Delusional infestation surges during COVID-19 pandemic

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Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

Dr. Peter Lepping

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge
Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

Dr. Dirk M. Elston


“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Dr. Scott A. Norton


Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

Dr. Anne Louise Oaklander


“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 
 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

Dr. John Koo


“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

Dr. Jason S. Reichenberg


“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.



In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

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Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

Dr. Peter Lepping

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge
Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

Dr. Dirk M. Elston


“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Dr. Scott A. Norton


Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

Dr. Anne Louise Oaklander


“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 
 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

Dr. John Koo


“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

Dr. Jason S. Reichenberg


“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.



In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

Psychiatrists with expertise in delusional infestation have some advice for dermatologists, infectious disease specialists, and primary care physicians who encounter affected patients: If you want to try to help them, initiate treatment yourself.

Dr. Peter Lepping

“If you see it, try and treat it. These patients are unlikely to agree to see a psychiatrist,” Peter Lepping, MD, said at the Entomology 2020 annual meeting.

Indeed, one of the hallmarks of delusional infestation (DI) is a refusal to even consider referral to a mental health professional, noted Dr. Lepping, a consultation-liaison psychiatrist at Bangor (Wales) University who, together with an infectious disease specialist, codirects one of the world’s few DI multispecialty referral clinics, located at the University of Liverpool School of Tropical Medicine.

That being said, he offered another piece of advice: “Accept that it is not easy to help these patients.”

Dr. Lepping was among a group of distinguished psychiatrists, dermatologists, entomologists, and a neurologist at the annual meeting who participated in a comprehensive session devoted to DI. The experts shared tips on making the diagnosis, establishing the rapport necessary to persuade affected patients to try taking a very-low-dose antipsychotic agent for their delusion, and how to achieve a high rate of therapeutic success. They also highlighted recent research advances in the field, including brain MRI evidence suggesting that impaired somatosensory neural networks mediate symptoms in DI, but not in nonsomatic delusional disorders.


 

COVID-19 pandemic triggers surge in DI

Entomologist Gail E. Ridge, PhD, has taken notes on all of her thousands of consultations with individuals with suspected DI since the late 1990s. A sharp jump in such contacts occurred during the Great Recession of 2008 in conjunction with the widespread social distress of job loss and threatened economic ruin. Now the same thing is happening as the catastrophic COVID-19 pandemic stretches on. Indeed, during the first 8 months of the pandemic she documented 500 interactions involving people with suspected DI. She’s learned to identify the clues, including a chattering mind, defensiveness, physician avoidance, and rigid body tension.

Courtesy Dr. Gale E. Ridge
Dr. Gale E. Ridge

“They’re fearful of judgment and suggestions of madness. And they’ll pounce on any perceived negativity. I never debunk beliefs; that can immediately backfire. If the medical profession was educated about DI, then many cases could be caught early. I, as the entomologist, and the mental health professionals are often last in line to be seen,” said Dr. Ridge, director of the Insect Information Office at the Connecticut Agricultural Experiment Station in New Haven.

She has noticed a recurring theme in her interactions with these patients: DI often starts with a real underlying medical condition, such as, for example, a cutaneous drug reaction, which over time, progresses to gain a psychiatric component. And she has found that a tipping point often occurs after roughly 6 months of unrelieved symptoms and sensations. Prior to that, affected individuals are concerned about their condition and will seek medical help in a genuine effort to understand what’s going on. They can be redirected. After about 6 months, however, Dr. Ridge has observed “they slide into the rabbit hole of fanaticism and despair.”
 

 

 

Arriving at the diagnosis

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), DI is classified as a “delusional disorder, somatic type 297.1 F22.” The diagnosis requires that the delusion be present for at least 1 month, criteria for schizophrenia are not met, and the condition cannot be attributed to other medical or neuropsychiatric conditions.

“Many of these people are very high-functioning. I have corporate CEOs who fly in to see me in their private jets. At work, they’re king of their domain. At home, their family is falling apart because of their delusion,” said Dirk M. Elston, MD, professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston.

Dr. Dirk M. Elston


“These people suffer, and the people around them suffer,” he emphasized.

Dozens of medical conditions can cause intractable itching or biting sensations. Far and away at the top of the medical differential diagnosis is thyroid disease, given its high incidence and frequent presentation with anxiety and itch. Other possibilities that can readily be ruled out via lab tests include substance use – especially involving amphetamine/methamphetamine, cocaine, or opioids – liver or kidney disease, diabetes and other sources of peripheral neuropathy, polycythemia, dermatitis herpetiformis, and pemphigus, Dr. Elston said.

Scott A. Norton, MD, MPH, MSc, a dermatologist and preventive medicine specialist at the Uniformed Services University of the Health Sciences in Bethesda, Md., noted that a diagnosis of DI requires three elements: The presence of abnormal sensations in the skin, a patient’s tenacious conviction that the sensations are caused by an infestation, and a lack of supporting evidence for that conviction.

Dr. Scott A. Norton


Taking an accurate medical history can be a challenge in these patients because they are often so guarded. They won’t disclose that they’ve already seen other health care providers, or that they’ve been self-treating with OTC veterinary medicine products, such as high-dose topical or oral ivermectin. They’ll often even deny repeated scratching despite clear evidence to the contrary from the skin exam.

As a dermatologist, Dr. Norton considers his first task to be a search for evidence of an infestation. Scabies is usually the first diagnosis proposed to account for the uncomfortable skin sensations. The presentation can be subtle. While the classic teaching is that the telltale signs of infestation by Sarcoptes scabiei are burrows in the skin and a rash in the web spaces between the fingers, he finds these features are often absent or equivocal.

“I think there are two more reliable presentations of scabies: Check to see if there’s symmetric involvement of the volar or palm side of the wrists; if there isn’t, I’m skeptical of the diagnosis. And every male older than 1 year of age with scabies will have scabies nodules on their genitalia. If the penis, the glans, or the scrotum aren’t involved with the nodules, I discard scabies as a possible diagnosis and look for evidence of other skin conditions that can plausibly explain the sensations and skin lesions, like eczema, contact dermatitis, scalp folliculitis, or dry skin,” he said.

If he can’t find evidence of infestation, he next systematically looks for another dermatologic cause of the patient’s sensations. When that proves fruitless, he tries to determine if there might be a biomedical or neuropsychiatric cause, such as depression, anxiety, schizophrenia, or dementia.

Taking a personal hygiene history is helpful. Patients who believe they have an infestation may bathe or shower three to five times daily with harsh soaps, causing dry, inflamed, itchy and uncomfortable skin.

“Many patients are thrilled to hear the good news that the history, physical examination, and lab tests do not show an infestation and that we have another explanation to account for their unwanted sensations. However, there are some patients who vehemently reject that idea and immediately return to their unwavering, unalterable belief that they are in fact infested. At this point, the possible diagnosis of DI looms large,” the dermatologist said.

Clues suggestive of DI include a patient’s obsessive focus on collecting “specimens” of the offending pathogen in Ziplock bags for assessment during the office visit – “usually a mix of unhelpful household debris and environmental detritus” – and eager presentation of a lengthy and detailed infestation diary, Dr. Norton said.

“Among the most distinctive signs that the patient is detached from reality are the biologically implausible descriptions and explanations of the supposed attacking organism. It’s a fanciful amalgamation of mutable features, behaviors, and life cycles composed of a composite of taxonomically unrelated organisms – for example, fungal hyphae with wings – that shapeshift at will to evade detection,” he said.

Dr. Elston observed that DI skin lesions are typically excoriated, sometimes because of a patient’s systematic use of a sharp object in an effort to dig out the infestation.

“One of the clues is the angularity of the lesion,” the dermatologist noted. “We always say round-to-oval lesions suggest an inside job; angulated lesions suggest an outside job, like fingernail work. There’s often a row of good healing border showing there’s really nothing wrong with wound healing, but a fibrinoid base where the excoriations have occurred. And the lesions are often in various stages of healing.”

Don’t forget neuropathic itch in nondelusional individuals as a potential cause of sensations of infestation and self-injury due to relentless scratching, urged Anne Louise Oaklander, MD, PhD, associate professor of neurology, Harvard Medical School, Boston, who is director of the nerve unit and the neurodiagnostic skin biopsy lab at Massachusetts General Hospital, Boston.

Dr. Anne Louise Oaklander


“There’s no one cause of patients’ impressions that they may have insects. Let’s be sympathetic: It is a normal assumption that insects may be present if the skin itches. One problem is that when patients don’t get good medical diagnoses they make up their own explanations, and sometimes these include persistent ideas of infestation. Many of them don’t realize that their scratching is a cause, not a result, of their skin lesions,” said Dr. Oaklander, who has conducted pioneering research on unintentional self-injury due to neuropathic itch accompanied by loss of pain signaling.


 
 

 

“Rapport first, medication later”

“The office visits are typically difficult to conclude, but skills can be learned and make it much easier to help these people,” Dr. Elston said.

John Koo, MD, emphasized that establishing rapport is “by far” the most important part of managing patients with DI.

Dr. John Koo


“Rapport first, medication later. This may require multiple visits,” said Dr. Koo, professor of dermatology at the University of California, San Francisco, who is a board-certified psychiatrist.

He makes sure he walks into the examination room all smiles and positivity. Patients with DI are eager to expound on their ailment; he lets them talk for a while, then when the timing is right, he actively encourages them to shift their focus away from etiology to treatment.

Dr. Koo and coworkers have described a spectrum of mental fixation in DI ranging from having only crawling and biting sensations, progressing to holding an overvalued idea as to their cause, then on to DSM-5 somatic preoccupation, followed by becoming truly delusional, and finally terminal delusion, where the patient doesn’t care about getting better, but only wants the physician to agree there is an infestation (J Clin Exp Dermatol Res. 2014 Oct. 3. doi: 10.4172/2155-9554.1000241).

“You cannot argue with people with delusions. How you talk to them as a clinician depends on whether they are entirely delusional or not,” he advised. “I cannot agree with their ideation, but I can agree with their misery – and that’s how I make a connection.”

Declining a DI patient’s request for a skin biopsy when it’s obvious there is no infestation can lead to a counterproductive power struggle. Instead, Dr. Koo turns the patient request into an opportunity to form a verbal contract: “I ask, ‘If the result comes back negative, can you be open-minded about the possibility of other etiologies besides parasites?’ ”

As for Dr. Norton, when his schedule shows a patient is coming in for a first visit for a supposed skin infestation, he tells his staff to expect a lengthy session as he works at establishing a good relationship.

“When my patients arrive with bags of specimens, I ask them to select two or three that they’re most confident will have a creature in them. Then I bring a two-headed microscope into the exam room and ask the patient to join me in examining the material. It helps with rapport by showing that I genuinely want to determine if there’s an infestation,” he explained.

He then sends the specimens to a laboratory, which provides a full report of the findings.

In performing a skin biopsy in a patient with suspected DI, Dr. Norton routinely biopsies two sites so the patient can’t claim sampling error when the pathology report comes back with no pathogens or parasites found. Also, he asks the patient to choose biopsy sites with intact skin where he or she believes the infestation exists. There is no point in biopsying excoriated lesions because they often contain snagged textile fibers.

Another rapport-building strategy: “I try to design a treatment regimen that will palliate the uncomfortable sensations and help relieve the patient’s misery while we continue working towards treating those delusions,” Dr. Norton said.

This might entail cutting back to one lukewarm shower per day with gentle or no soap, coupled with moisturizing, oral antihistamines or doxepin for itch, topical corticosteroids for the associated inflammation, and oral or topical antibiotics for any secondary bacterial skin infection.

What he doesn’t recommend as a rapport-building strategy or simply in order to get the patient out of the office is offering a therapeutic trial of an antiparasitic agent. That’s counterproductive. It may reinforce the false belief of infestation, and when the medication doesn’t bring lasting belief, the patient may conclude the infestation is resistant to conventional treatment.

Dr. Koo tells affected patients that he suspects they have Morgellons syndrome. He doesn’t call it DI in their presence.

“These people would not like their condition to be called delusional,” he explained. “Morgellons is a more neutral term. I tell them it’s a mysterious condition, and that what I’m really interested in is in trying to get them out of their misery.”
 
 

 

Treatment tips

Dr. Koo’s first-line medication for DI is pimozide (Orap), which in the United States has the advantage of being approved only for Tourette syndrome; it’s an antipsychotic without the perceived stigma of a psychiatric indication.

“Many of these patients will not consider taking any medication that has any psychiatric indication,” he noted.

Low-dose pimozide is highly effective, according to Dr. Koo, who recommends starting at 0.5 mg to 1 mg/day, increasing by 0.5 mg/day every 2-4 weeks. The drug is usually effective at a dose of 3 mg/day or less. Once a patient’s symptoms become clear or almost clear, the patient is maintained on that dose for another 3-4 months, then tapered by 0.5 mg/day every 2-4 weeks.

“In 35 years of seeing a new patient on average every week or two, I’ve had only five patients with one recurrence and one patient with two recurrences. All six responded to repeat therapy,” Dr. Koo said.

Side effects at these low doses are “very rare,” he added. Diphenhydramine (Benadryl) at 25 mg up to four times daily is effective for complaints of stiffness or restlessness. Prolongation of the QT interval is a potential concern, but Dr. Koo has never encountered it despite routinely ordering ECGs for patients on pimozide with known heart disease or who are over age 50.

When a patient can’t tolerate pimozide, Dr. Koo’s second-line antipsychotic for DI is low-dose risperidone (Risperdal), which is also highly effective.

Dr. Lepping noted that the European situation is different. There, unlike in the United States, pimozide has regulatory approval as an antipsychotic, so it loses the advantage of being an under-the-radar neuroleptic. His go-to medication is the first-generation antipsychotic sulpiride (Dogmatil), which he finds has a more favorable side effect profile than pimozide, particularly in the elderly. (Sulpiride is not approved in the United States.)

In treating DI, he prefers more dopaminergic-focused antipsychotics over those covering a broader spectrum of receptors. His alternatives to sulpiride include risperidone and olanzapine, atypical antipsychotics. He explains to patients that just as aspirin is used in low doses for its antiplatelet effect and in higher doses for pain relief, these medications can help them feel better at much lower doses than for schizophrenia.

“Once we get some rapport and a trusting relationship going, we normally try to persuade people to basically try something against their better judgment. We know that they don’t believe in it, but you try to get them to at least try something because everything else has failed,” Dr. Lepping explained. “We tell them it’s a condition we have seen before, and we have seen these medications to be useful because they are good for their distress, they help with making them calmer, and they might help with their symptoms. We say, ‘What do you have to lose if you trust us?’

“About 60% of our patients take the medication and almost invariably they all get better,” the psychiatrist said. “The others we either lose to follow-up or they just refuse to take the medication.”

A patient’s first visit to the Liverpool multispecialty DI referral clinic is 1 hour long. “They know that in advance, and we very much stick to that hour. We say to people up front, ‘We have an hour – that’s a lot, but we don’t have more,’ ” he said.

The initial visit is typically followed by two to four 30-minute follow-up visits. Dr. Lepping recommends that when possible, patients with DI should be seen jointly by a psychiatrist and a nonpsychiatrist physician. He finds this approach leads to substantially better clinical outcomes than with a single health care provider.

“If you have two people in the clinic with the patient, when you get really annoyed and your amygdala really starts going, that’s the time when you can then turn to your colleague and say, ‘Oh yes, and Professor Squire, what do you have to say to that?’ So as you see the red mist rising in yourself because you’re getting so exasperated, you have the other person there to take over so you can calm down. And then the other person does the same. That can be really important to deescalate a heated situation,” Dr. Lepping explained.

Roughly 10% of patients with DI have what is termed folie à deux, where the delusion of infestation is shared by another person.

“Anecdotally, I would say those are much more difficult to treat,” said Jason S. Reichenberg, MD, MBA, professor of medicine (dermatology) at the University of Texas at Austin and president of the Ascension Medical Group Texas.

Dr. Jason S. Reichenberg


“It’s like getting somebody to quit smoking when everybody else in the house is still smoking. It’s very hard to convince a single family member that they’re wrong when everybody else in their family keeps telling them they’re right,” he said.


Recent advances in DI research

Dr. Lepping and coinvestigators at multispecialist DI clinics in London, Italy, and Moscow reported in an unusually large observational study of 236 affected patients that longer duration of untreated psychosis was associated with significantly worse clinical outcome. It’s a finding consistent with Dr. Koo’s construct of progressive stages of delusionality, and it underscores the need for early treatment.

“Having said that, improvement is still possible, even if people have had quite a long time of untreated psychosis,” Dr. Lepping said. The same study also showed that older age at illness onset was inversely associated with good outcome.



In another study, Dr. Lepping and colleagues reported that substance use involving amphetamines, cocaine, opioids, and other drugs that can cause itch was roughly twice as common in a group of patients with DI compared to the general population. “I highly recommend, if at all possible, a drug screen in suspected DI,” he said.

In a large survey of U.S. and Canadian veterinarians, Dr. Lepping and coinvestigators found that these practitioners not infrequently encountered delusional infestation among pet owners who claimed their dog or cat is infested when it’s not. This is called “delusion by proxy,” and it often leads to unwarranted animal euthanasia. Some of these pet owners claim they, too, are infested, which the investigators termed “double delusional infestation.”

 

 

MRI studies

Recent structural brain MRI studies support the concept that impaired somatosensory neural networks mediate the delusional symptoms of DI, but not in delusional disorders without somatic content. This was demonstrated in an MRI study by Dr. Lepping and others conducted in 18 patients with DI, 19 others with nonsomatic delusional disorders centered on themes of persecution or jealousy, and 20 healthy volunteers. The DI group had lower gray matter volume in prefrontal, thalamic, striatal, and insular regions of the brain compared to the other two groups.

Of note, mapping of the insula and dorsal striatum indicates they are part of the peripersonal space network, which integrates tactile and visual perceptions involving the area near the body surface. The insula also mediates feelings of pain and disgust.

Some of the same investigators have also recently reported brain MRI evidence specifically of cerebellar dysfunction in patients with DI, who displayed decreased gray matter volume in left lobule VIIa of the cerebellum and increased gray matter volume in bilateral lobule VIIa/crus II compared to patients with non-somatic delusions. This points to a role for impaired cerebellar neural networks related to somatosensory perception in patients with DI but not in those with non-somatic delusions.
 

Delusional infestation: What’s in a name?

Ekbom syndrome. Delusional parasitosis. Morgellons syndrome. These and other terms are increasingly giving way to ‘delusional infestation’ as the preferred moniker for the disorder. That’s in part because the delusional focus in patients with this condition has shifted over time. In the 19th century, for example, affected patients often attributed their infestation to typhus.

In contemporary practice, roughly one-quarter of affected patients think they are infested by small inanimate objects, most commonly fibers or threads emerging from the skin, rather than by parasites, insects, or worms. In a study of 148 consecutive European patients with suspected DI, Dr. Lepping and coinvestigators reported only 35% believed they were infested by parasites.

“The name ‘delusional infestation’ emphasizes the constantly changing pathogens and covers all present and future variations of the theme that are bound to occur,” Dr. Lepping observed.

All speakers reported having no conflicts of interest.

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Scaly lesion on forearm

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Scaly lesion on forearm

Scaly lesion on forearm

The suspicion raised by the dermoscopy results led to a shave biopsy, which confirmed the diagnosis of squamous cell carcinoma (SCC) in situ, also known as Bowen disease.

Bowen disease typically manifests as a scaly erythematous patch, often on sun-exposed skin. If untreated, these lesions have the potential to develop into invasive SCCs. Generally, the lesions are preceded by the formation of actinic keratosis (AK). In a 2009 trial performed by the Department of Veterans Affairs, up to 65% of SCCs were found to have previously been diagnosed as AK lesions.1

The selection of treatments includes excision, electrodessication and curettage, cryotherapy, and topical options such as fluorouracil bid for 4 weeks or imiquimod qd for 9 weeks.

After the physician outlined the treatment options, this patient opted for an elliptical excision. At the patient’s next follow-up appointment, she was found to have multiple AKs on her face; they were treated with cryotherapy. Patients with a diagnosis of precancerous or cancerous skin lesions are at high risk for additional AKs and skin cancer, so they should be counseled regarding the use of sun protective measures and the importance of annual screening for new lesions.

Image courtesy of Carlos Cano, MD, and text courtesy of Carlos Cano, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. Cancer. 2009;115:2523-2530. doi: 10.1002/cncr.24284.

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Scaly lesion on forearm

The suspicion raised by the dermoscopy results led to a shave biopsy, which confirmed the diagnosis of squamous cell carcinoma (SCC) in situ, also known as Bowen disease.

Bowen disease typically manifests as a scaly erythematous patch, often on sun-exposed skin. If untreated, these lesions have the potential to develop into invasive SCCs. Generally, the lesions are preceded by the formation of actinic keratosis (AK). In a 2009 trial performed by the Department of Veterans Affairs, up to 65% of SCCs were found to have previously been diagnosed as AK lesions.1

The selection of treatments includes excision, electrodessication and curettage, cryotherapy, and topical options such as fluorouracil bid for 4 weeks or imiquimod qd for 9 weeks.

After the physician outlined the treatment options, this patient opted for an elliptical excision. At the patient’s next follow-up appointment, she was found to have multiple AKs on her face; they were treated with cryotherapy. Patients with a diagnosis of precancerous or cancerous skin lesions are at high risk for additional AKs and skin cancer, so they should be counseled regarding the use of sun protective measures and the importance of annual screening for new lesions.

Image courtesy of Carlos Cano, MD, and text courtesy of Carlos Cano, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Scaly lesion on forearm

The suspicion raised by the dermoscopy results led to a shave biopsy, which confirmed the diagnosis of squamous cell carcinoma (SCC) in situ, also known as Bowen disease.

Bowen disease typically manifests as a scaly erythematous patch, often on sun-exposed skin. If untreated, these lesions have the potential to develop into invasive SCCs. Generally, the lesions are preceded by the formation of actinic keratosis (AK). In a 2009 trial performed by the Department of Veterans Affairs, up to 65% of SCCs were found to have previously been diagnosed as AK lesions.1

The selection of treatments includes excision, electrodessication and curettage, cryotherapy, and topical options such as fluorouracil bid for 4 weeks or imiquimod qd for 9 weeks.

After the physician outlined the treatment options, this patient opted for an elliptical excision. At the patient’s next follow-up appointment, she was found to have multiple AKs on her face; they were treated with cryotherapy. Patients with a diagnosis of precancerous or cancerous skin lesions are at high risk for additional AKs and skin cancer, so they should be counseled regarding the use of sun protective measures and the importance of annual screening for new lesions.

Image courtesy of Carlos Cano, MD, and text courtesy of Carlos Cano, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. Cancer. 2009;115:2523-2530. doi: 10.1002/cncr.24284.

References

1. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the veterans affairs topical tretinoin chemoprevention trial. Cancer. 2009;115:2523-2530. doi: 10.1002/cncr.24284.

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Expert shares hyperhidrosis treatment pearls

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Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.

Koldunov/iStock/Getty Images

Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.

A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.

“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”

The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.

Dr. Adam Friedman

“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.

Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.

“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”

Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.

There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”

He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.



For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”

For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.

On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.

A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.

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Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.

Koldunov/iStock/Getty Images

Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.

A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.

“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”

The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.

Dr. Adam Friedman

“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.

Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.

“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”

Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.

There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”

He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.



For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”

For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.

On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.

A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.

Even though over-the-counter topical antiperspirants are a common go-to treatment for primary axillary hyperhidrosis, a large survey commissioned by the International Hyperhidrosis Society showed that, while OTC aluminum products are the most recommended, they offer the least satisfaction to patients.

Koldunov/iStock/Getty Images

Of the 1,985 survey respondents who self-identified as having excessive sweating, those who received treatment were most satisfied with injections and least satisfied with prescription and OTC antiperspirants and liposuction. “It’s important to recognize that, while these are not invasive, they’re simple, you need to keep up with it, and they’re really not that effective for primary hyperhidrosis,” Adam Friedman, MD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference.

A major development came in 2018, when the Food and Drug Administration approved topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis in adults and in children as young as age 9. It marked the first topical anticholinergic approved for the condition. Results from the pivotal phase 2 ATMOS-1 and ATMOS-2 randomized, controlled trials found that, after 4 weeks of daily use, 53%-66% of patients reported a 4-point improvement or greater on the ASDD item 2, which is defined as the worst sweating they experienced in a 24-hour period on an 11-point scale.

“Patients want to know: How quickly am I going to see improvement? The answer to this can be central to treatment compliance,” said Dr. Friedman, professor and interim chair of dermatology at the George Washington University, Washington. “We have data showing that 23%-29% of patients using glycopyrronium tosylate met that primary outcome within 1 week of use. So, you can tell patients: ‘Help is on the way. You may see a response relatively soon.’ ”

The most common adverse events in the two trials were dry mouth, which affected 24% of patients, followed by mydriasis (7%), and oropharyngeal pain (6%). He advises patients to apply it once at night. “I tell my patients make this the last thing you do during your nighttime routine,” said Dr. Friedman, who coauthored a case-based clinical algorithm for approaching primary hyperhidrosis patients.

Dr. Adam Friedman

“Open it up, one swipe to the right [underarm], flip it over, one wipe of the left [underarm], toss the towelette, and wash your hands thoroughly. You don’t need to remove axillary hair or occlude the area. I tell them they may find some improvement within one week of daily use, but I give realistic expectations, usually 2-3 weeks. Tell them about the potential for side effects, which certainly can happen,” he said.

Investigators are evaluating how this product could be delivered to other body sites. Dr. Friedman said that he uses glycopyrronium tosylate off label for palmar and plantar hyperhidrosis. He advises patients to rub their hands or feet the cloth until it dries, toss the towelette, apply an occlusive agent like Aquaphor followed by gloves/socks for at least an hour, and then wash their hands or feet. “If they can keep the gloves or socks on overnight, that’s fine, but that’s very rare,” Dr. Friedman added.

“Typically, an hour or 2 of occlusive covering will get the product in where it needs to be. The upside of this product is that it’s noninvasive, there’s minimal irritation, it’s effective, and FDA approved. On the downside, it’s a long-term therapy. This is forever, so cost can be an issue, and you have to think about the anticholinergic effects as well.”

Iontophoresis is a first-line treatment for moderate to severe palmar and plantar hyperhidrosis. It’s also effective for mild hyperhidrosis with limited side effects, but it’s cumbersome, he said, requiring thrice-weekly treatment of each palm or sole for approximately 30 minutes to a controlled electric current at 15-20 mA with tap water.

There are no systemic agents approved for hyperhidrosis, only case reports or small case series. For now, the two commonly used anticholinergics are glycopyrrolate and oxybutynin. Glycopyrrolate comes in 1- and 2-mg capsules. “You can break the tablets easily and it’s pretty cheap, with an estimated cost of 2 mg/day at $756 per year,” Dr. Friedman said. “I typically start patients on 1 mg twice per day for a week, then ask how they’re doing. If they notice improvement, have minimal side effects but think they can do better, then I increase it by 1 mg and reassess. I give them autonomy, and at most, want them to max out at 6 mg per day. There is an oral solution for kids, which can make this a little more accessible.”

He prescribes oxybutynin infrequently but considers it effective. “Most patients respond to 5- to 10-mg/day dosing, but doses up to 15 or 20 mg daily may be required,” he noted.



For persistent flushing with hyperhidrosis, Dr. Friedman typically recommends treatment with clonidine. “I start patients pretty low, sometimes 0.05 mg twice per day.”

For patients who sweat because of social phobias and performance anxiety, he typically recommends treatment with a beta-adrenergic blocker. “These are highly lipophilic, so I advise patients not to take them with food,” he said. “The peak concentration is 1-1.5 hours. Usually, I start at 10 mg and I have people do a test run at home. I also take a baseline blood pressure in the office to make sure they’re not hypotensive.” The use of beta-adrenergic blockers is contraindicated in patients with bradycardia, atrioventricular block, and asthma. They can also exacerbate psoriasis.

On Sept. 20, 2020, Brickell Biotech announced the approval of sofpironium bromide gel, 5%, in Japan for the treatment of primary axillary hyperhidrosis. Sofpironium bromide is an analog of glycopyrrolate “that gets metabolized very quickly in order to limit systemic absorption of the active agent and therefore mitigate side effects,” Dr. Friedman said.

A recently published Japanese study found that 54% of patients with primary axillary hyperhidrosis who received sofpironium bromide experienced a 1- or 2-point improvement on the Hyperhidrosis Disease Severity Scale and a 50% or greater reduction in gravimetric sweat production from baseline to week 6 of treatment, compared with 36% of patients in the control group (P = .003). According to Dr. Friedman, a 15% formulation of this product is being studied in the United States, “but the experience in Japan with the 5% formulation should give us some real-world information about this product,” he said. “Out of the gate, we’re going to know something about how it’s being used.”

Dr. Friedman reported that he serves as a consultant and/or advisor to numerous pharmaceutical companies, including some that produce cannabinoids. He is also a speaker for Regeneron, Abbvie, Novartis, LRP, Dermira, and Brickel Biotech, and has received grants from Pfizer, the Dermatology Foundation, Almirall, and Janssen.

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Consensus statement issued on retinoids for ichthyosis, disorders of cornification

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Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

Dr. Moise Levy

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

 

 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

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Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

Dr. Moise Levy

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

 

 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

Dr. Moise Levy

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

 

 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

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Are pediatric and adult dermatitis the same disease?

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Are pediatric atopic dermatitis and atopic dermatitis the same disease?

Dr. Jonathan I. Silverberg

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).



Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

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Are pediatric atopic dermatitis and atopic dermatitis the same disease?

Dr. Jonathan I. Silverberg

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).



Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

Are pediatric atopic dermatitis and atopic dermatitis the same disease?

Dr. Jonathan I. Silverberg

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).



Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

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Are there COVID-19–related ‘long-haul’ skin issues?

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A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

Dr. Esther Freeman

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News
Dr. Anthony Fernandez

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

 

 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.



Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Christine Ko

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

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A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

Dr. Esther Freeman

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News
Dr. Anthony Fernandez

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

 

 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.



Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Christine Ko

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

Dr. Esther Freeman

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News
Dr. Anthony Fernandez

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

 

 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.



Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Christine Ko

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

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A hard-to-reach bleeding lesion

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Ulcer

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

References

Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.

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Ulcer

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Ulcer

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

References

Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.

References

Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.

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Bathing now more widely accepted as an eczema treatment strategy

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According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Noreen Heer Nicol

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”



In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

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According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Noreen Heer Nicol

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”



In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Noreen Heer Nicol

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”



In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

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Guselkumab maintains psoriasis efficacy long after discontinuation

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Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.



The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.



In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

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Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.



The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.



In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.



The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.



In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

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Daily moisturizers a bedrock of atopic dermatitis management

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Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

Dr. Noreen Heer Nicol

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.



“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

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Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

Dr. Noreen Heer Nicol

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.



“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

Dr. Noreen Heer Nicol

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.



“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

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