they wait is very uncomfortable.



Fortunately, the psychology of waiting is well understood and there are best practices that can help. First, anxiety makes waiting much worse. Conveying confidence and reassuring patients they are in the right place and that everything will be OK makes the wait time feel shorter for them. Uncertainty also compounds their apprehension. If you believe the diagnosis will be melanoma, tell them that at the time of the biopsy and tell them what you expect next. This is better than saying, “Well, that could be cancer. We’ll see.”

Knowing a wait time is also much better than not. Have your staff advise patients on how much longer they can expect before seeing you (telling them they’re next isn’t as effective). Advise that test results should be back by the end of next week. Of course, under promise and over deliver. When the results are back on Tuesday, you’ve got a pleased patient.

Explaining that you had to add in an urgent patient helps. Even if it’s not your fault, it’s still better to apologize. For example, the 78 highway, the left anterior descending artery to our office, has been closed because of a sinkhole this month (not kidding). I’ve been apologizing to a lot of patients saying that all our patients are arriving late, which is putting us behind. As they can envision the linear parking lot that used to be a highway, it helps.

Lastly, as any child can tell you, waiting has to not only be, but to also appear, fair. The only thing worse than waiting for an appointment, or donut, is seeing someone who came in after you get their donut before you do. If you’re pulling both Mohs and cosmetics patients from the same waiting area, then your surgery patients will see a lot of patients come and go while they are sitting. Demarcating one sitting area for Mohs and one for clinics might help. So does ordering ahead. I’d show my daughter how to use the app so we don’t have to wait so long next week, but she’s 2 and I’m quite sure she already knows.

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. Write to him at [email protected].

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A 7-month-old male presents with pustules and inflamed papules on the scalp and extremities

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The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.

Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.

Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).

Dr. Catalina Matiz

EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.

In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.

Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.

If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.

Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.

Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.

In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
 

References

Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.

Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.

Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.

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The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.

Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.

Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).

Dr. Catalina Matiz

EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.

In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.

Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.

If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.

Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.

Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.

In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
 

References

Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.

Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.

Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.

The bacterial, fungal, and atypical mycobacterial cultures from the lesions performed at the emergency department were all negative.

Pediatric dermatology was consulted and a punch biopsy of one of the lesions was done. Histopathologic examination showed a mixed perifollicular infiltrate of predominantly eosinophils with some neutrophils and associated microabscesses. Periodic acid Schiff and Fite stains failed to reveal any organisms. CD1 immunostain was negative. Fresh tissue cultures for bacteria, fungi, and atypical mycobacteria were negative.

Given the clinical presentation of chronic recurrent sterile pustules on an infant with associated eosinophilia and the reported histopathologic findings, the patient was diagnosed with eosinophilic pustular folliculitis of infancy (EPFI).

Dr. Catalina Matiz

EPFI is a rare and idiopathic cutaneous disorder present in children. About 70% of the cases reported occur in the first 6 month of life and rarely present past 3 years of age. EPF encompasses a group of conditions including the classic adult form, or Ofuji disease. EPF is seen in immunosuppressed patients, mainly HIV positive, and EPF is also seen in infants and children.

In EPFI, males are most commonly affected. The condition presents, as it did in our patient, with recurrent crops of sterile papules and pustules mainly on the scalp, but they can occur in other parts of the body. The lesions go away within a few weeks to months without leaving any scars but it can take months to years to resolve. Histopathologic analysis of the lesions show an eosinophilic infiltrate which can be follicular, perifollicular, or periadnexal with associated flame figures in about 26% of cases.

Aggressive treatment is usually not needed as lesions are self-limited. Lesions can be treated with topical corticosteroids and oral antihistamine medications like cetirizine if symptomatic.

If the lesions start to present during the neonatal period, one may consider in the differential diagnosis, neonatal rashes like transient neonatal pustular melanosis and erythema toxicum neonatorum. Both of these neonatal conditions tend to resolve in the first month of life, compared with EPFI where lesions can come and go for months to years. EPFI lesions can be described as pustules and inflammatory papules, as well as furuncles and vesicles. All of the lesions may be seen in one patient at one time, which will not be typical for transient neonatal pustular melanosis or erythema toxicum. Eosinophils can be seen in erythema toxicum but folliculitis is not present. The inflammatory infiltrate seen in transient neonatal pustular melanosis is polymorphonuclear, not eosinophilic.

Early in the presentation, infectious conditions like staphylococcal or streptococcal folliculitis, cellulitis and furunculosis, tinea capitis, atypical mycobacterial infections, herpes simplex, and parasitic infections like scabies should be considered. In young infants, empiric antibiotic treatment may be started until cultures are finalized. If there is a family history of pruritic papules and pustules, scabies should be considered. A scabies prep can be done to rule out this entity.

Langerhans cell histiocytosis can also present with pustules and papules in early infancy and also has a predilection for the scalp. When this condition is in question, a skin biopsy should be performed which shows a CD1 positive histiocytic infiltrate.

In conclusion, EPFI is a benign rare condition that can present in infants as recurrent pustules and papules, mainly on the scalp, which are self-limited and if symptomatic can be treated with topical corticosteroids and antihistamines.
 

References

Alonso-Castro L et al. Dermatol Online J. 2012 Oct 15;18(10):6.

Frølunde AS et al. Clin Case Rep. 2021 May 11;9(5):e04167.

Hernández-Martín Á et al. J Am Acad Dermatol. 2013 Jan;68(1):150-5.

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A 7-month-old male is brought to the emergency department for evaluation of pustules and inflamed papules on the scalp and extremities for several weeks of duration. The parents report the lesions started about a month prior and he has already been treated with cephalexin, clindamycin, and sulfamethoxazole without any improvement. Cultures sent prior by the child's pediatrician did not reveal any fungus or bacteria. The parents report a low-grade fever for about 3 days.   


He was born via natural vaginal delivery with no instrumentation or external monitoring. Mom had prenatal care. Besides the skin lesions, the baby has been healthy and growing well. He has no history of eczema or severe infections. He has not been hospitalized before.  
On physical examination the baby was not febrile. On the scalp and forehead, he had diffusely distributed pustules, erythematous papules, and nodules. He also presented with scattered, fine, small, crusted 1-2-mm pink papules on the trunk and extremities. He had no adenopathy or hepatosplenomegaly.  
At the emergency department, samples from one of the pustules were sent for bacterial, fungal, and atypical mycobacteria cultures. Laboratory test showed a normal blood count with associated eosinophilia (2.8 x 109 L), and normal liver and kidney function. A head ultrasound showed three ill-defined hypoechoic foci within the scalp.  
The patient was admitted for treatment with broad-spectrum antibiotics and dermatology was consulted.

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Medicare expands CGM coverage to more with type 2 diabetes

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Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

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Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

Medicare is now covering continuous glucose monitoring (CGM) for all beneficiaries with diabetes who use insulin, as well as those with a “history of problematic hypoglycemia.”

The new policy decision, announced earlier this year by the Centers for Medicare and Medicaid Services, means that coverage is expanded to those who take even just a single dose of basal insulin daily or who don’t take insulin but who for other reasons experience “problematic” hypoglycemia, defined as a history of more than one level 2 event (glucose < 54 mg/dL) or at least one level 3 event (< 54 mg/dL requiring assistance).

Previously, coverage was limited to those taking frequent daily insulin doses.  

The additional number of people covered, most with type 2 diabetes, is estimated to be at least 1.5 million. That number could more than double if private insurers follow suit, reported an industry analyst.

Chuck Henderson, chief executive officer of the American Diabetes Association, said in a statement: “We applaud CMS’ decision allowing for all insulin-dependent people as well as others who have a history of problematic hypoglycemia to have access to a continuous glucose monitor, a potentially life-saving tool for diabetes management.”

According to Dexcom, which manufacturers the G6 and the recently approved G7 CGMs, the decision was based in part on their MOBILE study. The trial demonstrated the benefit of CGM in people with type 2 diabetes who use only basal insulin or have a history of problematic hypoglycemic events.

On April 14, Abbott, which manufactures the Freestyle Libre 2 and the recently approved Libre 3, received clearance from the U.S. Food and Drug Administration for the Libre 3’s stand-alone reader device. Previously, the Libre 3 had been approved for use only with a smartphone app. The small handheld reader is considered durable medical equipment, making it eligible for Medicare coverage. Abbott is “working on having the FreeStyle Libre 3 system available to Medicare beneficiaries,” the company said in a statement.

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

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