Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

Higher direct ultraviolet light exposure in the first 3 months of life was linked to lower incidence of proinflammatory immune markers and lower incidence of eczema in an early-stage double-blind, randomized controlled trial.  

Kristina Rueter, MD, with the University of Western Australia, Perth, who presented her team’s findings on Sunday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, said their study is the first to demonstrate the association.

“There has been a significant rise in allergic diseases, particularly within the last 20-30 years,” Dr. Rueter noted.  

“Changes to the genetic pool take thousands of years to have an impact,” she said, “so the question is why do we have the significant, very recent rise of allergic diseases?”

Suboptimal vitamin D levels during infancy, lifestyle changes, nutritional changes, and living at higher latitudes have emerged as explanations.

In this study, 195 high-risk newborns were randomized to receive oral vitamin D supplements (400 IU/day) or placebo until 6 months of age.

Researchers found that UV light exposure appears more beneficial than vitamin D supplements as an allergy prevention strategy in the critical early years of immune system development.

The researchers used a novel approach of attaching a personal UV dosimeter to the infants’ clothing to measure direct UV light exposure (290-380 nm). Vitamin D levels were measured at 3, 6, 12, and 30 months of age. Immune function was assessed at 6 months of age, and food allergy, eczema, and wheeze were assessed at 6, 12, and 30 months of age.

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater in the children who received vitamin D supplements than those who received placebo, but there was no difference in eczema incidence between groups. The finding matched those of previous studies that compared the supplements with placebo, Dr. Rueter said.

However, infants with eczema were found to have had less UV light exposure compared to those without eczema (median interquartile range [IQR], 555 J/m² vs. 998 J/m²; P = .023).

“We also found an inverse correlation between total UV light exposure and toll-like receptor cytokine production,” Dr. Rueter said.

“The more direct UV light exposure a child got, the less the chance to develop eczema,” she said.

Researchers then extended their analysis to see whether the effect of direct UV light exposure on reduced eczema would be maintained in the first 2.5 years of life, “and we could see again a significant difference, that the children who received higher UV light exposure had less eczema,” Dr. Rueter said.

Barbara Rogala, MD, PhD, professor at the Medical University of Silesia, Katowice, Poland, told this news organization that, just as in studies on vitamin D in adult populations, there must be a balance in infant studies between potential benefit of a therapeutic strategy of vitamin D and sunlight and risk of side effects. (Dr. Rogala was not involved in Dr. Rueter’s study.)

Although vitamin D supplements are a standard part of infant care, exposure to sunlight can come with cancer risk, she noted.

Dr. Rueter agreed caution is necessary.

“You have to follow the cancer guidelines,” she said. “Sunlight may play a role in causing skin cancer, and lots of research needs to be done to find the right balance between what is a good amount which may influence the immune system in a positive way and what, on the other hand, might be too much.”

As for vitamin D supplements, Dr. Rueter said, toxic levels require “extremely high doses,” so with 400 IU/day used in the study, children are likely not being overtreated by combining sunlight and vitamin D supplements.

The study was supported by grants from Telethon–New Children’s Hospital Research Fund, Australia; Asthma Foundation of Western Australia; and the Princess Margaret Hospital Foundation, Australia. Dr. Rueter and Dr. Rogala have reported no relevant financial relationships.

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

The Diagnosis: Cystic Panfolliculoma 

Panfolliculoma is a rare tumor of follicular origin.¹ Clinical examination can reveal a papule, nodule, or tumor that typically is mistaken for an epidermal inclusion cyst, trichoepithelioma, or basal cell carcinoma (BCC).² As with other benign follicular neoplasms, it often exhibits a protracted growth pattern.^3,4 Most cases reported in the literature have been shown to occur in the head or neck region. One hypothesis is that separation into the various components of the hair follicle occurs at a higher frequency in areas with a higher hair density such as the face and scalp.⁴ The lesion typically presents in patients aged 20 to 70 years, as in our patient, with cases equally distributed among males and females.^4,5 Neill et al1 reported a rare case of cystic panfolliculoma occurring on the right forearm of a 64-year-old woman. 

As its name suggests, panfolliculoma is exceptional in that it displays features of all segments of the hair follicle, including the infundibulum, isthmus, stem, and bulb.⁶ Although not necessary for diagnosis, immunohistochemical staining can be utilized to identify each hair follicle component on histopathologic examination. Panfolliculoma stains positive for 34βE12 and cytokeratin 5/6, highlighting infundibular and isthmus keratinocytes and the outer root sheath, respectively. Additionally, Ber-EP4 labels germinative cells, while CD34 highlights contiguous fibrotic stroma and trichilemmal areas.^3,4 

In our patient, histopathology revealed a cystic structure that was lined by an infundibular epithelium with a prominent granular layer. Solid collections of basaloid germinative cells that demonstrated peripheral palisading were observed (quiz image [top]). Cells with trichohyalin granules, indicative of inner root sheath differentiation, were encased by matrical cells (quiz image [bottom]).  

Historically, panfolliculomas characteristically have been known to reside in the dermis, with only focal connection to the epidermis, if at all present. Nevertheless, Harris et al⁷ detailed 2 cases that displayed predominant epidermal involvement, defined by the term epidermal panfolliculoma. In a study performed by Shan and Guo,² an additional 9 cases (19 panfolliculomas) were found to have similar findings, for which the term superficial panfolliculoma was suggested. In cases that display a primary epidermal component, common mimickers include tumor of the follicular infundibulum and the reactive process of follicular induction.⁷ 

Cystic panfolliculoma is a rare subtype further characterized as a lesion with distinctive features of a panfolliculoma that arises from a cyst wall composed of the follicular infundibulum.^2,6 The origin of cystic panfolliculoma has not been fully elucidated. It has been hypothesized that the formation of such lesions may arise due to epithelial-mesenchymal interactions. One explanation is that basal cells with stem cell capability may progress into hair follicle structures after communication with underlying dermal cells during invagination of the epidermis, while the epithelial cells not in close proximity to dermal cells maintain stem cell capability.⁸ 

The histologic differential diagnosis of cystic panfolliculoma includes dilated pore of Winer, epidermal inclusion cyst, pilar cyst, trichofolliculoma, folliculosebaceous cystic hamartoma, cystic trichoblastoma, and BCC.⁵ Panfolliculoma can mimic both trichoblastoma and trichoepithelioma on a low-power field; however, the latter follicular tumors lack differentiation to the infundibulum, isthmus, outer root sheath, or hair shaft, as in a panfolliculoma.⁴ Trichoblastoma is composed of germinative hair follicle cells, with differentiation limited to the hair germ and papilla (Figure 1).⁹ Panfolliculoma additionally differs from trichoblastoma by having a more prevalent epithelial factor compared to a more pronounced stromal factor in trichoblastoma.¹ The cystic subtype of trichoblastoma differs from cystic panfolliculoma in that the cyst wall develops from the infundibulum only and has germinative cells protruding outwards from the cyst wall.  

Although BCCs may arise in cystic structures, panfolliculomas can be discerned from this entity by their sharp demarcation, lack of peritumoral clefting, and presence of cytokeratin 20-positive Merkel cells.⁵ Unlike panfolliculoma, the tumor islands in BCC commonly display peripheral palisading of nuclei with a surrounding fibromyxoid stroma (Figure 2). Additionally, BCCs can exhibit crowding of nuclei, atypia, and mitoses.⁶ 

Folliculosebaceous cystic hamartomas and cystic panfolliculomas both contain a cystic structure with differentiation of the cyst wall to the hair follicle. However, folliculosebaceous cystic hamartomas are dilated infundibulocystic configurations that contain sebaceous glands emanating from the cyst wall (Figure 3). Kimura et al¹⁰ described defining features of the mesenchymal component of this follicular tumor, including an increase in fibroplasia, vascularity, and adipose tissue. In addition, the epithelial aspect exhibits clefting among the stroma and uninvolved dermis.⁶

Dilated pore of Winer consists of a cystic opening with connection to the epidermis. The cyst wall resembles the follicular infundibulum, and the cavity is filled with lamellar orthokeratosis (Figure 4).^5,11 Epidermal inclusion cysts also contain a cyst wall that resembles the infundibular epithelium, without differentiation to all segments of the hair follicle. They are lined by a stratified squamous epithelium, retain a granular layer, and contain lamellar keratin within the cyst cavity.^5,12 

In summary, panfolliculoma is a rare benign neoplasm that demonstrates differentiation to each component of the hair follicle structure. Our case demonstrates a unique subtype showcasing cystic changes that infrequently has been described in the literature. 

The Diagnosis: Cystic Panfolliculoma 

Panfolliculoma is a rare tumor of follicular origin.¹ Clinical examination can reveal a papule, nodule, or tumor that typically is mistaken for an epidermal inclusion cyst, trichoepithelioma, or basal cell carcinoma (BCC).² As with other benign follicular neoplasms, it often exhibits a protracted growth pattern.^3,4 Most cases reported in the literature have been shown to occur in the head or neck region. One hypothesis is that separation into the various components of the hair follicle occurs at a higher frequency in areas with a higher hair density such as the face and scalp.⁴ The lesion typically presents in patients aged 20 to 70 years, as in our patient, with cases equally distributed among males and females.^4,5 Neill et al1 reported a rare case of cystic panfolliculoma occurring on the right forearm of a 64-year-old woman. 

As its name suggests, panfolliculoma is exceptional in that it displays features of all segments of the hair follicle, including the infundibulum, isthmus, stem, and bulb.⁶ Although not necessary for diagnosis, immunohistochemical staining can be utilized to identify each hair follicle component on histopathologic examination. Panfolliculoma stains positive for 34βE12 and cytokeratin 5/6, highlighting infundibular and isthmus keratinocytes and the outer root sheath, respectively. Additionally, Ber-EP4 labels germinative cells, while CD34 highlights contiguous fibrotic stroma and trichilemmal areas.^3,4 

In our patient, histopathology revealed a cystic structure that was lined by an infundibular epithelium with a prominent granular layer. Solid collections of basaloid germinative cells that demonstrated peripheral palisading were observed (quiz image [top]). Cells with trichohyalin granules, indicative of inner root sheath differentiation, were encased by matrical cells (quiz image [bottom]).  

Historically, panfolliculomas characteristically have been known to reside in the dermis, with only focal connection to the epidermis, if at all present. Nevertheless, Harris et al⁷ detailed 2 cases that displayed predominant epidermal involvement, defined by the term epidermal panfolliculoma. In a study performed by Shan and Guo,² an additional 9 cases (19 panfolliculomas) were found to have similar findings, for which the term superficial panfolliculoma was suggested. In cases that display a primary epidermal component, common mimickers include tumor of the follicular infundibulum and the reactive process of follicular induction.⁷ 

Cystic panfolliculoma is a rare subtype further characterized as a lesion with distinctive features of a panfolliculoma that arises from a cyst wall composed of the follicular infundibulum.^2,6 The origin of cystic panfolliculoma has not been fully elucidated. It has been hypothesized that the formation of such lesions may arise due to epithelial-mesenchymal interactions. One explanation is that basal cells with stem cell capability may progress into hair follicle structures after communication with underlying dermal cells during invagination of the epidermis, while the epithelial cells not in close proximity to dermal cells maintain stem cell capability.⁸ 

The histologic differential diagnosis of cystic panfolliculoma includes dilated pore of Winer, epidermal inclusion cyst, pilar cyst, trichofolliculoma, folliculosebaceous cystic hamartoma, cystic trichoblastoma, and BCC.⁵ Panfolliculoma can mimic both trichoblastoma and trichoepithelioma on a low-power field; however, the latter follicular tumors lack differentiation to the infundibulum, isthmus, outer root sheath, or hair shaft, as in a panfolliculoma.⁴ Trichoblastoma is composed of germinative hair follicle cells, with differentiation limited to the hair germ and papilla (Figure 1).⁹ Panfolliculoma additionally differs from trichoblastoma by having a more prevalent epithelial factor compared to a more pronounced stromal factor in trichoblastoma.¹ The cystic subtype of trichoblastoma differs from cystic panfolliculoma in that the cyst wall develops from the infundibulum only and has germinative cells protruding outwards from the cyst wall.  

Although BCCs may arise in cystic structures, panfolliculomas can be discerned from this entity by their sharp demarcation, lack of peritumoral clefting, and presence of cytokeratin 20-positive Merkel cells.⁵ Unlike panfolliculoma, the tumor islands in BCC commonly display peripheral palisading of nuclei with a surrounding fibromyxoid stroma (Figure 2). Additionally, BCCs can exhibit crowding of nuclei, atypia, and mitoses.⁶ 

Folliculosebaceous cystic hamartomas and cystic panfolliculomas both contain a cystic structure with differentiation of the cyst wall to the hair follicle. However, folliculosebaceous cystic hamartomas are dilated infundibulocystic configurations that contain sebaceous glands emanating from the cyst wall (Figure 3). Kimura et al¹⁰ described defining features of the mesenchymal component of this follicular tumor, including an increase in fibroplasia, vascularity, and adipose tissue. In addition, the epithelial aspect exhibits clefting among the stroma and uninvolved dermis.⁶

Dilated pore of Winer consists of a cystic opening with connection to the epidermis. The cyst wall resembles the follicular infundibulum, and the cavity is filled with lamellar orthokeratosis (Figure 4).^5,11 Epidermal inclusion cysts also contain a cyst wall that resembles the infundibular epithelium, without differentiation to all segments of the hair follicle. They are lined by a stratified squamous epithelium, retain a granular layer, and contain lamellar keratin within the cyst cavity.^5,12 

In summary, panfolliculoma is a rare benign neoplasm that demonstrates differentiation to each component of the hair follicle structure. Our case demonstrates a unique subtype showcasing cystic changes that infrequently has been described in the literature. 

The Diagnosis: Cystic Panfolliculoma 

Panfolliculoma is a rare tumor of follicular origin.¹ Clinical examination can reveal a papule, nodule, or tumor that typically is mistaken for an epidermal inclusion cyst, trichoepithelioma, or basal cell carcinoma (BCC).² As with other benign follicular neoplasms, it often exhibits a protracted growth pattern.^3,4 Most cases reported in the literature have been shown to occur in the head or neck region. One hypothesis is that separation into the various components of the hair follicle occurs at a higher frequency in areas with a higher hair density such as the face and scalp.⁴ The lesion typically presents in patients aged 20 to 70 years, as in our patient, with cases equally distributed among males and females.^4,5 Neill et al1 reported a rare case of cystic panfolliculoma occurring on the right forearm of a 64-year-old woman. 

As its name suggests, panfolliculoma is exceptional in that it displays features of all segments of the hair follicle, including the infundibulum, isthmus, stem, and bulb.⁶ Although not necessary for diagnosis, immunohistochemical staining can be utilized to identify each hair follicle component on histopathologic examination. Panfolliculoma stains positive for 34βE12 and cytokeratin 5/6, highlighting infundibular and isthmus keratinocytes and the outer root sheath, respectively. Additionally, Ber-EP4 labels germinative cells, while CD34 highlights contiguous fibrotic stroma and trichilemmal areas.^3,4 

In our patient, histopathology revealed a cystic structure that was lined by an infundibular epithelium with a prominent granular layer. Solid collections of basaloid germinative cells that demonstrated peripheral palisading were observed (quiz image [top]). Cells with trichohyalin granules, indicative of inner root sheath differentiation, were encased by matrical cells (quiz image [bottom]).  

Historically, panfolliculomas characteristically have been known to reside in the dermis, with only focal connection to the epidermis, if at all present. Nevertheless, Harris et al⁷ detailed 2 cases that displayed predominant epidermal involvement, defined by the term epidermal panfolliculoma. In a study performed by Shan and Guo,² an additional 9 cases (19 panfolliculomas) were found to have similar findings, for which the term superficial panfolliculoma was suggested. In cases that display a primary epidermal component, common mimickers include tumor of the follicular infundibulum and the reactive process of follicular induction.⁷ 

Cystic panfolliculoma is a rare subtype further characterized as a lesion with distinctive features of a panfolliculoma that arises from a cyst wall composed of the follicular infundibulum.^2,6 The origin of cystic panfolliculoma has not been fully elucidated. It has been hypothesized that the formation of such lesions may arise due to epithelial-mesenchymal interactions. One explanation is that basal cells with stem cell capability may progress into hair follicle structures after communication with underlying dermal cells during invagination of the epidermis, while the epithelial cells not in close proximity to dermal cells maintain stem cell capability.⁸ 

The histologic differential diagnosis of cystic panfolliculoma includes dilated pore of Winer, epidermal inclusion cyst, pilar cyst, trichofolliculoma, folliculosebaceous cystic hamartoma, cystic trichoblastoma, and BCC.⁵ Panfolliculoma can mimic both trichoblastoma and trichoepithelioma on a low-power field; however, the latter follicular tumors lack differentiation to the infundibulum, isthmus, outer root sheath, or hair shaft, as in a panfolliculoma.⁴ Trichoblastoma is composed of germinative hair follicle cells, with differentiation limited to the hair germ and papilla (Figure 1).⁹ Panfolliculoma additionally differs from trichoblastoma by having a more prevalent epithelial factor compared to a more pronounced stromal factor in trichoblastoma.¹ The cystic subtype of trichoblastoma differs from cystic panfolliculoma in that the cyst wall develops from the infundibulum only and has germinative cells protruding outwards from the cyst wall.  

Although BCCs may arise in cystic structures, panfolliculomas can be discerned from this entity by their sharp demarcation, lack of peritumoral clefting, and presence of cytokeratin 20-positive Merkel cells.⁵ Unlike panfolliculoma, the tumor islands in BCC commonly display peripheral palisading of nuclei with a surrounding fibromyxoid stroma (Figure 2). Additionally, BCCs can exhibit crowding of nuclei, atypia, and mitoses.⁶ 

Folliculosebaceous cystic hamartomas and cystic panfolliculomas both contain a cystic structure with differentiation of the cyst wall to the hair follicle. However, folliculosebaceous cystic hamartomas are dilated infundibulocystic configurations that contain sebaceous glands emanating from the cyst wall (Figure 3). Kimura et al¹⁰ described defining features of the mesenchymal component of this follicular tumor, including an increase in fibroplasia, vascularity, and adipose tissue. In addition, the epithelial aspect exhibits clefting among the stroma and uninvolved dermis.⁶

Dilated pore of Winer consists of a cystic opening with connection to the epidermis. The cyst wall resembles the follicular infundibulum, and the cavity is filled with lamellar orthokeratosis (Figure 4).^5,11 Epidermal inclusion cysts also contain a cyst wall that resembles the infundibular epithelium, without differentiation to all segments of the hair follicle. They are lined by a stratified squamous epithelium, retain a granular layer, and contain lamellar keratin within the cyst cavity.^5,12 

In summary, panfolliculoma is a rare benign neoplasm that demonstrates differentiation to each component of the hair follicle structure. Our case demonstrates a unique subtype showcasing cystic changes that infrequently has been described in the literature. 

The Diagnosis: Cutaneous Angiosarcoma 

Biopsy revealed a cellular neoplasm consisting of atypical polygonal cells with a hobnailed appearance, vasoformative characteristics, and rare extravasated erythrocytes. The tumor had an infiltrative growth pattern as demonstrated by dissecting dermal collagen and a poorly defined border with adjacent normal tissue (Figure 1). Immunohistochemistry revealed that the lesion was positive for CD31 and D2-40 (Figure 2) but negative for cytokeratin, CD10, CD68, human herpesvirus 8, CD34, and Melan A, thus confirming the endothelial origin of the tumor cells and the diagnosis of cutaneous angiosarcoma (CAS). The patient was treated with extended surgical excision and radiation therapy. No recurrence or metastasis was found throughout 2 years of follow-up.  

Radical resection with a negative margin is considered the first-line treatment of choice. Although there is a paucity of studies assessing the specific width of surgical margins, application of no less than a 3-cm peripheral margin as well as a clear deep margin is recommended.⁵ Adjuvant radiation therapy also is essential to prevent local recurrence. Patients receiving combination therapy have a superior overall survival rate when compared to those undergoing surgery or radiation therapy alone.⁴  

Cutaneous follicle center lymphoma also may present as 1 or more localized erythematous papules, plaques, and/or nodules, commonly arising on the scalp/forehead or trunk of middle-aged men. Despite being a low-grade lymphoma with a favorable prognosis, it may have a relatively fast growth and locally aggressive course if left untreated. The distinguishing histologic feature is a dense proliferation of neoplastic infiltrates in the dermis, which is separated from the epidermis by the grenz zone.⁶ 

The clinical presentation of cutaneous metastatic carcinomas varies greatly, with 1 or multiple localized or widespread lesions commonly involving the abdominal wall, scalp, and face. The lesions also may mimic benign dermatologic conditions, thus potentially resulting in erroneous clinical diagnosis and delayed therapy of the primary malignancy. Obtaining clinical history is crucial; however, a precise diagnosis may require histologic examination.⁷ 

Atypical fibroxanthoma is a rare superficial cutaneous sarcoma that typically occurs on the head and neck in sun-damaged elderly individuals. Clinically, AFX presents as well-circumscribed red or pink nodules or plaques with or without ulceration, crust, or scale.⁸ Atypical fibroxanthoma lesions usually are small, with a median diameter of 1 cm, while those greater than 2 cm reportedly account for less than 5% of cases.⁹ Atypical fibroxanthoma typically grows rapidly with no pain or discomfort. Histologically, AFX is characterized by a well-circumscribed dermal nodule consisting of pleomorphic spindle cells and multinucleated giant cells that can stain positively for CD10 and procollagen 1.¹⁰ 

Cutaneous pseudolymphoma is a benign inflammatory response process that stimulates polyclonal T- or B-cell lymphoproliferation. The clinical presentation may appear as localized or disseminated flesh-colored or red papules, infiltrated plaques, and nodules.¹¹ Histopathology will show mixtures of B and T cells along with dendritic cells and macrophages, but irregular vascular structure and dissecting dermal collagen are not involved. 

We present an unusual case of CAS with multiple pink nodules on the scalp. Early biopsy of these lesions is important to reach a correct diagnosis and to initiate appropriate treatment. 

The Diagnosis: Cutaneous Angiosarcoma 

Biopsy revealed a cellular neoplasm consisting of atypical polygonal cells with a hobnailed appearance, vasoformative characteristics, and rare extravasated erythrocytes. The tumor had an infiltrative growth pattern as demonstrated by dissecting dermal collagen and a poorly defined border with adjacent normal tissue (Figure 1). Immunohistochemistry revealed that the lesion was positive for CD31 and D2-40 (Figure 2) but negative for cytokeratin, CD10, CD68, human herpesvirus 8, CD34, and Melan A, thus confirming the endothelial origin of the tumor cells and the diagnosis of cutaneous angiosarcoma (CAS). The patient was treated with extended surgical excision and radiation therapy. No recurrence or metastasis was found throughout 2 years of follow-up.  

Radical resection with a negative margin is considered the first-line treatment of choice. Although there is a paucity of studies assessing the specific width of surgical margins, application of no less than a 3-cm peripheral margin as well as a clear deep margin is recommended.⁵ Adjuvant radiation therapy also is essential to prevent local recurrence. Patients receiving combination therapy have a superior overall survival rate when compared to those undergoing surgery or radiation therapy alone.⁴  

Cutaneous follicle center lymphoma also may present as 1 or more localized erythematous papules, plaques, and/or nodules, commonly arising on the scalp/forehead or trunk of middle-aged men. Despite being a low-grade lymphoma with a favorable prognosis, it may have a relatively fast growth and locally aggressive course if left untreated. The distinguishing histologic feature is a dense proliferation of neoplastic infiltrates in the dermis, which is separated from the epidermis by the grenz zone.⁶ 

The clinical presentation of cutaneous metastatic carcinomas varies greatly, with 1 or multiple localized or widespread lesions commonly involving the abdominal wall, scalp, and face. The lesions also may mimic benign dermatologic conditions, thus potentially resulting in erroneous clinical diagnosis and delayed therapy of the primary malignancy. Obtaining clinical history is crucial; however, a precise diagnosis may require histologic examination.⁷ 

Atypical fibroxanthoma is a rare superficial cutaneous sarcoma that typically occurs on the head and neck in sun-damaged elderly individuals. Clinically, AFX presents as well-circumscribed red or pink nodules or plaques with or without ulceration, crust, or scale.⁸ Atypical fibroxanthoma lesions usually are small, with a median diameter of 1 cm, while those greater than 2 cm reportedly account for less than 5% of cases.⁹ Atypical fibroxanthoma typically grows rapidly with no pain or discomfort. Histologically, AFX is characterized by a well-circumscribed dermal nodule consisting of pleomorphic spindle cells and multinucleated giant cells that can stain positively for CD10 and procollagen 1.¹⁰ 

Cutaneous pseudolymphoma is a benign inflammatory response process that stimulates polyclonal T- or B-cell lymphoproliferation. The clinical presentation may appear as localized or disseminated flesh-colored or red papules, infiltrated plaques, and nodules.¹¹ Histopathology will show mixtures of B and T cells along with dendritic cells and macrophages, but irregular vascular structure and dissecting dermal collagen are not involved. 

We present an unusual case of CAS with multiple pink nodules on the scalp. Early biopsy of these lesions is important to reach a correct diagnosis and to initiate appropriate treatment. 

The Diagnosis: Cutaneous Angiosarcoma 

Biopsy revealed a cellular neoplasm consisting of atypical polygonal cells with a hobnailed appearance, vasoformative characteristics, and rare extravasated erythrocytes. The tumor had an infiltrative growth pattern as demonstrated by dissecting dermal collagen and a poorly defined border with adjacent normal tissue (Figure 1). Immunohistochemistry revealed that the lesion was positive for CD31 and D2-40 (Figure 2) but negative for cytokeratin, CD10, CD68, human herpesvirus 8, CD34, and Melan A, thus confirming the endothelial origin of the tumor cells and the diagnosis of cutaneous angiosarcoma (CAS). The patient was treated with extended surgical excision and radiation therapy. No recurrence or metastasis was found throughout 2 years of follow-up.  

Radical resection with a negative margin is considered the first-line treatment of choice. Although there is a paucity of studies assessing the specific width of surgical margins, application of no less than a 3-cm peripheral margin as well as a clear deep margin is recommended.⁵ Adjuvant radiation therapy also is essential to prevent local recurrence. Patients receiving combination therapy have a superior overall survival rate when compared to those undergoing surgery or radiation therapy alone.⁴  

Cutaneous follicle center lymphoma also may present as 1 or more localized erythematous papules, plaques, and/or nodules, commonly arising on the scalp/forehead or trunk of middle-aged men. Despite being a low-grade lymphoma with a favorable prognosis, it may have a relatively fast growth and locally aggressive course if left untreated. The distinguishing histologic feature is a dense proliferation of neoplastic infiltrates in the dermis, which is separated from the epidermis by the grenz zone.⁶ 

The clinical presentation of cutaneous metastatic carcinomas varies greatly, with 1 or multiple localized or widespread lesions commonly involving the abdominal wall, scalp, and face. The lesions also may mimic benign dermatologic conditions, thus potentially resulting in erroneous clinical diagnosis and delayed therapy of the primary malignancy. Obtaining clinical history is crucial; however, a precise diagnosis may require histologic examination.⁷ 

Atypical fibroxanthoma is a rare superficial cutaneous sarcoma that typically occurs on the head and neck in sun-damaged elderly individuals. Clinically, AFX presents as well-circumscribed red or pink nodules or plaques with or without ulceration, crust, or scale.⁸ Atypical fibroxanthoma lesions usually are small, with a median diameter of 1 cm, while those greater than 2 cm reportedly account for less than 5% of cases.⁹ Atypical fibroxanthoma typically grows rapidly with no pain or discomfort. Histologically, AFX is characterized by a well-circumscribed dermal nodule consisting of pleomorphic spindle cells and multinucleated giant cells that can stain positively for CD10 and procollagen 1.¹⁰ 

Cutaneous pseudolymphoma is a benign inflammatory response process that stimulates polyclonal T- or B-cell lymphoproliferation. The clinical presentation may appear as localized or disseminated flesh-colored or red papules, infiltrated plaques, and nodules.¹¹ Histopathology will show mixtures of B and T cells along with dendritic cells and macrophages, but irregular vascular structure and dissecting dermal collagen are not involved. 

We present an unusual case of CAS with multiple pink nodules on the scalp. Early biopsy of these lesions is important to reach a correct diagnosis and to initiate appropriate treatment. 

To the Editor:

We read with great interest the article by Chu et al¹ (Cutis. 2021;107:157-159) and commend them for noting the underrepresentation of skin of color (SOC) in the American Academy of Dermatology (AAD) Basic Dermatology Curriculum. The AAD Basic Dermatology Curriculum represents one introductory resource that is ubiquitously utilized by medical students. Herein, we add an analysis of the representation of SOC in the following resources that also comprise the first exposure medical students have to dermatology: Dermatology Clinics Clinical Advisor articles (https://www.clinicaladvisor.com/home/dermatology/dermatology-clinics/), Learn Derm Module (LDM) by VisualDx (https://www.visualdx.com/learnderm/), Lookingbill and Marks’ Principles of Dermatology (6th ed)(LB&M),2 and DermNet NZ (https://dermnetnz.org/). We performed a focused search of the DermNet NZ database for images of the following common dermatologic conditions: acne, rosacea, alopecia, urticaria, arthropod bites, blistering diseases (bullous pemphigoid and pemphigus vulgaris), connective tissue diseases (dermatomyositis and lupus), inflammatory conditions (atopic dermatitis, contact dermatitis, and psoriasis), keloids, benign and malignant neoplasms (nevi, seborrheic keratosis, actinic keratosis, basal and squamous cell carcinomas, and melanoma including acral melanoma), bacterial skin infections (impetigo, erysipelas, cellulitis, staphylococcal scalded skin syndrome, and syphilis), fungal infections (dermatophyte infections), and viral skin infections (herpes, molluscum contagiosum, varicella-zoster virus, and warts). We classified images as light (Fitzpatrick phototypes I–IV) or dark (Fitzpatrick phototypes V or VI). We excluded images without visible background skin (eg, images of oral mucosa, genitalia, nails, palms and soles, dermoscopic images, histopathologic images).

We found the representation of SOC in the resources we selected to be as follows: Dermatology Clinics Clinical Advisor articles (70/367 or 19%); LDM (26/150 or 17%); LB&M (52/374 or 14%); DermNet NZ (11/310 or 4%). Representation of SOC in common dermatologic conditions such as actinic keratosis, alopecia, rosacea, urticaria, and warts was entirely absent across all resources. Other common skin diseases were represented in only one of the resources we analyzed: acne (represented only in LB&M, where only 3/11 images of acne were depicted in SOC); contact dermatitis (represented only in LB&M, where only 1/6 images of contact dermatitis were depicted in SOC); psoriasis (represented only on DermNet NZ, where only 2/25 images of psoriasis were depicted in SOC); seborrheic keratosis (represented only in LB&M, where 1/2 images of seborrheic keratosis were depicted in SOC). Furthermore, none of the resources we analyzed depicted malignancy (basal cell carcinoma, squamous cell carcinoma, and melanoma) in SOC. Although the poor representation of SOC in malignancies can be explained by the predilection of skin cancer for light skin, other dermatologic conditions that are more common in SOC also were poorly represented in these resources in SOC: acral melanoma, not represented in any of the resources we analyzed; subacute cutaneous lupus erythematosus and systemic lupus erythematosus, also not represented in any of the resources we analyzed; keloids, represented only in LB&M.

Although no study has investigated the true prevalence of Fitzpatrick phototypes in the United States, He et al³ demonstrated the prevalence of Fitzpatrick phototypes V and VI to be 25.0% and 18.8%, respectively, in an ethnically diverse study of 3386 participants. Indeed, the representation of SOC in the resources we analyzed falls short of this plausible estimate of SOC in an increasingly diverse US population.

Our work adds to the growing body of literature exposing the deficiencies in SOC representation in dermatology. As Lester et al⁴ noted, such poor representation of SOC is deleterious not just to patients, who may be misdiagnosed, but also more generally to the integrity of the field of dermatology. Moreover, our study, which analyzes introductory resources referenced by the junior medical student, highlights a potential danger of poor SOC representation for trainees—limited exposure to SOC may leave medical students unprepared to recognize lesions in SOC during clerkships and residency. Furthermore, we note an additional concern with minimal SOC representation in online modules such as the AAD and LDM module as well as online databases such as DermNet NZ; images from these resources may be used as training sets for machine learning (ML) software (indeed, DermNet NZ has been used as a training set for ML programs⁵). However, if data sets with poor representation of SOC are used to train ML algorithms, then ML software may be unable to recognize lesions in SOC.⁶ Thus, inadequate representation of SOC in online modules and databases may exacerbate existing inequities in dermatology.

To address the paucity of SOC representation, students can be directed to resources devoted to depicting SOC; however, as discussed eloquently by Chu et al,¹ an attempt to update existing resources also must be made. The senior author in our study (S.J.K.) embraced such an approach, updating the dermatology lectures given to medical students to include more images of SOC. Such a top-down approach may represent a major step in dismantling the systemic biases that pervade dermatology.

A limitation of our analysis was use of the Fitzpatrick scale, which was conceived as a phenotypic scale to assess cutaneous responses to UV irradiation.⁷ Although it is the most commonly used scale to describe race/ethnicity and/or constitute skin color, it is not possible to include all non-White skin types and classify strictly under this umbrella term.

References

1. Chu B, Fathy R, Onyekaba G, et al. Distribution of skin-type diversity in photographs in AAD online educational modules. Cutis. 2021;107:157-159. doi:10.12788/cutis.0196

2. Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Saunders Elsevier; 2018.

3. He SY, McCulloch CE, Boscardin WJ, et al. Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population. J Am Acad Dermatol. 2014;71:731-737. doi:10.1016/j.jaad.2014.05.023

4. Lester JC, Taylor SC, Chren M-M. Under‐representation of skin of colour in dermatology images: not just an educational issue. Br J Dermatol. 2019;180:1521-1522. doi:10.1111/bjd.17608

5. Aggarwal P. Data augmentation in dermatology image recognition using machine learning. Skin Res Technol. 2019;25:815-820. doi:10.1111/srt.12726

6. Adamson AS, Smith A. Machine learning and health care disparities in dermatology. JAMA Dermatol. 2018;154:1247-1248. doi:10.1001/jamadermatol.2018.2348

7. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

Authors’ Response

We thank Mr. Joshi and Dr. Kim for their reply to our article and their added contribution to the literature on inadequate representation of skin of color (SOC) in dermatology educational materials. In recent years, multiple analyses have reviewed textbooks and popular online resources for SOC representation.¹ These resources encompass all levels of education—from the laypatient to the medical student, and to residency and beyond—demonstrating the significant challenges to overcome.

In addition, as Mr. Joshi and Dr. Kim state, the potential for these inadequately representative resources to serve as training data for prediction and classification tools adds further urgency to the broader task at hand, as we do not wish to perpetuate disparities. Several tools already exist, including Derm Assist, a recent Google-produced tool that suggests a list of diagnoses from patient-provided images.² Although Derm Assist has been marked as a CE Class I (low risk) medical device in the European Union, the original research it is built on relied on training data with low representation of darker skin types (2.7% Fitzpatrick V and 0% Fitzpatrick VI),³ drawing concern for its generalizability.

These concerns about SOC representation are not new; dermatology advocates, scholars, and organizations such as the Skin of Color Society have been working to address these deficiencies for many years, contributing to education (including writing of resources and textbooks) and academic research. This work continues today. For instance, Lester et al⁴ described best practices for clinical photography in SOC; this guidance was not yet published at the time of our original submission. Not only should dermatology strive for increased quantity of representation but also quality. This metric is particularly important if the images are intended not just for education but also for use as training data for prediction and classification tools.

Examples of more recent actions at the organizational level include the American Academy of Dermatology (AAD) announcing a 3-year plan to promote diversity, equity, and inclusion⁵ and VisualDx establishing #ProjectIMPACT, a collaboration to reduce health care biases in SOC.⁶ In the AAD 3-year plan, one goal is to “[i]ncrease use of images reflecting full spectrum of skin types and highlight topics on skin of color, health disparities, and cultural competency across all AAD education.”⁵ Although not specifically mentioned, we hope that the AAD has included updating the Basic Dermatology Curriculum, given its inadequate SOC representation, as part of its short-term goals. The greater recognition of these issues through more prevalent analyses published in leading dermatology journals is encouraging, and we hope both that improvements can be successfully implemented and that future studies will reveal improvements in representation.

Brian Chu, BS; Ramie Fathy, AB; Ginikanwa Onyekaba, BS; Jules B. Lipoff, MD

From the Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Lipoff is from the Department of Dermatology and the Leonard Davis Institute of Health Economics.

The authors report no conflict of interest.

Correspondence: Jules B. Lipoff, MD, Department of Dermatology, University of Pennsylvania, Penn Medicine University City, 3737 Market St, Ste 1100, Philadelphia, PA 19104 ([email protected]).

References

1. Perlman KL, Williams NM, Egbeto IA, et al. Skin of color lacks representation in medical student resources: a cross-sectional study. Int J Womens Dermatol. 2021;7:195-196. doi:10.1016/j.ijwd.2020.12.018

2. Bui P, Liu Y. Using AI to help find answers to common skin conditions. Published May 18, 2021. Accessed June 12, 2021. https://blog.google/technology/health/ai-dermatology-preview-io-2021

3. Liu Y, Jain A, Eng C, et al. A deep learning system for differential diagnosis of skin diseases. Nature Medicine. 2020;26:900-908. doi:10.1038/s41591-020-0842-3

4. Lester JC, Clark L, Linos E, et al. Clinical photography in skin of colour: tips and best practices. Br J Dermatol. 2021;184:1177-1179. doi:10.1111/bjd.19811

5. American Academy of Dermatology Association. Diversity in dermatology: diversity committee approved plan 2021-2023. Published January 26, 2021. Accessed June 24, 2021. https://assets.ctfassets.net/1ny4yoiyrqia/xQgnCE6ji5skUlcZQHS2b/65f0a9072811e11afcc33d043e02cd4d/DEI_Plan.pdf

6. VisualDx. #ProjectIMPACT. Accessed June 24, 2021. https://www.visualdx.com/projectimpact/

To the Editor:

We read with great interest the article by Chu et al¹ (Cutis. 2021;107:157-159) and commend them for noting the underrepresentation of skin of color (SOC) in the American Academy of Dermatology (AAD) Basic Dermatology Curriculum. The AAD Basic Dermatology Curriculum represents one introductory resource that is ubiquitously utilized by medical students. Herein, we add an analysis of the representation of SOC in the following resources that also comprise the first exposure medical students have to dermatology: Dermatology Clinics Clinical Advisor articles (https://www.clinicaladvisor.com/home/dermatology/dermatology-clinics/), Learn Derm Module (LDM) by VisualDx (https://www.visualdx.com/learnderm/), Lookingbill and Marks’ Principles of Dermatology (6th ed)(LB&M),2 and DermNet NZ (https://dermnetnz.org/). We performed a focused search of the DermNet NZ database for images of the following common dermatologic conditions: acne, rosacea, alopecia, urticaria, arthropod bites, blistering diseases (bullous pemphigoid and pemphigus vulgaris), connective tissue diseases (dermatomyositis and lupus), inflammatory conditions (atopic dermatitis, contact dermatitis, and psoriasis), keloids, benign and malignant neoplasms (nevi, seborrheic keratosis, actinic keratosis, basal and squamous cell carcinomas, and melanoma including acral melanoma), bacterial skin infections (impetigo, erysipelas, cellulitis, staphylococcal scalded skin syndrome, and syphilis), fungal infections (dermatophyte infections), and viral skin infections (herpes, molluscum contagiosum, varicella-zoster virus, and warts). We classified images as light (Fitzpatrick phototypes I–IV) or dark (Fitzpatrick phototypes V or VI). We excluded images without visible background skin (eg, images of oral mucosa, genitalia, nails, palms and soles, dermoscopic images, histopathologic images).

We found the representation of SOC in the resources we selected to be as follows: Dermatology Clinics Clinical Advisor articles (70/367 or 19%); LDM (26/150 or 17%); LB&M (52/374 or 14%); DermNet NZ (11/310 or 4%). Representation of SOC in common dermatologic conditions such as actinic keratosis, alopecia, rosacea, urticaria, and warts was entirely absent across all resources. Other common skin diseases were represented in only one of the resources we analyzed: acne (represented only in LB&M, where only 3/11 images of acne were depicted in SOC); contact dermatitis (represented only in LB&M, where only 1/6 images of contact dermatitis were depicted in SOC); psoriasis (represented only on DermNet NZ, where only 2/25 images of psoriasis were depicted in SOC); seborrheic keratosis (represented only in LB&M, where 1/2 images of seborrheic keratosis were depicted in SOC). Furthermore, none of the resources we analyzed depicted malignancy (basal cell carcinoma, squamous cell carcinoma, and melanoma) in SOC. Although the poor representation of SOC in malignancies can be explained by the predilection of skin cancer for light skin, other dermatologic conditions that are more common in SOC also were poorly represented in these resources in SOC: acral melanoma, not represented in any of the resources we analyzed; subacute cutaneous lupus erythematosus and systemic lupus erythematosus, also not represented in any of the resources we analyzed; keloids, represented only in LB&M.

Although no study has investigated the true prevalence of Fitzpatrick phototypes in the United States, He et al³ demonstrated the prevalence of Fitzpatrick phototypes V and VI to be 25.0% and 18.8%, respectively, in an ethnically diverse study of 3386 participants. Indeed, the representation of SOC in the resources we analyzed falls short of this plausible estimate of SOC in an increasingly diverse US population.

Our work adds to the growing body of literature exposing the deficiencies in SOC representation in dermatology. As Lester et al⁴ noted, such poor representation of SOC is deleterious not just to patients, who may be misdiagnosed, but also more generally to the integrity of the field of dermatology. Moreover, our study, which analyzes introductory resources referenced by the junior medical student, highlights a potential danger of poor SOC representation for trainees—limited exposure to SOC may leave medical students unprepared to recognize lesions in SOC during clerkships and residency. Furthermore, we note an additional concern with minimal SOC representation in online modules such as the AAD and LDM module as well as online databases such as DermNet NZ; images from these resources may be used as training sets for machine learning (ML) software (indeed, DermNet NZ has been used as a training set for ML programs⁵). However, if data sets with poor representation of SOC are used to train ML algorithms, then ML software may be unable to recognize lesions in SOC.⁶ Thus, inadequate representation of SOC in online modules and databases may exacerbate existing inequities in dermatology.

To address the paucity of SOC representation, students can be directed to resources devoted to depicting SOC; however, as discussed eloquently by Chu et al,¹ an attempt to update existing resources also must be made. The senior author in our study (S.J.K.) embraced such an approach, updating the dermatology lectures given to medical students to include more images of SOC. Such a top-down approach may represent a major step in dismantling the systemic biases that pervade dermatology.

A limitation of our analysis was use of the Fitzpatrick scale, which was conceived as a phenotypic scale to assess cutaneous responses to UV irradiation.⁷ Although it is the most commonly used scale to describe race/ethnicity and/or constitute skin color, it is not possible to include all non-White skin types and classify strictly under this umbrella term.

References

1. Chu B, Fathy R, Onyekaba G, et al. Distribution of skin-type diversity in photographs in AAD online educational modules. Cutis. 2021;107:157-159. doi:10.12788/cutis.0196

2. Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Saunders Elsevier; 2018.

3. He SY, McCulloch CE, Boscardin WJ, et al. Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population. J Am Acad Dermatol. 2014;71:731-737. doi:10.1016/j.jaad.2014.05.023

4. Lester JC, Taylor SC, Chren M-M. Under‐representation of skin of colour in dermatology images: not just an educational issue. Br J Dermatol. 2019;180:1521-1522. doi:10.1111/bjd.17608

5. Aggarwal P. Data augmentation in dermatology image recognition using machine learning. Skin Res Technol. 2019;25:815-820. doi:10.1111/srt.12726

6. Adamson AS, Smith A. Machine learning and health care disparities in dermatology. JAMA Dermatol. 2018;154:1247-1248. doi:10.1001/jamadermatol.2018.2348

7. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

Authors’ Response

We thank Mr. Joshi and Dr. Kim for their reply to our article and their added contribution to the literature on inadequate representation of skin of color (SOC) in dermatology educational materials. In recent years, multiple analyses have reviewed textbooks and popular online resources for SOC representation.¹ These resources encompass all levels of education—from the laypatient to the medical student, and to residency and beyond—demonstrating the significant challenges to overcome.

In addition, as Mr. Joshi and Dr. Kim state, the potential for these inadequately representative resources to serve as training data for prediction and classification tools adds further urgency to the broader task at hand, as we do not wish to perpetuate disparities. Several tools already exist, including Derm Assist, a recent Google-produced tool that suggests a list of diagnoses from patient-provided images.² Although Derm Assist has been marked as a CE Class I (low risk) medical device in the European Union, the original research it is built on relied on training data with low representation of darker skin types (2.7% Fitzpatrick V and 0% Fitzpatrick VI),³ drawing concern for its generalizability.

These concerns about SOC representation are not new; dermatology advocates, scholars, and organizations such as the Skin of Color Society have been working to address these deficiencies for many years, contributing to education (including writing of resources and textbooks) and academic research. This work continues today. For instance, Lester et al⁴ described best practices for clinical photography in SOC; this guidance was not yet published at the time of our original submission. Not only should dermatology strive for increased quantity of representation but also quality. This metric is particularly important if the images are intended not just for education but also for use as training data for prediction and classification tools.

Examples of more recent actions at the organizational level include the American Academy of Dermatology (AAD) announcing a 3-year plan to promote diversity, equity, and inclusion⁵ and VisualDx establishing #ProjectIMPACT, a collaboration to reduce health care biases in SOC.⁶ In the AAD 3-year plan, one goal is to “[i]ncrease use of images reflecting full spectrum of skin types and highlight topics on skin of color, health disparities, and cultural competency across all AAD education.”⁵ Although not specifically mentioned, we hope that the AAD has included updating the Basic Dermatology Curriculum, given its inadequate SOC representation, as part of its short-term goals. The greater recognition of these issues through more prevalent analyses published in leading dermatology journals is encouraging, and we hope both that improvements can be successfully implemented and that future studies will reveal improvements in representation.

Brian Chu, BS; Ramie Fathy, AB; Ginikanwa Onyekaba, BS; Jules B. Lipoff, MD

From the Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Lipoff is from the Department of Dermatology and the Leonard Davis Institute of Health Economics.

The authors report no conflict of interest.

Correspondence: Jules B. Lipoff, MD, Department of Dermatology, University of Pennsylvania, Penn Medicine University City, 3737 Market St, Ste 1100, Philadelphia, PA 19104 ([email protected]).

References

1. Perlman KL, Williams NM, Egbeto IA, et al. Skin of color lacks representation in medical student resources: a cross-sectional study. Int J Womens Dermatol. 2021;7:195-196. doi:10.1016/j.ijwd.2020.12.018

2. Bui P, Liu Y. Using AI to help find answers to common skin conditions. Published May 18, 2021. Accessed June 12, 2021. https://blog.google/technology/health/ai-dermatology-preview-io-2021

3. Liu Y, Jain A, Eng C, et al. A deep learning system for differential diagnosis of skin diseases. Nature Medicine. 2020;26:900-908. doi:10.1038/s41591-020-0842-3

4. Lester JC, Clark L, Linos E, et al. Clinical photography in skin of colour: tips and best practices. Br J Dermatol. 2021;184:1177-1179. doi:10.1111/bjd.19811

5. American Academy of Dermatology Association. Diversity in dermatology: diversity committee approved plan 2021-2023. Published January 26, 2021. Accessed June 24, 2021. https://assets.ctfassets.net/1ny4yoiyrqia/xQgnCE6ji5skUlcZQHS2b/65f0a9072811e11afcc33d043e02cd4d/DEI_Plan.pdf

6. VisualDx. #ProjectIMPACT. Accessed June 24, 2021. https://www.visualdx.com/projectimpact/

To the Editor:

We read with great interest the article by Chu et al¹ (Cutis. 2021;107:157-159) and commend them for noting the underrepresentation of skin of color (SOC) in the American Academy of Dermatology (AAD) Basic Dermatology Curriculum. The AAD Basic Dermatology Curriculum represents one introductory resource that is ubiquitously utilized by medical students. Herein, we add an analysis of the representation of SOC in the following resources that also comprise the first exposure medical students have to dermatology: Dermatology Clinics Clinical Advisor articles (https://www.clinicaladvisor.com/home/dermatology/dermatology-clinics/), Learn Derm Module (LDM) by VisualDx (https://www.visualdx.com/learnderm/), Lookingbill and Marks’ Principles of Dermatology (6th ed)(LB&M),2 and DermNet NZ (https://dermnetnz.org/). We performed a focused search of the DermNet NZ database for images of the following common dermatologic conditions: acne, rosacea, alopecia, urticaria, arthropod bites, blistering diseases (bullous pemphigoid and pemphigus vulgaris), connective tissue diseases (dermatomyositis and lupus), inflammatory conditions (atopic dermatitis, contact dermatitis, and psoriasis), keloids, benign and malignant neoplasms (nevi, seborrheic keratosis, actinic keratosis, basal and squamous cell carcinomas, and melanoma including acral melanoma), bacterial skin infections (impetigo, erysipelas, cellulitis, staphylococcal scalded skin syndrome, and syphilis), fungal infections (dermatophyte infections), and viral skin infections (herpes, molluscum contagiosum, varicella-zoster virus, and warts). We classified images as light (Fitzpatrick phototypes I–IV) or dark (Fitzpatrick phototypes V or VI). We excluded images without visible background skin (eg, images of oral mucosa, genitalia, nails, palms and soles, dermoscopic images, histopathologic images).

We found the representation of SOC in the resources we selected to be as follows: Dermatology Clinics Clinical Advisor articles (70/367 or 19%); LDM (26/150 or 17%); LB&M (52/374 or 14%); DermNet NZ (11/310 or 4%). Representation of SOC in common dermatologic conditions such as actinic keratosis, alopecia, rosacea, urticaria, and warts was entirely absent across all resources. Other common skin diseases were represented in only one of the resources we analyzed: acne (represented only in LB&M, where only 3/11 images of acne were depicted in SOC); contact dermatitis (represented only in LB&M, where only 1/6 images of contact dermatitis were depicted in SOC); psoriasis (represented only on DermNet NZ, where only 2/25 images of psoriasis were depicted in SOC); seborrheic keratosis (represented only in LB&M, where 1/2 images of seborrheic keratosis were depicted in SOC). Furthermore, none of the resources we analyzed depicted malignancy (basal cell carcinoma, squamous cell carcinoma, and melanoma) in SOC. Although the poor representation of SOC in malignancies can be explained by the predilection of skin cancer for light skin, other dermatologic conditions that are more common in SOC also were poorly represented in these resources in SOC: acral melanoma, not represented in any of the resources we analyzed; subacute cutaneous lupus erythematosus and systemic lupus erythematosus, also not represented in any of the resources we analyzed; keloids, represented only in LB&M.

Although no study has investigated the true prevalence of Fitzpatrick phototypes in the United States, He et al³ demonstrated the prevalence of Fitzpatrick phototypes V and VI to be 25.0% and 18.8%, respectively, in an ethnically diverse study of 3386 participants. Indeed, the representation of SOC in the resources we analyzed falls short of this plausible estimate of SOC in an increasingly diverse US population.

Our work adds to the growing body of literature exposing the deficiencies in SOC representation in dermatology. As Lester et al⁴ noted, such poor representation of SOC is deleterious not just to patients, who may be misdiagnosed, but also more generally to the integrity of the field of dermatology. Moreover, our study, which analyzes introductory resources referenced by the junior medical student, highlights a potential danger of poor SOC representation for trainees—limited exposure to SOC may leave medical students unprepared to recognize lesions in SOC during clerkships and residency. Furthermore, we note an additional concern with minimal SOC representation in online modules such as the AAD and LDM module as well as online databases such as DermNet NZ; images from these resources may be used as training sets for machine learning (ML) software (indeed, DermNet NZ has been used as a training set for ML programs⁵). However, if data sets with poor representation of SOC are used to train ML algorithms, then ML software may be unable to recognize lesions in SOC.⁶ Thus, inadequate representation of SOC in online modules and databases may exacerbate existing inequities in dermatology.

To address the paucity of SOC representation, students can be directed to resources devoted to depicting SOC; however, as discussed eloquently by Chu et al,¹ an attempt to update existing resources also must be made. The senior author in our study (S.J.K.) embraced such an approach, updating the dermatology lectures given to medical students to include more images of SOC. Such a top-down approach may represent a major step in dismantling the systemic biases that pervade dermatology.

A limitation of our analysis was use of the Fitzpatrick scale, which was conceived as a phenotypic scale to assess cutaneous responses to UV irradiation.⁷ Although it is the most commonly used scale to describe race/ethnicity and/or constitute skin color, it is not possible to include all non-White skin types and classify strictly under this umbrella term.

References

1. Chu B, Fathy R, Onyekaba G, et al. Distribution of skin-type diversity in photographs in AAD online educational modules. Cutis. 2021;107:157-159. doi:10.12788/cutis.0196

2. Marks JG Jr, Miller JJ. Lookingbill and Marks’ Principles of Dermatology. 6th ed. Saunders Elsevier; 2018.

3. He SY, McCulloch CE, Boscardin WJ, et al. Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population. J Am Acad Dermatol. 2014;71:731-737. doi:10.1016/j.jaad.2014.05.023

4. Lester JC, Taylor SC, Chren M-M. Under‐representation of skin of colour in dermatology images: not just an educational issue. Br J Dermatol. 2019;180:1521-1522. doi:10.1111/bjd.17608

5. Aggarwal P. Data augmentation in dermatology image recognition using machine learning. Skin Res Technol. 2019;25:815-820. doi:10.1111/srt.12726

6. Adamson AS, Smith A. Machine learning and health care disparities in dermatology. JAMA Dermatol. 2018;154:1247-1248. doi:10.1001/jamadermatol.2018.2348

7. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

Authors’ Response

We thank Mr. Joshi and Dr. Kim for their reply to our article and their added contribution to the literature on inadequate representation of skin of color (SOC) in dermatology educational materials. In recent years, multiple analyses have reviewed textbooks and popular online resources for SOC representation.¹ These resources encompass all levels of education—from the laypatient to the medical student, and to residency and beyond—demonstrating the significant challenges to overcome.

In addition, as Mr. Joshi and Dr. Kim state, the potential for these inadequately representative resources to serve as training data for prediction and classification tools adds further urgency to the broader task at hand, as we do not wish to perpetuate disparities. Several tools already exist, including Derm Assist, a recent Google-produced tool that suggests a list of diagnoses from patient-provided images.² Although Derm Assist has been marked as a CE Class I (low risk) medical device in the European Union, the original research it is built on relied on training data with low representation of darker skin types (2.7% Fitzpatrick V and 0% Fitzpatrick VI),³ drawing concern for its generalizability.

These concerns about SOC representation are not new; dermatology advocates, scholars, and organizations such as the Skin of Color Society have been working to address these deficiencies for many years, contributing to education (including writing of resources and textbooks) and academic research. This work continues today. For instance, Lester et al⁴ described best practices for clinical photography in SOC; this guidance was not yet published at the time of our original submission. Not only should dermatology strive for increased quantity of representation but also quality. This metric is particularly important if the images are intended not just for education but also for use as training data for prediction and classification tools.

Examples of more recent actions at the organizational level include the American Academy of Dermatology (AAD) announcing a 3-year plan to promote diversity, equity, and inclusion⁵ and VisualDx establishing #ProjectIMPACT, a collaboration to reduce health care biases in SOC.⁶ In the AAD 3-year plan, one goal is to “[i]ncrease use of images reflecting full spectrum of skin types and highlight topics on skin of color, health disparities, and cultural competency across all AAD education.”⁵ Although not specifically mentioned, we hope that the AAD has included updating the Basic Dermatology Curriculum, given its inadequate SOC representation, as part of its short-term goals. The greater recognition of these issues through more prevalent analyses published in leading dermatology journals is encouraging, and we hope both that improvements can be successfully implemented and that future studies will reveal improvements in representation.

Brian Chu, BS; Ramie Fathy, AB; Ginikanwa Onyekaba, BS; Jules B. Lipoff, MD

From the Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Lipoff is from the Department of Dermatology and the Leonard Davis Institute of Health Economics.

The authors report no conflict of interest.

Correspondence: Jules B. Lipoff, MD, Department of Dermatology, University of Pennsylvania, Penn Medicine University City, 3737 Market St, Ste 1100, Philadelphia, PA 19104 ([email protected]).

References

1. Perlman KL, Williams NM, Egbeto IA, et al. Skin of color lacks representation in medical student resources: a cross-sectional study. Int J Womens Dermatol. 2021;7:195-196. doi:10.1016/j.ijwd.2020.12.018

2. Bui P, Liu Y. Using AI to help find answers to common skin conditions. Published May 18, 2021. Accessed June 12, 2021. https://blog.google/technology/health/ai-dermatology-preview-io-2021

3. Liu Y, Jain A, Eng C, et al. A deep learning system for differential diagnosis of skin diseases. Nature Medicine. 2020;26:900-908. doi:10.1038/s41591-020-0842-3

4. Lester JC, Clark L, Linos E, et al. Clinical photography in skin of colour: tips and best practices. Br J Dermatol. 2021;184:1177-1179. doi:10.1111/bjd.19811

5. American Academy of Dermatology Association. Diversity in dermatology: diversity committee approved plan 2021-2023. Published January 26, 2021. Accessed June 24, 2021. https://assets.ctfassets.net/1ny4yoiyrqia/xQgnCE6ji5skUlcZQHS2b/65f0a9072811e11afcc33d043e02cd4d/DEI_Plan.pdf

6. VisualDx. #ProjectIMPACT. Accessed June 24, 2021. https://www.visualdx.com/projectimpact/

Rosacea fulminans (RF) is a rare facial dermatosis characterized by its fulminating course. ¹ It presents with superficial and deep-seated papules, pustules, and nodules combined with an intense reddish or cyanotic erythema localized to the face. Furthermore, there is an absence of comedones and involvement of the chest or back. ² Rosacea fulminans primarily affects women and often is, but not always, proceeded by seborrhea, chronic acne vulgaris, or rosacea. Although the etiology of RF remains unknown, immunologic, hormonal, and vascular factors have been implicated. ³ We report a case of RF in a pregnant patient with a history of mild acne as a teenager that was long ago resolved.

Case Report

A 32-year-old pregnant woman (10 weeks’ gestation) presented with a rapidly progressing inflammatory disorder of the face of 1 month’s duration. The lesions developed 3 weeks after beginning progesterone therapy (200 mg vaginal suppository) for infertility due to polycystic ovary syndrome. Despite discontinuing progesterone for the last month, the patient’s lesions had dramatically worsened (Figure 1). Empiric cephalosporin treatment prescribed by her primary care physician yielded no improvement. Physical examination at the current presentation revealed erythematous nodules and pustules all over the face, coalescing into large thick plaques on the patient’s right cheek and chin. Submental nodes were palpable and tender. Based on the initial clinical findings, acne conglobata secondary to progesterone therapy was considered. The patient was given intralesional triamcinolone (2.5 mg/cc) injections to all larger nodules and several blue light treatments.

The injected areas had improved 5 days after the initial visit; however, the chin and right paranasal cheek developed even more nodules and papules coalescing into large plaques. After consulting the patient’s obstetrician, prednisone (20 mg once daily) was initiated. Three weeks later, the patient’s nodular lesions had improved, but there was a showering of more than 100 pustules and increased general erythema of the entire face (Figure 2). Crotamiton cream 10% (every day before noon), ivermectin cream 1% (every night at bedtime), and sodium sulfacetamide cleanser 10% once daily were added to the treatment plan.

The patient delivered a healthy girl (birth weight, 1.985 kg) prematurely at 34 weeks’ gestation. At 2 months postpartum, the patient’s existing lesions continued to spontaneously improve; however, she still had numerous nodules and papules and continued to develop new lesions and form additional scars. Isotretinoin was instituted at 3 months postpartum upon cessation of nursing. Three months later (40 mg/d isotretinoin), the patient was nearly clear. At 8 months postpartum, isotretinoin was discontinued after a course of 150 mg/kg.

Comment

Rosacea fulminans initially was called pyoderma faciale but was later regarded as a severe form of rosacea and was renamed rosacea fulminans.² According to a PubMed search of articles indexed for MEDLINE using the terms pregnancy and rosacea fulminans or pyoderma faciale, we identified 12 publications reporting 20 cases of RF associated with pregnancy (Table). Although there is no substantial evidence regarding the exact mechanism, these cases indicate that pregnancy can be an exacerbating or causative factor in the pathogenesis of RF.

In addition to pregnancy, RF has been associated with inflammatory bowel disease, thyroid and liver disease, erythema nodosum, and severe emotional trauma. However, no organism has been consistently isolated, and no evidence of family history has been reported.¹ Histopathologic findings are dependent on the stage of disease. Massive infiltrates of neutrophils may be observed in early stages. In older lesions, infiltrates take the form of epithelioid cell granulomas.²

Treatment of RF during pregnancy is challenging. Early and aggressive treatment with retinoids, tetracycline antibiotics, antiandrogenic contraceptives, and dapsone is recommended in patients who are not pregnant; these therapies are all contraindicated in pregnancy. Topical steroids can be safely used; however, systemic steroids usually are required to control RF. The use of systemic steroids can only be justified if the risks for intrauterine growth retardation, maternal diabetes mellitus, and hypertension outweigh the benefits of treating this severe disfiguring skin condition.¹⁰ A study by Bakar et al¹³ indicated that azithromycin is an effective and safe alternative in the treatment of RF. It has a superior pharmacokinetic profile compared to other macrolides and does not pose increased risks for congenital malformation or miscarriage. Because of the concomitant use of both azithromycin and prednisone, it is not possible to determine which had the larger role in the patient’s improvement.

Isotretinoin therapy in our patient led to substantial improvement of RF. Time will tell if the response will be durable. Also unknown is the risk for recurrence with subsequent pregnancies, which has not been reported in the literature. Although it is difficult to confidently say that pregnancy was the inciting factor in this patient’s RF, this case certainly provides more evidence for a link between pregnancy and RF.

Rosacea fulminans (RF) is a rare facial dermatosis characterized by its fulminating course. ¹ It presents with superficial and deep-seated papules, pustules, and nodules combined with an intense reddish or cyanotic erythema localized to the face. Furthermore, there is an absence of comedones and involvement of the chest or back. ² Rosacea fulminans primarily affects women and often is, but not always, proceeded by seborrhea, chronic acne vulgaris, or rosacea. Although the etiology of RF remains unknown, immunologic, hormonal, and vascular factors have been implicated. ³ We report a case of RF in a pregnant patient with a history of mild acne as a teenager that was long ago resolved.

Case Report

A 32-year-old pregnant woman (10 weeks’ gestation) presented with a rapidly progressing inflammatory disorder of the face of 1 month’s duration. The lesions developed 3 weeks after beginning progesterone therapy (200 mg vaginal suppository) for infertility due to polycystic ovary syndrome. Despite discontinuing progesterone for the last month, the patient’s lesions had dramatically worsened (Figure 1). Empiric cephalosporin treatment prescribed by her primary care physician yielded no improvement. Physical examination at the current presentation revealed erythematous nodules and pustules all over the face, coalescing into large thick plaques on the patient’s right cheek and chin. Submental nodes were palpable and tender. Based on the initial clinical findings, acne conglobata secondary to progesterone therapy was considered. The patient was given intralesional triamcinolone (2.5 mg/cc) injections to all larger nodules and several blue light treatments.

The injected areas had improved 5 days after the initial visit; however, the chin and right paranasal cheek developed even more nodules and papules coalescing into large plaques. After consulting the patient’s obstetrician, prednisone (20 mg once daily) was initiated. Three weeks later, the patient’s nodular lesions had improved, but there was a showering of more than 100 pustules and increased general erythema of the entire face (Figure 2). Crotamiton cream 10% (every day before noon), ivermectin cream 1% (every night at bedtime), and sodium sulfacetamide cleanser 10% once daily were added to the treatment plan.

The patient delivered a healthy girl (birth weight, 1.985 kg) prematurely at 34 weeks’ gestation. At 2 months postpartum, the patient’s existing lesions continued to spontaneously improve; however, she still had numerous nodules and papules and continued to develop new lesions and form additional scars. Isotretinoin was instituted at 3 months postpartum upon cessation of nursing. Three months later (40 mg/d isotretinoin), the patient was nearly clear. At 8 months postpartum, isotretinoin was discontinued after a course of 150 mg/kg.

Comment

Rosacea fulminans initially was called pyoderma faciale but was later regarded as a severe form of rosacea and was renamed rosacea fulminans.² According to a PubMed search of articles indexed for MEDLINE using the terms pregnancy and rosacea fulminans or pyoderma faciale, we identified 12 publications reporting 20 cases of RF associated with pregnancy (Table). Although there is no substantial evidence regarding the exact mechanism, these cases indicate that pregnancy can be an exacerbating or causative factor in the pathogenesis of RF.

In addition to pregnancy, RF has been associated with inflammatory bowel disease, thyroid and liver disease, erythema nodosum, and severe emotional trauma. However, no organism has been consistently isolated, and no evidence of family history has been reported.¹ Histopathologic findings are dependent on the stage of disease. Massive infiltrates of neutrophils may be observed in early stages. In older lesions, infiltrates take the form of epithelioid cell granulomas.²

Treatment of RF during pregnancy is challenging. Early and aggressive treatment with retinoids, tetracycline antibiotics, antiandrogenic contraceptives, and dapsone is recommended in patients who are not pregnant; these therapies are all contraindicated in pregnancy. Topical steroids can be safely used; however, systemic steroids usually are required to control RF. The use of systemic steroids can only be justified if the risks for intrauterine growth retardation, maternal diabetes mellitus, and hypertension outweigh the benefits of treating this severe disfiguring skin condition.¹⁰ A study by Bakar et al¹³ indicated that azithromycin is an effective and safe alternative in the treatment of RF. It has a superior pharmacokinetic profile compared to other macrolides and does not pose increased risks for congenital malformation or miscarriage. Because of the concomitant use of both azithromycin and prednisone, it is not possible to determine which had the larger role in the patient’s improvement.

Isotretinoin therapy in our patient led to substantial improvement of RF. Time will tell if the response will be durable. Also unknown is the risk for recurrence with subsequent pregnancies, which has not been reported in the literature. Although it is difficult to confidently say that pregnancy was the inciting factor in this patient’s RF, this case certainly provides more evidence for a link between pregnancy and RF.

Rosacea fulminans (RF) is a rare facial dermatosis characterized by its fulminating course. ¹ It presents with superficial and deep-seated papules, pustules, and nodules combined with an intense reddish or cyanotic erythema localized to the face. Furthermore, there is an absence of comedones and involvement of the chest or back. ² Rosacea fulminans primarily affects women and often is, but not always, proceeded by seborrhea, chronic acne vulgaris, or rosacea. Although the etiology of RF remains unknown, immunologic, hormonal, and vascular factors have been implicated. ³ We report a case of RF in a pregnant patient with a history of mild acne as a teenager that was long ago resolved.

Case Report

A 32-year-old pregnant woman (10 weeks’ gestation) presented with a rapidly progressing inflammatory disorder of the face of 1 month’s duration. The lesions developed 3 weeks after beginning progesterone therapy (200 mg vaginal suppository) for infertility due to polycystic ovary syndrome. Despite discontinuing progesterone for the last month, the patient’s lesions had dramatically worsened (Figure 1). Empiric cephalosporin treatment prescribed by her primary care physician yielded no improvement. Physical examination at the current presentation revealed erythematous nodules and pustules all over the face, coalescing into large thick plaques on the patient’s right cheek and chin. Submental nodes were palpable and tender. Based on the initial clinical findings, acne conglobata secondary to progesterone therapy was considered. The patient was given intralesional triamcinolone (2.5 mg/cc) injections to all larger nodules and several blue light treatments.

The injected areas had improved 5 days after the initial visit; however, the chin and right paranasal cheek developed even more nodules and papules coalescing into large plaques. After consulting the patient’s obstetrician, prednisone (20 mg once daily) was initiated. Three weeks later, the patient’s nodular lesions had improved, but there was a showering of more than 100 pustules and increased general erythema of the entire face (Figure 2). Crotamiton cream 10% (every day before noon), ivermectin cream 1% (every night at bedtime), and sodium sulfacetamide cleanser 10% once daily were added to the treatment plan.

The patient delivered a healthy girl (birth weight, 1.985 kg) prematurely at 34 weeks’ gestation. At 2 months postpartum, the patient’s existing lesions continued to spontaneously improve; however, she still had numerous nodules and papules and continued to develop new lesions and form additional scars. Isotretinoin was instituted at 3 months postpartum upon cessation of nursing. Three months later (40 mg/d isotretinoin), the patient was nearly clear. At 8 months postpartum, isotretinoin was discontinued after a course of 150 mg/kg.

Comment

Rosacea fulminans initially was called pyoderma faciale but was later regarded as a severe form of rosacea and was renamed rosacea fulminans.² According to a PubMed search of articles indexed for MEDLINE using the terms pregnancy and rosacea fulminans or pyoderma faciale, we identified 12 publications reporting 20 cases of RF associated with pregnancy (Table). Although there is no substantial evidence regarding the exact mechanism, these cases indicate that pregnancy can be an exacerbating or causative factor in the pathogenesis of RF.

In addition to pregnancy, RF has been associated with inflammatory bowel disease, thyroid and liver disease, erythema nodosum, and severe emotional trauma. However, no organism has been consistently isolated, and no evidence of family history has been reported.¹ Histopathologic findings are dependent on the stage of disease. Massive infiltrates of neutrophils may be observed in early stages. In older lesions, infiltrates take the form of epithelioid cell granulomas.²

Treatment of RF during pregnancy is challenging. Early and aggressive treatment with retinoids, tetracycline antibiotics, antiandrogenic contraceptives, and dapsone is recommended in patients who are not pregnant; these therapies are all contraindicated in pregnancy. Topical steroids can be safely used; however, systemic steroids usually are required to control RF. The use of systemic steroids can only be justified if the risks for intrauterine growth retardation, maternal diabetes mellitus, and hypertension outweigh the benefits of treating this severe disfiguring skin condition.¹⁰ A study by Bakar et al¹³ indicated that azithromycin is an effective and safe alternative in the treatment of RF. It has a superior pharmacokinetic profile compared to other macrolides and does not pose increased risks for congenital malformation or miscarriage. Because of the concomitant use of both azithromycin and prednisone, it is not possible to determine which had the larger role in the patient’s improvement.

Isotretinoin therapy in our patient led to substantial improvement of RF. Time will tell if the response will be durable. Also unknown is the risk for recurrence with subsequent pregnancies, which has not been reported in the literature. Although it is difficult to confidently say that pregnancy was the inciting factor in this patient’s RF, this case certainly provides more evidence for a link between pregnancy and RF.

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

Practice Gap

Perioperative anxiety is common in patients undergoing nail surgery. Patients might worry about seeing blood; about the procedure itself, including nail avulsion; and about associated pain and disfigurement. Nail surgery causes a high level of anxiety that correlates positively with postoperative pain¹ and overall patient dissatisfaction. Furthermore, surgery-related anxiety is a predictor of increased postoperative analgesic use² and delayed recovery.³

Therefore, implementing strategies that reduce perioperative anxiety may help minimize postoperative pain. Squeezing a stress ball, hand-holding, virtual reality, and music are tools that have been studied to reduce anxiety in the context of Mohs micrographic surgery; these strategies have not been studied for nail surgery.

The Technique

Using a sleep mask is a practical solution to reduce patient anxiety during nail surgery. A minority of patients will choose to watch their surgical procedure; most become unnerved observing their nail surgery. Using a sleep mask diverts visual attention from the surgical field without physically interfering with the nail surgeon. Utilizing a sleep mask is cost-effective, with disposable sleep masks available online for less than $0.30 each. Patients can bring their own mask, or a mask can be offered prior to surgery.

If desired, patients are instructed to wear the sleep mask during the entirety of the procedure, starting from anesthetic infiltration until wound closure and dressing application. Any adjustments can be made with the patient’s free hand. The sleep mask can be offered to patients of all ages undergoing nail surgery under local anesthesia, except babies and young children, who require general anesthesia.

Practical Implications

Distraction is an important strategy to reduce anxiety and pain in patients undergoing surgical procedures. In an observational study of 3087 surgical patients, 36% reported that self-distraction was the most helpful strategy for coping with preoperative anxiety.⁴ In a randomized, open-label clinical trial of 72 patients undergoing peripheral venous catheterization, asking the patients simple questions during the procedure was more effective than local anesthesia in reducing the perception of pain.⁵

It is crucial to implement strategies to reduce anxiety in patients undergoing nail surgery. Using a sleep mask impedes direct visualization of the surgical field, thus distracting the patient’s sight and attention from the procedure. Furthermore, this technique is safe and cost-effective.

Controlled clinical trials are necessary to assess the efficacy of this method in reducing nail surgery–related anxiety in comparison to other techniques.

As your patients return to your offices for annual exams and sports physicals before the school year starts, everyone will still be processing the challenges, losses, and grief that have marked end of the COVID experience. There will be questions about the safety of vaccines for younger children, whether foreign travel is now a reasonable option, and about how best to help children – school age and teenagers, vulnerable and secure – get their footing socially and academically in the new school year. But dig a little, and you may hear about the silver linings of this past year: children who enjoyed having more time with their parents, parents who were with their families rather than in a car commuting for hours a day or traveling many days a month, grocery deliveries that eased the parent’s workload, adolescents who were able to pull back from overscheduled days, and opportunities for calm conversations that occurred quite naturally during nightly family dinners. Office visits present a dual opportunity to review – what were the psychological costs of COVID and what were positive personal and family adaptations to COVID they may want to continue as the pandemic ends?

Family dinner: Whether because sports practice was suspended, schooling was virtual, or working was at home, many families returned to eating dinner together during the pandemic year. Nightly dinners are a simple but powerful routine allowing all members of a family to reconnect and recharge together, and they are often the first things to disappear in the face of school, sports, and work demands. Research over the past several decades has demonstrated that regular family dinners are associated with better academic performance and higher self-esteem in children. They are also associated with lower rates of depression, substance abuse, eating disorders, and pregnancy in adolescents. Finally, they are associated with better cardiovascular health and lower rates of obesity in both youth and parents. The response is dose dependent, with more regular dinners leading to better outcomes. The food can be simple, what matters most is that the tone is warm, sharing, and curious, not rigid and controlling. Families can be an essential source of support as they help put events and feelings into context, giving them meaning or a framework based on the parents’ past, values, or perspective and on the family’s cultural history. Everyone benefits as family members cope with small and large setbacks, share values, and celebrate one another’s small and large successes. The return of the family dinner table, as often as is reasonable, is one “consequence” of COVID that families should try to preserve.

Consistent virtual family visits: Many families managed the cancellation of holiday visits or supported elderly relatives by connecting with family virtually. For some families, a weekly Zoom call came to function like a weekly family dinner with cousins and grandparents. Not only do these regular video calls protect elderly relatives from loneliness and isolation, but they also made it very easy for extended families to stay connected. Children cannot have too many caring adults around them, and regular calls mean that aunts, uncles, and grandparents can be an enthusiastic audience for their achievements and can offer perspective and guidance when needed. Staying connected without having to manage hours of travel makes it easy to build and maintain these family connections, creating bonds that will be deeper and stronger. Like family dinner, regular virtual gatherings with extended family are unequivocally beneficial for younger and older children and a valuable legacy of COVID.

Lowering the pressure: Many children struggled to stay engaged with virtual school and deeply missed time with friends or in activities like woodshop, soccer, or theater. But many other children had a chance to slow down from a relentless schedule of school, homework, sports, clubs, music lessons, tutoring, and on and on. For these children, many of whom are intensely ambitious and were not willing to voluntarily give up any activities, the forced slowdown of COVID has offered a new perspective on how they might manage their time. The COVID slowdown shone a light on the value of spending enough time in an activity to really learn it, and then choosing which activities to continue to explore and master, while opening time to explore new activities. There was also more time for “senseless fun,” activities that do not lead to achievement or recognition, but are simply fun, e.g., playing video games, splashing in a pool, or surfing the web. This process is critical to healthy development in early and later adolescence, and for many driven teenagers, it has been replaced by a tightly packed schedule of activities they felt they “should” be doing. If these young people hear from you that not only does the COVID pace feel better, but it can also contribute to better health and more meaningful learning and engagement, they may adopt a more thoughtful and intentional approach to managing their most precious asset – their time. Your discussion about prioritizing healthy exercise, virtual visits with friends, hobbies, or even senseless fun might reset the pressure gauge from high to moderate.

Homework help: Many children (and teenagers) found that their parents became an important source of academic support during the year of virtual school. While few parents welcomed the chance to master calculus, it is powerful for parents to know what their children are facing at school and for children to know that their parents are available to help them when they face a challenge. When parents can bear uncertainty, frustration, and even failure alongside their children, they help their children to cultivate tenacity and resilience, whether or not they can help them with a chemistry problem. Some parents will have special skills like knowing a language, being a good writer, or an academic expertise related to their work. But what matters more is working out how to help, not pressure or argue – how to share knowledge in a pleasurable manner. While it is important for children to have access to teachers and tutors with the knowledge and skills to help them learn specific subjects, the positive presence and involvement of their parents can make a valuable contribution to their psychological and educational development.

New ritual: Over the past 16 months, families found many creative ways to pass time together, from evening walks to reading aloud, listening to music, and even mastering new card games. The family evenings of a century earlier, when family members listened together to radio programs, practiced music, or played board games, seemed to have returned. While everyone could still escape to their own space to be on a screen activity alone, solitary computer time was leavened by collective time. Families may have rediscovered joy in shared recreation, exploration, or diversion. This kind of family time is a reward in itself, but it also deepens a child’s connections to everyone in their family. Such time provides lessons in how to turn boredom into something meaningful and even fun. COVID forced families inward and gave them more time. There were many costs including illness, deaths of friends and relatives, loss of time with peers, missed activities and milestones, and an impaired education. However, many of the coerced adaptations had a silver lining or unanticipated benefit. Keeping some of those benefits post COVID could enhance the lives of every member of the family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

As your patients return to your offices for annual exams and sports physicals before the school year starts, everyone will still be processing the challenges, losses, and grief that have marked end of the COVID experience. There will be questions about the safety of vaccines for younger children, whether foreign travel is now a reasonable option, and about how best to help children – school age and teenagers, vulnerable and secure – get their footing socially and academically in the new school year. But dig a little, and you may hear about the silver linings of this past year: children who enjoyed having more time with their parents, parents who were with their families rather than in a car commuting for hours a day or traveling many days a month, grocery deliveries that eased the parent’s workload, adolescents who were able to pull back from overscheduled days, and opportunities for calm conversations that occurred quite naturally during nightly family dinners. Office visits present a dual opportunity to review – what were the psychological costs of COVID and what were positive personal and family adaptations to COVID they may want to continue as the pandemic ends?

Family dinner: Whether because sports practice was suspended, schooling was virtual, or working was at home, many families returned to eating dinner together during the pandemic year. Nightly dinners are a simple but powerful routine allowing all members of a family to reconnect and recharge together, and they are often the first things to disappear in the face of school, sports, and work demands. Research over the past several decades has demonstrated that regular family dinners are associated with better academic performance and higher self-esteem in children. They are also associated with lower rates of depression, substance abuse, eating disorders, and pregnancy in adolescents. Finally, they are associated with better cardiovascular health and lower rates of obesity in both youth and parents. The response is dose dependent, with more regular dinners leading to better outcomes. The food can be simple, what matters most is that the tone is warm, sharing, and curious, not rigid and controlling. Families can be an essential source of support as they help put events and feelings into context, giving them meaning or a framework based on the parents’ past, values, or perspective and on the family’s cultural history. Everyone benefits as family members cope with small and large setbacks, share values, and celebrate one another’s small and large successes. The return of the family dinner table, as often as is reasonable, is one “consequence” of COVID that families should try to preserve.

Consistent virtual family visits: Many families managed the cancellation of holiday visits or supported elderly relatives by connecting with family virtually. For some families, a weekly Zoom call came to function like a weekly family dinner with cousins and grandparents. Not only do these regular video calls protect elderly relatives from loneliness and isolation, but they also made it very easy for extended families to stay connected. Children cannot have too many caring adults around them, and regular calls mean that aunts, uncles, and grandparents can be an enthusiastic audience for their achievements and can offer perspective and guidance when needed. Staying connected without having to manage hours of travel makes it easy to build and maintain these family connections, creating bonds that will be deeper and stronger. Like family dinner, regular virtual gatherings with extended family are unequivocally beneficial for younger and older children and a valuable legacy of COVID.

Lowering the pressure: Many children struggled to stay engaged with virtual school and deeply missed time with friends or in activities like woodshop, soccer, or theater. But many other children had a chance to slow down from a relentless schedule of school, homework, sports, clubs, music lessons, tutoring, and on and on. For these children, many of whom are intensely ambitious and were not willing to voluntarily give up any activities, the forced slowdown of COVID has offered a new perspective on how they might manage their time. The COVID slowdown shone a light on the value of spending enough time in an activity to really learn it, and then choosing which activities to continue to explore and master, while opening time to explore new activities. There was also more time for “senseless fun,” activities that do not lead to achievement or recognition, but are simply fun, e.g., playing video games, splashing in a pool, or surfing the web. This process is critical to healthy development in early and later adolescence, and for many driven teenagers, it has been replaced by a tightly packed schedule of activities they felt they “should” be doing. If these young people hear from you that not only does the COVID pace feel better, but it can also contribute to better health and more meaningful learning and engagement, they may adopt a more thoughtful and intentional approach to managing their most precious asset – their time. Your discussion about prioritizing healthy exercise, virtual visits with friends, hobbies, or even senseless fun might reset the pressure gauge from high to moderate.

Homework help: Many children (and teenagers) found that their parents became an important source of academic support during the year of virtual school. While few parents welcomed the chance to master calculus, it is powerful for parents to know what their children are facing at school and for children to know that their parents are available to help them when they face a challenge. When parents can bear uncertainty, frustration, and even failure alongside their children, they help their children to cultivate tenacity and resilience, whether or not they can help them with a chemistry problem. Some parents will have special skills like knowing a language, being a good writer, or an academic expertise related to their work. But what matters more is working out how to help, not pressure or argue – how to share knowledge in a pleasurable manner. While it is important for children to have access to teachers and tutors with the knowledge and skills to help them learn specific subjects, the positive presence and involvement of their parents can make a valuable contribution to their psychological and educational development.

New ritual: Over the past 16 months, families found many creative ways to pass time together, from evening walks to reading aloud, listening to music, and even mastering new card games. The family evenings of a century earlier, when family members listened together to radio programs, practiced music, or played board games, seemed to have returned. While everyone could still escape to their own space to be on a screen activity alone, solitary computer time was leavened by collective time. Families may have rediscovered joy in shared recreation, exploration, or diversion. This kind of family time is a reward in itself, but it also deepens a child’s connections to everyone in their family. Such time provides lessons in how to turn boredom into something meaningful and even fun. COVID forced families inward and gave them more time. There were many costs including illness, deaths of friends and relatives, loss of time with peers, missed activities and milestones, and an impaired education. However, many of the coerced adaptations had a silver lining or unanticipated benefit. Keeping some of those benefits post COVID could enhance the lives of every member of the family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

As your patients return to your offices for annual exams and sports physicals before the school year starts, everyone will still be processing the challenges, losses, and grief that have marked end of the COVID experience. There will be questions about the safety of vaccines for younger children, whether foreign travel is now a reasonable option, and about how best to help children – school age and teenagers, vulnerable and secure – get their footing socially and academically in the new school year. But dig a little, and you may hear about the silver linings of this past year: children who enjoyed having more time with their parents, parents who were with their families rather than in a car commuting for hours a day or traveling many days a month, grocery deliveries that eased the parent’s workload, adolescents who were able to pull back from overscheduled days, and opportunities for calm conversations that occurred quite naturally during nightly family dinners. Office visits present a dual opportunity to review – what were the psychological costs of COVID and what were positive personal and family adaptations to COVID they may want to continue as the pandemic ends?

Family dinner: Whether because sports practice was suspended, schooling was virtual, or working was at home, many families returned to eating dinner together during the pandemic year. Nightly dinners are a simple but powerful routine allowing all members of a family to reconnect and recharge together, and they are often the first things to disappear in the face of school, sports, and work demands. Research over the past several decades has demonstrated that regular family dinners are associated with better academic performance and higher self-esteem in children. They are also associated with lower rates of depression, substance abuse, eating disorders, and pregnancy in adolescents. Finally, they are associated with better cardiovascular health and lower rates of obesity in both youth and parents. The response is dose dependent, with more regular dinners leading to better outcomes. The food can be simple, what matters most is that the tone is warm, sharing, and curious, not rigid and controlling. Families can be an essential source of support as they help put events and feelings into context, giving them meaning or a framework based on the parents’ past, values, or perspective and on the family’s cultural history. Everyone benefits as family members cope with small and large setbacks, share values, and celebrate one another’s small and large successes. The return of the family dinner table, as often as is reasonable, is one “consequence” of COVID that families should try to preserve.

Consistent virtual family visits: Many families managed the cancellation of holiday visits or supported elderly relatives by connecting with family virtually. For some families, a weekly Zoom call came to function like a weekly family dinner with cousins and grandparents. Not only do these regular video calls protect elderly relatives from loneliness and isolation, but they also made it very easy for extended families to stay connected. Children cannot have too many caring adults around them, and regular calls mean that aunts, uncles, and grandparents can be an enthusiastic audience for their achievements and can offer perspective and guidance when needed. Staying connected without having to manage hours of travel makes it easy to build and maintain these family connections, creating bonds that will be deeper and stronger. Like family dinner, regular virtual gatherings with extended family are unequivocally beneficial for younger and older children and a valuable legacy of COVID.

Lowering the pressure: Many children struggled to stay engaged with virtual school and deeply missed time with friends or in activities like woodshop, soccer, or theater. But many other children had a chance to slow down from a relentless schedule of school, homework, sports, clubs, music lessons, tutoring, and on and on. For these children, many of whom are intensely ambitious and were not willing to voluntarily give up any activities, the forced slowdown of COVID has offered a new perspective on how they might manage their time. The COVID slowdown shone a light on the value of spending enough time in an activity to really learn it, and then choosing which activities to continue to explore and master, while opening time to explore new activities. There was also more time for “senseless fun,” activities that do not lead to achievement or recognition, but are simply fun, e.g., playing video games, splashing in a pool, or surfing the web. This process is critical to healthy development in early and later adolescence, and for many driven teenagers, it has been replaced by a tightly packed schedule of activities they felt they “should” be doing. If these young people hear from you that not only does the COVID pace feel better, but it can also contribute to better health and more meaningful learning and engagement, they may adopt a more thoughtful and intentional approach to managing their most precious asset – their time. Your discussion about prioritizing healthy exercise, virtual visits with friends, hobbies, or even senseless fun might reset the pressure gauge from high to moderate.

Homework help: Many children (and teenagers) found that their parents became an important source of academic support during the year of virtual school. While few parents welcomed the chance to master calculus, it is powerful for parents to know what their children are facing at school and for children to know that their parents are available to help them when they face a challenge. When parents can bear uncertainty, frustration, and even failure alongside their children, they help their children to cultivate tenacity and resilience, whether or not they can help them with a chemistry problem. Some parents will have special skills like knowing a language, being a good writer, or an academic expertise related to their work. But what matters more is working out how to help, not pressure or argue – how to share knowledge in a pleasurable manner. While it is important for children to have access to teachers and tutors with the knowledge and skills to help them learn specific subjects, the positive presence and involvement of their parents can make a valuable contribution to their psychological and educational development.

New ritual: Over the past 16 months, families found many creative ways to pass time together, from evening walks to reading aloud, listening to music, and even mastering new card games. The family evenings of a century earlier, when family members listened together to radio programs, practiced music, or played board games, seemed to have returned. While everyone could still escape to their own space to be on a screen activity alone, solitary computer time was leavened by collective time. Families may have rediscovered joy in shared recreation, exploration, or diversion. This kind of family time is a reward in itself, but it also deepens a child’s connections to everyone in their family. Such time provides lessons in how to turn boredom into something meaningful and even fun. COVID forced families inward and gave them more time. There were many costs including illness, deaths of friends and relatives, loss of time with peers, missed activities and milestones, and an impaired education. However, many of the coerced adaptations had a silver lining or unanticipated benefit. Keeping some of those benefits post COVID could enhance the lives of every member of the family.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

A new draft consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes (EASD) addresses diagnosis and management of type 1 diabetes in adults.  

The impetus for the document comes from the “highly influential” EASD-ADA consensus report on the management of type 2 diabetes, which led to the realization that a comparable document was needed for adults with type 1 diabetes, said writing panel cochair Anne L. Peters, MD, professor of clinical medicine at the University of Southern California, Los Angeles.

“In recent years, there have been rapid advances in the treatment of type 1 diabetes together with a growing recognition of the psychosocial burden of living with [it],” Dr. Peters said.

She noted that although there is already some guidance available for the management of type 1 diabetes in adults, “this gets admixed into broader guidelines, and many of those are mostly derived from data in people with type 2 diabetes.”  

The new draft document was coauthored by 14 content experts in type 1 diabetes, with equal numbers from the United States and Europe.
 

We want to be helpful to clinicians

Topics covered include diagnosis of type 1 diabetes, goals of therapy and glycemic targets, schedule of care, diabetes self-management education and additional behavioral considerations, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis, pancreas and islet cell transplantation, adjunctive therapies, special populations (including pregnant women, older adults, and inpatient management), and emergent/future perspectives, including beta-cell replacement and immunotherapy.

At the end of the document are tables of glycemic targets for adults with type 1 diabetes, schedule of care, nonglycemic factors that alter A1c levels, standardized continuous glucose meter (CGM) metrics for clinical care, examples of subcutaneous insulin regimens, and the various properties of approved and nonapproved adjunctive therapies for type 1 diabetes, including metformin, pramlintide, GLP-1 agonists, and SGLT2 inhibitors.  

Several colorful flowcharts are also provided, including algorithms for diagnosing and managing type 1 diabetes in adults.

Document coauthor M. Sue Kirkman, MD, of the Diabetes Care Center’s Clinical Trials Unit at the University of North Carolina, Chapel Hill, told this news organization: “We want it to be helpful to clinicians who are diagnosing type 1 diabetes in adults or caring for adults with type 1 diabetes, whether diagnosed in childhood or adulthood.”

The authors presented an overview of the document in a symposium on June 28 at the virtual ADA scientific sessions. The final version will be presented Oct. 1 at the EASD 2021 annual meeting.

The draft document and video of the ADA meeting presentation are both available on the ADA website.
 

New algorithm to reduce misdiagnosis of type 1 diabetes in adults

Misdiagnosis of adult-onset type 1 diabetes is common, occurring in up to 40% of those who develop the condition after age 30 years, said J. Hans de Vries, MD, PhD, medical director, Profil Institute for Metabolic Research, Neuss, Germany.

There are multiple reasons for this, including the fact that obesity and type 2 diabetes are becoming more prevalent at younger ages, C-peptide levels may still be relatively high at the time of clinical type 1 diabetes onset, and islet autoantibodies don’t have 100% positive predictive value.

“No single feature confirms type 1 diabetes in isolation,” Dr. de Vries noted.

The document provides a detailed diagnostic algorithm specifically for adults in whom type 1 diabetes is suspected, starting with autoantibody measurement. If the diagnosis isn’t confirmed that way, the algorithm advises investigating for monogenic diabetes, including use of a maturity-onset diabetes of the young (MODY) calculator and subsequent C-peptide measurement.

Measurement of C-peptide is also recommended if the diabetes type is still uncertain more than 3 years after diabetes onset in those treated with insulin, because by that point it is likely to be <200 pmol/L in people with type 1 diabetes.  
 

Clear statements on diabetes technology, preferred insulins

The draft document clearly states that physiologic insulin replacement using a pump or multiple daily injections, CGM, and analog rather than human insulin are standards of care for adults with type 1 diabetes. Use of hybrid closed-loop insulin delivery systems is advised when available, as they offer the “greatest benefits.”

However, the document also notes that in cases of cost barriers, subcutaneous regimens of human regular and NPH insulin may be used. It cautions, though, that these may result in higher glucose variability, higher risk of hypoglycemia, and less lifestyle flexibility.

Dr. Kirkman told this news organization: “Using human insulins such as NPH and Regular in type 1 diabetes is definitely not preferred, but sometimes due to people’s inability to afford analogs we have to use them. People need to know how to use them safely.”

As for the do-it-yourself insulin delivery systems, which many with type 1 diabetes now use with open-source software algorithms that reverse-engineer older pumps, the document advises that health care providers shouldn’t actively recommend them as they’re not approved by regulatory authorities, but should also “respect the individual’s right to make informed choices and continue to offer support,” Dr. Kirkman said when presenting the insulin therapy section.
 

Psychosocial aspects of type 1 diabetes ‘underappreciated’

Special emphasis is placed on psychosocial support, which may be overlooked in adults, Dr. Kirkman noted.

“Clinicians probably underappreciate what people with type 1 diabetes go through on a daily basis. A lot of the evidence out there regarding psychosocial issues is in children and families of children with type 1 diabetes, or in adults with type 2 diabetes ... Maximizing quality of life needs to be at the forefront of care, not just focusing on glycemic goals.”

Indeed, between 20% and 40% of people with type 1 diabetes experience diabetes-related emotional distress – including 15% with depression – particularly at the time of diagnosis and when complications develop, noted Frank J. Snoek, PhD, professor of medical psychology at Amsterdam University Medical Center, the Netherlands.

To address this, the draft advises that “self-management difficulties, psychological, and social problems” be screened periodically and monitored using validated screening tools.

“Health care providers should be proficient at asking questions about and discussing emotional health, psychological needs, and social challenges as part of the consultation,” Dr. Snoek said.

Dr. Peters disclosed ties with Abbott Diabetes Care, AstraZeneca, Lilly, Medscape, Novo Nordisk, Vertex, and Zealand, Omada, and Teladoc. Dr. Kirkman has received research support from Novo Nordisk and Bayer. Dr. de Vries disclosed ties with Adocia, Novo Nordisk, Zealand, Eli Lilly, and Afon Technology. Dr. Snoek reported ties with Roche Diabetes, Novo Nordisk, Sanofi, and Eli Lilly.

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

A new draft consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes (EASD) addresses diagnosis and management of type 1 diabetes in adults.  

The impetus for the document comes from the “highly influential” EASD-ADA consensus report on the management of type 2 diabetes, which led to the realization that a comparable document was needed for adults with type 1 diabetes, said writing panel cochair Anne L. Peters, MD, professor of clinical medicine at the University of Southern California, Los Angeles.

“In recent years, there have been rapid advances in the treatment of type 1 diabetes together with a growing recognition of the psychosocial burden of living with [it],” Dr. Peters said.

She noted that although there is already some guidance available for the management of type 1 diabetes in adults, “this gets admixed into broader guidelines, and many of those are mostly derived from data in people with type 2 diabetes.”  

The new draft document was coauthored by 14 content experts in type 1 diabetes, with equal numbers from the United States and Europe.
 

We want to be helpful to clinicians

Topics covered include diagnosis of type 1 diabetes, goals of therapy and glycemic targets, schedule of care, diabetes self-management education and additional behavioral considerations, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis, pancreas and islet cell transplantation, adjunctive therapies, special populations (including pregnant women, older adults, and inpatient management), and emergent/future perspectives, including beta-cell replacement and immunotherapy.

At the end of the document are tables of glycemic targets for adults with type 1 diabetes, schedule of care, nonglycemic factors that alter A1c levels, standardized continuous glucose meter (CGM) metrics for clinical care, examples of subcutaneous insulin regimens, and the various properties of approved and nonapproved adjunctive therapies for type 1 diabetes, including metformin, pramlintide, GLP-1 agonists, and SGLT2 inhibitors.  

Several colorful flowcharts are also provided, including algorithms for diagnosing and managing type 1 diabetes in adults.

Document coauthor M. Sue Kirkman, MD, of the Diabetes Care Center’s Clinical Trials Unit at the University of North Carolina, Chapel Hill, told this news organization: “We want it to be helpful to clinicians who are diagnosing type 1 diabetes in adults or caring for adults with type 1 diabetes, whether diagnosed in childhood or adulthood.”

The authors presented an overview of the document in a symposium on June 28 at the virtual ADA scientific sessions. The final version will be presented Oct. 1 at the EASD 2021 annual meeting.

The draft document and video of the ADA meeting presentation are both available on the ADA website.
 

New algorithm to reduce misdiagnosis of type 1 diabetes in adults

Misdiagnosis of adult-onset type 1 diabetes is common, occurring in up to 40% of those who develop the condition after age 30 years, said J. Hans de Vries, MD, PhD, medical director, Profil Institute for Metabolic Research, Neuss, Germany.

There are multiple reasons for this, including the fact that obesity and type 2 diabetes are becoming more prevalent at younger ages, C-peptide levels may still be relatively high at the time of clinical type 1 diabetes onset, and islet autoantibodies don’t have 100% positive predictive value.

“No single feature confirms type 1 diabetes in isolation,” Dr. de Vries noted.

The document provides a detailed diagnostic algorithm specifically for adults in whom type 1 diabetes is suspected, starting with autoantibody measurement. If the diagnosis isn’t confirmed that way, the algorithm advises investigating for monogenic diabetes, including use of a maturity-onset diabetes of the young (MODY) calculator and subsequent C-peptide measurement.

Measurement of C-peptide is also recommended if the diabetes type is still uncertain more than 3 years after diabetes onset in those treated with insulin, because by that point it is likely to be <200 pmol/L in people with type 1 diabetes.  
 

Clear statements on diabetes technology, preferred insulins

The draft document clearly states that physiologic insulin replacement using a pump or multiple daily injections, CGM, and analog rather than human insulin are standards of care for adults with type 1 diabetes. Use of hybrid closed-loop insulin delivery systems is advised when available, as they offer the “greatest benefits.”

However, the document also notes that in cases of cost barriers, subcutaneous regimens of human regular and NPH insulin may be used. It cautions, though, that these may result in higher glucose variability, higher risk of hypoglycemia, and less lifestyle flexibility.

Dr. Kirkman told this news organization: “Using human insulins such as NPH and Regular in type 1 diabetes is definitely not preferred, but sometimes due to people’s inability to afford analogs we have to use them. People need to know how to use them safely.”

As for the do-it-yourself insulin delivery systems, which many with type 1 diabetes now use with open-source software algorithms that reverse-engineer older pumps, the document advises that health care providers shouldn’t actively recommend them as they’re not approved by regulatory authorities, but should also “respect the individual’s right to make informed choices and continue to offer support,” Dr. Kirkman said when presenting the insulin therapy section.
 

Psychosocial aspects of type 1 diabetes ‘underappreciated’

Special emphasis is placed on psychosocial support, which may be overlooked in adults, Dr. Kirkman noted.

“Clinicians probably underappreciate what people with type 1 diabetes go through on a daily basis. A lot of the evidence out there regarding psychosocial issues is in children and families of children with type 1 diabetes, or in adults with type 2 diabetes ... Maximizing quality of life needs to be at the forefront of care, not just focusing on glycemic goals.”

Indeed, between 20% and 40% of people with type 1 diabetes experience diabetes-related emotional distress – including 15% with depression – particularly at the time of diagnosis and when complications develop, noted Frank J. Snoek, PhD, professor of medical psychology at Amsterdam University Medical Center, the Netherlands.

To address this, the draft advises that “self-management difficulties, psychological, and social problems” be screened periodically and monitored using validated screening tools.

“Health care providers should be proficient at asking questions about and discussing emotional health, psychological needs, and social challenges as part of the consultation,” Dr. Snoek said.

Dr. Peters disclosed ties with Abbott Diabetes Care, AstraZeneca, Lilly, Medscape, Novo Nordisk, Vertex, and Zealand, Omada, and Teladoc. Dr. Kirkman has received research support from Novo Nordisk and Bayer. Dr. de Vries disclosed ties with Adocia, Novo Nordisk, Zealand, Eli Lilly, and Afon Technology. Dr. Snoek reported ties with Roche Diabetes, Novo Nordisk, Sanofi, and Eli Lilly.

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

A new draft consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes (EASD) addresses diagnosis and management of type 1 diabetes in adults.  

The impetus for the document comes from the “highly influential” EASD-ADA consensus report on the management of type 2 diabetes, which led to the realization that a comparable document was needed for adults with type 1 diabetes, said writing panel cochair Anne L. Peters, MD, professor of clinical medicine at the University of Southern California, Los Angeles.

“In recent years, there have been rapid advances in the treatment of type 1 diabetes together with a growing recognition of the psychosocial burden of living with [it],” Dr. Peters said.

She noted that although there is already some guidance available for the management of type 1 diabetes in adults, “this gets admixed into broader guidelines, and many of those are mostly derived from data in people with type 2 diabetes.”  

The new draft document was coauthored by 14 content experts in type 1 diabetes, with equal numbers from the United States and Europe.
 

We want to be helpful to clinicians

Topics covered include diagnosis of type 1 diabetes, goals of therapy and glycemic targets, schedule of care, diabetes self-management education and additional behavioral considerations, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis, pancreas and islet cell transplantation, adjunctive therapies, special populations (including pregnant women, older adults, and inpatient management), and emergent/future perspectives, including beta-cell replacement and immunotherapy.

At the end of the document are tables of glycemic targets for adults with type 1 diabetes, schedule of care, nonglycemic factors that alter A1c levels, standardized continuous glucose meter (CGM) metrics for clinical care, examples of subcutaneous insulin regimens, and the various properties of approved and nonapproved adjunctive therapies for type 1 diabetes, including metformin, pramlintide, GLP-1 agonists, and SGLT2 inhibitors.  

Several colorful flowcharts are also provided, including algorithms for diagnosing and managing type 1 diabetes in adults.

Document coauthor M. Sue Kirkman, MD, of the Diabetes Care Center’s Clinical Trials Unit at the University of North Carolina, Chapel Hill, told this news organization: “We want it to be helpful to clinicians who are diagnosing type 1 diabetes in adults or caring for adults with type 1 diabetes, whether diagnosed in childhood or adulthood.”

The authors presented an overview of the document in a symposium on June 28 at the virtual ADA scientific sessions. The final version will be presented Oct. 1 at the EASD 2021 annual meeting.

The draft document and video of the ADA meeting presentation are both available on the ADA website.
 

New algorithm to reduce misdiagnosis of type 1 diabetes in adults

Misdiagnosis of adult-onset type 1 diabetes is common, occurring in up to 40% of those who develop the condition after age 30 years, said J. Hans de Vries, MD, PhD, medical director, Profil Institute for Metabolic Research, Neuss, Germany.

There are multiple reasons for this, including the fact that obesity and type 2 diabetes are becoming more prevalent at younger ages, C-peptide levels may still be relatively high at the time of clinical type 1 diabetes onset, and islet autoantibodies don’t have 100% positive predictive value.

“No single feature confirms type 1 diabetes in isolation,” Dr. de Vries noted.

The document provides a detailed diagnostic algorithm specifically for adults in whom type 1 diabetes is suspected, starting with autoantibody measurement. If the diagnosis isn’t confirmed that way, the algorithm advises investigating for monogenic diabetes, including use of a maturity-onset diabetes of the young (MODY) calculator and subsequent C-peptide measurement.

Measurement of C-peptide is also recommended if the diabetes type is still uncertain more than 3 years after diabetes onset in those treated with insulin, because by that point it is likely to be <200 pmol/L in people with type 1 diabetes.  
 

Clear statements on diabetes technology, preferred insulins

The draft document clearly states that physiologic insulin replacement using a pump or multiple daily injections, CGM, and analog rather than human insulin are standards of care for adults with type 1 diabetes. Use of hybrid closed-loop insulin delivery systems is advised when available, as they offer the “greatest benefits.”

However, the document also notes that in cases of cost barriers, subcutaneous regimens of human regular and NPH insulin may be used. It cautions, though, that these may result in higher glucose variability, higher risk of hypoglycemia, and less lifestyle flexibility.

Dr. Kirkman told this news organization: “Using human insulins such as NPH and Regular in type 1 diabetes is definitely not preferred, but sometimes due to people’s inability to afford analogs we have to use them. People need to know how to use them safely.”

As for the do-it-yourself insulin delivery systems, which many with type 1 diabetes now use with open-source software algorithms that reverse-engineer older pumps, the document advises that health care providers shouldn’t actively recommend them as they’re not approved by regulatory authorities, but should also “respect the individual’s right to make informed choices and continue to offer support,” Dr. Kirkman said when presenting the insulin therapy section.
 

Psychosocial aspects of type 1 diabetes ‘underappreciated’

Special emphasis is placed on psychosocial support, which may be overlooked in adults, Dr. Kirkman noted.

“Clinicians probably underappreciate what people with type 1 diabetes go through on a daily basis. A lot of the evidence out there regarding psychosocial issues is in children and families of children with type 1 diabetes, or in adults with type 2 diabetes ... Maximizing quality of life needs to be at the forefront of care, not just focusing on glycemic goals.”

Indeed, between 20% and 40% of people with type 1 diabetes experience diabetes-related emotional distress – including 15% with depression – particularly at the time of diagnosis and when complications develop, noted Frank J. Snoek, PhD, professor of medical psychology at Amsterdam University Medical Center, the Netherlands.

To address this, the draft advises that “self-management difficulties, psychological, and social problems” be screened periodically and monitored using validated screening tools.

“Health care providers should be proficient at asking questions about and discussing emotional health, psychological needs, and social challenges as part of the consultation,” Dr. Snoek said.

Dr. Peters disclosed ties with Abbott Diabetes Care, AstraZeneca, Lilly, Medscape, Novo Nordisk, Vertex, and Zealand, Omada, and Teladoc. Dr. Kirkman has received research support from Novo Nordisk and Bayer. Dr. de Vries disclosed ties with Adocia, Novo Nordisk, Zealand, Eli Lilly, and Afon Technology. Dr. Snoek reported ties with Roche Diabetes, Novo Nordisk, Sanofi, and Eli Lilly.

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

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

A network meta-analysis of current first-line dual, triple, and quadruple therapies for Helicobacter pylori infection found that vonoprazan triple therapy was most effective, while standard triple therapy of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin was least effective. Levofloxacin-containing triple therapy performed best in Western countries and West Asia, while reverse hybrid therapy was most effective in East Asia.

The results “[suggest that] a new approach concerning H. pylori treatment is now needed and that the time for transitioning from trial and error to antimicrobial stewardship [of H. pylori infection] has arrived,” wrote Theodore Rokkas, PhD, MD, of the European University of Cyprus in Engomi, and colleagues. Their study was published online April 8 in Gastroenterology.

H. pylori infection is the primary cause of gastritis, peptic ulcer disease, gastric mucosa–associated lymphoid tissue lymphoma, and gastric cancer.

Since H. pylori infection was first recognized, physicians have employed a range of drugs in double, triple, and quadruple combinations to combat it.

Despite those efforts, treatment success is lower than with many other infectious diseases. A newcomer is the potassium-competing acid blocker vonoprazan, which increases efficacy of amoxicillin combination therapies and has, thereby, generated renewed interest in all combination therapies, according to the study authors. Vonoprazan is currently available in some Asian countries, but not the United States or Europe.

Current guidelines for H. pylori treatment relied on randomized controlled trials and relevant pair-wise meta-analyses, but no previous pairwise analysis has included all currently available medications, the authors noted. Network meta-analyses can help fill this evidence gap: They incorporate both direct and indirect evidence from a collection of randomized controlled trials to estimate the comparative effectiveness of three or more regimens.

The researchers conducted a network meta-analysis that included 68 randomized, controlled trials totaling 22,975 patients. The following regimens were included in the analysis: Concomitant quadruple bismuth treatment (bismuth quadruple therapy), concomitant quadruple nonbismuth treatment (nonbismuth quadruple therapy), high-dose amoxicillin double treatment (Amox-dual therapy), levofloxacin-containing treatment (Levo-therapy), reverse hybrid therapy (R-hybrid therapy), sequential quadruple treatment (sequential therapy), standard triple treatment (triple therapy), and vonoprazan-containing therapy (Vono-triple therapy).

Statistically significant results were found with Vono-triple therapy versus triple therapy (odds ratio, 3.80; 95% confidence interval, 1.62-8.94), sequential therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53), nonbismuth quadruple therapy versus triple therapy (OR, 2.08; 95% CI, 1.45-2.98), bismuth quadruple therapy versus triple therapy (OR, 1.47; 95% CI, 1.02-2.11), and Levo-therapy versus triple therapy (OR, 1.79; 95% CI, 1.26-2.53).

In the overall data, mean cure rates greater than 90% were seen only in Vono-triple therapy (91.4%; 95% CI, 88.5-93.5%) and R-hybrid therapy (93.6%; 95% CI, 90.4-96.8%). Cure rates were lower for Nonbismuth quadruple therapy (84.3%; 95% CI, 82.7-85.8%), Levo-therapy (83.8%; 95% CI, 82.1-85.4%), Sequential therapy (83.7%; 95% CI, 82.7-84.7%), bismuth quadruple therapy (81.3%; 95% CI, 79.5-83.1%), Amox-dual therapy (80.2%; 75.3%-84.4%), and triple therapy (75.7%; 95% CI, 74.9-76.4%). Levo-therapy performed best in Western countries (88.5%; 95% CI, 86.5-90.5%) and West Asia (88.4%; 95% CI, 84.6-91.1%). R-hybrid therapy performed best in East Asia (93.6%; 95% CI, 90.4-96.8%).

A surface under the cumulative ranking (SUCRA) value, which represents the efficacy of the intervention compared to an ideal intervention, was 92.4% for Vono-triple therapy. The second highest SUCRA value was for 68.8% for nonbismuth quadruple therapy. The SUCRA value of standard triple therapy was 4.7%.

A key limitation to the study is that Vono-triple therapy was tested only in Japan, and requires additional study in other geographic regions.

The study received support from the Department of Veteran Affairs. The authors have consulted for and received research funding from various pharmaceutical companies.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck, PhD,  of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck, PhD,  of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.

In a small study of Hirschsprung’s disease (HSCR) patients, those with a low-fiber colonic mucosal acetylcholinesterase-positive (AChE+) innervation phenotype were more likely to suffer from postoperative enterocolitis, which can be life-threatening.

The study lends insight into crosstalk between the human enteric nervous and immune systems. It suggests a role for acetylcholine-secreting (cholinergic) nerve fibers in aganglionic sections of colon in patients with HSCR, which is a congenital disorder marked by the absence of enteric neuronal cells in the distal part of the gut.

There are also potential clinical implications. “These observations suggest that HSCR patients with low-fiber phenotype might have a higher risk of developing postoperative enterocolitis and that the fiber phenotype could serve as a predictive marker for development of prophylactic therapy,” wrote Simone Keck, PhD,  of the University of Basel (Switzerland) and colleagues in a study published in Cellular and Molecular Gastroenterology and Hepatology.

HSCR is a multigenetic congenital condition that includes a lack of enteric ganglia cells (aganglionosis) in the distal part of the colon, leading to intestinal obstruction and prestenotic megacolon. Treatment consists of pull-through surgery to remove the aganglionic portion of the bowel, but 20%-50% of patients develop life-threatening HSCR-associated enterocolitis before or after surgery. Although the mechanism of the complication is uncertain, immune cells, intestinal barrier function, and the microbiome may play a role.

Mouse models have shown connections between the immune and nervous system, but it has been challenging to study the effects of specific neurotransmitters in humans. There are more than 30 separate neurotransmitters in the enteric nervous system, making it difficult to tease apart individual functions. But there are comparatively few enteric nervous system neurotransmitters in patients with HSCR and the aganglionic colon in these patients contains enlarged AChE+ nerve fibers, “neuronal cholinergic function can be examined particularly well” among these patients. .

The researchers of the current study from analyzed tissue from 44 pediatric HSCR patients who underwent pull-through surgery, along with 6 non-HSCR controls who had surgery for various other reasons. Tissue samples were semiquantitatively categorized according to the extent of colonic mucosal AChE+ innervation: Low-fiber rectosigmoid tissue lacked intrinsic nerve cell bodies and mucosal ACHe+ innervation, while high-fiber tissue lacked nerve cell bodies but had mucosal AChE+ innervation. The researchers also determined tissue cytokine profile and immune cell frequencies, and used confocal immunofluorescence microscopy to determine proximity of macrophages to nerve fibers and 16S-rDNA sequencing to determine microbial populations.

They found that aganglionic low-fiber samples had higher levels of inflammatory cytokines such as interleukin-17, IL-1-beta, and IL6. Levels of these cytokines were lower in both ganglionic sections of the colon and in high-fiber samples with mucosal AChE+ nerve fibers. Low-fiber samples also had elevated Th17 T cells, compared with high-fiber, aganglionic, and ganglionic distal colon samples. Regulatory T cells were highest in cholinergic high-fiber segments.

Out of 42 patients, 9 developed enterocolitis within 1 year of surgery; 7 had a low-fiber phenotype, while 2 were high-fiber. This difference was not statistically significant, but the researchers then performed a retrospective analysis of 29 HSCR patients to validate the findings. Of these, 14 developed enterocolitis after surgery, with 12 of the cases occurring among children with the low-fiber phenotype, and 2 cases occurred among those with the high-fiber phenotype.

The findings could help guide postsurgical management of HSCR by allowing clinicians to employ preventive measures against enterocolitis, such as high-volume enemas, antibiotics, prebiotics, probiotics, or dietary changes. Th17 cells are known to migrate to nearby mesenteric lymph nodes, where they may promote enterocolitis, and this site is usually not removed during HSCR surgery. Fiber phenotype could prompt a surgeon to also remove mesenteric lymph nodes to reduce enterocolitis risk. A potential therapeutic strategy is to target IL-17 or IL-23.

The study was funded by the University of Basel. The authors have no relevant financial disclosures.