Contact Dermatitis

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

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

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

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

Children with atopic dermatitis (AD) were significantly more likely to have positive patch test results than were children without AD, according to a study of over 900 children evaluated for allergic contact dermatitis (ACD) with patch testing, a finding that investigators say underscores the value of considering ACD in patients with AD and referring more children for testing.

ACD is underdetected in children with AD. In some cases, it may be misconstrued to be AD, and patch testing, the gold standard for diagnosing ACD, is often not performed, said senior author JiaDe Yu, MD, MS, a pediatric dermatologist and director of contact and occupational dermatology at Massachusetts General Hospital, Boston, and his co-authors, in the study published in the Journal of the American Academy of Dermatology.

Dr. JiaDe Yu

UCHealth

Top allergens

The top 10 allergens between children with and without AD were largely similar, the authors of the study report. Nickel was the most common allergen identified in both groups, and cobalt was in the top five for both groups. Fragrances (including hydroperoxides of linalool), preservatives (including methylisothiazolinone [MI]), and neomycin ranked in the top 10 in both groups, though prevalence differed.

MI, a preservative frequently used in personal care products and in other products like school glue and paint, was the second most common allergen identified in children with AD. Allergy to MI has “recently become an epidemic in the United States, with rapidly increasing prevalence and importance as a source of ACD among both children and adults,” the authors note.

Children with AD were significantly more likely, however, to have ACD to bacitracin (OR, 3.23; P = .030) and to cocamidopropyl betaine (OR, 3.69; P = .0007), the latter of which is a popular surfactant used in “baby” and “gentle” skincare products. This is unsurprising, given that children with AD are “more often exposed to a myriad of topical treatments,” Dr. Yu and his colleagues write.

Although not a top 10 allergen for either group, ACD to “carba mix,” a combination of three chemicals used to make medical adhesives and other rubber products (such as pacifiers, toys, school supplies, and rubber gloves) was significantly more common in children with AD than in those without (OR, 3.36; P = .025).

Among other findings from the study: Children with AD were more likely to have a longer history of dermatitis (4.1 vs. 1.6 years, P < .0001) prior to patch testing. Testing occurred at a mean age of 11 and 12.3 years for children with and without AD, respectively.

The number of allergens tested and the patch testing series chosen per patient were “not statistically different” between the children with and without AD, the researchers report.

Patch testing availability

Clinicians may be hesitant to subject a child to patch testing, but the process is well tolerated in most children, Dr. Perryman said. She uses a modified panel for children that omits less relevant allergens and usually limits patch testing to age 2 years or older due to a young child’s smaller surface area.

Dr. Yu, who developed an interest in patch testing during his residency at the Medical College of Wisconsin, Milwaukee, where he worked with a patch-testing expert, will test children as young as 3-4 months with a “small selection of patches.”

The challenge with a call for more patch testing is a shortage of trained physicians. “In all of Boston, where we have hundreds of dermatologists, there are only about four of us who really do patch testing. My wait time is about 6 months,” said Dr. Yu, who is also an assistant professor at Harvard Medical School, Boston.

Allergists at Massachusetts General Hospital do “some patch testing ... but they refer a lot of the most complicated cases to me,” he said, noting that patch testing and management of ACD involves detailed counseling for patients about avoidance of allergens. “Overall dermatologists represent the largest group of doctors who have proficiency in patch testing, and there just aren’t many of us.”

Dr. Perryman also said that patch testing is often performed by dermatologists who specialize in treating ACD and AD, though there seems to be “regional variance” in the level of involvement of dermatologists and allergists in patch testing.

Not all residency programs have hands-on patch testing opportunities, Dr. Yu said. A study published in Dermatitis, which he co-authored, showed that in 2020, 47.5% of dermatology residency programs had formal patch testing rotations. This represented improvement but is still not enough, he said.

The American Contact Dermatitis Society offers patch-testing mentorship programs, and the American Academy of Dermatology has recently begun offered a patch testing workshop at its annual meetings, said Dr. Yu, who received 4 weeks of training in the Society’s mentorship program and is now involved in the American Academy of Dermatology’s workshops and as a trainer/lecturer at the Contact Dermatitis Institute.

The study was supported by the Dermatology Foundation. Dr. Yu and his co-investigators reported no conflicts of interest. Dr. Perryman had no disclosures.

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

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The tropical rat mite (Ornithonyssus bacoti) belongs to the family Macronyssidae. Theses mites are commonly mistaken for red bird mites or Nordic bird mites because they belong to the same family and have similar characteristics.¹ Although O bacoti is called the tropical rat mite, it also can be found in moderate climates.^2,3

Characteristics

The life cycle of a tropical rat mite lasts 11 to 13 days and includes 5 stages: egg, larva, protonymph, deutonymph, and adult.^1,2 The length of the mite (0.3–0.7 mm) varies with the stage of development.¹ Adults can reach 0.75 to 1.40 mm, with females larger than males and possibly visible with the naked eye.^1,2

Two or 3 days after a blood meal, the female mite lays approximately 100 eggs in its nest but not on the surface of a host. The eggs hatch into larvae after 1 to 4 days and go on to complete their life cyle.¹ During developmental stages, mites occupy their hosts for blood meals. Mites search for their hosts at night and prefer wild or pet rodents for blood meals but are not host specific and can be found on many mammals including birds, cats, racoons, and squirrels.⁴

Although tropical rat mites prefer rodent hosts, they can infest humans when their preferred host is unavailable. In the United States, the first case of human dermatitis due to a tropical rate mite occurred in 1923. In Europe, rat mite dermatitis was first reported in a human in 1931, possibly due to contamination of sailing vessels.⁴

Infestation and Transmission

Tropical rat mites prefer wild and pet rodents as hosts because the mites are able to feed on their blood over long periods.⁴ During the day, the mite spends most of its time hiding in dark dry spaces; it is most active during the night, traveling to find a host for meals.^3-5 If a preferred host is not present, the mite may choose to infest a human.⁵

Human infestation occurs most often upon close bodily contact with an infected animal or pet rodent that was sold without parasites having been eliminated.^3-5 Mites are able to survive without a host for as long as 6 months; they may travel after a meal.^1,2 Therefore, individuals who do not have a pet rodent can be infested if an infected wild rodent has infested their living space.^1,3-5

Clinical Presentation of Infestation

Patients infested with tropical rat mites present with pruritic cutaneous lesions, most often on unclothed parts of the body that are easily exposed to mites; lesions rarely occur on the scalp.⁵ People of any age or gender can be infested. Rat mite bites can present as single or grouped, pruritic, erythematous papules ranging in size from 4 to 10 mm in diameter.^5-7 Excoriations may be present due to excessive scratching. Although rare, vesicles or nodules have been reported.^5,7

Diagnosis of the underlying cause of the cutaneous manifestations often is difficult because mites are not visible during the day, as they are less active then.² Lesions often are misdiagnosed as an allergic response, a bacterial infection, or various forms of dermatitis.¹ A parasitic cause often is not considered unless the physician or patient detects a mite or many trials of therapies fail to provide relief.^1,3-5 Eliciting a thorough history may disclose that the patient has had close contact with rodents or lives in a community center, shelter, or shared space. If any of the patient’s close contacts have a similar presentation, infestation with mites should be considered.

 

 

Treatment and Prevention

Patients should be educated about treatment options and measures that need to be taken to prevent reinfection. It has been reported that tropical rat mites can survive without a blood meal for as long as 6 months; therefore, meticulous inspection and decontamination of all living spaces is required.^1,4 Once identified, physicians may prescribe an antiparasitic such as permethrin or pyriproxyfen to prevent further infestation and eliminate mites on the host.⁵ Lindane and benzyl benzoate previously were reported to be effective but should be prescribed only in correctly diagnosed cases due to the potential adverse effects of both therapies.^4,7-10 For effective treatment, physicians should thoroughly review the proper application of topical treatments with patients. Topical creams should be massaged into the skin from the head to the soles of the feet, covering all creases of the skin and between the fingers and toes. Antiparasitic creams should be left on the skin for 8 to 14 hours, and all members of the household should be examined and treated, if necessary, by a physician. A thorough bath removes tropical rat mites, but preventive measures should be taken to prevent reinfestation.⁴ Antihistamines or glucocorticoids also can be used as symptomatic treatment.^6,8

Avoiding Reinfestation—Preventive measures should be taken to prevent reinfestation, including evaluation by an exterminator for any wild rodents to remove nests and treat the living space with an acaricide.⁵ Insecticides administered by exterminators, including malathion, methyl carbamate, and lindane, also have been reported to be effective for preventing reinfestation.^5,7-9 A veterinarian should be consulted if the patient owns any pets to ensure proper identification of any potential tropical rat mites and treatments that may be necessary for any household pets.¹

Case Report

A 68-year-old man presented to the dermatology outpatient clinic with diffuse pruritus of the skin and scalp. He reported no other symptoms and had never had a total-body skin examination. His primary care physician recently prescribed a dose pack of methylprednisolone 4-mg tablets, which relieved the symptoms except for a mild scalp itch. His wife did not experience itching, and he denied noticing mites or fleas on his pet dog. Physical examination did not reveal any contributory findings, such as erythema or rash. Ketoconazole shampoo 2% and fluocinolone solution 0.01% were prescribed for scalp pruritus; however, he could not afford those medications and therefore did not take them.

Two weeks later, the patient presented with diffuse itching that involved the scalp, trunk, and extremities. He denied groin pruritus. He reported that the itching was worse at night. His wife continued to be asymptomatic. The patient reported that his health screening was up-to-date, and he had no interval health changes. A complete blood cell count, thyroid studies, and a comprehensive metabolic panel performed recently were within reference range. He denied recent travel or taking new medications. Physical examination revealed a somewhat linear distribution of erythematous urticarial papules on the right side of the abdomen. Red dermatographic excoriations were noted on the back. No burrows were visualized. He was given intramuscular triamcinolone 60 mg and was advised to have his house evaluated for bed bugs and his pet dog evaluated by a veterinarian for mites. During the triamcinolone injection, the medical assistant observed a 1- to 2-mm red insect, which fell into his clothing and could not be further evaluated.

After 1 month, the patient had no improvement of the pruritus; instead, it became worse. During this time, his wife developed intermittent urticarial-like eruptions. He was taking oral diphenhydramine nightly and applying triamcinolone cream 0.5% that he had at home from an earlier skin problem as needed. Physical examination findings correlated with worsening symptoms. He had multiple erythematous urticarial papules—many of which were excoriated—across the chest, abdomen, buttocks, and back. The arms had multiple excoriations. The urticarial papules coalesced in the anterior axillary folds, yet no burrows were visualized. In the left anterior axillary fold adjacent to one of the urticarial papules, a 1-mm mobile mite was identified on dermoscopy. Further evaluation by microscopy showed morphologic characteristics of a tropical rat mite (Figure). The patient admitted that his house had a mouse infestation that he was struggling to eliminate. Permethrin cream 5% was prescribed. Because the patient could not afford the prescription, he was advised to use the triamcinolone cream 0.5%and oral diphenhydramine that he had at home nightly for symptomatic relief. He was advised to hire an exterminator to eradicate the mouse and mite infestation to prevent reinfestation.

Identification of Rate Mite Dermatitis

The characteristics of tropical rat mite dermatitis can be confused with many other conditions, such as infection. Even when a mite is identified, it can be difficult to classify it as a tropical rat mite. To confirm the diagnosis of tropical rat mite dermatitis, the parasite needs to be identified. Skin scrapings can be collected from pruritic lesions and examined microscopically in the hope of revealing the rat mites. The recommendation is to collect skin scrapings from the dorsal aspect of the hands or from the neck.⁵ Patients may report finding mites in their living space or on their bedding or clothing.

Although the tropical rat mite was reported as a vector for endemic typhus between humans, no other cases of transmission between humans have been reported since.^11,12 Studies reporting non–human subject research and case reports have shown that O bacoti is a vector for Rickettsia akari, Coxiella burnetii, Francisella tularensis, Yersinia pestis, Eastern equine encephalitis virus (Alphavirus), Enterovirus (Picornaviridae), Langat virus (Flavivirus), and Hantaan orthohantavirus.^5,11-17 However, no cases of these infectious diseases being transmitted naturally have been reported.⁵

Confirmation of O bacoti as a vector for human pathogens is difficult because it relies on identification of the mite in the clinic.⁵ The epidemiologic importance of the mite in transmitting infectious disease is unknown; reports of human cases of mite infestation are rare. We present this information to increase awareness and help dermatologists and other health care providers identify O bacoti.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

Clinicians are using dupilumab off label to treat a wider range of allergic conditions in adults and children.

The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.

As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.

The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
 

A well-tolerated – if expensive – drug

Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.

Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.

“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”

Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.

“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.

Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.

“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”

Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.

“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.

Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.

As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.

Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.

“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”

“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”

Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.

“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”

Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.

“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”

Making injections less bothersome

Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.

“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”

Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.

For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”

Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
 

Off-label dupixent can be expensive, difficult to obtain

The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”

Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.

“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”

The experts who commented have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Clinicians are using dupilumab off label to treat a wider range of allergic conditions in adults and children.

The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.

As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.

The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
 

A well-tolerated – if expensive – drug

Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.

Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.

“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”

Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.

“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.

Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.

“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”

Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.

“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.

Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.

As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.

Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.

“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”

“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”

Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.

“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”

Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.

“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”

Making injections less bothersome

Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.

“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”

Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.

For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”

Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
 

Off-label dupixent can be expensive, difficult to obtain

The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”

Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.

“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”

The experts who commented have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Clinicians are using dupilumab off label to treat a wider range of allergic conditions in adults and children.

The drug, marketed as Dupixent, is currently approved in the United States to treat atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis in adults. Dupilumab is also approved to treat eosinophilic esophagitis in patients aged 12 years and older and atopic dermatitis and asthma in some patients as young as age 6 months.

As the roster of approved and off-label indications grows, skin specialists said, pediatricians and other primary care providers should become familiar with the drug – given the increasing likelihood that their patients may be taking the medication.

The U.S. Food and Drug Administration first approved dupilumab in 2017 for eczema and has continued to add new treatment indications, the most recent being for prurigo nodularis, in 2022. Sanofi, which markets the drug with Regeneron, announced in April 2022 that some 430,000 patients worldwide were taking the drug – a figure it hoped to raise by 1.5 million by 2025.
 

A well-tolerated – if expensive – drug

Dupilumab, an interleukin-4 (IL-4) receptor alpha-antagonist biologic, blocks both IL-4 and IL-13 signaling, Marlys Fassett, MD, PhD, associate professor of dermatology at the University of California, San Francisco, told this news organization.

Dr. Fassett said she prescribes the drug off label for chronic idiopathic urticaria, including in older patients, and finds that the side effects in older patients are similar to those in younger people. The medication costs $36,000 per year, although some patients can get it more cheaply.

“Dupixent is a super-safe drug because it doesn’t immunosuppress any other part of the immune system, so you still have good antibacterial, antiviral, and antifungal immunity,” she added. “That makes perfect sense as a biological mechanism, and it’s been found safe in clinical trials.”

Case reports of potential adverse reactions to dupilumab have included ocular surface disease, lichen planus, and rash on the face and neck.

“We’re still learning about complications and are watching patients carefully,” said Marissa J. Perman, MD, section chief of dermatology at Children’s Hospital of Philadelphia.

Many people with atopic dermatitis also have other allergic conditions, such as contact dermatitis, asthma, prurigo nodularis, allergic rhinitis, and seasonal allergies. Each of these conditions has a pathway that depends on IL-4 receptors, Dr. Fassett said.

“It’s amazing how many conditions Dupixent improves. Sometimes we prescribe on-label Dupixent for atopic dermatitis, and inadvertently, the drug also improves that patient’s other, off-label conditions,” Dr. Fassett said. “I think that’s the best evidence that Dupixent works in these off-label cases.”

Lindsay C. Strowd, MD, associate professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she uses off-label dupilumab to treat bullous pemphigoid and intense pruritus of unknown etiology.

“And several times I have treated drug reaction with eosinophilia and systemic symptoms, a rare adverse drug reaction that causes a rash and eosinophilia,” Dr. Strowd added.

Tissa Hata, MD, professor of medicine and clinical service chief at the University of California, San Diego, mainly treats elderly patients. She uses dupilumab to treat bullous pemphigoid and chronic pruritus. “There have been reports of using Dupixent to treat adult alopecia areata, chronic urticaria, localized scleroderma, and even keloids,” she told this news organization.

As a pediatric dermatologist, Dr. Perman treats children with atopic dermatitis as young as 3 months of age. She also uses dupilumab for alopecia areata, graft vs. host disease, and pruritus not otherwise specified.

Conjunctivitis and facial redness are two side effects Dr. Fassett sometimes sees with dupilumab. They occur similarly with all conditions and in all age groups. “We don’t know why they occur, and we don’t always know how to alleviate them,” she said. “So a small number of patients stop using Dupixent because they can’t tolerate those two side effects.

“We’re not worried about infection risk,” Dr. Fassett said. “Your patients may have heard of dupilumab as an immunosuppressant, but its immunosuppression is very focused. You can reassure them that they’re not at increased risk for viral or bacterial infections when they’re on this drug.”

“I don’t think there are any different safety signals to watch for with on-label vs. off-label Dupixent use,” Dr. Strowd added. “In general, the medicine is very safe.”

Dr. Hata said she is impressed with dupilumab’s safety in her elderly patients. All her patients older than 85 years who have taken the drug for bullous pemphigoid have tolerated it well, she said.

“Dupixent seems to be a safe alternative for elderly patients with pruritus because they often cannot tolerate sedating antihistamines due to the risk of falling,” Dr. Hata said. “And UV therapy may be difficult for elderly patients due to problems with transport.”

Although some of Dr. Hata’s elderly patients with atopic dermatitis have discontinued use of the drug after developing conjunctivitis, none taking the drug off label have discontinued it because of side effects, she noted.

“Dupixent manages the condition, but it is not a cure,” Dr. Fassett noted. “Based on the current data, we think it’s safe and effective to take long term, potentially for life.”

Making injections less bothersome

Dupilumab is injected subcutaneously from a single-dose prefilled syringe or a prefilled pen (syringe hidden in an opaque sheath), typically in the thigh, arm, abdomen, or buttocks. According to Sanofi and Regeneron, patients receive dupilumab injections every 2 to 4 weeks in doses based on their age and weight.

“The medication is somewhat viscous, so taking the syringe or pen out of the refrigerator ahead of time to warm it up can make the experience less painful,” Dr. Strowd advised. “For pediatric patients, I sometimes prescribe topical lidocaine applied 30 minutes before injection.”

Dr. Hata suggested icing the skin prior to injecting or distracting the patient by tapping a different area of the skin.

For her pediatric patients, Dr. Perman said she uses “lots of distraction, EMLA cream, and having one person hold the child while a second person injects.”

Clinic and pharmacy staff may show patients how to inject properly, Dr. Fassett added; and the product website provides injection tutorials.
 

Off-label dupixent can be expensive, difficult to obtain

The list price per injection, regardless of dose, is around $1,800. But according to the company’s website, most patients have health insurance or qualify for other assistance, so “very few patients pay the list price.”

Even so, “due to cost and insurance coverage hurdles, obtaining Dupixent for off-label use can be difficult,” Dr. Strowd said.

“In academic medicine, we can obtain drugs for our patients that community doctors may not get approval for,” Dr. Fassett added. “Community doctors can use information in the medical literature and in news articles to press insurance companies to spend money to provide their patients with Dupixent.”

The experts who commented have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Lanolin was announced as the Allergen of the Year by the American Contact Dermatitis Society in March 2023.¹ However, allergic contact dermatitis (ACD) to lanolin remains a matter of fierce debate among dermatologists. Herein, we discuss this important contact allergen, emphasizing the controversy behind its allergenicity and nuances to consider when patch testing.

What is Lanolin?

Lanolin is a greasy, yellow, fatlike substance derived from the sebaceous glands of sheep. It is extracted from wool using an intricate process of scouring with dilute alkali, centrifuging, and refining with hot alkali and bleach.² It is comprised of a complex mixture of esters, alcohols, sterols, fatty acids, lactose, and hydrocarbons.³

The hydrophobic property of lanolin helps sheep shed water from their coats.³ In humans, this hydrophobicity benefits the skin by retaining moisture already present in the epidermis. Lanolin can hold as much as twice its weight in water and may reduce transepidermal water loss by 20% to 30%.^4-6 In addition, lanolin maintains tissue breathability, which supports proper gas exchange, promoting wound healing and protecting against infection.^3,7

Many personal care products (PCPs), cosmetics, and topical medicaments contain lanolin, particularly products marketed to help restore dry cracked skin. The range of permitted concentrations of lanolin in over-the-counter products in the United States is 12.5% to 50%.³ Lanolin also may be found in industrial goods. The Table provides a comprehensive list of common items that may contain lanolin.^1,3,8,9

A Wolf in Sheep’s Clothing?

Despite its benefits, lanolin is a potential source of ACD. The first reported positive patch test (PPT) to lanolin worldwide was in the late 1920s.¹⁰ Subsequent cases of ACD to lanolin were described over the next 30 years, reaching a peak of recognition in the latter half of the 20th century with rates of PPT ranging from 0% to 7.4%, though the patient population and lanolin patch-test formulation used differed across studies.⁹ The North American Contact Dermatitis Group observed that 3.3% (1431/43,691) of patients tested from 2001 to 2018 had a PPT to either lanolin alcohol 30% in petrolatum (pet) or Amerchol L101 (10% lanolin alcohol dissolved in mineral oil) 50% pet.¹¹ Compared to patients referred for patch testing, the prevalence of contact allergy to lanolin is lower in the general population; 0.4% of the general population in Europe (N=3119) tested positive to wool alcohols 1.0 mg/cm² on the thin-layer rapid use Epicutaneous (TRUE) test.¹²

Allergic contact dermatitis to lanolin is unrelated to an allergy to wool itself, which probably does not exist, though wool is well known to cause irritant contact dermatitis, particularly in atopic individuals.¹³

Who Is at Risk for Lanolin Allergy?

In a recent comprehensive review of lanolin allergy, Jenkins and Belsito¹ summarized 4 high-risk subgroups of patients for the development of lanolin contact allergy: stasis dermatitis, chronic leg ulcers, atopic dermatitis (AD), and perianal/genital dermatitis. These chronic inflammatory skin conditions may increase the risk for ACD to lanolin via increased exposure in topical therapies and/or increased allergen penetration through an impaired epidermal barrier.^14-16 Demographically, older adults and children are at-risk groups, likely secondary to the higher prevalence of stasis dermatitis/leg ulcers in the former group and AD in the latter.¹

 

 

Lanolin Controversies

The allergenicity of lanolin is far from straightforward. In 1996, Wolf¹⁷ first described the “lanolin paradox,” modeled after the earlier “paraben paradox” described by Fisher.¹⁸ There are 4 clinical phenomena of the lanolin paradox¹⁷:

• Lanolin generally does not cause contact allergy when found in PCPs but may cause ACD when found in topical medicaments.
• Some patients can use lanolin-containing PCPs on healthy skin without issue but will develop ACD when a lanolin-containing topical medicament is applied to inflamed skin. This is because inflamed skin is more easily sensitized.
• False-negative patch test reactions to pure lanolin may occur. Since Wolf’s¹⁷ initial description of the paradox, free alcohols of lanolin have been found to be its principal allergen, though it also is possible that oxidation of lanolin could generate additional allergenic substances.¹
• Patch testing with wool alcohol 30% can generate both false-negative and false-positive results.

At one extreme, Kligman¹⁹ also was concerned about false-positive reactions to lanolin, describing lanolin allergy as a myth attributed to overzealous patch testing and a failure to appreciate the limitations of this diagnostic modality. Indeed, just having a PPT to lanolin (ie, contact allergy) does not automatically translate to a relevant ACD,¹ and determining the clinical relevance of a PPT is of utmost importance. In 2001, Wakelin et al²⁰ reported that the majority (71% [92/130]) of positive reactions to Amerchol L101 50% or 100% pet showed current clinical relevance. Data from the North American Contact Dermatitis Group in 2009 and in 2022 were similar, with 83.4% (529/634) of positive reactions to lanolin alcohol 30% pet and 86.5% (1238/1431) of positive reactions to Amerchol L101 50% pet classified as current clinical relevance.^11,21 These findings demonstrate that although lanolin may be a weak sensitizer, a PPT usually represents a highly relevant cause of dermatitis.

Considerations for Patch Testing

Considering Wolf’s¹⁷ claim that even pure lanolin is not an appropriate formulation to use for patch testing due to the risk for inaccurate results, you might now be wondering which preparation should be used. Mortensen²² popularized another compound, Amerchol L101, in 1979. In this small study of 60 patients with a PPT to lanolin and/or its derivatives, the highest proportion (37% [22/60]) were positive to Amerchol L101 but negative to wool alcohol 30%, suggesting the need to test to more than one preparation simultaneously.²² In a larger study by Miest et al,²³ 3.9% (11/268) of patients had a PPT to Amerchol L101 50% pet, whereas only 1.1% (3/268) had a PPT to lanolin alcohol 30% pet. This highlighted the importance of including Amerchol L101 when patch testing because it was thought to capture more positive results; however, some studies suggest that Amerchol L101 is not superior at predicting lanolin contact allergy vs lanolin alcohol 30% pet. The risk for an irritant reaction when patch testing with Amerchol L101 should be considered due to its mineral oil component.²⁴

Although there is no universal consensus to date, some investigators suggest patch testing both lanolin alcohol 30% pet and Amerchol L101 50% pet simultaneously.¹ The TRUE test utilizes 1000 µg/cm² of wool alcohols, while the North American 80 Comprehensive Series and the American Contact Dermatitis Society Core 90 Series contain Amerchol L101 50% pet. Patch testing to the most allergenic component of lanolin—the free fatty alcohols (particularly alkane-α,β-diols and alkane-α,ω-diols)—has been suggested,¹ though these formulations are not yet commercially available.

When available, the patient’s own lanolin-containing PCPs should be tested.¹ Performing a repeat open application test (ROAT) to a lanolin-containing product also may be highly useful to distinguish weak-positive from irritant patch test reactions and to determine if sensitized patients can tolerate lanolin-containing products on intact skin. To complete a ROAT, a patient should apply the suspected leave-on product to a patch of unaffected skin (classically the volar forearm) twice daily for at least 10 days.²⁵ If the application site is clear after 10 days, the patient is unlikely to have ACD to the product in question. Compared to patch testing, ROAT more accurately mimics a true use situation, which is particularly important for lanolin given its tendency to preferentially impact damaged or inflamed skin while sparing healthy skin.

Alternatives to Lanolin

Patients with confirmed ACD to lanolin may use plain petrolatum, a safe and inexpensive substitute with equivalent moisturizing efficacy. It can reduce transepidermal water loss by more than 98%,⁴ with essentially no risk for ACD. Humectants such as glycerin, sorbitol, and α-hydroxy acids also have moisturizing properties akin to those of lanolin. In addition, some oils may provide benefit to patients with chronic skin conditions. Sunflower seed oil and extra virgin coconut oil have anti-inflammatory, antibacterial, and barrier repair properties.^26,27 Allergic contact dermatitis to these oils rarely, if ever, occurs.²⁸

Final Interpretation

Lanolin is a well-known yet controversial contact allergen that is widely used in PCPs, cosmetics, topical medicaments, and industrial goods. Lanolin ACD preferentially impacts patients with stasis dermatitis, chronic leg ulcers, AD, and perianal/genital dermatitis. Patch testing with more than one lanolin formulation, including lanolin alcohol 30% pet and/or Amerchol L101 50% pet, as well as testing the patient’s own products may be necessary to confirm the diagnosis. In cases of ACD to lanolin, an alternative agent, such as plain petrolatum, may be used.

Lanolin was announced as the Allergen of the Year by the American Contact Dermatitis Society in March 2023.¹ However, allergic contact dermatitis (ACD) to lanolin remains a matter of fierce debate among dermatologists. Herein, we discuss this important contact allergen, emphasizing the controversy behind its allergenicity and nuances to consider when patch testing.

What is Lanolin?

Lanolin is a greasy, yellow, fatlike substance derived from the sebaceous glands of sheep. It is extracted from wool using an intricate process of scouring with dilute alkali, centrifuging, and refining with hot alkali and bleach.² It is comprised of a complex mixture of esters, alcohols, sterols, fatty acids, lactose, and hydrocarbons.³

The hydrophobic property of lanolin helps sheep shed water from their coats.³ In humans, this hydrophobicity benefits the skin by retaining moisture already present in the epidermis. Lanolin can hold as much as twice its weight in water and may reduce transepidermal water loss by 20% to 30%.^4-6 In addition, lanolin maintains tissue breathability, which supports proper gas exchange, promoting wound healing and protecting against infection.^3,7

Many personal care products (PCPs), cosmetics, and topical medicaments contain lanolin, particularly products marketed to help restore dry cracked skin. The range of permitted concentrations of lanolin in over-the-counter products in the United States is 12.5% to 50%.³ Lanolin also may be found in industrial goods. The Table provides a comprehensive list of common items that may contain lanolin.^1,3,8,9

A Wolf in Sheep’s Clothing?

Despite its benefits, lanolin is a potential source of ACD. The first reported positive patch test (PPT) to lanolin worldwide was in the late 1920s.¹⁰ Subsequent cases of ACD to lanolin were described over the next 30 years, reaching a peak of recognition in the latter half of the 20th century with rates of PPT ranging from 0% to 7.4%, though the patient population and lanolin patch-test formulation used differed across studies.⁹ The North American Contact Dermatitis Group observed that 3.3% (1431/43,691) of patients tested from 2001 to 2018 had a PPT to either lanolin alcohol 30% in petrolatum (pet) or Amerchol L101 (10% lanolin alcohol dissolved in mineral oil) 50% pet.¹¹ Compared to patients referred for patch testing, the prevalence of contact allergy to lanolin is lower in the general population; 0.4% of the general population in Europe (N=3119) tested positive to wool alcohols 1.0 mg/cm² on the thin-layer rapid use Epicutaneous (TRUE) test.¹²

Allergic contact dermatitis to lanolin is unrelated to an allergy to wool itself, which probably does not exist, though wool is well known to cause irritant contact dermatitis, particularly in atopic individuals.¹³

Who Is at Risk for Lanolin Allergy?

In a recent comprehensive review of lanolin allergy, Jenkins and Belsito¹ summarized 4 high-risk subgroups of patients for the development of lanolin contact allergy: stasis dermatitis, chronic leg ulcers, atopic dermatitis (AD), and perianal/genital dermatitis. These chronic inflammatory skin conditions may increase the risk for ACD to lanolin via increased exposure in topical therapies and/or increased allergen penetration through an impaired epidermal barrier.^14-16 Demographically, older adults and children are at-risk groups, likely secondary to the higher prevalence of stasis dermatitis/leg ulcers in the former group and AD in the latter.¹

 

 

Lanolin Controversies

The allergenicity of lanolin is far from straightforward. In 1996, Wolf¹⁷ first described the “lanolin paradox,” modeled after the earlier “paraben paradox” described by Fisher.¹⁸ There are 4 clinical phenomena of the lanolin paradox¹⁷:

• Lanolin generally does not cause contact allergy when found in PCPs but may cause ACD when found in topical medicaments.
• Some patients can use lanolin-containing PCPs on healthy skin without issue but will develop ACD when a lanolin-containing topical medicament is applied to inflamed skin. This is because inflamed skin is more easily sensitized.
• False-negative patch test reactions to pure lanolin may occur. Since Wolf’s¹⁷ initial description of the paradox, free alcohols of lanolin have been found to be its principal allergen, though it also is possible that oxidation of lanolin could generate additional allergenic substances.¹
• Patch testing with wool alcohol 30% can generate both false-negative and false-positive results.

At one extreme, Kligman¹⁹ also was concerned about false-positive reactions to lanolin, describing lanolin allergy as a myth attributed to overzealous patch testing and a failure to appreciate the limitations of this diagnostic modality. Indeed, just having a PPT to lanolin (ie, contact allergy) does not automatically translate to a relevant ACD,¹ and determining the clinical relevance of a PPT is of utmost importance. In 2001, Wakelin et al²⁰ reported that the majority (71% [92/130]) of positive reactions to Amerchol L101 50% or 100% pet showed current clinical relevance. Data from the North American Contact Dermatitis Group in 2009 and in 2022 were similar, with 83.4% (529/634) of positive reactions to lanolin alcohol 30% pet and 86.5% (1238/1431) of positive reactions to Amerchol L101 50% pet classified as current clinical relevance.^11,21 These findings demonstrate that although lanolin may be a weak sensitizer, a PPT usually represents a highly relevant cause of dermatitis.

Considerations for Patch Testing

Considering Wolf’s¹⁷ claim that even pure lanolin is not an appropriate formulation to use for patch testing due to the risk for inaccurate results, you might now be wondering which preparation should be used. Mortensen²² popularized another compound, Amerchol L101, in 1979. In this small study of 60 patients with a PPT to lanolin and/or its derivatives, the highest proportion (37% [22/60]) were positive to Amerchol L101 but negative to wool alcohol 30%, suggesting the need to test to more than one preparation simultaneously.²² In a larger study by Miest et al,²³ 3.9% (11/268) of patients had a PPT to Amerchol L101 50% pet, whereas only 1.1% (3/268) had a PPT to lanolin alcohol 30% pet. This highlighted the importance of including Amerchol L101 when patch testing because it was thought to capture more positive results; however, some studies suggest that Amerchol L101 is not superior at predicting lanolin contact allergy vs lanolin alcohol 30% pet. The risk for an irritant reaction when patch testing with Amerchol L101 should be considered due to its mineral oil component.²⁴

Although there is no universal consensus to date, some investigators suggest patch testing both lanolin alcohol 30% pet and Amerchol L101 50% pet simultaneously.¹ The TRUE test utilizes 1000 µg/cm² of wool alcohols, while the North American 80 Comprehensive Series and the American Contact Dermatitis Society Core 90 Series contain Amerchol L101 50% pet. Patch testing to the most allergenic component of lanolin—the free fatty alcohols (particularly alkane-α,β-diols and alkane-α,ω-diols)—has been suggested,¹ though these formulations are not yet commercially available.

When available, the patient’s own lanolin-containing PCPs should be tested.¹ Performing a repeat open application test (ROAT) to a lanolin-containing product also may be highly useful to distinguish weak-positive from irritant patch test reactions and to determine if sensitized patients can tolerate lanolin-containing products on intact skin. To complete a ROAT, a patient should apply the suspected leave-on product to a patch of unaffected skin (classically the volar forearm) twice daily for at least 10 days.²⁵ If the application site is clear after 10 days, the patient is unlikely to have ACD to the product in question. Compared to patch testing, ROAT more accurately mimics a true use situation, which is particularly important for lanolin given its tendency to preferentially impact damaged or inflamed skin while sparing healthy skin.

Alternatives to Lanolin

Patients with confirmed ACD to lanolin may use plain petrolatum, a safe and inexpensive substitute with equivalent moisturizing efficacy. It can reduce transepidermal water loss by more than 98%,⁴ with essentially no risk for ACD. Humectants such as glycerin, sorbitol, and α-hydroxy acids also have moisturizing properties akin to those of lanolin. In addition, some oils may provide benefit to patients with chronic skin conditions. Sunflower seed oil and extra virgin coconut oil have anti-inflammatory, antibacterial, and barrier repair properties.^26,27 Allergic contact dermatitis to these oils rarely, if ever, occurs.²⁸

Final Interpretation

Lanolin is a well-known yet controversial contact allergen that is widely used in PCPs, cosmetics, topical medicaments, and industrial goods. Lanolin ACD preferentially impacts patients with stasis dermatitis, chronic leg ulcers, AD, and perianal/genital dermatitis. Patch testing with more than one lanolin formulation, including lanolin alcohol 30% pet and/or Amerchol L101 50% pet, as well as testing the patient’s own products may be necessary to confirm the diagnosis. In cases of ACD to lanolin, an alternative agent, such as plain petrolatum, may be used.

Lanolin was announced as the Allergen of the Year by the American Contact Dermatitis Society in March 2023.¹ However, allergic contact dermatitis (ACD) to lanolin remains a matter of fierce debate among dermatologists. Herein, we discuss this important contact allergen, emphasizing the controversy behind its allergenicity and nuances to consider when patch testing.

What is Lanolin?

Lanolin is a greasy, yellow, fatlike substance derived from the sebaceous glands of sheep. It is extracted from wool using an intricate process of scouring with dilute alkali, centrifuging, and refining with hot alkali and bleach.² It is comprised of a complex mixture of esters, alcohols, sterols, fatty acids, lactose, and hydrocarbons.³

The hydrophobic property of lanolin helps sheep shed water from their coats.³ In humans, this hydrophobicity benefits the skin by retaining moisture already present in the epidermis. Lanolin can hold as much as twice its weight in water and may reduce transepidermal water loss by 20% to 30%.^4-6 In addition, lanolin maintains tissue breathability, which supports proper gas exchange, promoting wound healing and protecting against infection.^3,7

Many personal care products (PCPs), cosmetics, and topical medicaments contain lanolin, particularly products marketed to help restore dry cracked skin. The range of permitted concentrations of lanolin in over-the-counter products in the United States is 12.5% to 50%.³ Lanolin also may be found in industrial goods. The Table provides a comprehensive list of common items that may contain lanolin.^1,3,8,9

A Wolf in Sheep’s Clothing?

Despite its benefits, lanolin is a potential source of ACD. The first reported positive patch test (PPT) to lanolin worldwide was in the late 1920s.¹⁰ Subsequent cases of ACD to lanolin were described over the next 30 years, reaching a peak of recognition in the latter half of the 20th century with rates of PPT ranging from 0% to 7.4%, though the patient population and lanolin patch-test formulation used differed across studies.⁹ The North American Contact Dermatitis Group observed that 3.3% (1431/43,691) of patients tested from 2001 to 2018 had a PPT to either lanolin alcohol 30% in petrolatum (pet) or Amerchol L101 (10% lanolin alcohol dissolved in mineral oil) 50% pet.¹¹ Compared to patients referred for patch testing, the prevalence of contact allergy to lanolin is lower in the general population; 0.4% of the general population in Europe (N=3119) tested positive to wool alcohols 1.0 mg/cm² on the thin-layer rapid use Epicutaneous (TRUE) test.¹²

Allergic contact dermatitis to lanolin is unrelated to an allergy to wool itself, which probably does not exist, though wool is well known to cause irritant contact dermatitis, particularly in atopic individuals.¹³

Who Is at Risk for Lanolin Allergy?

In a recent comprehensive review of lanolin allergy, Jenkins and Belsito¹ summarized 4 high-risk subgroups of patients for the development of lanolin contact allergy: stasis dermatitis, chronic leg ulcers, atopic dermatitis (AD), and perianal/genital dermatitis. These chronic inflammatory skin conditions may increase the risk for ACD to lanolin via increased exposure in topical therapies and/or increased allergen penetration through an impaired epidermal barrier.^14-16 Demographically, older adults and children are at-risk groups, likely secondary to the higher prevalence of stasis dermatitis/leg ulcers in the former group and AD in the latter.¹

 

 

Lanolin Controversies

The allergenicity of lanolin is far from straightforward. In 1996, Wolf¹⁷ first described the “lanolin paradox,” modeled after the earlier “paraben paradox” described by Fisher.¹⁸ There are 4 clinical phenomena of the lanolin paradox¹⁷:

• Lanolin generally does not cause contact allergy when found in PCPs but may cause ACD when found in topical medicaments.
• Some patients can use lanolin-containing PCPs on healthy skin without issue but will develop ACD when a lanolin-containing topical medicament is applied to inflamed skin. This is because inflamed skin is more easily sensitized.
• False-negative patch test reactions to pure lanolin may occur. Since Wolf’s¹⁷ initial description of the paradox, free alcohols of lanolin have been found to be its principal allergen, though it also is possible that oxidation of lanolin could generate additional allergenic substances.¹
• Patch testing with wool alcohol 30% can generate both false-negative and false-positive results.

At one extreme, Kligman¹⁹ also was concerned about false-positive reactions to lanolin, describing lanolin allergy as a myth attributed to overzealous patch testing and a failure to appreciate the limitations of this diagnostic modality. Indeed, just having a PPT to lanolin (ie, contact allergy) does not automatically translate to a relevant ACD,¹ and determining the clinical relevance of a PPT is of utmost importance. In 2001, Wakelin et al²⁰ reported that the majority (71% [92/130]) of positive reactions to Amerchol L101 50% or 100% pet showed current clinical relevance. Data from the North American Contact Dermatitis Group in 2009 and in 2022 were similar, with 83.4% (529/634) of positive reactions to lanolin alcohol 30% pet and 86.5% (1238/1431) of positive reactions to Amerchol L101 50% pet classified as current clinical relevance.^11,21 These findings demonstrate that although lanolin may be a weak sensitizer, a PPT usually represents a highly relevant cause of dermatitis.

Considerations for Patch Testing

Considering Wolf’s¹⁷ claim that even pure lanolin is not an appropriate formulation to use for patch testing due to the risk for inaccurate results, you might now be wondering which preparation should be used. Mortensen²² popularized another compound, Amerchol L101, in 1979. In this small study of 60 patients with a PPT to lanolin and/or its derivatives, the highest proportion (37% [22/60]) were positive to Amerchol L101 but negative to wool alcohol 30%, suggesting the need to test to more than one preparation simultaneously.²² In a larger study by Miest et al,²³ 3.9% (11/268) of patients had a PPT to Amerchol L101 50% pet, whereas only 1.1% (3/268) had a PPT to lanolin alcohol 30% pet. This highlighted the importance of including Amerchol L101 when patch testing because it was thought to capture more positive results; however, some studies suggest that Amerchol L101 is not superior at predicting lanolin contact allergy vs lanolin alcohol 30% pet. The risk for an irritant reaction when patch testing with Amerchol L101 should be considered due to its mineral oil component.²⁴

Although there is no universal consensus to date, some investigators suggest patch testing both lanolin alcohol 30% pet and Amerchol L101 50% pet simultaneously.¹ The TRUE test utilizes 1000 µg/cm² of wool alcohols, while the North American 80 Comprehensive Series and the American Contact Dermatitis Society Core 90 Series contain Amerchol L101 50% pet. Patch testing to the most allergenic component of lanolin—the free fatty alcohols (particularly alkane-α,β-diols and alkane-α,ω-diols)—has been suggested,¹ though these formulations are not yet commercially available.

When available, the patient’s own lanolin-containing PCPs should be tested.¹ Performing a repeat open application test (ROAT) to a lanolin-containing product also may be highly useful to distinguish weak-positive from irritant patch test reactions and to determine if sensitized patients can tolerate lanolin-containing products on intact skin. To complete a ROAT, a patient should apply the suspected leave-on product to a patch of unaffected skin (classically the volar forearm) twice daily for at least 10 days.²⁵ If the application site is clear after 10 days, the patient is unlikely to have ACD to the product in question. Compared to patch testing, ROAT more accurately mimics a true use situation, which is particularly important for lanolin given its tendency to preferentially impact damaged or inflamed skin while sparing healthy skin.

Alternatives to Lanolin

Patients with confirmed ACD to lanolin may use plain petrolatum, a safe and inexpensive substitute with equivalent moisturizing efficacy. It can reduce transepidermal water loss by more than 98%,⁴ with essentially no risk for ACD. Humectants such as glycerin, sorbitol, and α-hydroxy acids also have moisturizing properties akin to those of lanolin. In addition, some oils may provide benefit to patients with chronic skin conditions. Sunflower seed oil and extra virgin coconut oil have anti-inflammatory, antibacterial, and barrier repair properties.^26,27 Allergic contact dermatitis to these oils rarely, if ever, occurs.²⁸

Final Interpretation

Lanolin is a well-known yet controversial contact allergen that is widely used in PCPs, cosmetics, topical medicaments, and industrial goods. Lanolin ACD preferentially impacts patients with stasis dermatitis, chronic leg ulcers, AD, and perianal/genital dermatitis. Patch testing with more than one lanolin formulation, including lanolin alcohol 30% pet and/or Amerchol L101 50% pet, as well as testing the patient’s own products may be necessary to confirm the diagnosis. In cases of ACD to lanolin, an alternative agent, such as plain petrolatum, may be used.

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.

To the Editor:

A 58-year-old woman presented to our dermatology clinic with a pruritic weeping eruption circumferentially on the distal digits of both hands of 5 weeks’ duration. The patient disclosed that she had been receiving dip powder manicures at a local nail salon approximately every 2 weeks over the last 3 to 6 months. She had received frequent acrylic nail extensions over the last 8 years prior to starting the dip powder manicures. Physical examination revealed well-demarcated eczematous plaques involving the lateral and proximal nail folds of the right thumb with an overlying serous crust and loss of the cuticle (Figure 1A). Erythematous plaques with firm deep-seated microvesicles also were present on the other digits, distributed distal to the distal interphalangeal joints (Figure 1B). She was diagnosed with dyshidroticlike contact dermatitis and paronychia. Treatment included phenol 1.5% colorless solution and clobetasol ointment 0.05% for twice-daily application to the affected areas. The patient also was advised to stop receiving manicures. At 1-month follow-up, the paronychia had resolved and the dermatitis had nearly resolved.

Dip powder manicures use a wet adhesive base coat with acrylic powder and an activator topcoat to initiate a chemical reaction that hardens and sets the nail polish. The colored powder typically is applied by dipping the digit up to the distal interphalangeal joint into a small container of loose powder and then brushing away the excess (Figure 2). Acrylate, a chemical present in dip powders, is a known allergen and has been associated with the development of allergic contact dermatitis and onychodystrophy in patients after receiving acrylic and UV-cured gel polish manicures.^1,2 Inadequate sanitation practices at nail salons also have been associated with infection transmission.^3,4 Additionally, the news media has covered the potential risk of infection due to contamination from reused dip manicure powder and the use of communal powder containers.⁵

To increase clinical awareness of the dip manicure technique, we describe the presentation and successful treatment of dyshidroticlike contact dermatitis and paronychia that occurred in a patient after she received a dip powder manicure. Dermatoses and infection limited to the distal phalanges will present in patients more frequently as dip powder manicures continue to increase in popularity and frequency.

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

The Diagnosis: Poroma

Histopathology showed an endophytic expansion of the epidermis by bland, uniform, basaloid epithelial cells with focal ductal differentiation and an abrupt transition with surrounding epidermal keratinocytes (Figure), consistent with a diagnosis of poroma. The patient elected to monitor the lesion rather than to have it excised.

Eccrine poroma, used interchangeably with the term poroma, is a rare benign adnexal tumor of the eccrine sweat glands resulting from proliferation of the acrosyringium.^1,2 It often occurs on the palms or soles, though it also can arise anywhere sweat glands are present.¹ Eccrine poromas often appear in middle-aged individuals as singular, well-circumscribed, red-brown papules or nodules.³ A characteristic feature is a shallow, cup-shaped depression within the larger papule or nodule.¹

Because the condition is benign and often asymptomatic, it can be safely monitored for progression.¹ However, if the lesion is symptomatic or located in a sensitive area, complete excision is curative.⁴ Eccrine poromas can recur, making close monitoring following excision important.⁵ The development of bleeding, itching, or pain in a previously asymptomatic lesion may indicate possible malignant transformation, which occurs in only 18% of cases.⁶

The differential diagnosis includes basal cell carcinoma, circumscribed acral hypokeratosis, Kaposi sarcoma, and pyogenic granuloma. Basal cell carcinoma is the most common type of skin cancer.⁷ In rare cases it has been shown to present on the palms or soles as a slowgrowing, reddish-pink papule or plaque with central ulceration. It typically is asymptomatic. Histopathology shows dermal nests of basaloid cells with peripheral palisading, stromal mucin, and peritumoral clefts. Treatment is surgical excision.⁷

Circumscribed acral hypokeratosis presents on the palms or soles as a solitary, shallow, well-defined lesion with a flat base and raised border.⁸ It often is red-pink in color and most frequently occurs in middle-aged women. Although the cause of the condition is unknown, it is thought to be the result of trauma or human papillomavirus infection.8 Biopsy results characteristically show hypokeratosis demarcated by a sharp and frayed cutoff from uninvolved acral skin with discrete hypogranulosis, dilated blood vessels in the papillary dermis, and slightly thickened collagen fibers in the reticular dermis.⁹ Surgical excision is a potential treatment option, as topical corticosteroids, retinoids, and calcipotriene have not been shown to be effective; spontaneous resolution has been reported.⁸

Kaposi sarcoma is a vascular neoplasm that is associated with human herpesvirus 8 infection.¹⁰ It typically presents on mucocutaneous sites and the lower extremities. Palmar involvement has been reported in rare cases, occurring as a solitary, well-demarcated, violaceous macule or patch that may be painful.^10-12 Characteristic histopathologic features include a proliferation in the dermis of slitlike vascular spaces and spindle cell proliferation.¹³ Treatment options include cryosurgery; pulsed dye laser; and topical, intralesional, or systemic chemotherapy agents, depending on the stage of the patient’s disease. Antiretroviral therapy is indicated for patients with Kaposi sarcoma secondary to AIDS.¹⁴

Pyogenic granuloma presents as a solitary red-brown or bluish-black papule or nodule that bleeds easily when manipulated.¹⁵ It commonly occurs following trauma, typically on the fingers, feet, and lips.⁶ Although benign, potential complications include ulceration and blood loss. Pyogenic granulomas can be treated via curettage and cautery, excision, cryosurgery, or pulsed dye laser.¹⁵

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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

Around 5% of patients treated with dupilumab (Dupixent) for moderate-to-severe atopic dermatitis experience musculoskeletal (MSK) symptoms, according to the results of a descriptive study.

The main MSK symptom seen in the observational cohort was enthesitis, but some patients also experienced arthritis and tenosynovitis a median of 17 weeks after starting dupilumab treatment. Together these symptoms represent a new MSK syndrome, say researchers from the United Kingdom.

“The pattern of MSK symptoms and signs is characteristic of psoriatic arthritis/peripheral spondyloarthritis,” Bruce Kirkham, MD, and collaborators report in Arthritis & Rheumatology.

“We started a few years ago and have been following the patients for quite a long time,” Dr. Kirkham, a consultant rheumatologist at Guy’s and St. Thomas’ NHS Foundation Trust, London, told this news organization.

Characterizing the MSK symptoms

Of 470 patients with atopic dermatitis who started treatment with dupilumab at Guy’s and St. Thomas’ NHS Foundation Trust between October 2018 and February 2021, 36 (7.65%) developed rheumatic symptoms and were referred to the rheumatology department. These individuals had their family history assessed and thorough MSK evaluations, which included antibody and inflammatory markers, ultrasound of the peripheral small joints, and MRI of the large joints and spine.

A total of 26 (5.5%) patients – 14 of whom were male – had inflammatory enthesitis, arthritis, and/or tenosynovitis. Of the others, seven had osteoarthritis and three had degenerative spine disease.

Enthesitis was the most common finding in those with rheumatic symptoms, occurring on its own in 11 patients, with arthritis in three patients, and tenosynovitis in two patients.  

These symptoms appeared 2-48 weeks after starting dupilumab treatment and were categorized as mild in 16 (61%) cases, moderate in six cases, and severe in four cases.

No specific predictors of the MSK symptoms seen were noted. Patient age, sex, duration of their atopic dermatitis, or how their skin condition had been previously treated did not help identify those who might develop rheumatic problems.
 

Conservative management approach

All patients had “outstanding” responses to treatment, Dr. Kirkham noted: The mean Eczema Area and Severity Index score before dupilumab treatment was 21, falling to 4.2 with treatment, indicating a mean 80% improvement.

Co-author Joseph Nathan, MBChB, of London North West Healthcare NHS Trust, who collaborated on the research while working within Dr. Kirkham’s group, said separately: “The concern that patients have is that when they start a medication and develop a side effect is that the medication is going to be stopped.”

Clinicians treating the patients took a conservative approach, prescribing NSAIDs such as cyclooxygenase-2 inhibitors or altering the frequency with which dupilumab was given.

With this approach, MSK symptoms resolved in 15 patients who remained on treatment and in seven who had to stop dupilumab. There were four patients, however, who had unresolved symptoms even once dupilumab treatment had been stopped.
 

Altering the local cytokine balance

Dupilumab is a monoclonal antibody that binds to the alpha subunit of the interleukin-4 receptor. This results in blocking the function of not only IL-4 but also IL-13.

Dr. Kirkham and colleagues think this might not only alter the balance of cytokines in the skin but also in the joints and entheses with IL-17, IL-23, or even tumor necrosis factor playing a possible role. Another thought is that many circulating T-cells in the skin move to the joints and entheses to trigger symptoms.

IL-13 inhibition does seem to be important, as another British research team, from the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), has found.

At the recent annual meeting of the British Society for Rheumatology, Sizheng Steven Zhao, MBChB, PhD, and colleagues reported that among people who carried a genetic variant predisposing them to having low IL-13 function, there was a higher risk for inflammatory diseases such as psoriatic arthritis and other spondyloarthropathy-related diseases.

Sara Freeman/Frontline Medical News

Dermatology perspective

Approved by the U.S. Food and Drug Administration in 2017, dupilumab has since been hailed as a “breakthrough” in atopic dermatitis treatment. Given as a subcutaneous injection every 2 weeks, it provides a much-needed option for people who have moderate-to-severe disease and have tried other available treatments, including corticosteroids.

Dupilumab has since also been approved for asthma, chronic sinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis and is used off-label for other skin conditions such as contact dermatitis, chronic spontaneous urticaria, and alopecia areata.

“Dupilumab, like a lot of medications for atopic dermatitis, is a relatively new drug, and we are still learning about its safety,” Joel M. Gelfand, MD, MSCE, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, told this news organization.

“Inflammatory arthritis has been reported in patients treated with dupilumab, and this new study provides some useful estimates,” added Dr. Gelfand, who is a professor of dermatology and epidemiology and directs the Psoriasis and Phototherapy Treatment Center, Philadelphia.

“There was no control group,” Dr. Gelfand said, so “a causal relationship cannot be well established based on these data alone. The mechanism is not known but may result from a shifting of the immune system.”

Dr. Zhao observed: “We don’t know what the natural history of these adverse events is. We don’t know if stopping the drug early will prevent long-term adverse events. So, we don’t know if people will ultimately develop permanent psoriatic arthritis if we don’t intervene quick enough when we observe an adverse event.”

Being aware of the possibility of rheumatic side effects occurring with dupilumab and similar agents is key, Dr. Gelfand and Dr. Kirkham both said independently.

“I have personally seen this entity in my practice,” Dr. Gelfand said. “It is important to clinicians prescribing dupilumab to alert patients about this potential side effect and ask about joint symptoms in follow-up.”

Dr. Kirkham said: “Prescribers need to be aware of it, because up until now it’s been just very vaguely discussed as sort of aches and pains, arthralgias, and it’s a much more specific of a kind of syndrome of enthesitis, arthritis, tenosynovitis – a little like psoriatic arthritis.”

Not everyone has come across these side effects, however, as Steven Daveluy, MD, associate professor and dermatology program director at Wayne State University, Detroit, said in an interview.

“This article and the other case series both noted the musculoskeletal symptoms occurred in about 5% of patients, which surprised me since I haven’t seen it in my practice and have enough patients being treated with dupilumab that I would expect to see a case at that rate,” Dr. Daveluy said.

“The majority of cases are mild and respond to treatment with anti-inflammatories like naproxen, which is available over the counter. It’s likely that patients with a mild case could simply treat their pain with naproxen that’s already in their medicine cabinet until it resolves, never bringing it to the doctor’s attention,” he suggested.

“Dupilumab is still a safe and effective medication that can change the lives of patients suffering from atopic dermatitis,” he said.

“Awareness of this potential side effect can help dermatologists recognize it early and work together with patients to determine the best course of action.”

All research mentioned in this article was independently supported. Dr. Kirkham, Mr. Nathan, Dr. Zhao, and Dr. Daveluy report no relevant financial relationships. Dr. Gelfand has served as a consultant for numerous pharmaceutical companies and receives research grants from Amgen, Boehringer Ingelheim, and Pfizer. He is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma.

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

Diabetes devices represent a major advancement in the management of diabetes, but they can cause skin reactions that affect patient adherence and quality of life, Jennifer K. Chen, MD, said in a presentation at the annual meeting of the American Contact Dermatitis Society.

Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.

Dr. Chen

Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”

Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.

Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
 

Consider isobornyl acrylate

An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.

Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.

An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.

Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.

IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.

In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.

Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
 

Patch testing

When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.

Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.

Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
 

Management strategies

For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.

For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system

Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.

Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
 

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

Diabetes devices represent a major advancement in the management of diabetes, but they can cause skin reactions that affect patient adherence and quality of life, Jennifer K. Chen, MD, said in a presentation at the annual meeting of the American Contact Dermatitis Society.

Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.

Dr. Chen

Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”

Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.

Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
 

Consider isobornyl acrylate

An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.

Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.

An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.

Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.

IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.

In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.

Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
 

Patch testing

When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.

Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.

Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
 

Management strategies

For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.

For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system

Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.

Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
 

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

Diabetes devices represent a major advancement in the management of diabetes, but they can cause skin reactions that affect patient adherence and quality of life, Jennifer K. Chen, MD, said in a presentation at the annual meeting of the American Contact Dermatitis Society.

Advanced technologies used for the management of diabetes fall into three main categories, said Dr. Chen, of the department of dermatology, Stanford University, Redwood City, Calif. Continuous glucose monitoring (CGM) devices, which are worn on the body, collect glucose measurements. Continuous subcutaneous insulin infusion (CSII) devices are attached to the body via an infusion set and are now available as tubing-free patch pumps that are attached directly to the skin via a catheter. Glucose-responsive insulin delivery systems combine the sensing and delivery features of the other two types of devices.

Dr. Chen

Once thought to be rare, reports of skin complications related to diabetes devices have been increasing in recent years, she said. Some reports suggest that at any given time, skin complications may affect as many as one quarter to one half of patients who use these devices, “so this is an important issue,” she emphasized. “Skin reactions are a major factor in device discontinuation, so we as clinicians need to be really proactive about treating these reactions.”

Risk factors for skin complications related to diabetes devices include sensitization to the adhesive used with the devices, as well as prolonged exposure to the device, Dr. Chen said. Younger age also appears to be a risk factor, as is a compromised skin barrier in the area where the device is used.

Unfortunately, obtaining details on the specific adhesives and the raw materials used in these devices, so as to customize patch testing, remains a challenge, she said. “Patch testing initially was often negative to commercially available allergens, even while patients were testing positive to pieces of device adhesive,” she noted.
 

Consider isobornyl acrylate

An article published in 2017 in Contact Dermatitis was “a major breakthrough” in that it identified isobornyl acrylate (IBOA) as an allergen in connection with the Freestyle Libre, a CGM device that was relatively new at the time. The finding was serendipitous, Dr. Chen said. A patient being treated for suspected allergic contact dermatitis in connection with use of a Freestyle Libre device was tested for IBOA accidentally, after the nurse administering the patch test thought that this was part of the standard acrylate series, she explained.

Subsequently, researchers identified 15 patients who had experienced reactions to the Freestyle Libre; 12 of 13 patients who were patch tested for IBOA tested positive. IBOA was found throughout the device, particularly where the top and bottom plastic components were connected, Dr. Chen said. This suggested that the IBOA was in the device housing and had diffused into the adhesive that attached the device to the skin.

An article published in 2018 in the Journal of Diabetes Science described three patients who developed severe allergic contact dermatitis from IBOA while using a CGM device, Dr. Chen said. The investigators confirmed that there were no reactions to the adhesive itself, again suggesting that IBOA had diffused into the adhesive from other parts of the device.

Although the authors were bound by a confidentiality agreement regarding the individual adhesive components, “the authors noted most of the acrylates in the adhesive were not present in commercially available acrylate series for patch testing,” she said.

IBOA, the ACDS’ Allergen of the Year in 2020, is common in sealants, glues, and adhesives, Dr. Chen said. Although IBOA had been reported infrequently as an allergen, it has now been identified as a “potential culprit” behind skin reactions in many diabetes devices, including CSII and CGM devices, she added.

In addition, N,N-dimethylacrylamide (DMAA) is an allergen that has been identified in several diabetes devices and often occurs with IBOA in medical-grade UV-cured adhesives, Dr. Chen noted. Other allergens identified in diabetes devices include colophony, which is present in many adhesives, as well as other acrylates and epoxy resin.

Diabetes devices are constantly evolving. IBOA is no longer found in Freestyle Libre devices. It is important that clinicians stay up to date with the medical literature and advocate for partnership with device manufacturers, she emphasized.
 

Patch testing

When diabetes devices are suspected as the source of allergic contact dermatitis, a minimum of a baseline series that contains colophony at a concentration of 20% in petrolatum should be carried out, Dr. Chen said. Commercialized patch test trays, which include plastics, glues, acrylates, epoxy resins/isocyanates, and colophony derivatives, should be ideal. “Personal-care products should be included if they are potentially relevant,” she added.

Dr. Chen shared tables published in Contact Dermatitis in 2021 with examples of screening test series. She said to consider including screening for other allergens more recently discovered in diabetes devices, including 2,2’-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate (MBPA) 1.5% pet; dipropylene glycol diacrylate (DPGDA) 0.1% pet; and butylated hydroxytoluene (BHT) 2% pet.

Testing for monomethyl ether of hydroquinone should also be considered; this may be included in the test preparations for IBOA and DMAA.
 

Management strategies

For patients who experience skin reactions to their diabetes devices, consideration may given to relocating the device to another area of skin or changing sensors more frequently, according to Dr. Chen.

For some patients, the reaction can be managed with corticosteroid cream, ointment, solution, or nasal spray. Topical antibiotics or topical antihistamines can be helpful, as can barrier dressings, solutions, or sprays, she said. The best solution is to change to a device that does not have the culprit allergen, “but that is difficult, since we don’t know what is in these devices,” she added. Good alternatives include the Eversense CGM device or devices that have been demonstrated not to contain IBOA, such as the Freestyle Libre 2 or the newer version of the Omnipod, an insulin delivery system

Looking ahead, Dr. Chen said that “mandatory labeling is needed, as devices with the same name may have different compositions, depending on the date of manufacture.” Allergens relevant to people with diabetes are constantly evolving, and many are still unidentified, so clinicians and manufacturers need to work together to identify the culprit allergens and their sources, she said.

Dr. Chen has served as principal investigator or subinvestigator for Amgen, AbbVie, and Sanofi Regeneron and as a consultant for Purity Brands.
 

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