Mixed Topics

A rigorously conducted trial in men with androgenetic alopecia found that low-dose oral minoxidil was as effective in promoting hair growth as was topical minoxidil.

Oral minoxidil, 5 mg once a day, “did not demonstrate superiority” over topical minoxidil, 5%, applied twice a day, after 24 weeks, reported Mariana Alvares Penha, MD, of the department of dermatology at São Paulo State University, in Botucatu, Brazil, and coauthors. Their randomized, controlled, double-blind study was published online in JAMA Dermatology.

Topical minoxidil is approved by the US Food and Drug Administration (FDA) for androgenetic alopecia (AGA), but there has been increasing interest worldwide in the use of low-dose oral minoxidil, a vasodilator approved as an antihypertensive, as an alternative treatment.

The trial “is important information that’s never been elucidated before,” Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview. The data, he added, can be used to reassure patients who do not want to take the oral form of the drug that a topical is just as effective.

“This study does let us counsel patients better and really give them the evidence,” said Shari Lipner, MD, PhD, associate professor of clinical dermatology at Weill Cornell Medicine, New York, who was also asked to comment on the results.

Both Dr. Lipner and Dr. Friedman said the study was well-designed.

The investigators enrolled 90 men aged 18-55; 68 completed the trial. Most had mild to moderate AGA. Men were excluded if they had received treatment for alopecia in the previous 6 months, a history of hair transplant, cardiopathy, nephropathy, dermatoses involving the scalp, any clinical conditions causing hair loss, or hypersensitivity to minoxidil.

They were randomized to receive either 5 mg of oral minoxidil a day, plus a placebo solution to apply to the scalp, or topical minoxidil solution (5%) applied twice a day plus placebo capsules. They were told to take a capsule at bedtime and to apply 1 mL of the solution to dry hair in the morning and at night.

The final analysis included 35 men in the topical group and 33 in the oral group (mean age, 36.6 years). Seven people in the topical group and 11 in the oral group were not able to attend the final appointment at 24 weeks. Three additional patients in the topical group dropped out for insomnia, hair shedding, and scalp eczema, while one dropped out of the oral group because of headache.

At 24 weeks, the percentage increase in terminal hair density in the oral minoxidil group was 27% higher (P = .005) in the vertex and 13% higher (P = .15) in the frontal scalp, compared with the topical-treated group.

Total hair density increased by 2% in the oral group compared with topical treatment in the vertex and decreased by 0.2% in the frontal area compared with topical treatment. None of these differences were statistically significant.

Three dermatologists blinded to the treatments, who analyzed photographs, determined that 60% of the men in the oral group and 48% in the topical group had clinical improvement in the frontal area, which was not statistically significant. More orally-treated patients had improvement in the vertex area: 70% compared with 46% of those on topical treatment (P = .04).

Hypertrichosis, Headache

Of the original 90 patients in the trial, more men taking oral minoxidil had hypertrichosis: 49% compared with 25% in the topical formulation group. Headache was also more common among those on oral minoxidil: six cases (14%) vs. one case (2%) among those on topical minoxidil. There was no difference in mean arterial blood pressure or resting heart rate between the two groups. Transient hair loss was more common with topical treatment, but it was not significant.

Dr. Friedman said that the study results would not change how he practices, but that it would give him data to use to inform patients who do not want to take oral minoxidil. He generally prescribes the oral form, unless patients do not want to take it or there is a medical contraindication, which he said is rare.

“I personally think oral is superior to topical,” mainly “because the patient’s actually using it,” said Dr. Friedman. “They’re more likely to take a pill a day versus apply something topically twice a day,” he added.

Both Dr. Lipner and Dr. Friedman said that they doubted that individuals could — or would want to — follow the twice-daily topical regimen used in the trial.

“In real life, not in the clinical trial scenario, it may be very hard for patients to comply with putting on the topical minoxidil twice a day or even once a day,” Dr. Lipner said.

However, she continues to prescribe more topical minoxidil than oral, because she believes “there’s less potential for side effects.” For patients who can adhere to the topical regimen, the study shows that they will get results, said Dr. Lipner.

Dr. Friedman, however, said that for patients who are looking at a lifetime of medication, “an oral will always win out on a topical to the scalp from an adherence perspective.”

The study was supported by the Brazilian Dermatology Society Support Fund. Dr. Penha reported receiving grants from the fund; no other disclosures were reported. Dr. Friedman and Dr. Lipner reported no conflicts related to minoxidil.

A rigorously conducted trial in men with androgenetic alopecia found that low-dose oral minoxidil was as effective in promoting hair growth as was topical minoxidil.

Oral minoxidil, 5 mg once a day, “did not demonstrate superiority” over topical minoxidil, 5%, applied twice a day, after 24 weeks, reported Mariana Alvares Penha, MD, of the department of dermatology at São Paulo State University, in Botucatu, Brazil, and coauthors. Their randomized, controlled, double-blind study was published online in JAMA Dermatology.

Topical minoxidil is approved by the US Food and Drug Administration (FDA) for androgenetic alopecia (AGA), but there has been increasing interest worldwide in the use of low-dose oral minoxidil, a vasodilator approved as an antihypertensive, as an alternative treatment.

The trial “is important information that’s never been elucidated before,” Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview. The data, he added, can be used to reassure patients who do not want to take the oral form of the drug that a topical is just as effective.

“This study does let us counsel patients better and really give them the evidence,” said Shari Lipner, MD, PhD, associate professor of clinical dermatology at Weill Cornell Medicine, New York, who was also asked to comment on the results.

Both Dr. Lipner and Dr. Friedman said the study was well-designed.

The investigators enrolled 90 men aged 18-55; 68 completed the trial. Most had mild to moderate AGA. Men were excluded if they had received treatment for alopecia in the previous 6 months, a history of hair transplant, cardiopathy, nephropathy, dermatoses involving the scalp, any clinical conditions causing hair loss, or hypersensitivity to minoxidil.

They were randomized to receive either 5 mg of oral minoxidil a day, plus a placebo solution to apply to the scalp, or topical minoxidil solution (5%) applied twice a day plus placebo capsules. They were told to take a capsule at bedtime and to apply 1 mL of the solution to dry hair in the morning and at night.

The final analysis included 35 men in the topical group and 33 in the oral group (mean age, 36.6 years). Seven people in the topical group and 11 in the oral group were not able to attend the final appointment at 24 weeks. Three additional patients in the topical group dropped out for insomnia, hair shedding, and scalp eczema, while one dropped out of the oral group because of headache.

At 24 weeks, the percentage increase in terminal hair density in the oral minoxidil group was 27% higher (P = .005) in the vertex and 13% higher (P = .15) in the frontal scalp, compared with the topical-treated group.

Total hair density increased by 2% in the oral group compared with topical treatment in the vertex and decreased by 0.2% in the frontal area compared with topical treatment. None of these differences were statistically significant.

Three dermatologists blinded to the treatments, who analyzed photographs, determined that 60% of the men in the oral group and 48% in the topical group had clinical improvement in the frontal area, which was not statistically significant. More orally-treated patients had improvement in the vertex area: 70% compared with 46% of those on topical treatment (P = .04).

Hypertrichosis, Headache

Of the original 90 patients in the trial, more men taking oral minoxidil had hypertrichosis: 49% compared with 25% in the topical formulation group. Headache was also more common among those on oral minoxidil: six cases (14%) vs. one case (2%) among those on topical minoxidil. There was no difference in mean arterial blood pressure or resting heart rate between the two groups. Transient hair loss was more common with topical treatment, but it was not significant.

Dr. Friedman said that the study results would not change how he practices, but that it would give him data to use to inform patients who do not want to take oral minoxidil. He generally prescribes the oral form, unless patients do not want to take it or there is a medical contraindication, which he said is rare.

“I personally think oral is superior to topical,” mainly “because the patient’s actually using it,” said Dr. Friedman. “They’re more likely to take a pill a day versus apply something topically twice a day,” he added.

Both Dr. Lipner and Dr. Friedman said that they doubted that individuals could — or would want to — follow the twice-daily topical regimen used in the trial.

“In real life, not in the clinical trial scenario, it may be very hard for patients to comply with putting on the topical minoxidil twice a day or even once a day,” Dr. Lipner said.

However, she continues to prescribe more topical minoxidil than oral, because she believes “there’s less potential for side effects.” For patients who can adhere to the topical regimen, the study shows that they will get results, said Dr. Lipner.

Dr. Friedman, however, said that for patients who are looking at a lifetime of medication, “an oral will always win out on a topical to the scalp from an adherence perspective.”

The study was supported by the Brazilian Dermatology Society Support Fund. Dr. Penha reported receiving grants from the fund; no other disclosures were reported. Dr. Friedman and Dr. Lipner reported no conflicts related to minoxidil.

A rigorously conducted trial in men with androgenetic alopecia found that low-dose oral minoxidil was as effective in promoting hair growth as was topical minoxidil.

Oral minoxidil, 5 mg once a day, “did not demonstrate superiority” over topical minoxidil, 5%, applied twice a day, after 24 weeks, reported Mariana Alvares Penha, MD, of the department of dermatology at São Paulo State University, in Botucatu, Brazil, and coauthors. Their randomized, controlled, double-blind study was published online in JAMA Dermatology.

Topical minoxidil is approved by the US Food and Drug Administration (FDA) for androgenetic alopecia (AGA), but there has been increasing interest worldwide in the use of low-dose oral minoxidil, a vasodilator approved as an antihypertensive, as an alternative treatment.

The trial “is important information that’s never been elucidated before,” Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview. The data, he added, can be used to reassure patients who do not want to take the oral form of the drug that a topical is just as effective.

“This study does let us counsel patients better and really give them the evidence,” said Shari Lipner, MD, PhD, associate professor of clinical dermatology at Weill Cornell Medicine, New York, who was also asked to comment on the results.

Both Dr. Lipner and Dr. Friedman said the study was well-designed.

The investigators enrolled 90 men aged 18-55; 68 completed the trial. Most had mild to moderate AGA. Men were excluded if they had received treatment for alopecia in the previous 6 months, a history of hair transplant, cardiopathy, nephropathy, dermatoses involving the scalp, any clinical conditions causing hair loss, or hypersensitivity to minoxidil.

They were randomized to receive either 5 mg of oral minoxidil a day, plus a placebo solution to apply to the scalp, or topical minoxidil solution (5%) applied twice a day plus placebo capsules. They were told to take a capsule at bedtime and to apply 1 mL of the solution to dry hair in the morning and at night.

The final analysis included 35 men in the topical group and 33 in the oral group (mean age, 36.6 years). Seven people in the topical group and 11 in the oral group were not able to attend the final appointment at 24 weeks. Three additional patients in the topical group dropped out for insomnia, hair shedding, and scalp eczema, while one dropped out of the oral group because of headache.

At 24 weeks, the percentage increase in terminal hair density in the oral minoxidil group was 27% higher (P = .005) in the vertex and 13% higher (P = .15) in the frontal scalp, compared with the topical-treated group.

Total hair density increased by 2% in the oral group compared with topical treatment in the vertex and decreased by 0.2% in the frontal area compared with topical treatment. None of these differences were statistically significant.

Three dermatologists blinded to the treatments, who analyzed photographs, determined that 60% of the men in the oral group and 48% in the topical group had clinical improvement in the frontal area, which was not statistically significant. More orally-treated patients had improvement in the vertex area: 70% compared with 46% of those on topical treatment (P = .04).

Hypertrichosis, Headache

Of the original 90 patients in the trial, more men taking oral minoxidil had hypertrichosis: 49% compared with 25% in the topical formulation group. Headache was also more common among those on oral minoxidil: six cases (14%) vs. one case (2%) among those on topical minoxidil. There was no difference in mean arterial blood pressure or resting heart rate between the two groups. Transient hair loss was more common with topical treatment, but it was not significant.

Dr. Friedman said that the study results would not change how he practices, but that it would give him data to use to inform patients who do not want to take oral minoxidil. He generally prescribes the oral form, unless patients do not want to take it or there is a medical contraindication, which he said is rare.

“I personally think oral is superior to topical,” mainly “because the patient’s actually using it,” said Dr. Friedman. “They’re more likely to take a pill a day versus apply something topically twice a day,” he added.

Both Dr. Lipner and Dr. Friedman said that they doubted that individuals could — or would want to — follow the twice-daily topical regimen used in the trial.

“In real life, not in the clinical trial scenario, it may be very hard for patients to comply with putting on the topical minoxidil twice a day or even once a day,” Dr. Lipner said.

However, she continues to prescribe more topical minoxidil than oral, because she believes “there’s less potential for side effects.” For patients who can adhere to the topical regimen, the study shows that they will get results, said Dr. Lipner.

Dr. Friedman, however, said that for patients who are looking at a lifetime of medication, “an oral will always win out on a topical to the scalp from an adherence perspective.”

The study was supported by the Brazilian Dermatology Society Support Fund. Dr. Penha reported receiving grants from the fund; no other disclosures were reported. Dr. Friedman and Dr. Lipner reported no conflicts related to minoxidil.

A new American Gastroenterological Association (AGA) clinical practice update shines a light on cannabinoid hyperemesis syndrome (CHS).

CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.

Courtesy Cleveland Clinic

“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”

According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:

• Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
• Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
• Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.

As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.

During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.

The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.

Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.

Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.

While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.

“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.

Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.

“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”

Dr. Rubio Tapia and colleagues concluded with a call for more research.

“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.

This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.

A new American Gastroenterological Association (AGA) clinical practice update shines a light on cannabinoid hyperemesis syndrome (CHS).

CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.

Courtesy Cleveland Clinic

“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”

According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:

• Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
• Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
• Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.

As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.

During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.

The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.

Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.

Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.

While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.

“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.

Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.

“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”

Dr. Rubio Tapia and colleagues concluded with a call for more research.

“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.

This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.

A new American Gastroenterological Association (AGA) clinical practice update shines a light on cannabinoid hyperemesis syndrome (CHS).

CHS, which is triggered by chronic cannabis usage and manifests with GI and autonomic symptoms, is on the rise in the United States, yet underdiagnosis remains a challenge and clinical data are scarce, reported lead update panelist Alberto Rubio Tapia, MD, of Cleveland Clinic, Cleveland, Ohio, and colleagues.

Courtesy Cleveland Clinic

“Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed CHS, were noted relatively recently,” the panelists wrote in Gastroenterology. “The objective of this article was to help practitioners define the appropriate approach to the diagnosis and management of CHS.”

According to the update, the typical CHS patient is male with a years-long history of daily or near-daily cannabis use. Paradoxically, while cannabis use drives this condition, some patients with CHS report that cannabis use relieves their symptoms.The update describes CHS as a subtype of cyclical vomiting syndrome (CVS), and offers diagnostic criteria for CHS, reproduced below verbatim:

• Clinical features: stereotypical episodic vomiting resembling CVS in terms of onset, with frequency 3 or more times annually;
• Cannabis use patterns: duration of cannabis use more than 1 year before symptom onset; frequency more than 4 times per week, on average;
• Cannabis cessation: resolution of symptoms after a period of abstinence from cannabis use for at least 6 months, or at least equal to the total duration of 3 typical vomiting cycles in that patient.

As CHS is a subtype of CVS, the update also provides an outline and management guide for this broader condition, which is characterized by four phases: inter-episodic, prodromal, emetic, and recovery.

During the inter-episodic phase, patients will have minimal or no symptoms, although almost one third will describe dyspepsia or nausea. Prophylactic medications in this period include tricyclics, mitochondrial supplements like CoQ10 and vitamin B12, NK1 antagonists, and anticonvulsants.

The prodromal phase is characterized by abdominal pain and nausea with a duration of 30-90 minutes. During this time patients may have autonomic symptoms like sweating and feeling hot or cold. Psychological symptoms may include feelings of panic and being “out of control.” Abortive medications are appropriate during this period, according to the update, like triptans and antiemetics.

Next comes the emetic phase, in which patients exhibit “relentless vomiting,” retching, abdominal pain, neurological symptoms and extreme thirst. Because an empty stomach may provide relief, inducing emesis may be considered, along with rest in a quiet dark room and supportive care.

Finally, the vomiting subsides during the recovery phase, when it is possible to restart oral intake and resume normal activities.

While this framework may be useful when managing patients with CHS, intervention should be centered around cannabis cessation, according to the update.

“For long-term management, counseling to achieve marijuana cessation and tricyclic antidepressants, such as amitriptyline, are the mainstay of therapy,” Dr. Rubio Tapia and colleagues wrote.

Advising patients to stop cannabis “cold turkey” is not recommended, they added, as this may bring on withdrawal symptoms, and it tends to be ineffective in this population, which has a high recidivism rate.

“Co-management with a psychologist or psychiatrist may be helpful for patients who have a lack of response to standard therapies or extensive psychiatric comorbidity,” the panelists wrote. “Anxiety and depression are very common associated conditions.”

Dr. Rubio Tapia and colleagues concluded with a call for more research.

“Further understanding of CHS pathophysiology and evidence-based therapies are urgently needed,” they wrote.

This update was commissioned and approved by the AGA. The update panelists disclosed relationships with Evoke Pharma, RedHill Biopharma, Takeda, and others.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

To the Editor:

Recurrent aphthous stomatitis (RAS) is a mucocutaneous condition characterized by single or multiple, painful,^1,2 round ulcerations of variable sizes with a tendency for recurrence, most commonly located in nonkeratinized areas of the oral mucosa. Pathergy commonly is observed.³ Although many authors consider the terms RAS andaphtha to be synonymous,^4,5 differentiating the clinical lesion (aphthous ulceration) from the disease (aphtha or RAS) can be useful, as several other diseases can at times manifest with similar ulcers (called aphthoid lesions), such as pemphigus vulgaris, mucous membrane pemphigoid, and erythema multiforme.⁶

It is estimated that approximately 20% of individuals worldwide have at least one episode of aphtha during their lifetime,⁷ and it is considered the most common disease of the oral mucosa.^8,9 However, only patients presenting with severe acute outbreaks or frequent relapses typically seek medical treatment. Clinically, aphthous ulcers are classified as aphtha minor (small number of small lesions), aphtha major (large deep lesions that also can affect the minor salivary glands with intense necrosis, difficulty in healing, and mucosal scarring), and aphtha herpetiformis (innumerous tiny lesions that reappear in recurring outbreaks).^1-3 The term complex aphthosis was introduced in 1985¹⁰ and is defined as recurrent oral and genital aphthous ulcerations or recurring multiple oral aphthous ulcers in the absence of systemic manifestations or Behçet disease^11,12; however, complex aphthosis also has been reported as frequent episodes of ulcerations that may be associated with systemic diseases including Behçet disease.^13,14

Currently, RAS is considered an immunologically mediated alteration in cutaneous mucosal reactivity with a multifactorial systemic cause. Underlying conditions such as Behçet disease, inflammatory bowel disease (IBD), iatrogenic immunosuppression (eg, following solid organ transplantation), AIDS, and cyclic neutropenia may or may not be detected.^11-13

Our retrospective study explored the systemic nature of RAS. We reviewed patient records to evaluate underlying systemic conditions associated with the diagnosis of RAS and the use of oral medications in managing the disease. Medical records from the Department of Dermatology of the University of São Paulo, Brazil, from 2003 to 2017 were reviewed to identify patients with a diagnosis of RAS. Clinical classification of RAS—minor, major, or herpetiform—as well as the presence of aphthous lesions in other locations and the presence of other associated inflammatory cutaneous manifestations also were noted. Associated systemic diseases and treatments for RAS were recorded. Patients for whom the diagnosis of RAS was changed during follow-up were excluded. Because this was a retrospective analysis of medical records and without any patient risk, informed consent was not needed.

Medical records for 125 patients were reviewed; 63 were male (50.4%), and 62 were female (49.6%). The age at onset of symptoms, which ranged from a few months after birth to 74 years, was reported in only 92 (73.6%) patient medical records. Of these, 30 (32.6%) reported onset before 20 years of age, 39 (42.4%) between 20 and 39 years, 17 (18.5%) between 40 and 59 years, and 6 (6.5%) at 60 years or older. Morphologically, 72 (57.6%) had minor, 42 (33.6%) had major, and 11 (8.8%) had herpetiform aphthous ulcers. None of the patients presented with sporadic lesions; the disease was long-standing and persistent in all cases (complex aphthosis).

Regarding the location of the ulcers, 92 (73.6%) patients had lesions on the oral mucosa only. Some patients had lesions in more than one site in addition to the oral mucosa: 32 (25.6%) had aphthae in the genital/groin region and 4 (3.2%) presented with perianal/anal aphthae. Nineteen patients (19.2%) presented other cutaneous manifestations in addition to aphthae: 11 (45.8%) had folliculitis/pseudofolliculitis, and 8 (33.3%) had erythema nodosum (EN). Eight patients (33.3%) presented with uveitis, and 6 (25%) presented with concomitant arthralgia/arthritis. Fifty-four patients (43.2%) had confirmed or suspected associated disease: Behçet disease (21 [38.9%]), IBD (10 [18.5%]), solid organ transplantation (7 [13.0%])(kidney, 4 [57.1%]; heart, 2 [28.6%]; liver, 1 [14.3%]), HIV infection (6 [11.1%]), lymphoma (1 [1.9%]), aplastic anemia (1 [1.9%]), or myelodysplastic syndrome (1 [1.9%]). Ten patients (18.5%) presented with other diseases under investigation (eg, unidentified rheumatologic disease, unexplained neutropenia, undiagnosed immunodeficiencies, autoinflammatory syndromes, possible cyclic neutropenia).

Biopsies of the oral mucosa were performed in 31 patients. Histopathologic findings will be discussed in a future publication (unpublished data).

Five patients (4.0%) were lost to follow-up and did not receive treatment; 10 (8.0%) received only topical treatment (analgesics and/or corticosteroids). All 9 (7.2%) patients undergoing intralesional corticosteroid injections also were on a systemic treatment. One hundred ten (88.0%) patients were treated systemically—with colchicine (84/110 [76.4%]), thalidomide (43/110 [39.1%]), small pulses of oral corticosteroids (26 [23.6%]), dapsone (12/110 [10.9%]), or pentoxifylline (3 [2.7%]). Furthermore, in patients with associated diseases, treatment of the underlying condition was conducted when available, and follow-up was carried out in conjunction with the appropriate specialists. For treatment of the associated disease, patients received other medications such as methotrexate, azathioprine, cyclophosphamide, intravenous corticosteroid pulse, and immunobiologics.

The prevalence of RAS between sexes in our study population was similar (50.4% male; 49.6% female). Results from prior studies have been mixed; some reported a higher prevalence in females,^15-18 while others found no predilection for sex among patients diagnosed with RAS.^19,20 In our analysis, 75% of patients experienced symptoms of RAS before 40 years of age; in prior studies, up to 56% of patients experienced symptoms between the ages of 20 and 40 years.^21,22

In our study, 26.4% of patients had extraoral aphthae. Genital lesions have been described as infrequent,²³ and lesions manifesting in other mucous membranes or on the skin are rare.²⁴ A study reported genital involvement in 8% to 13% of patients with oral aphtha.²⁵ We observed genital involvement in 25.6% of patients. Likewise, this higher value may be due to our study population of patients referred to our university hospital. In our study, 19.2% of patients presented with other inflammatory manifestations in addition to aphthous ulcerations (eg, folliculitis, EN, uveitis, arthritis). As dermatologists in a tertiary reference hospital, we actively look for such associations in every aphtha patient, which may not be the case in many nondermatologic oral care services.

In our study population, 43.2% of patients were diagnosed with or were under investigation for systemic diseases known to be associated with RAS. We found associations with Behçet disease most frequently, followed by IBD,²⁶ solid organ transplantation, and HIV. In this group of patients, the respective systemic disease was active or poorly controlled. In transplant recipients, aphtha major was the most common type, similar to other studies.²⁷ We observed no notable difference in the clinical picture of the oral ulcers in patients with a well-established systemic disease vs those without.

Most of our cases did not present findings other than aphtha, indicating that the intrinsic defect that predisposes to RAS is always systemic. Even mild and sporadic cases may be attributable to a systemic disorder of cutaneous-mucosal reactivity. The predisposition to RAS never originates in the oral cavity, hence the confusion caused and the uselessness of studies that relate aphthae to factors such as local food allergies, pH changes, or local infection with microorganisms.^5,28 The disease course (reducing the frequency of lesion appearance and accelerating the healing of extensive lesions) is only modified with systemic treatment, with local measures proving to be only moderately useful to relieve pain. We believe that RAS can in many ways be compared to EN and pyoderma gangrenosum (PG): some systemic conditions that predispose patients to EN and PG also may predispose them to RAS (eg, IBD, hematologic disorders). Similar to RAS, many cases of EN and PG are idiopathic. In addition, pathergy also occurs in PG.^11,13

We were unable to observe or establish any predictive clinical element that could indicate a better or worse response to the prescribed treatments, which also has been noted by other authors.^3,4 Treatment of RAS is empiric, generally starting with drugs that are easier to prescribe and with fewer adverse effects, then progressing to more complex drugs when a good response is not obtained. Colchicine was the most commonly prescribed medication (76.4% [84/110]). It has been proposed by several authors^3,4 as a first-line systemic medication for the treatment of recurrent aphthae, as it has been shown to be effective and safe. The dosage ranged from 0.5 mg twice daily to 0.5 mg 4 times daily. Dapsone is an established drug for aphtha^29,30 and was used in 12 of our patients. The dosage used in our patients ranged from 50 to 100 mg/d. Adverse effects such as hemolytic anemia frequently are seen, and one of the patients in our study developed DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome in response to dapsone. In 7 cases, colchicine and dapsone were used together, which is believed to potentiate the therapeutic effects. This combination may be useful in patients for whom thalidomide cannot be used or those who have not improved with monotherapy.²⁹ Thalidomide is considered one of the most effective drugs for RAS.^30,31 Forty-three patients in our analysis were treated with thalidomide, usually as a first choice. The dosage ranged from 100 to 200 mg/d. It was mainly chosen in disabling pediatric cases, adult men with aphthous major, and women with no risk for pregnancy. Due to its potential adverse effects, thalidomide has been recommended when there is no response with other medications that are dose dependent; severe adverse effects such as thromboembolism and peripheral neuropathy are rare.³¹ Oral corticosteroids were used in 26 patients, aiming at rapid improvement in very symptomatic cases; however, due to the potential for long-term adverse effects, in all cases they were prescribed in combination with another medication that was maintained after the corticosteroid was discontinued.

We highlight the systemic nature of RAS as well as its frequent association with systemic diseases and other correlated manifestations (pustules, EN, arthralgia). We also emphasize the importance of using oral medications to adequately control the disease and do not recommend topical medications aimed at treating local causes. Dermatologists should be consulted in managing severe cases of RAS.

To the Editor:

Recurrent aphthous stomatitis (RAS) is a mucocutaneous condition characterized by single or multiple, painful,^1,2 round ulcerations of variable sizes with a tendency for recurrence, most commonly located in nonkeratinized areas of the oral mucosa. Pathergy commonly is observed.³ Although many authors consider the terms RAS andaphtha to be synonymous,^4,5 differentiating the clinical lesion (aphthous ulceration) from the disease (aphtha or RAS) can be useful, as several other diseases can at times manifest with similar ulcers (called aphthoid lesions), such as pemphigus vulgaris, mucous membrane pemphigoid, and erythema multiforme.⁶

It is estimated that approximately 20% of individuals worldwide have at least one episode of aphtha during their lifetime,⁷ and it is considered the most common disease of the oral mucosa.^8,9 However, only patients presenting with severe acute outbreaks or frequent relapses typically seek medical treatment. Clinically, aphthous ulcers are classified as aphtha minor (small number of small lesions), aphtha major (large deep lesions that also can affect the minor salivary glands with intense necrosis, difficulty in healing, and mucosal scarring), and aphtha herpetiformis (innumerous tiny lesions that reappear in recurring outbreaks).^1-3 The term complex aphthosis was introduced in 1985¹⁰ and is defined as recurrent oral and genital aphthous ulcerations or recurring multiple oral aphthous ulcers in the absence of systemic manifestations or Behçet disease^11,12; however, complex aphthosis also has been reported as frequent episodes of ulcerations that may be associated with systemic diseases including Behçet disease.^13,14

Currently, RAS is considered an immunologically mediated alteration in cutaneous mucosal reactivity with a multifactorial systemic cause. Underlying conditions such as Behçet disease, inflammatory bowel disease (IBD), iatrogenic immunosuppression (eg, following solid organ transplantation), AIDS, and cyclic neutropenia may or may not be detected.^11-13

Our retrospective study explored the systemic nature of RAS. We reviewed patient records to evaluate underlying systemic conditions associated with the diagnosis of RAS and the use of oral medications in managing the disease. Medical records from the Department of Dermatology of the University of São Paulo, Brazil, from 2003 to 2017 were reviewed to identify patients with a diagnosis of RAS. Clinical classification of RAS—minor, major, or herpetiform—as well as the presence of aphthous lesions in other locations and the presence of other associated inflammatory cutaneous manifestations also were noted. Associated systemic diseases and treatments for RAS were recorded. Patients for whom the diagnosis of RAS was changed during follow-up were excluded. Because this was a retrospective analysis of medical records and without any patient risk, informed consent was not needed.

Medical records for 125 patients were reviewed; 63 were male (50.4%), and 62 were female (49.6%). The age at onset of symptoms, which ranged from a few months after birth to 74 years, was reported in only 92 (73.6%) patient medical records. Of these, 30 (32.6%) reported onset before 20 years of age, 39 (42.4%) between 20 and 39 years, 17 (18.5%) between 40 and 59 years, and 6 (6.5%) at 60 years or older. Morphologically, 72 (57.6%) had minor, 42 (33.6%) had major, and 11 (8.8%) had herpetiform aphthous ulcers. None of the patients presented with sporadic lesions; the disease was long-standing and persistent in all cases (complex aphthosis).

Regarding the location of the ulcers, 92 (73.6%) patients had lesions on the oral mucosa only. Some patients had lesions in more than one site in addition to the oral mucosa: 32 (25.6%) had aphthae in the genital/groin region and 4 (3.2%) presented with perianal/anal aphthae. Nineteen patients (19.2%) presented other cutaneous manifestations in addition to aphthae: 11 (45.8%) had folliculitis/pseudofolliculitis, and 8 (33.3%) had erythema nodosum (EN). Eight patients (33.3%) presented with uveitis, and 6 (25%) presented with concomitant arthralgia/arthritis. Fifty-four patients (43.2%) had confirmed or suspected associated disease: Behçet disease (21 [38.9%]), IBD (10 [18.5%]), solid organ transplantation (7 [13.0%])(kidney, 4 [57.1%]; heart, 2 [28.6%]; liver, 1 [14.3%]), HIV infection (6 [11.1%]), lymphoma (1 [1.9%]), aplastic anemia (1 [1.9%]), or myelodysplastic syndrome (1 [1.9%]). Ten patients (18.5%) presented with other diseases under investigation (eg, unidentified rheumatologic disease, unexplained neutropenia, undiagnosed immunodeficiencies, autoinflammatory syndromes, possible cyclic neutropenia).

Biopsies of the oral mucosa were performed in 31 patients. Histopathologic findings will be discussed in a future publication (unpublished data).

Five patients (4.0%) were lost to follow-up and did not receive treatment; 10 (8.0%) received only topical treatment (analgesics and/or corticosteroids). All 9 (7.2%) patients undergoing intralesional corticosteroid injections also were on a systemic treatment. One hundred ten (88.0%) patients were treated systemically—with colchicine (84/110 [76.4%]), thalidomide (43/110 [39.1%]), small pulses of oral corticosteroids (26 [23.6%]), dapsone (12/110 [10.9%]), or pentoxifylline (3 [2.7%]). Furthermore, in patients with associated diseases, treatment of the underlying condition was conducted when available, and follow-up was carried out in conjunction with the appropriate specialists. For treatment of the associated disease, patients received other medications such as methotrexate, azathioprine, cyclophosphamide, intravenous corticosteroid pulse, and immunobiologics.

The prevalence of RAS between sexes in our study population was similar (50.4% male; 49.6% female). Results from prior studies have been mixed; some reported a higher prevalence in females,^15-18 while others found no predilection for sex among patients diagnosed with RAS.^19,20 In our analysis, 75% of patients experienced symptoms of RAS before 40 years of age; in prior studies, up to 56% of patients experienced symptoms between the ages of 20 and 40 years.^21,22

In our study, 26.4% of patients had extraoral aphthae. Genital lesions have been described as infrequent,²³ and lesions manifesting in other mucous membranes or on the skin are rare.²⁴ A study reported genital involvement in 8% to 13% of patients with oral aphtha.²⁵ We observed genital involvement in 25.6% of patients. Likewise, this higher value may be due to our study population of patients referred to our university hospital. In our study, 19.2% of patients presented with other inflammatory manifestations in addition to aphthous ulcerations (eg, folliculitis, EN, uveitis, arthritis). As dermatologists in a tertiary reference hospital, we actively look for such associations in every aphtha patient, which may not be the case in many nondermatologic oral care services.

In our study population, 43.2% of patients were diagnosed with or were under investigation for systemic diseases known to be associated with RAS. We found associations with Behçet disease most frequently, followed by IBD,²⁶ solid organ transplantation, and HIV. In this group of patients, the respective systemic disease was active or poorly controlled. In transplant recipients, aphtha major was the most common type, similar to other studies.²⁷ We observed no notable difference in the clinical picture of the oral ulcers in patients with a well-established systemic disease vs those without.

Most of our cases did not present findings other than aphtha, indicating that the intrinsic defect that predisposes to RAS is always systemic. Even mild and sporadic cases may be attributable to a systemic disorder of cutaneous-mucosal reactivity. The predisposition to RAS never originates in the oral cavity, hence the confusion caused and the uselessness of studies that relate aphthae to factors such as local food allergies, pH changes, or local infection with microorganisms.^5,28 The disease course (reducing the frequency of lesion appearance and accelerating the healing of extensive lesions) is only modified with systemic treatment, with local measures proving to be only moderately useful to relieve pain. We believe that RAS can in many ways be compared to EN and pyoderma gangrenosum (PG): some systemic conditions that predispose patients to EN and PG also may predispose them to RAS (eg, IBD, hematologic disorders). Similar to RAS, many cases of EN and PG are idiopathic. In addition, pathergy also occurs in PG.^11,13

We were unable to observe or establish any predictive clinical element that could indicate a better or worse response to the prescribed treatments, which also has been noted by other authors.^3,4 Treatment of RAS is empiric, generally starting with drugs that are easier to prescribe and with fewer adverse effects, then progressing to more complex drugs when a good response is not obtained. Colchicine was the most commonly prescribed medication (76.4% [84/110]). It has been proposed by several authors^3,4 as a first-line systemic medication for the treatment of recurrent aphthae, as it has been shown to be effective and safe. The dosage ranged from 0.5 mg twice daily to 0.5 mg 4 times daily. Dapsone is an established drug for aphtha^29,30 and was used in 12 of our patients. The dosage used in our patients ranged from 50 to 100 mg/d. Adverse effects such as hemolytic anemia frequently are seen, and one of the patients in our study developed DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome in response to dapsone. In 7 cases, colchicine and dapsone were used together, which is believed to potentiate the therapeutic effects. This combination may be useful in patients for whom thalidomide cannot be used or those who have not improved with monotherapy.²⁹ Thalidomide is considered one of the most effective drugs for RAS.^30,31 Forty-three patients in our analysis were treated with thalidomide, usually as a first choice. The dosage ranged from 100 to 200 mg/d. It was mainly chosen in disabling pediatric cases, adult men with aphthous major, and women with no risk for pregnancy. Due to its potential adverse effects, thalidomide has been recommended when there is no response with other medications that are dose dependent; severe adverse effects such as thromboembolism and peripheral neuropathy are rare.³¹ Oral corticosteroids were used in 26 patients, aiming at rapid improvement in very symptomatic cases; however, due to the potential for long-term adverse effects, in all cases they were prescribed in combination with another medication that was maintained after the corticosteroid was discontinued.

We highlight the systemic nature of RAS as well as its frequent association with systemic diseases and other correlated manifestations (pustules, EN, arthralgia). We also emphasize the importance of using oral medications to adequately control the disease and do not recommend topical medications aimed at treating local causes. Dermatologists should be consulted in managing severe cases of RAS.

To the Editor:

Recurrent aphthous stomatitis (RAS) is a mucocutaneous condition characterized by single or multiple, painful,^1,2 round ulcerations of variable sizes with a tendency for recurrence, most commonly located in nonkeratinized areas of the oral mucosa. Pathergy commonly is observed.³ Although many authors consider the terms RAS andaphtha to be synonymous,^4,5 differentiating the clinical lesion (aphthous ulceration) from the disease (aphtha or RAS) can be useful, as several other diseases can at times manifest with similar ulcers (called aphthoid lesions), such as pemphigus vulgaris, mucous membrane pemphigoid, and erythema multiforme.⁶

It is estimated that approximately 20% of individuals worldwide have at least one episode of aphtha during their lifetime,⁷ and it is considered the most common disease of the oral mucosa.^8,9 However, only patients presenting with severe acute outbreaks or frequent relapses typically seek medical treatment. Clinically, aphthous ulcers are classified as aphtha minor (small number of small lesions), aphtha major (large deep lesions that also can affect the minor salivary glands with intense necrosis, difficulty in healing, and mucosal scarring), and aphtha herpetiformis (innumerous tiny lesions that reappear in recurring outbreaks).^1-3 The term complex aphthosis was introduced in 1985¹⁰ and is defined as recurrent oral and genital aphthous ulcerations or recurring multiple oral aphthous ulcers in the absence of systemic manifestations or Behçet disease^11,12; however, complex aphthosis also has been reported as frequent episodes of ulcerations that may be associated with systemic diseases including Behçet disease.^13,14

Currently, RAS is considered an immunologically mediated alteration in cutaneous mucosal reactivity with a multifactorial systemic cause. Underlying conditions such as Behçet disease, inflammatory bowel disease (IBD), iatrogenic immunosuppression (eg, following solid organ transplantation), AIDS, and cyclic neutropenia may or may not be detected.^11-13

Our retrospective study explored the systemic nature of RAS. We reviewed patient records to evaluate underlying systemic conditions associated with the diagnosis of RAS and the use of oral medications in managing the disease. Medical records from the Department of Dermatology of the University of São Paulo, Brazil, from 2003 to 2017 were reviewed to identify patients with a diagnosis of RAS. Clinical classification of RAS—minor, major, or herpetiform—as well as the presence of aphthous lesions in other locations and the presence of other associated inflammatory cutaneous manifestations also were noted. Associated systemic diseases and treatments for RAS were recorded. Patients for whom the diagnosis of RAS was changed during follow-up were excluded. Because this was a retrospective analysis of medical records and without any patient risk, informed consent was not needed.

Medical records for 125 patients were reviewed; 63 were male (50.4%), and 62 were female (49.6%). The age at onset of symptoms, which ranged from a few months after birth to 74 years, was reported in only 92 (73.6%) patient medical records. Of these, 30 (32.6%) reported onset before 20 years of age, 39 (42.4%) between 20 and 39 years, 17 (18.5%) between 40 and 59 years, and 6 (6.5%) at 60 years or older. Morphologically, 72 (57.6%) had minor, 42 (33.6%) had major, and 11 (8.8%) had herpetiform aphthous ulcers. None of the patients presented with sporadic lesions; the disease was long-standing and persistent in all cases (complex aphthosis).

Regarding the location of the ulcers, 92 (73.6%) patients had lesions on the oral mucosa only. Some patients had lesions in more than one site in addition to the oral mucosa: 32 (25.6%) had aphthae in the genital/groin region and 4 (3.2%) presented with perianal/anal aphthae. Nineteen patients (19.2%) presented other cutaneous manifestations in addition to aphthae: 11 (45.8%) had folliculitis/pseudofolliculitis, and 8 (33.3%) had erythema nodosum (EN). Eight patients (33.3%) presented with uveitis, and 6 (25%) presented with concomitant arthralgia/arthritis. Fifty-four patients (43.2%) had confirmed or suspected associated disease: Behçet disease (21 [38.9%]), IBD (10 [18.5%]), solid organ transplantation (7 [13.0%])(kidney, 4 [57.1%]; heart, 2 [28.6%]; liver, 1 [14.3%]), HIV infection (6 [11.1%]), lymphoma (1 [1.9%]), aplastic anemia (1 [1.9%]), or myelodysplastic syndrome (1 [1.9%]). Ten patients (18.5%) presented with other diseases under investigation (eg, unidentified rheumatologic disease, unexplained neutropenia, undiagnosed immunodeficiencies, autoinflammatory syndromes, possible cyclic neutropenia).

Biopsies of the oral mucosa were performed in 31 patients. Histopathologic findings will be discussed in a future publication (unpublished data).

Five patients (4.0%) were lost to follow-up and did not receive treatment; 10 (8.0%) received only topical treatment (analgesics and/or corticosteroids). All 9 (7.2%) patients undergoing intralesional corticosteroid injections also were on a systemic treatment. One hundred ten (88.0%) patients were treated systemically—with colchicine (84/110 [76.4%]), thalidomide (43/110 [39.1%]), small pulses of oral corticosteroids (26 [23.6%]), dapsone (12/110 [10.9%]), or pentoxifylline (3 [2.7%]). Furthermore, in patients with associated diseases, treatment of the underlying condition was conducted when available, and follow-up was carried out in conjunction with the appropriate specialists. For treatment of the associated disease, patients received other medications such as methotrexate, azathioprine, cyclophosphamide, intravenous corticosteroid pulse, and immunobiologics.

The prevalence of RAS between sexes in our study population was similar (50.4% male; 49.6% female). Results from prior studies have been mixed; some reported a higher prevalence in females,^15-18 while others found no predilection for sex among patients diagnosed with RAS.^19,20 In our analysis, 75% of patients experienced symptoms of RAS before 40 years of age; in prior studies, up to 56% of patients experienced symptoms between the ages of 20 and 40 years.^21,22

In our study, 26.4% of patients had extraoral aphthae. Genital lesions have been described as infrequent,²³ and lesions manifesting in other mucous membranes or on the skin are rare.²⁴ A study reported genital involvement in 8% to 13% of patients with oral aphtha.²⁵ We observed genital involvement in 25.6% of patients. Likewise, this higher value may be due to our study population of patients referred to our university hospital. In our study, 19.2% of patients presented with other inflammatory manifestations in addition to aphthous ulcerations (eg, folliculitis, EN, uveitis, arthritis). As dermatologists in a tertiary reference hospital, we actively look for such associations in every aphtha patient, which may not be the case in many nondermatologic oral care services.

In our study population, 43.2% of patients were diagnosed with or were under investigation for systemic diseases known to be associated with RAS. We found associations with Behçet disease most frequently, followed by IBD,²⁶ solid organ transplantation, and HIV. In this group of patients, the respective systemic disease was active or poorly controlled. In transplant recipients, aphtha major was the most common type, similar to other studies.²⁷ We observed no notable difference in the clinical picture of the oral ulcers in patients with a well-established systemic disease vs those without.

Most of our cases did not present findings other than aphtha, indicating that the intrinsic defect that predisposes to RAS is always systemic. Even mild and sporadic cases may be attributable to a systemic disorder of cutaneous-mucosal reactivity. The predisposition to RAS never originates in the oral cavity, hence the confusion caused and the uselessness of studies that relate aphthae to factors such as local food allergies, pH changes, or local infection with microorganisms.^5,28 The disease course (reducing the frequency of lesion appearance and accelerating the healing of extensive lesions) is only modified with systemic treatment, with local measures proving to be only moderately useful to relieve pain. We believe that RAS can in many ways be compared to EN and pyoderma gangrenosum (PG): some systemic conditions that predispose patients to EN and PG also may predispose them to RAS (eg, IBD, hematologic disorders). Similar to RAS, many cases of EN and PG are idiopathic. In addition, pathergy also occurs in PG.^11,13

We were unable to observe or establish any predictive clinical element that could indicate a better or worse response to the prescribed treatments, which also has been noted by other authors.^3,4 Treatment of RAS is empiric, generally starting with drugs that are easier to prescribe and with fewer adverse effects, then progressing to more complex drugs when a good response is not obtained. Colchicine was the most commonly prescribed medication (76.4% [84/110]). It has been proposed by several authors^3,4 as a first-line systemic medication for the treatment of recurrent aphthae, as it has been shown to be effective and safe. The dosage ranged from 0.5 mg twice daily to 0.5 mg 4 times daily. Dapsone is an established drug for aphtha^29,30 and was used in 12 of our patients. The dosage used in our patients ranged from 50 to 100 mg/d. Adverse effects such as hemolytic anemia frequently are seen, and one of the patients in our study developed DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome in response to dapsone. In 7 cases, colchicine and dapsone were used together, which is believed to potentiate the therapeutic effects. This combination may be useful in patients for whom thalidomide cannot be used or those who have not improved with monotherapy.²⁹ Thalidomide is considered one of the most effective drugs for RAS.^30,31 Forty-three patients in our analysis were treated with thalidomide, usually as a first choice. The dosage ranged from 100 to 200 mg/d. It was mainly chosen in disabling pediatric cases, adult men with aphthous major, and women with no risk for pregnancy. Due to its potential adverse effects, thalidomide has been recommended when there is no response with other medications that are dose dependent; severe adverse effects such as thromboembolism and peripheral neuropathy are rare.³¹ Oral corticosteroids were used in 26 patients, aiming at rapid improvement in very symptomatic cases; however, due to the potential for long-term adverse effects, in all cases they were prescribed in combination with another medication that was maintained after the corticosteroid was discontinued.

We highlight the systemic nature of RAS as well as its frequent association with systemic diseases and other correlated manifestations (pustules, EN, arthralgia). We also emphasize the importance of using oral medications to adequately control the disease and do not recommend topical medications aimed at treating local causes. Dermatologists should be consulted in managing severe cases of RAS.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

Healthcare providers hold wide-ranging opinions about prescribing opioids for chronic cancer pain, and many are haunted by the conflicting factors driving their views, from legal concerns to threats of violence, say the authors of new research.

These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.

“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
 

Who Should Manage Chronic Cancer Pain?

Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.

“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
 

What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?

To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.

These interviews yielded three themes.

First, no “medical home” exists for chronic pain management in cancer survivors.

“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.

Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.

“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”

The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.

“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”

Meanwhile, a palliative care provider described legal pressure from the opposite direction:

“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”

Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
 

What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?

After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.

They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.

Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.

This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.