Cutis

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The Diagnosis: Subungual Exostosis

Subungual exostosis should be considered as a possible cause of an exophytic subungual nodule in a young active female. In our patient, the involvement of the great toe was a clue, as the hallux is the most common location of subungual exostosis. The patient’s age and sex also were supportive, as subungual exostosis is most common in female children and adolescents— particularly those who are active, as trauma is thought to play a possible role in development of this benign tumor.^1-3 Radiography is the preferred modality for diagnosis; in our case, it showed a trabecular bony overgrowth (Figure 1), which confirmed the diagnosis. Subungual exostosis is a rare, benign, osteocartilaginous tumor of trabecular bone. The etiology is unknown but is hypothesized to be related to trauma, infection, or activation of a cartilaginous cyst.^1,3 The subungual nodule may be asymptomatic or painful. Disruption and elevation of the nail plate is common.⁴ The differential diagnosis includes amelanotic melanoma, fibroma, fibrokeratoma, osteochondroma, pyogenic granuloma, squamous cell carcinoma, glomus tumor, and verruca vulgaris, among others.⁵

doswicubarasofrocheslosi

Physical examination demonstrates a firm, fixed, subungual nodule, often with an accompanying nail deformity. Further workup is required to confirm the benign nature of the lesion and exclude nail tumors such as melanoma or squamous cell carcinoma. Radiography is the gold standard for diagnosis, demonstrating a trabecular bony overgrowth.⁶ Performing a radiograph as the initial diagnostic test spares the patient from unnecessary procedures such as biopsy or expensive imaging techniques such as magnetic resonance imaging. Early lesions may not demonstrate sufficient bone formation shown on radiography. In these situations, a combination of dermoscopy and histopathologic examination may aid in diagnosis (Figure 2).⁴ Vascular ectasia, hyperkeratosis, onycholysis, and ulceration are the most common findings on dermoscopy (in ascending order).⁷ Histopathology typically demonstrates a base or stalk of normal-appearing trabecular bone with a fibrocartilage cap.⁸ However, initial clinical workup via radiography allows for the least-invasive and highest-yield intervention. Clinical suspicion for this condition is important, as it can be diagnosed with noninvasive inexpensive imaging rather than biopsy or more specialized imaging modalities. Appropriate recognition can save young patients from unnecessary and expensive procedures. Treatment typically involves surgical excision; to prevent regrowth, removal of the lesion at the base of the bone is recommended.²

degecuboviditrusifrokowujimeranujadasuhogufraslufrejatid

Although amelanotic melanoma also can manifest as a subungual nail tumor, it would be unusual in a young child and would not be expected to show characteristic changes on radiography. A glomus tumor would be painful, is more common on the fingers than on the toes, and typically has a bluish hue.⁹ Verruca vulgaris can occur subungually but is more common around the nailfold and often has the characteristic dermoscopic finding of thrombosed capillaries. It also would not be expected to show characteristic radiographic findings. Osteochondroma can occur in young patients and can appear clinically similar to subungual exostosis; however, it typically is painful.¹⁰

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

couagestemaclubacikofraswospetrauadraphibristochicreletocrecrodusispelithimathatethivodoswotivabegevofrushudrocovufrebrovepespiridedrawiwrephuladuphakohelaphukutrokekapre

theveslufrufrilitonosecihefroclufriuipephuwalustovigumespispewutradrophinunujepareprodushecrephohekiclah

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

couagestemaclubacikofraswospetrauadraphibristochicreletocrecrodusispelithimathatethivodoswotivabegevofrushudrocovufrebrovepespiridedrawiwrephuladuphakohelaphukutrokekapre

theveslufrufrilitonosecihefroclufriuipephuwalustovigumespispewutradrophinunujepareprodushecrephohekiclah

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

The filamentous cyanobacterium Lyngbya majuscula causes irritant contact dermatitis in beachgoers, fishers, and divers in tropical and subtropical marine environments worldwide.¹ If fragments of L majuscula lodge in swimmers’ bathing suits, the toxins can become trapped against the skin and cause seaweed dermatitis.² With climate change resulting in warmer oceans and more extreme storms, L majuscula blooms likely will become more frequent and widespread, thereby increasing the risk for human exposure.^3,4 Herein, we describe the irritants that lead to dermatitis, clinical presentation, and prevention and management of seaweed dermatitis.

Identifying Features and Distribution of Plant

Lyngbya majuscula belongs to the family Oscillatoriaceae; these cyanobacteria grow as filaments and exhibit slow oscillating movements. Commonly referred to as blanketweed or mermaid’s hair due to its appearance, L majuscula grows fine hairlike clumps resembling a mass of olive-colored matted hair.¹ Its thin filaments are 10- to 30-cm long and vary in color from red to white to brown.⁵ Microscopically, a rouleauxlike arrangement of discs provides the structure of each filament.⁶

First identified in Hawaii in 1912, L majuscula was not associated with seaweed dermatitis or dermatotoxicity by the medical community until the first outbreak occurred in Oahu in 1958, though fishermen and beachgoers previously had recognized a relationship between this particular seaweed and skin irritation.^5,7 The first reporting included 125 confirmed cases, with many more mild unreported cases suspected.⁶ Now reported in about 100 locations worldwide, seaweed dermatitis outbreaks have occurred in Australia; Okinawa, Japan; Florida; and the Hawaiian and Marshall islands.^1,2

Exposure to Seaweed

Lyngbya majuscula produces more than 70 biologically active compounds that irritate the skin, eyes, and respiratory system.^2,8 It grows in marine and estuarine environments attached to seagrass, sand, and bedrock at depths of up to 30 m. Warm waters and maximal sunlight provide optimal growth conditions for L majuscula; therefore, the greatest risk for exposure occurs in the Northern and Southern hemispheres in the 1- to 2-month period following their summer solstices.⁵ Runoff during heavy rainfall, which is rich in soil extracts such as phosphorous, iron, and organic carbon, stimulates L majuscula growth and contributes to increased algal blooms.⁴

Dermatitis and Irritants

The dermatoxins Lyngbyatoxin A (LA) and debromoaplysiatoxin (DAT) cause the inflammatory and necrotic appearance of seaweed dermatitis.^1,2,5,8 Lyngbyatoxin A is an indole alkaloid that is closely related to telocidin B, a poisonous compound associated with Streptomyces bacteria.⁹ Sampling of L majuscula and extraction of the dermatoxin, along with human and animal studies, confirmed DAT irritates the skin and induces dermatitis.^5,6Stylocheilus longicauda (sea hare) feeds on L majuscula and contains isolates of DAT in its digestive tract.

Samples of L majuscula taken from several Hawaiian Islands where seaweed dermatitis outbreaks have occurred were examined for differences in toxicities via 6-hour patch tests on human skin.⁶ The samples obtained from the windward side of Oahu contained DAT and aplysiatoxin, while those obtained from the leeward side and Kahala Beach primarily contained LA. Although DAT and LA are vastly different in their molecular structures, testing elicited the same biologic response and induced the same level of skin irritation.⁶ Interestingly, not all strands of L majuscula produced LA and DAT and caused seaweed dermatitis; those that did lead to irritation were more red in color than nontoxic blooms.^5,9

Cutaneous Manifestations

Seaweed dermatitis resembles chemical and thermal burns, ranging from a mild skin rash to severe contact dermatitis with itchy, swollen, ulcerated lesions.^1,7 Patients typically develop a burning or itching sensation beneath their bathing suit or wetsuit that progresses to an erythematous papulovesicular eruption 2 to 24 hours after exposure.^2,6 Within a week, vesicles and bullae desquamate, leaving behind tender erosions.^1,2,6,8 Inframammary lesions are common in females and scrotal swelling in males.^1,6 There is no known association between length of time spent in the water and severity of symptoms.⁵

Most reactions to L majuscula occur from exposure in the water; however, particles that become aerosolized during strong winds or storms can cause seaweed dermatitis on the face. Inhalation of L majuscula may lead to mucous membrane ulceration and pulmonary edema.^1,5,6 Noncutaneous manifestations of seaweed dermatitis include headache, fatigue, and swelling of the eyes, nose, and throat (Figures 1 and 2).^1,5

Prevention and Management

To prevent seaweed dermatitis, avoid swimming in ocean water during L majuscula blooms,¹⁰ which frequently occur following the summer solstices in the Northern and Southern hemispheres.⁵ The National Centers for Coastal Ocean Science Harmful Algae Bloom Monitoring System provides real-time access to algae bloom locations.¹¹ Although this monitoring system is not specific to L majuscula, it may be helpful in determining where potential blooms are. Wearing protective clothing such as coveralls may benefit individuals who enter the water during blooms, but it does not guarantee protection.¹⁰

couagestemaclubacikofraswospetrauadraphibristochicreletocrecrodusispelithimathatethivodoswotivabegevofrushudrocovufrebrovepespiridedrawiwrephuladuphakohelaphukutrokekapre

theveslufrufrilitonosecihefroclufriuipephuwalustovigumespispewutradrophinunujepareprodushecrephohekiclah

Currently, there is no treatment for seaweed dermatitis, but symptom management may reduce discomfort and pain. Washing affected skin with soap and water within an hour of exposure may help reduce the severity of seaweed dermatitis, though studies have shown mixed results.^6,7 Application of cool compresses and soothing ointments (eg, calamine) provide symptomatic relief and promote healing.⁷ The dermatitis typically self-resolves within 1 week.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

stogoshogogirosinesiwuthumesoclipretratecriswestaswesweshiclofrocrojobrovuspinospiribrobestiphomotrothithigesalovospadisuwahamithacajireuahehaphojuwumastadruviwekewasus

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

stogoshogogirosinesiwuthumesoclipretratecriswestaswesweshiclofrocrojobrovuspinospiribrobestiphomotrothithigesalovospadisuwahamithacajireuahehaphojuwumastadruviwekewasus

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.

Folliculitis decalvans (FD) is classified as a rare primary neutrophilic cicatricial alopecia occurring predominantly in middle-aged adults. Although the true etiology is still unknown, the pathogenesis behind the inflammatory follicular lesions stems from possible Staphylococcus aureus infection and an impaired host immune system in response to released superantigens. ¹ The clinical severity of this inflammatory scalp disorder can range from mild to severe and debilitating. Multiple treatment regimens have been developed with the goal of maintaining full remission. We provide a summary of tumor necrosis factor (TNF) inhibitors, Janus kinase (JAK) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and monoclonal antibodies being utilized for patients with therapy-recalcitrant FD.

Methods

We conducted a PubMed, Medline, and Google Scholar search for the terms refractory FD, recalcitrant FD, or therapy-resistant FD to identify articles published in English from 1998 to 2022. Articles that reported recalcitrant cases and subsequent therapy with TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies were included. Articles were excluded if recalcitrant cases were not clearly defined. Remission was defined as no recurrence in lesions or pustules or as a reduction in the inflammatory process with stabilization upon continuation or discontinuation of the therapy regimen. Two reviewers (T.F. and K.U.) independently searched for and screened each report.

Results 

Treatment of recalcitrant FD with biologics or small molecule inhibitors was discussed in 9 studies with a combined total of 35 patients.^2-10 The treatment regimens included TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies (Table).

stogoshogogirosinesiwuthumesoclipretratecriswestaswesweshiclofrocrojobrovuspinospiribrobestiphomotrothithigesalovospadisuwahamithacajireuahehaphojuwumastadruviwekewasus

The TNF inhibitors were utilized in 6 reports with a combined total of 29 patients. Treatments included adalimumab or biosimilar adalimumab (27/29 patients), infliximab (1/29 patients), and certolizumab pegol (1/29 patients). Remission was reported in 26 of 29 cases. There were 2 nonresponders to adalimumab and marked improvement with certolizumab pegol without complete resolution. The use of the JAK inhibitor baricitinib in 4 patients resulted in remission. In all 4 patients, baricitinib was used with concurrent treatments, and remission was achieved in an average of 2.25 months. The use of a PDE4 inhibitor, apremilast, was reported in 1 case; remission was achieved in 3 weeks. Secukinumab, a monoclonal antibody that targets IL-17, was utilized in 1 patient. Marked improvement was seen after 2 months, with complete remission in 7 months. 

Comment

Traditional treatment regimens for FD most often include a combination of topical and oral antibiotics; isotretinoin; and oral, topical, or intralesional corticosteroids. In the past, interventions typically were suppressive as opposed to curative; however, recent treatment advancements have shown promise in achieving lasting remission.

Most reports targeting treatment-resistant FD involved the use of TNF inhibitors, including adalimumab, biosimilar adalimumab, infliximab, and certolizumab pegol.  Adalimumab was the most frequently used TNF inhibitor, with 24 of 26 treated patients achieving remission. Adalimumab may have been used the most in the treatment of FD because TNF is pronounced in other neutrophilic dermatoses that have been successfully treated with TNF inhibitors. It has been reported that adalimumab needs to be continued, as stoppage or interruption led to relapse.³

Although there are few reports of the use of JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies for FD, these treatment modalities show promise, as their use led to marked improvement or lasting remission with ongoing treatment. The use of the PDE4 inhibitor apremilast displayed the most rapid improvement of any of the reviewed treatments, with remission achieved in just 3 weeks.⁹ The rapid success of apremilast may be attributed to the inhibitory effect on neutrophils.

Miguel-Gómez et al¹¹ provided a therapeutic protocol for FD based on the severity of disease (N=60). The protocol included rifampicin plus clindamycin for the treatment of severe disease, as 90.5% (19/21) of resistant cases showed clinical response, with remission of 5 months’ duration. Although this may be acceptable for some patients, others may require an alternative approach. Tietze et al¹² showed that rifampicin and clindamycin had the lowest success rate for long-term remission, with 8 of 10 patients relapsing within 2 to 4 months. In addition, the emergence of antimicrobial resistance remains a major concern in the treatment of FD. Upon the review of the most recent reports of successful treatment of ­therapy-resistant FD, biologics and small molecule inhibitors have shown remission extending through a 12-month follow-up period. We suggest considering the addition of biologics and small molecule inhibitors to the treatment protocol for severe or resistant disease.

Limitations—In the articles reviewed, the definition of remission was inconsistent among authors—some characterized it as no recurrence in lesions or pustules and some as a reduction in the inflammatory process. True duration of remission was difficult to assess from case reports, as follow-up periods varied prior to publication. The studies included in this review consisted mainly of small sample sizes owing to the rarity of FD, and consequently, strength of evidence is lacking. Inherent to the nature of systematic reviews, publication bias may have occurred. Lastly, several studies were impacted by difficulty in obtaining optimal treatment due to financial hardship, and regimens were adjusted accordingly.

Conclusion

The relapsing nature of FD leads to frustration and poor quality of life for patients. There is a paucity of data to guide treatment when FD remains recalcitrant to traditional therapy. Therapies such as TNF inhibitors, JAK inhibitors, PDE4 inhibitors, and monoclonal antibodies have shown success in the treatment of this often ­difficult-to-treat disease. Small sample sizes in reports discussing treatment for resistant cases as well as conflicting results make it challenging to draw conclusions about treatment efficacy. Larger studies are needed to understand the long-term outcomes of treatment options. Regardless, disease severity, patient history, patient preferences, and treatment goals can guide the selection of therapeutic options.

Attendees of the 2024 American Academy of Dermatology annual meeting in San Diego, California, were eager to delve into the latest trends and advancements in dermatology and dermatologic surgery. This article provides a few key takeaways for residents from a range of engaging sessions, with an emphasis on procedural dermatology and physician health and well-being.

Practical Applications of Surgical Enhancements

In an informative session dedicated to dermatologic surgeons and their patients, “Simple Tricks and Practical Tips to Optimize the Surgical Experience for You and Your Patients,” attendees learned practical tips for enhancing the surgical experience. The discussion spanned various aspects of surgery, from managing preoperative anxiety with anxiolytics such as midazolam to the strategic use of skin hooks for delicate tissue manipulation. Midazolam is fast acting and its use is tailored to patient factors such as weight, hepatic function, and prior use. An innovative anxiety management algorithm combining “talkesethesia” with other methods such as anodynes and benzodiazepines underscored the importance of a calm patient in successful surgical outcomes. Talkesthesia involves engaging patients in soothing and distracting conversation throughout the procedure. This technique can include discussing nonmedical topics of interest with the patient—such as their hobbies, family, or favorite movies—to divert their attention from the surgical process and reduce anxiety. By creating a friendly and reassuring atmosphere, talkesthesia helps to establish trust between the patient and the medical team, ultimately contributing to a more relaxed and cooperative patient.¹

The utility of skin hooks also was discussed, with an emphasis on their role in ensuring gentle tissue handling. The modified buried vertical mattress technique was discussed for its added benefits in wound approximation and strength. Emphasis was placed on the importance of maintaining a clear surgical field by electrocautery to ensure optimal visibility.

Focusing on the treatment of skin cancer, curettage alone was touted as a viable alternative to electrodesiccation and curettage, especially in reducing postoperative hypopigmentation while maintaining high cure rates. This method was shown to be effective in treating basal cell carcinoma and well-differentiated squamous cell carcinoma.^2,3

Suturing techniques such as pulley, purse-string, and buried sutures offer efficiencies in time, cost, and improved healing in high-tension areas. These methods can contribute to postsurgical aesthetic and functional outcomes. Additionally, Dr. Desiree Ratner shared her tips for painless local anesthesia techniques, emphasizing the importance of patient comfort through methods such as slow injection and buffering of lidocaine. The next time you give a local anesthetic, try this technique to minimize pain: using a 30-gauge needle, hold the syringe with the bevel up, insert only the bevel into the skin (needle tip goes into the papillary dermis), and numb superficially around the periphery using as little volume as possible. Keep pressure slow and steady without moving the needle, then insert the needle only in previously anesthetized areas, numbing deeply only after the entire periphery has been anesthetized.

The session concluded with the recommendation to provide patients with a goody bag containing postoperative supplies. This thoughtful gesture not only enhances patient satisfaction but also addresses the practical aspect of postsurgery care, offering an inexpensive yet impactful way to ensure patients have the necessary supplies for their recovery.

Take-Home Point—This session distilled essential surgical enhancements into practical applications, emphasizing the importance of anxiety management, delicate tissue handling, innovative suturing techniques, and thoughtful patient care postsurgery. The overarching message highlighted the synergy between technical skill and patient-centric approaches in optimizing surgical outcomes, underscoring the significance of attention to detail in every aspect of patient care, from preoperative preparation to postoperative recovery.

Optimizing Safety and Ergonomics in Surgical Practices

Understanding the dynamics of surgical plume is crucial to safety in the operating room. The carcinogenic risk associated with surgical smoke is not trivial: exposure to the plume generated by monopolar electrocautery in a single day can be equivalent to smoking approximately 30 cigarettes, and a surgeon’s lifetime cancer risk from polycyclic aromatic hydrocarbons exposure is alarmingly high.⁴ To mitigate these risks, several strategies were recommended, including using lower-energy settings, choosing indirect or bipolar cautery, and ensuring efficient room ventilation with HEPA (high-efficiency particulate absorbing) filters to turn over air frequently. Additionally, employing the use of smoke evacuators and suction devices with proper filters can reduce particulate matter in the operating room.

The importance of the surgeon’s posture during procedures also was emphasized for ergonomic benefits and to minimize fatigue. Maintaining a neutral stance with the core and glutes engaged, standing on the balls of the feet, and aligning the table height to keep the hands at the lower chest level were recommended; this not only helps in reducing strain but also in maintaining precision during surgical tasks.

The surgeons on the panel also highlighted the novel use of hydrocolloid dressings with tattoo lasers, electrodesiccation and curettage for treating rhinophyma, and purse-string closure for chest defects as evolving practices to enhance outcomes and safety.

The session offered valuable insights into suturing techniques, advocating for the use of deep sutures—­ideally Monocryl (Ethicon US, LLC)—for superficial closures and fast-absorbing gut sutures for patients who are not expected to return for suture removal. Keith LeBlanc Jr, MD, shared one of his favorite tricks for suturing fragile, sun-damaged skin on the forearm in elderly patients: apply adhesive skin closures aligned parallel to the suture line, then suture through them for extra support. This can help ensure a more secure closure.

In situations when no deep sutures are required, such as on the hair-bearing scalp, large bites through the galea using monofilament nonabsorbable sutures for up to 14 days or staples can offer favorable closures and enhanced hemostasis. Tranexamic acid has emerged as a versatile hemostatic agent—available in multiple forms ranging from direct injection to topical applications—and is cost-effective, enhancing its accessibility in various surgical settings.

A high proportion of patients are taken aback by the length of the scar following removal of what they perceive as a small skin cancer. Leslie Storey, MD, cleverly recommended using the back of a glove to mark surgical ­planning, giving the patient a visual guide for anticipating the size of the excision. This is a simple yet effective approach to enhance patient understanding and informed consent. 

Lastly, the notion that “patients remember you if you don’t cause them pain” resonated deeply, underlining the importance of gentle techniques such as pinching the suture rather than pushing the wound edges together and asking assistants to maintain tension without obstructing the field. In the words of Seth Matarasso, MD: “If you pain ‘em, you won’t retain ‘em!”

Take-Home Point—The take-home message from the session was a comprehensive approach to surgical excellence that aligns technical proficiency with a strong emphasis on safety, patient comfort, and operative efficiency. Surgeons were advised to adopt practices that reduce the risks associated with surgical plume, maintain ergonomic discipline, and apply innovative suturing techniques to enhance patient outcomes. Compassionate patient care, innovative use of materials and methods, and a commitment to continual learning and adaptation of new evidence-based practices are paramount for the modern surgeon.

Approaches for Facial Reconstruction

The intricacies of multisubunit facial reconstruction were explored in a session that blended the pursuit of aesthetic harmony with functional restoration, “Simplifying the Complex: Reconstructing Multisubunit Defects.” The session began with an introduction to flap design principles, emphasizing the importance of thorough defect analysis and the strategic design of flaps. A key objective within this framework is the integration of the flap within existing cosmetic subunits to avoid unwanted effects such as unintended eyebrow elevation.

The concept of tissue reservoirs was discussed,focusing on regions such as the glabella as potential sources for skin recruitment. This then transitioned into a nuanced discussion on incision planning, underscoring the significance of aligning incision lines with relaxed skin tension lines to enhance healing and minimize scarring.

The topic of delayed reconstruction also was introduced as a deliberate tactic for high-risk tumor management. This approach allows for an in-depth pathologic examination and provides patients with more time for psychological adjustment, which may be particularly important for those with complex medical histories or those who require staged surgical interventions.

In a thorough examination of flap design techniques, the session highlighted the bilobed transposition flap as a versatile choice for nasal reconstruction, particularly apt for the distal third of the nose due to its design that harnesses skin from nonadjacent areas. Accompanying this was an exploration of Zitelli modifications, which enhance the bilobed flap by reducing issues such as pincushioning through a moderated rotation angle and the strategic incorporation of a Burow triangle.

Finally, the interpolated paranasal flap was discussed. This technique is designed to reduce the risk for cheek asymmetry and is suitable for patients with generous donor sites; however, this method requires diligent evaluation to avoid complications such as external nasal valve collapse.

Take-Home Point—This session highlighted approaches in facial reconstruction, emphasizing the necessity of strategic flap design and meticulous incision planning to maintain aesthetic harmony and functional integrity.

Strategies for Improving Physician Well-Being

Evidence-based recommendations to support physicians’ well-being are crucial as the health care system becomes increasingly demanding. Instead of focusing on aspects of the health care system that frequently are outside of physicians’ control, the session “A Realistic and Evidence-Based Roadmap for Thriving in Life and Career” discussed many practical, self-empowering tools and strategies to lead a happier and healthier life—both personally and professionally.

The speakers cautioned against the concept of an “unlimited ceiling” for achieving a certain goal, where an unlimited amount of time and energy is allowed to be dedicated to a given task over a period of time. They highlighted the potential consequences of this approach, such as stress, dissatisfaction, and ultimately burnout. The speakers explored the concept of well-being as a continuous journey rather than a destination, emphasizing that it is not the opposite of burnout. To promote well-being, the speakers advocated for utilizing concepts rooted in positive psychology to empower the individual rather than longing for a different environment. They hypothesized that changing one’s life can be accomplished by changing one’s mind, independent of the environment.

The roadmap for physician well-being, as presented by clinical psychologist Amy MacDonald, PsyD, commenced with urging the audience to introspect on situations and experiences, categorizing them into “feel good” and “feel bad” buckets. For every feel-good event, Dr. MacDonald proposed 5 mental exercises for optimized well-being: (1) control/increase: evaluate whether one can control or increase the frequency of the event; (2) consider: reflect on why this event feels good and explore other aspects to gain any additional joy from the event; (3) share: recognize that some feel goods are more joyous when shared; (4) value: connect the feel-good experiences with personal core values, as research shows value affirmations can buffer neuroendocrine and psychological stress responses; and (5) savor: deliberately relish each small or notable feel-good moment.

Similarly, after labeling an event as a feel-bad experience, Dr. MacDonald encouraged the audience to go through mental exercises to strengthen their well-being journey; however, before proceeding, she highlighted the importance of arming ourselves with self-compassion. The 5 mental exercises to address feel bads include (1) solve: assess whether we have control over the situation and attempt to make changes if possible; (2) reframe: explore new perspectives and assess assumptions without minimizing the situation; (3) connect: embrace the positive impact of safe human connections on our stress response; (4) reflect: search curiously using a compassionate lens for any existing patterns of reactions; and (5) accept and pivot: allow thoughts and feelings to exist and pivot to values-based engagement without waiting for the environment to change. Consistently seeking and appreciating feel goods while addressing rather than suppressing the feel bads can lead to joyful satisfaction and overall well-being.

Additional pearls for optimizing physician well-being included accurately labeling emotions rather than lumping them into an overarching theme (eg, stressed), avoiding comparisons with others, choosing courage over comfort, celebrating vulnerability, and embracing the ability to say no to prioritize engagements aligned with one’s purpose and values. Additional resources were shared for further reading, including Emotional Agility by Susan David, Daring Greatly and Rising Strong by Brené Brown, and Self-Compassion by Kristin Neff.

Take-Home Point—This lecture highlighted key strategies for physicians to improve their well-being, emphasizing self-empowerment and practical tools over external circumstances. It distinguished between productive and destructive influences on satisfaction, and emphasized decision-making aligned with personal values. The concept of well-being as a journey, not a destination, was central, encouraging positive psychology and self-reflection to enhance fulfillment. By focusing on amplifying feel-good experiences and addressing feel-bad experiences with resilience, the lecture advocated for internal over external change, offering a pathway to a balanced and satisfying professional and personal life for physicians.

Final Thoughts

The recent American Academy of Dermatology meeting offered valuable insights and practical pearls to enhance surgical practices and promote physician well-being, in addition to a wide range of topics beyond what is mentioned in this article. From optimizing surgical techniques to prioritizing patient care and safety, the sessions underscored the importance of continuous learning and adaptation in the ever-evolving field of dermatology. As we reflect on the lessons learned and the camaraderie shared during this gathering, let us carry forward these teachings to improve patient outcomes, foster innovation, and cultivate resilience in our pursuit of excellence. Together, we can continue to push the boundaries of dermatologic care while nurturing our own well-being and that of our colleagues, ensuring a brighter future for both patients and practitioners alike.



Acknowledgments—Sultan H. Qiblawi, MD, MBA; Eva Shelton, MD; and Christy T. Behnam, MD (all from Madison, Wisconsin), shared their insights and key takeaways from American Academy of Dermatology lecturers, which enriched the content of this article.

Attendees of the 2024 American Academy of Dermatology annual meeting in San Diego, California, were eager to delve into the latest trends and advancements in dermatology and dermatologic surgery. This article provides a few key takeaways for residents from a range of engaging sessions, with an emphasis on procedural dermatology and physician health and well-being.

Practical Applications of Surgical Enhancements

In an informative session dedicated to dermatologic surgeons and their patients, “Simple Tricks and Practical Tips to Optimize the Surgical Experience for You and Your Patients,” attendees learned practical tips for enhancing the surgical experience. The discussion spanned various aspects of surgery, from managing preoperative anxiety with anxiolytics such as midazolam to the strategic use of skin hooks for delicate tissue manipulation. Midazolam is fast acting and its use is tailored to patient factors such as weight, hepatic function, and prior use. An innovative anxiety management algorithm combining “talkesethesia” with other methods such as anodynes and benzodiazepines underscored the importance of a calm patient in successful surgical outcomes. Talkesthesia involves engaging patients in soothing and distracting conversation throughout the procedure. This technique can include discussing nonmedical topics of interest with the patient—such as their hobbies, family, or favorite movies—to divert their attention from the surgical process and reduce anxiety. By creating a friendly and reassuring atmosphere, talkesthesia helps to establish trust between the patient and the medical team, ultimately contributing to a more relaxed and cooperative patient.¹

The utility of skin hooks also was discussed, with an emphasis on their role in ensuring gentle tissue handling. The modified buried vertical mattress technique was discussed for its added benefits in wound approximation and strength. Emphasis was placed on the importance of maintaining a clear surgical field by electrocautery to ensure optimal visibility.

Focusing on the treatment of skin cancer, curettage alone was touted as a viable alternative to electrodesiccation and curettage, especially in reducing postoperative hypopigmentation while maintaining high cure rates. This method was shown to be effective in treating basal cell carcinoma and well-differentiated squamous cell carcinoma.^2,3

Suturing techniques such as pulley, purse-string, and buried sutures offer efficiencies in time, cost, and improved healing in high-tension areas. These methods can contribute to postsurgical aesthetic and functional outcomes. Additionally, Dr. Desiree Ratner shared her tips for painless local anesthesia techniques, emphasizing the importance of patient comfort through methods such as slow injection and buffering of lidocaine. The next time you give a local anesthetic, try this technique to minimize pain: using a 30-gauge needle, hold the syringe with the bevel up, insert only the bevel into the skin (needle tip goes into the papillary dermis), and numb superficially around the periphery using as little volume as possible. Keep pressure slow and steady without moving the needle, then insert the needle only in previously anesthetized areas, numbing deeply only after the entire periphery has been anesthetized.

The session concluded with the recommendation to provide patients with a goody bag containing postoperative supplies. This thoughtful gesture not only enhances patient satisfaction but also addresses the practical aspect of postsurgery care, offering an inexpensive yet impactful way to ensure patients have the necessary supplies for their recovery.

Take-Home Point—This session distilled essential surgical enhancements into practical applications, emphasizing the importance of anxiety management, delicate tissue handling, innovative suturing techniques, and thoughtful patient care postsurgery. The overarching message highlighted the synergy between technical skill and patient-centric approaches in optimizing surgical outcomes, underscoring the significance of attention to detail in every aspect of patient care, from preoperative preparation to postoperative recovery.

Optimizing Safety and Ergonomics in Surgical Practices

Understanding the dynamics of surgical plume is crucial to safety in the operating room. The carcinogenic risk associated with surgical smoke is not trivial: exposure to the plume generated by monopolar electrocautery in a single day can be equivalent to smoking approximately 30 cigarettes, and a surgeon’s lifetime cancer risk from polycyclic aromatic hydrocarbons exposure is alarmingly high.⁴ To mitigate these risks, several strategies were recommended, including using lower-energy settings, choosing indirect or bipolar cautery, and ensuring efficient room ventilation with HEPA (high-efficiency particulate absorbing) filters to turn over air frequently. Additionally, employing the use of smoke evacuators and suction devices with proper filters can reduce particulate matter in the operating room.

The importance of the surgeon’s posture during procedures also was emphasized for ergonomic benefits and to minimize fatigue. Maintaining a neutral stance with the core and glutes engaged, standing on the balls of the feet, and aligning the table height to keep the hands at the lower chest level were recommended; this not only helps in reducing strain but also in maintaining precision during surgical tasks.

The surgeons on the panel also highlighted the novel use of hydrocolloid dressings with tattoo lasers, electrodesiccation and curettage for treating rhinophyma, and purse-string closure for chest defects as evolving practices to enhance outcomes and safety.

The session offered valuable insights into suturing techniques, advocating for the use of deep sutures—­ideally Monocryl (Ethicon US, LLC)—for superficial closures and fast-absorbing gut sutures for patients who are not expected to return for suture removal. Keith LeBlanc Jr, MD, shared one of his favorite tricks for suturing fragile, sun-damaged skin on the forearm in elderly patients: apply adhesive skin closures aligned parallel to the suture line, then suture through them for extra support. This can help ensure a more secure closure.

In situations when no deep sutures are required, such as on the hair-bearing scalp, large bites through the galea using monofilament nonabsorbable sutures for up to 14 days or staples can offer favorable closures and enhanced hemostasis. Tranexamic acid has emerged as a versatile hemostatic agent—available in multiple forms ranging from direct injection to topical applications—and is cost-effective, enhancing its accessibility in various surgical settings.

A high proportion of patients are taken aback by the length of the scar following removal of what they perceive as a small skin cancer. Leslie Storey, MD, cleverly recommended using the back of a glove to mark surgical ­planning, giving the patient a visual guide for anticipating the size of the excision. This is a simple yet effective approach to enhance patient understanding and informed consent. 

Lastly, the notion that “patients remember you if you don’t cause them pain” resonated deeply, underlining the importance of gentle techniques such as pinching the suture rather than pushing the wound edges together and asking assistants to maintain tension without obstructing the field. In the words of Seth Matarasso, MD: “If you pain ‘em, you won’t retain ‘em!”

Take-Home Point—The take-home message from the session was a comprehensive approach to surgical excellence that aligns technical proficiency with a strong emphasis on safety, patient comfort, and operative efficiency. Surgeons were advised to adopt practices that reduce the risks associated with surgical plume, maintain ergonomic discipline, and apply innovative suturing techniques to enhance patient outcomes. Compassionate patient care, innovative use of materials and methods, and a commitment to continual learning and adaptation of new evidence-based practices are paramount for the modern surgeon.

Approaches for Facial Reconstruction

The intricacies of multisubunit facial reconstruction were explored in a session that blended the pursuit of aesthetic harmony with functional restoration, “Simplifying the Complex: Reconstructing Multisubunit Defects.” The session began with an introduction to flap design principles, emphasizing the importance of thorough defect analysis and the strategic design of flaps. A key objective within this framework is the integration of the flap within existing cosmetic subunits to avoid unwanted effects such as unintended eyebrow elevation.

The concept of tissue reservoirs was discussed,focusing on regions such as the glabella as potential sources for skin recruitment. This then transitioned into a nuanced discussion on incision planning, underscoring the significance of aligning incision lines with relaxed skin tension lines to enhance healing and minimize scarring.

The topic of delayed reconstruction also was introduced as a deliberate tactic for high-risk tumor management. This approach allows for an in-depth pathologic examination and provides patients with more time for psychological adjustment, which may be particularly important for those with complex medical histories or those who require staged surgical interventions.

In a thorough examination of flap design techniques, the session highlighted the bilobed transposition flap as a versatile choice for nasal reconstruction, particularly apt for the distal third of the nose due to its design that harnesses skin from nonadjacent areas. Accompanying this was an exploration of Zitelli modifications, which enhance the bilobed flap by reducing issues such as pincushioning through a moderated rotation angle and the strategic incorporation of a Burow triangle.

Finally, the interpolated paranasal flap was discussed. This technique is designed to reduce the risk for cheek asymmetry and is suitable for patients with generous donor sites; however, this method requires diligent evaluation to avoid complications such as external nasal valve collapse.

Take-Home Point—This session highlighted approaches in facial reconstruction, emphasizing the necessity of strategic flap design and meticulous incision planning to maintain aesthetic harmony and functional integrity.

Strategies for Improving Physician Well-Being

Evidence-based recommendations to support physicians’ well-being are crucial as the health care system becomes increasingly demanding. Instead of focusing on aspects of the health care system that frequently are outside of physicians’ control, the session “A Realistic and Evidence-Based Roadmap for Thriving in Life and Career” discussed many practical, self-empowering tools and strategies to lead a happier and healthier life—both personally and professionally.

The speakers cautioned against the concept of an “unlimited ceiling” for achieving a certain goal, where an unlimited amount of time and energy is allowed to be dedicated to a given task over a period of time. They highlighted the potential consequences of this approach, such as stress, dissatisfaction, and ultimately burnout. The speakers explored the concept of well-being as a continuous journey rather than a destination, emphasizing that it is not the opposite of burnout. To promote well-being, the speakers advocated for utilizing concepts rooted in positive psychology to empower the individual rather than longing for a different environment. They hypothesized that changing one’s life can be accomplished by changing one’s mind, independent of the environment.

The roadmap for physician well-being, as presented by clinical psychologist Amy MacDonald, PsyD, commenced with urging the audience to introspect on situations and experiences, categorizing them into “feel good” and “feel bad” buckets. For every feel-good event, Dr. MacDonald proposed 5 mental exercises for optimized well-being: (1) control/increase: evaluate whether one can control or increase the frequency of the event; (2) consider: reflect on why this event feels good and explore other aspects to gain any additional joy from the event; (3) share: recognize that some feel goods are more joyous when shared; (4) value: connect the feel-good experiences with personal core values, as research shows value affirmations can buffer neuroendocrine and psychological stress responses; and (5) savor: deliberately relish each small or notable feel-good moment.

Similarly, after labeling an event as a feel-bad experience, Dr. MacDonald encouraged the audience to go through mental exercises to strengthen their well-being journey; however, before proceeding, she highlighted the importance of arming ourselves with self-compassion. The 5 mental exercises to address feel bads include (1) solve: assess whether we have control over the situation and attempt to make changes if possible; (2) reframe: explore new perspectives and assess assumptions without minimizing the situation; (3) connect: embrace the positive impact of safe human connections on our stress response; (4) reflect: search curiously using a compassionate lens for any existing patterns of reactions; and (5) accept and pivot: allow thoughts and feelings to exist and pivot to values-based engagement without waiting for the environment to change. Consistently seeking and appreciating feel goods while addressing rather than suppressing the feel bads can lead to joyful satisfaction and overall well-being.

Additional pearls for optimizing physician well-being included accurately labeling emotions rather than lumping them into an overarching theme (eg, stressed), avoiding comparisons with others, choosing courage over comfort, celebrating vulnerability, and embracing the ability to say no to prioritize engagements aligned with one’s purpose and values. Additional resources were shared for further reading, including Emotional Agility by Susan David, Daring Greatly and Rising Strong by Brené Brown, and Self-Compassion by Kristin Neff.

Take-Home Point—This lecture highlighted key strategies for physicians to improve their well-being, emphasizing self-empowerment and practical tools over external circumstances. It distinguished between productive and destructive influences on satisfaction, and emphasized decision-making aligned with personal values. The concept of well-being as a journey, not a destination, was central, encouraging positive psychology and self-reflection to enhance fulfillment. By focusing on amplifying feel-good experiences and addressing feel-bad experiences with resilience, the lecture advocated for internal over external change, offering a pathway to a balanced and satisfying professional and personal life for physicians.

Final Thoughts

The recent American Academy of Dermatology meeting offered valuable insights and practical pearls to enhance surgical practices and promote physician well-being, in addition to a wide range of topics beyond what is mentioned in this article. From optimizing surgical techniques to prioritizing patient care and safety, the sessions underscored the importance of continuous learning and adaptation in the ever-evolving field of dermatology. As we reflect on the lessons learned and the camaraderie shared during this gathering, let us carry forward these teachings to improve patient outcomes, foster innovation, and cultivate resilience in our pursuit of excellence. Together, we can continue to push the boundaries of dermatologic care while nurturing our own well-being and that of our colleagues, ensuring a brighter future for both patients and practitioners alike.



Acknowledgments—Sultan H. Qiblawi, MD, MBA; Eva Shelton, MD; and Christy T. Behnam, MD (all from Madison, Wisconsin), shared their insights and key takeaways from American Academy of Dermatology lecturers, which enriched the content of this article.

Attendees of the 2024 American Academy of Dermatology annual meeting in San Diego, California, were eager to delve into the latest trends and advancements in dermatology and dermatologic surgery. This article provides a few key takeaways for residents from a range of engaging sessions, with an emphasis on procedural dermatology and physician health and well-being.

Practical Applications of Surgical Enhancements

In an informative session dedicated to dermatologic surgeons and their patients, “Simple Tricks and Practical Tips to Optimize the Surgical Experience for You and Your Patients,” attendees learned practical tips for enhancing the surgical experience. The discussion spanned various aspects of surgery, from managing preoperative anxiety with anxiolytics such as midazolam to the strategic use of skin hooks for delicate tissue manipulation. Midazolam is fast acting and its use is tailored to patient factors such as weight, hepatic function, and prior use. An innovative anxiety management algorithm combining “talkesethesia” with other methods such as anodynes and benzodiazepines underscored the importance of a calm patient in successful surgical outcomes. Talkesthesia involves engaging patients in soothing and distracting conversation throughout the procedure. This technique can include discussing nonmedical topics of interest with the patient—such as their hobbies, family, or favorite movies—to divert their attention from the surgical process and reduce anxiety. By creating a friendly and reassuring atmosphere, talkesthesia helps to establish trust between the patient and the medical team, ultimately contributing to a more relaxed and cooperative patient.¹

The utility of skin hooks also was discussed, with an emphasis on their role in ensuring gentle tissue handling. The modified buried vertical mattress technique was discussed for its added benefits in wound approximation and strength. Emphasis was placed on the importance of maintaining a clear surgical field by electrocautery to ensure optimal visibility.

Focusing on the treatment of skin cancer, curettage alone was touted as a viable alternative to electrodesiccation and curettage, especially in reducing postoperative hypopigmentation while maintaining high cure rates. This method was shown to be effective in treating basal cell carcinoma and well-differentiated squamous cell carcinoma.^2,3

Suturing techniques such as pulley, purse-string, and buried sutures offer efficiencies in time, cost, and improved healing in high-tension areas. These methods can contribute to postsurgical aesthetic and functional outcomes. Additionally, Dr. Desiree Ratner shared her tips for painless local anesthesia techniques, emphasizing the importance of patient comfort through methods such as slow injection and buffering of lidocaine. The next time you give a local anesthetic, try this technique to minimize pain: using a 30-gauge needle, hold the syringe with the bevel up, insert only the bevel into the skin (needle tip goes into the papillary dermis), and numb superficially around the periphery using as little volume as possible. Keep pressure slow and steady without moving the needle, then insert the needle only in previously anesthetized areas, numbing deeply only after the entire periphery has been anesthetized.

The session concluded with the recommendation to provide patients with a goody bag containing postoperative supplies. This thoughtful gesture not only enhances patient satisfaction but also addresses the practical aspect of postsurgery care, offering an inexpensive yet impactful way to ensure patients have the necessary supplies for their recovery.

Take-Home Point—This session distilled essential surgical enhancements into practical applications, emphasizing the importance of anxiety management, delicate tissue handling, innovative suturing techniques, and thoughtful patient care postsurgery. The overarching message highlighted the synergy between technical skill and patient-centric approaches in optimizing surgical outcomes, underscoring the significance of attention to detail in every aspect of patient care, from preoperative preparation to postoperative recovery.

Optimizing Safety and Ergonomics in Surgical Practices

Understanding the dynamics of surgical plume is crucial to safety in the operating room. The carcinogenic risk associated with surgical smoke is not trivial: exposure to the plume generated by monopolar electrocautery in a single day can be equivalent to smoking approximately 30 cigarettes, and a surgeon’s lifetime cancer risk from polycyclic aromatic hydrocarbons exposure is alarmingly high.⁴ To mitigate these risks, several strategies were recommended, including using lower-energy settings, choosing indirect or bipolar cautery, and ensuring efficient room ventilation with HEPA (high-efficiency particulate absorbing) filters to turn over air frequently. Additionally, employing the use of smoke evacuators and suction devices with proper filters can reduce particulate matter in the operating room.

The importance of the surgeon’s posture during procedures also was emphasized for ergonomic benefits and to minimize fatigue. Maintaining a neutral stance with the core and glutes engaged, standing on the balls of the feet, and aligning the table height to keep the hands at the lower chest level were recommended; this not only helps in reducing strain but also in maintaining precision during surgical tasks.

The surgeons on the panel also highlighted the novel use of hydrocolloid dressings with tattoo lasers, electrodesiccation and curettage for treating rhinophyma, and purse-string closure for chest defects as evolving practices to enhance outcomes and safety.

The session offered valuable insights into suturing techniques, advocating for the use of deep sutures—­ideally Monocryl (Ethicon US, LLC)—for superficial closures and fast-absorbing gut sutures for patients who are not expected to return for suture removal. Keith LeBlanc Jr, MD, shared one of his favorite tricks for suturing fragile, sun-damaged skin on the forearm in elderly patients: apply adhesive skin closures aligned parallel to the suture line, then suture through them for extra support. This can help ensure a more secure closure.

In situations when no deep sutures are required, such as on the hair-bearing scalp, large bites through the galea using monofilament nonabsorbable sutures for up to 14 days or staples can offer favorable closures and enhanced hemostasis. Tranexamic acid has emerged as a versatile hemostatic agent—available in multiple forms ranging from direct injection to topical applications—and is cost-effective, enhancing its accessibility in various surgical settings.

A high proportion of patients are taken aback by the length of the scar following removal of what they perceive as a small skin cancer. Leslie Storey, MD, cleverly recommended using the back of a glove to mark surgical ­planning, giving the patient a visual guide for anticipating the size of the excision. This is a simple yet effective approach to enhance patient understanding and informed consent. 

Lastly, the notion that “patients remember you if you don’t cause them pain” resonated deeply, underlining the importance of gentle techniques such as pinching the suture rather than pushing the wound edges together and asking assistants to maintain tension without obstructing the field. In the words of Seth Matarasso, MD: “If you pain ‘em, you won’t retain ‘em!”

Take-Home Point—The take-home message from the session was a comprehensive approach to surgical excellence that aligns technical proficiency with a strong emphasis on safety, patient comfort, and operative efficiency. Surgeons were advised to adopt practices that reduce the risks associated with surgical plume, maintain ergonomic discipline, and apply innovative suturing techniques to enhance patient outcomes. Compassionate patient care, innovative use of materials and methods, and a commitment to continual learning and adaptation of new evidence-based practices are paramount for the modern surgeon.

Approaches for Facial Reconstruction

The intricacies of multisubunit facial reconstruction were explored in a session that blended the pursuit of aesthetic harmony with functional restoration, “Simplifying the Complex: Reconstructing Multisubunit Defects.” The session began with an introduction to flap design principles, emphasizing the importance of thorough defect analysis and the strategic design of flaps. A key objective within this framework is the integration of the flap within existing cosmetic subunits to avoid unwanted effects such as unintended eyebrow elevation.

The concept of tissue reservoirs was discussed,focusing on regions such as the glabella as potential sources for skin recruitment. This then transitioned into a nuanced discussion on incision planning, underscoring the significance of aligning incision lines with relaxed skin tension lines to enhance healing and minimize scarring.

The topic of delayed reconstruction also was introduced as a deliberate tactic for high-risk tumor management. This approach allows for an in-depth pathologic examination and provides patients with more time for psychological adjustment, which may be particularly important for those with complex medical histories or those who require staged surgical interventions.

In a thorough examination of flap design techniques, the session highlighted the bilobed transposition flap as a versatile choice for nasal reconstruction, particularly apt for the distal third of the nose due to its design that harnesses skin from nonadjacent areas. Accompanying this was an exploration of Zitelli modifications, which enhance the bilobed flap by reducing issues such as pincushioning through a moderated rotation angle and the strategic incorporation of a Burow triangle.

Finally, the interpolated paranasal flap was discussed. This technique is designed to reduce the risk for cheek asymmetry and is suitable for patients with generous donor sites; however, this method requires diligent evaluation to avoid complications such as external nasal valve collapse.

Take-Home Point—This session highlighted approaches in facial reconstruction, emphasizing the necessity of strategic flap design and meticulous incision planning to maintain aesthetic harmony and functional integrity.

Strategies for Improving Physician Well-Being

Evidence-based recommendations to support physicians’ well-being are crucial as the health care system becomes increasingly demanding. Instead of focusing on aspects of the health care system that frequently are outside of physicians’ control, the session “A Realistic and Evidence-Based Roadmap for Thriving in Life and Career” discussed many practical, self-empowering tools and strategies to lead a happier and healthier life—both personally and professionally.

The speakers cautioned against the concept of an “unlimited ceiling” for achieving a certain goal, where an unlimited amount of time and energy is allowed to be dedicated to a given task over a period of time. They highlighted the potential consequences of this approach, such as stress, dissatisfaction, and ultimately burnout. The speakers explored the concept of well-being as a continuous journey rather than a destination, emphasizing that it is not the opposite of burnout. To promote well-being, the speakers advocated for utilizing concepts rooted in positive psychology to empower the individual rather than longing for a different environment. They hypothesized that changing one’s life can be accomplished by changing one’s mind, independent of the environment.

The roadmap for physician well-being, as presented by clinical psychologist Amy MacDonald, PsyD, commenced with urging the audience to introspect on situations and experiences, categorizing them into “feel good” and “feel bad” buckets. For every feel-good event, Dr. MacDonald proposed 5 mental exercises for optimized well-being: (1) control/increase: evaluate whether one can control or increase the frequency of the event; (2) consider: reflect on why this event feels good and explore other aspects to gain any additional joy from the event; (3) share: recognize that some feel goods are more joyous when shared; (4) value: connect the feel-good experiences with personal core values, as research shows value affirmations can buffer neuroendocrine and psychological stress responses; and (5) savor: deliberately relish each small or notable feel-good moment.

Similarly, after labeling an event as a feel-bad experience, Dr. MacDonald encouraged the audience to go through mental exercises to strengthen their well-being journey; however, before proceeding, she highlighted the importance of arming ourselves with self-compassion. The 5 mental exercises to address feel bads include (1) solve: assess whether we have control over the situation and attempt to make changes if possible; (2) reframe: explore new perspectives and assess assumptions without minimizing the situation; (3) connect: embrace the positive impact of safe human connections on our stress response; (4) reflect: search curiously using a compassionate lens for any existing patterns of reactions; and (5) accept and pivot: allow thoughts and feelings to exist and pivot to values-based engagement without waiting for the environment to change. Consistently seeking and appreciating feel goods while addressing rather than suppressing the feel bads can lead to joyful satisfaction and overall well-being.

Additional pearls for optimizing physician well-being included accurately labeling emotions rather than lumping them into an overarching theme (eg, stressed), avoiding comparisons with others, choosing courage over comfort, celebrating vulnerability, and embracing the ability to say no to prioritize engagements aligned with one’s purpose and values. Additional resources were shared for further reading, including Emotional Agility by Susan David, Daring Greatly and Rising Strong by Brené Brown, and Self-Compassion by Kristin Neff.

Take-Home Point—This lecture highlighted key strategies for physicians to improve their well-being, emphasizing self-empowerment and practical tools over external circumstances. It distinguished between productive and destructive influences on satisfaction, and emphasized decision-making aligned with personal values. The concept of well-being as a journey, not a destination, was central, encouraging positive psychology and self-reflection to enhance fulfillment. By focusing on amplifying feel-good experiences and addressing feel-bad experiences with resilience, the lecture advocated for internal over external change, offering a pathway to a balanced and satisfying professional and personal life for physicians.

Final Thoughts

The recent American Academy of Dermatology meeting offered valuable insights and practical pearls to enhance surgical practices and promote physician well-being, in addition to a wide range of topics beyond what is mentioned in this article. From optimizing surgical techniques to prioritizing patient care and safety, the sessions underscored the importance of continuous learning and adaptation in the ever-evolving field of dermatology. As we reflect on the lessons learned and the camaraderie shared during this gathering, let us carry forward these teachings to improve patient outcomes, foster innovation, and cultivate resilience in our pursuit of excellence. Together, we can continue to push the boundaries of dermatologic care while nurturing our own well-being and that of our colleagues, ensuring a brighter future for both patients and practitioners alike.



Acknowledgments—Sultan H. Qiblawi, MD, MBA; Eva Shelton, MD; and Christy T. Behnam, MD (all from Madison, Wisconsin), shared their insights and key takeaways from American Academy of Dermatology lecturers, which enriched the content of this article.

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

The Diagnosis: BASCULE Syndrome

The patient had previously been thought to have livedo reticularis by primary care. Repeat antinuclear antibody (ANA) testing was positive (1:1280 homogeneous [reflexive titers all negative]). However, upon dermatologic evaluation, the manifestation of the rash in addition to onset occurring with postural changes challenged the livedo reticularis diagnosis. Extensive research and consultation with dermatologic colleagues led to the diagnosis of the rare entity BASCULE syndrome. BASCULE (Bier anemic spots, cyanosis, and urticarialike eruption) syndrome was described by Bessis et al¹ in 2016. It is a rare condition but may be underreported.² It is a benign pediatric disorder in the vascular acrosyndrome family that is characterized by underlying vasomotor dysfunction in distal regions of the body. Raynaud phenomenon is a widely known member of this family. As seen in our patient, it typically presents on the distal legs and feet with numerous irregular hypopigmented macules on a cyanotic background. Red-orange papules may appear on the hypopigmented macules and often are pruritic. Lesions on the distal upper extremities are less common, and a case involving the trunk has been reported.³ Onset generally begins within a couple of minutes of standing or mechanical compression of the lower legs, with full reversal of symptoms occurring within minutes of laying down or walking. Commonly reported associated symptoms include tenderness, pruritus, edema, and pain; however, the cutaneous lesions may be asymptomatic. The condition tends to affect adolescents, as seen in our patient; however, there have been reports in infants as young as 3 months to adults aged 19 years.²

The pathophysiology behind BASCULE syndrome remains unclear but is believed to be centered around the role of physiologic venous stasis that occurs when standing. The hypoxia secondary to stasis is thought to induce amplified vasoconstriction of arterioles. These responses are further exaggerated due to absence of venoarteriolar reflexes in dermal ascending arterioles, leading to Bier spots.² The role of mast cells and eosinophils remains unclear. It is a clinical diagnosis without clear histologic findings; therefore, biopsy was not pursued in our patient.

Although BASCULE syndrome is a benign entity, it is imperative that it be recognized to avoid a time consuming, expensive, and anxiety-producing diagnostic workup, as occurred in our patient. Although not a manifestation of systemic disease, BASCULE syndrome may be associated with orthostatic hypotension in up to 20% of cases.^2,4 Therefore, these patients should undergo orthostatic testing, including the tilt table test. In our patient, these manifestations were not appreciated.

There are no current guidelines for effective treatment of BASCULE syndrome. Given the possible role of mast cells in the condition, H1 antihistamines are proposed as first-line treatment. Desloratadine (10 mg/d for 7 days) has been found to be associated with improvement of pruritus. However, a recent literature review found little evidence to support the use of H1 antihistamines for resolution of other symptoms.²

The differential diagnosis includes livedo reticularis, Bier spots, Sneddon syndrome, and urticarial vasculitis. Livedo reticularis presents as distinct, netlike, blue-erythematousviolaceous discoloration, which differs from the distinct orange-red macules in BASCULE syndrome.⁵ In addition to distinct variances in dermatologic presentation, livedo reticularis typically is associated with cold exposure as a causative agent, with cold avoidance as the treatment for this benign and often transient condition.⁶ This phenomenon was not appreciated in our patient. Livedo reticularis commonly occurs with antiphospholipid syndrome.⁵ This association in combination with our patient's positive ANA findings and her mother's history of miscarriages resulted in the misdiagnosis as livedo reticularis.

Bier spots manifest as white macules with surrounding erythema and typically present in young adults. When first described in the literature, it was debated if BASCULE syndrome was simply another manifestation of Bier spots or postural orthostatic intolerance,⁴ as there was a large consensus that postural orthostatic intolerance was associated with BASCULE syndrome, with the majority of patients not meeting criteria for the condition. Heymann⁴ addressed the differences in BASCULE manifestations vs typical Bier spots. The author extended the syndrome to include cyanosis, an urticarialike eruption of red-orange macules with central papules located centrally, pruritus, tenderness, and partial or diffuse edema, in addition to Bier spots.⁴

Sneddon syndrome is a rare progressive disorder that affects small- to medium-sized blood vessels resulting in multiple episodes of ischemia in the brain. Skin manifestations of these repeated strokes are similar to livedo reticularis, typically manifesting as livedo racemosa—irregular reticular patterns of skin mottling with reddish-blue hues.⁶ However, Sneddon syndrome is more generalized and widespread and differs from BASCULE syndrome in shape and histologic findings. Our patient presented with findings on the legs, which is more characteristic of livedo reticularis vs livedo racemosa. Our patient experienced resolution upon laying down and sitting, and Sneddon syndrome persists beyond postural changes. Furthermore, patients with Sneddon syndrome present with neurologic symptoms such as prodromal headaches.⁶

Urticarial vasculitis was ruled out in our patient because of the duration of symptoms as well as the spatial changes. Urticarial vasculitis is a rare skin condition characterized by chronic recurring urticarial lesions that may persist for more than a day. This condition typically presents in middle-aged women and rarely in children. Urticarial vasculitis is thought to be immune-complex mediated, but its cause is largely unknown. It is a common manifestation of underlying conditions such as systemic lupus erythematosus.⁶ Our patient had a positive ANA and possible autoimmune history from her mother; however, urticarial vasculitis does not present transiently on the legs or in the rash pattern appreciated in our patient.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

spudrichacrukap

slecospathocunaprubritrilulapriwrecuwonuclukogihadrinarobuwrofrophehisteprethituniclodichadetrimipiprocludeuastethipesteswochestophucricrumasigospiphadreshovucrinu

biclarehiprosticinalifroslestostapretuda

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The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

spudrichacrukap

slecospathocunaprubritrilulapriwrecuwonuclukogihadrinarobuwrofrophehisteprethituniclodichadetrimipiprocludeuastethipesteswochestophucricrumasigospiphadreshovucrinu

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The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

To the Editor:

Langerhans cell histiocytosis (LCH) is a rare inflammatory neoplasia caused by accumulation of clonal Langerhans cells in 1 or more organs. The clinical spectrum is diverse, ranging from mild, single-organ involvement that may resolve spontaneously to severe progressive multisystem disease that can be fatal. It is most prevalent in children, affecting an estimated 4 to 5 children for every 1 million annually, with male predominance.¹ The pathogenesis is driven by activating mutations in the mitogen-activated protein kinase pathway, with the BRAF V600E mutation detected in most LCH patients, resulting in proliferation of pathologic Langerhans cells and dysregulated expression of inflammatory cytokines in LCH lesions.² A biopsy of lesional tissue is required for definitive diagnosis. Histopathology reveals a mixed inflammatory infiltrate and characteristic mononuclear cells with reniform nuclei that are positive for CD1a and CD207 proteins on immunohistochemical staining.³

Langerhans cell histiocytosis is categorized by the extent of organ involvement. It commonly affects the bones, skin, pituitary gland, liver, lungs, bone marrow, and lymph nodes.⁴ Single-system LCH involves a single organ with unifocal or multifocal lesions; multisystem LCH involves 2 or more organs and has a worse prognosis if risk organs (eg, liver, spleen, bone marrow) are involved.⁴

Skin lesions are reported in more than half of LCH cases and are the most common initial manifestation in patients younger than 2 years.⁴ Cutaneous findings are highly variable, which poses a diagnostic challenge. Common morphologies include erythematous papules, pustules, papulovesicles, scaly plaques, erosions, and petechiae. Lesions can be solitary or widespread and favor the trunk, head, and face.⁴ We describe an atypical case of hypopigmented cutaneous LCH and review the literature on this morphology in patients with skin of color.

A 7-month-old Hispanic male infant who was otherwise healthy presented with numerous hypopigmented macules and pink papules on the trunk and groin that had progressed since birth. A review of systems was unremarkable. Physical examination revealed 1- to 3-mm, discrete, hypopigmented macules intermixed with 1- to 2-mm pearly pink papules scattered on the back, chest, abdomen, and inguinal folds (Figure 1). Some lesions appeared koebnerized; however, the parents denied a history of scratching or trauma.

Histopathology of a lesion in the inguinal fold showed aggregates of mononuclear cells with reniform nuclei and abundant amphophilic cytoplasm in the papillary dermis, with focal extension into the epidermis. Scattered eosinophils and multinucleated giant cells were present in the dermal inflammatory infiltrate (Figure 2). Immunohistochemical staining was positive for CD1a (Figure 3) and S-100 protein (Figure 4). Although epidermal Langerhans cell collections also can be seen in allergic contact dermatitis,⁵ predominant involvement of the papillary dermis and the presence of multinucleated giant cells are characteristic of LCH.⁴ Given these findings, which were consistent with LCH, the dermatopathology deemed BRAF V600E immunostaining unnecessary for diagnostic purposes.

spudrichacrukap

slecospathocunaprubritrilulapriwrecuwonuclukogihadrinarobuwrofrophehisteprethituniclodichadetrimipiprocludeuastethipesteswochestophucricrumasigospiphadreshovucrinu

biclarehiprosticinalifroslestostapretuda

luludalecupacrimes

thekonaphechaswamuclawiproswochospostibrufrihuwrocloworunufradrakidospefraphiuechehoprithojuslowewrucothiphatrewr

The patient was referred to the hematology and oncology department to undergo thorough evaluation for extracutaneous involvement. The workup included a complete blood cell count, liver function testing, electrolyte assessment, skeletal survey, chest radiography, and ultrasonography of the liver and spleen. All results were negative, suggesting a diagnosis of single-system cutaneous LCH.

Three months later, the patient presented to dermatology with spontaneous regression of all skin lesions. Continued follow-up—every 6 months for 5 years—was recommended to monitor for disease recurrence or progression to multisystem disease.

Cutaneous LCH is a clinically heterogeneous disease with the potential for multisystem involvement and long-term sequelae; therefore, timely diagnosis is paramount to optimize outcomes. However, delayed diagnosis is common because of the spectrum of skin findings that can mimic common pediatric dermatoses, such as seborrheic dermatitis, atopic dermatitis, and diaper dermatitis.⁴ In one study, the median time from onset of skin lesions to diagnostic biopsy was longer than 3 months (maximum, 5 years).⁶ Our patient was referred to dermatology 7 months after onset of hypopigmented macules, a rarely reported cutaneous manifestation of LCH.

A PubMed search of articles indexed for MEDLINE from 1994 to 2019 using the terms Langerhans cell histiocytotis and hypopigmented yielded 17 cases of LCH presenting as hypopigmented skin lesions (Table).^7-22 All cases occurred in patients with skin of color (ie, patients of Asian, Hispanic, or African descent). Hypopigmented macules were the only cutaneous manifestation in 10 (59%) cases. Lesions most commonly were distributed on the trunk (16/17 [94%]) and extremities (8/17 [47%]). The median age of onset was 1 month; 76% (13/17) of patients developed skin lesions before 1 year of age, indicating that this morphology may be more common in newborns. In most patients, the diagnosis was single-system cutaneous LCH; they exhibited spontaneous regression by 8 months of age on average, suggesting that this variant may be associated with a better prognosis. Mori and colleagues²¹ hypothesized that hypopigmented lesions may represent the resolving stage of active LCH based on histopathologic findings of dermal pallor and fibrosis in a hypopigmented LCH lesion. However, systemic involvement was reported in 7 cases of hypopigmented LCH, highlighting the importance of assessing for multisystem disease regardless of cutaneous morphology.²¹Langerhans cell histiocytosis should be considered in the differential diagnosis when evaluating hypopigmented skin eruptions in infants with darker skin types. Prompt diagnosis of this atypical variant requires a higher index of suspicion because of its rarity and the polymorphic nature of cutaneous LCH. This morphology may go undiagnosed in the setting of mild or spontaneously resolving disease; notwithstanding, accurate diagnosis and longitudinal surveillance are necessary given the potential for progressive systemic involvement.

The risk for developing skin cancer can be somewhat attributed to variations in skin pigmentation. Historically, lighter skin pigmentation has been observed in populations living in higher latitudes and darker pigmentation in populations near the equator. Although skin pigmentation is a conglomeration of genetic and environmental factors, anthropologic studies have demonstrated an association of human skin lightening with historic human migratory patterns.¹ It is postulated that migration to latitudes with less UVB light penetration has resulted in a compensatory natural selection of lighter skin types. Furthermore, the driving force behind this migration-associated skin lightening has remained unclear.¹

The need for folate metabolism, vitamin D synthesis, and barrier protection, as well as cultural practices, has been postulated as driving factors for skin pigmentation variation. Synthesis of vitamin D is a UV radiation (UVR)–dependent process and has remained a prominent theoretical driver for the basis of evolutionary skin lightening. Vitamin D can be acquired both exogenously or endogenously via dietary supplementation or sunlight; however, historically it has been obtained through UVB exposure primarily. Once UVB is absorbed by the skin, it catalyzes conversion of 7-dehydrocholesterol to previtamin D₃, which is converted to vitamin D in the kidneys.^2,3 It is suggested that lighter skin tones have an advantage over darker skin tones in synthesizing vitamin D at higher latitudes where there is less UVB, thus leading to the adaptation process.1 In this systematic review, we analyzed the evolutionary vitamin D adaptation hypothesis and assessed the validity of evidence supporting this theory in the literature.

Methods

A search of PubMed, Embase, and the Cochrane Reviews database was conducted using the terms evolution, vitamin D, and skin to generate articles published from 2010 to 2022 that evaluated the influence of UVR-dependent production of vitamin D on skin pigmentation through historical migration patterns (Figure). Studies were excluded during an initial screening of abstracts followed by full-text assessment if they only had abstracts and if articles were inaccessible for review or in the form of case reports and commentaries.

The following data were extracted from each included study: reference citation, affiliated institutions of authors, author specialties, journal name, year of publication, study period, type of article, type of study, mechanism of adaptation, data concluding or supporting vitamin D as the driver, and data concluding or suggesting against vitamin D as the driver. Data concluding or supporting vitamin D as the driver were recorded from statistically significant results, study conclusions, and direct quotations. Data concluding or suggesting against vitamin D as the driver also were recorded from significant results, study conclusions, and direct quotes. The mechanism of adaptation was based on vitamin D synthesis modulation, melanin upregulation, genetic selections, genetic drift, mating patterns, increased vitamin D sensitivity, interbreeding, and diet.

Studies included in the analysis were placed into 1 of 3 categories: supporting, neutral, and against. Strength of Recommendation Taxonomy (SORT) criteria were used to classify the level of evidence of each article.⁴ Each article’s level of evidence was then graded (Table 1). The SORT grading levels were based on quality and evidence type: level 1 signified good-quality, patient-oriented evidence; level 2 signified limited-quality, patient-oriented evidence; and level 3 signified other evidence.⁴

Results

Article Selection—A total of 229 articles were identified for screening, and 39 studies met inclusion criteria.^1-3,5-40 Systematic and retrospective reviews were the most common types of studies. Genomic analysis/sequencing/genome-wide association studies (GWAS) were the most common methods of analysis. Of these 39 articles, 26 were classified as supporting the evolutionary vitamin D adaptation hypothesis, 10 were classified as neutral, and 3 were classified as against (Table 1). 

Of the articles classified as supporting the vitamin D hypothesis, 13 articles were level 1 evidence, 9 were level 2, and 4 were level 3. Key findings supporting the vitamin D hypothesis included genetic natural selection favoring vitamin D synthesis genes at higher latitudes with lower UVR and the skin lightening that occurred to protect against vitamin D deficiency (Table 1). Specific genes supporting these findings included 7-dehydrocholesterol reductase (DHCR7), vitamin D receptor (VDR), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), oculocutaneous albinism type 2 melanosomal transmembrane protein (OCA2), solute carrier family 45 member 2 (SLC45A2), solute carrier family 4 member 5 (SLC24A5), Kit ligand (KITLG), melanocortin 1 receptor (MC1R), and HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)(Table 2).

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Comment

The importance of appropriate vitamin D levels is hypothesized as a potent driver in skin lightening because the vitamin is essential for many biochemical processes within the human body. Proper calcification of bones requires activated vitamin D to prevent rickets in childhood. Pelvic deformation in women with rickets can obstruct childbirth in primitive medical environments.¹⁵ This direct reproductive impairment suggests a strong selective pressure for skin lightening in populations that migrated northward to enhance vitamin D synthesis. 

Of the 39 articles that we reviewed, the majority (n=26 [66.7%]) supported the hypothesis that vitamin D synthesis was the main driver behind skin lightening, whereas 3 (7.7%) did not support the hypothesis and 10 (25.6%) were neutral. Other leading theories explaining skin lightening included the idea that enhanced melanogenesis protected against folate degradation; genetic selection for light-skin alleles due to genetic drift; skin lightening being the result of sexual selection; and a combination of factors, including dietary choices, clothing preferences, and skin permeability barriers. 

Articles With Supporting Evidence for the Vitamin D Theory—As Homo sapiens migrated out of Africa, migration patterns demonstrated the correlation between distance from the equator and skin pigmentation from natural selection. Individuals with darker skin pigment required higher levels of UVR to synthesize vitamin D. According to Beleza et al,1 as humans migrated to areas of higher latitudes with lower levels of UVR, natural selection favored the development of lighter skin to maximize vitamin D production. Vitamin D is linked to calcium metabolism, and its deficiency can lead to bone malformations and poor immune function.³⁵ Several genes affecting melanogenesis and skin pigment have been found to have geospatial patterns that map to different geographic locations of various populations, indicating how human migration patterns out of Africa created this natural selection for skin lightening. The gene KITLG—associated with lighter skin pigmentation—has been found in high frequencies in both European and East Asian populations and is proposed to have increased in frequency after the migration out of Africa. However, the genes TYRP1, SLC24A5, and SLC45A2 were found at high frequencies only in European populations, and this selection occurred 11,000 to 19,000 years ago during the Last Glacial Maximum (15,000–20,000 years ago), demonstrating the selection for European over East Asian characteristics. During this period, seasonal changes increased the risk for vitamin D deficiency and provided an urgency for selection to a lighter skin pigment.¹

The migration of H sapiens to northern latitudes prompted the selection of alleles that would increasevitamin D synthesis to counteract the reduced UV exposure. Genetic analysis studies have found key associations between genes encoding for the metabolism of vitamin D and pigmentation. Among this complex network are the essential downstream enzymes in the melanocortin receptor 1 pathway, including TYR and TYRP1. Forty-six of 960 single-nucleotide polymorphisms located in 29 different genes involved in skin pigmentation that were analyzed in a cohort of 2970 individuals were significantly associated with serum vitamin D levels (P<.05). The exocyst complex component 2 (EXOC2), TYR, and TYRP1 gene variants were shown to have the greatest influence on vitamin D status.⁹ These data reveal how pigment genotypes are predictive of vitamin D levels and the epistatic potential among many genes in this complex network. 

Gene variation plays an important role in vitamin D status when comparing genetic polymorphisms in populations in northern latitudes to African populations. Vitamin D₃ precursor availability is decreased by 7-DHCR catalyzing the precursors substrate to cholesterol. In a study using GWAS, it was found that “variations in DHCR7 may aid vitamin D production by conserving cutaneous 7-DHC levels. A high prevalence of DHCR7 variants were found in European and Northeast Asian populations but not in African populations, suggesting that selection occurred for these DHCR7 mutations in populations who migrated to more northern latitudes.⁵ Multilocus networks have been established between the VDR promotor and skin color genes (Table 2) that exhibit a strong in-Africa vs out-of-Africa frequency pattern. It also has been shown that genetic variation (suggesting a long-term evolutionary inclination) and epigenetic modification (indicative of short-term exposure) of VDR lends support to the vitamin D hypothesis. As latitude decreases, prevalence of VDR FokI (F allele), BsmI (B allele), ApaI (A allele), and TaqI (T allele) also decreases in a linear manner, linking latitude to VDR polymorphisms. Plasma vitamin D levels and photoperiod of conception—UV exposure during the periconceptional period—also were extrapolative of VDR methylation in a study involving 80 participants, where these 2 factors accounted for 17% of variance in methylation.⁶

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Other noteworthy genes included HERC2, which has implications in the expression of OCA2 (melanocyte-specific transporter protein), and IRF4, which encodes for an important enzyme in folate-dependent melanin production. In an Australian cross-sectional study that analyzed vitamin D and pigmentation gene polymorphisms in conjunction with plasma vitamin D levels, the most notable rate of vitamin D loss occurred in individuals with the darkest pigmentation HERC2 (AA) genotype.³¹ In contrast, the lightest pigmentation HERC2 (GG) genotypes had increased vitamin D₃ photosynthesis. Interestingly, the lightest interferon regulatory factor 4 (IRF4) TT genotype and the darkest HERC2 AA genotype, rendering the greatest folate loss and largest synthesis of vitamin D₃, were not seen in combination in any of the participants.³⁰ In addition to HERC2, derived alleles from pigment-associated genes SLC24A5*A and SLC45A2*G demonstrated greater frequencies in Europeans (>90%) compared to Africans and East Asians, where the allelic frequencies were either rare or absent.1 This evidence delineates not only the complexity but also the strong relationship between skin pigmentation, latitude, and vitamin D status. The GWAS also have supported this concept. In comparing European populations to African populations, there was a 4-fold increase in the frequencies of “derived alleles of the vitamin D transport protein (GC, rs3755967), the 25(OH)D₃ synthesizing enzyme (CYP2R1, rs10741657), VDR (rs2228570 (commonly known as FokI polymorphism), rs1544410 (Bsm1), and rs731236 (Taq1) and the VDR target genes CYP24A1 (rs17216707), CD14 (rs2569190), and CARD9 (rs4077515).”³²

Articles With Evidence Against the Vitamin D Theory—This review analyzed the level of support for the theory that vitamin D was the main driver for skin lightening. Although most articles supported this theory, there were articles that listed other plausible counterarguments. Jablonski and Chaplin3 suggested that humans living in higher latitudes compensated for increased demand of vitamin D by placing cultural importance on a diet of vitamin D–rich foods and thus would not have experienced decreased vitamin D levels, which we hypothesize were the driver for skin lightening. Elias et al³⁹ argued that initial pigment dilution may have instead served to improve metabolic conservation, as the authors found no evidence of rickets—the sequelae of vitamin D deficiency—in pre–industrial age human fossils. Elias and Williams3⁸ proposed that differences in skin pigment are due to a more intact skin permeability barrier as “a requirement for life in a desiccating terrestrial environment,” which is seen in darker skin tones compared to lighter skin tones and thus can survive better in warmer climates with less risk of infections or dehydration.

Articles With Neutral Evidence for the Vitamin D Theory—Greaves⁴¹ argued against the idea that skin evolved to become lighter to protect against vitamin D deficiency. They proposed that the chimpanzee, which is the human’s most closely related species, had light skin covered by hair, and the loss of this hair led to exposed pale skin that created a need for increased melanin production for protection from UVR. Greaves⁴¹ stated that the MC1R gene (associated with darker pigmentation) was selected for in African populations, and those with pale skin retained their original pigment as they migrated to higher latitudes. Further research has demonstrated that the genetic natural selection for skin pigment is a complex process that involves multiple gene variants found throughout cultures across the globe.

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Conclusion

Skin pigmentation has continuously evolved alongside humans. Genetic selection for lighter skin coincides with a favorable selection for genes involved in vitamin D synthesis as humans migrated to northern latitudes, which enabled humans to produce adequate levels of exogenous vitamin D in low-UVR areas and in turn promoted survival. Early humans without access to supplementation or foods rich in vitamin D acquired vitamin D primarily through sunlight. In comparison to modern society, where vitamin D supplementation is accessible and human lifespans are prolonged, lighter skin tone is now a risk factor for malignant cancers of the skin rather than being a protective adaptation. Current sun behavior recommendations conclude that the body’s need for vitamin D is satisfied by UV exposure to the arms, legs, hands, and/or face for only 5 to 30 minutes between 10 am and 4 pm daily without sunscreen.^42-44 Approximately 600 IU of vitamin D supplementation daily is recommended in a typical adult younger than 70 years to avoid deficiency. In adults 70 years and older who are not receiving adequate sunlight exposure, 800 IU of daily vitamin D supplementation is recommended.⁴⁵

The hypothesis that skin lightening primarily was driven by the need for vitamin D can only be partially supported by our review. Studies have shown that there is a corresponding complex network of genes that determines skin pigmentation as well as vitamin D synthesis and conservation. However, there is sufficient evidence that skin lightening is multifactorial in nature, and vitamin D alone may not be the sole driver. The information in this review can be used by health care providers to educate patients on sun protection, given the lesser threat of severe vitamin D deficiency in developed communities today that have access to adequate nutrition and supplementation.

Skin lightening and its coinciding evolutionary drivers are a rather neglected area of research. Due to heterogeneous cohorts and conservative data analysis, GWAS studies run the risk of type II error, yielding a limitation in our data analysis.⁹ Furthermore, the data regarding specific time frames in evolutionary skin lightening as well as the intensity of gene polymorphisms are limited.1 Further studies are needed to determine the interconnectedness of the current skin-lightening theories to identify other important factors that may play a role in the process. Determining the key event can help us better understand skin-adaptation mechanisms and create a framework for understanding the vital process involved in adaptation, survival, and disease manifestation in different patient populations.

The risk for developing skin cancer can be somewhat attributed to variations in skin pigmentation. Historically, lighter skin pigmentation has been observed in populations living in higher latitudes and darker pigmentation in populations near the equator. Although skin pigmentation is a conglomeration of genetic and environmental factors, anthropologic studies have demonstrated an association of human skin lightening with historic human migratory patterns.¹ It is postulated that migration to latitudes with less UVB light penetration has resulted in a compensatory natural selection of lighter skin types. Furthermore, the driving force behind this migration-associated skin lightening has remained unclear.¹

The need for folate metabolism, vitamin D synthesis, and barrier protection, as well as cultural practices, has been postulated as driving factors for skin pigmentation variation. Synthesis of vitamin D is a UV radiation (UVR)–dependent process and has remained a prominent theoretical driver for the basis of evolutionary skin lightening. Vitamin D can be acquired both exogenously or endogenously via dietary supplementation or sunlight; however, historically it has been obtained through UVB exposure primarily. Once UVB is absorbed by the skin, it catalyzes conversion of 7-dehydrocholesterol to previtamin D₃, which is converted to vitamin D in the kidneys.^2,3 It is suggested that lighter skin tones have an advantage over darker skin tones in synthesizing vitamin D at higher latitudes where there is less UVB, thus leading to the adaptation process.1 In this systematic review, we analyzed the evolutionary vitamin D adaptation hypothesis and assessed the validity of evidence supporting this theory in the literature.

Methods

A search of PubMed, Embase, and the Cochrane Reviews database was conducted using the terms evolution, vitamin D, and skin to generate articles published from 2010 to 2022 that evaluated the influence of UVR-dependent production of vitamin D on skin pigmentation through historical migration patterns (Figure). Studies were excluded during an initial screening of abstracts followed by full-text assessment if they only had abstracts and if articles were inaccessible for review or in the form of case reports and commentaries.

The following data were extracted from each included study: reference citation, affiliated institutions of authors, author specialties, journal name, year of publication, study period, type of article, type of study, mechanism of adaptation, data concluding or supporting vitamin D as the driver, and data concluding or suggesting against vitamin D as the driver. Data concluding or supporting vitamin D as the driver were recorded from statistically significant results, study conclusions, and direct quotations. Data concluding or suggesting against vitamin D as the driver also were recorded from significant results, study conclusions, and direct quotes. The mechanism of adaptation was based on vitamin D synthesis modulation, melanin upregulation, genetic selections, genetic drift, mating patterns, increased vitamin D sensitivity, interbreeding, and diet.

Studies included in the analysis were placed into 1 of 3 categories: supporting, neutral, and against. Strength of Recommendation Taxonomy (SORT) criteria were used to classify the level of evidence of each article.⁴ Each article’s level of evidence was then graded (Table 1). The SORT grading levels were based on quality and evidence type: level 1 signified good-quality, patient-oriented evidence; level 2 signified limited-quality, patient-oriented evidence; and level 3 signified other evidence.⁴

Results

Article Selection—A total of 229 articles were identified for screening, and 39 studies met inclusion criteria.^1-3,5-40 Systematic and retrospective reviews were the most common types of studies. Genomic analysis/sequencing/genome-wide association studies (GWAS) were the most common methods of analysis. Of these 39 articles, 26 were classified as supporting the evolutionary vitamin D adaptation hypothesis, 10 were classified as neutral, and 3 were classified as against (Table 1). 

Of the articles classified as supporting the vitamin D hypothesis, 13 articles were level 1 evidence, 9 were level 2, and 4 were level 3. Key findings supporting the vitamin D hypothesis included genetic natural selection favoring vitamin D synthesis genes at higher latitudes with lower UVR and the skin lightening that occurred to protect against vitamin D deficiency (Table 1). Specific genes supporting these findings included 7-dehydrocholesterol reductase (DHCR7), vitamin D receptor (VDR), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), oculocutaneous albinism type 2 melanosomal transmembrane protein (OCA2), solute carrier family 45 member 2 (SLC45A2), solute carrier family 4 member 5 (SLC24A5), Kit ligand (KITLG), melanocortin 1 receptor (MC1R), and HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)(Table 2).

uolaslecluveclojibratigudrojimashedespehafrefregicubrivedesofrispeswajoswavatrulostikuspabroshiboswonewrusharuwrusokustetuchauokuuepavawrowrephikakideswijugidrupijechawatorophufruvecegonibroraprubestidramusp

Comment

The importance of appropriate vitamin D levels is hypothesized as a potent driver in skin lightening because the vitamin is essential for many biochemical processes within the human body. Proper calcification of bones requires activated vitamin D to prevent rickets in childhood. Pelvic deformation in women with rickets can obstruct childbirth in primitive medical environments.¹⁵ This direct reproductive impairment suggests a strong selective pressure for skin lightening in populations that migrated northward to enhance vitamin D synthesis. 

Of the 39 articles that we reviewed, the majority (n=26 [66.7%]) supported the hypothesis that vitamin D synthesis was the main driver behind skin lightening, whereas 3 (7.7%) did not support the hypothesis and 10 (25.6%) were neutral. Other leading theories explaining skin lightening included the idea that enhanced melanogenesis protected against folate degradation; genetic selection for light-skin alleles due to genetic drift; skin lightening being the result of sexual selection; and a combination of factors, including dietary choices, clothing preferences, and skin permeability barriers. 

Articles With Supporting Evidence for the Vitamin D Theory—As Homo sapiens migrated out of Africa, migration patterns demonstrated the correlation between distance from the equator and skin pigmentation from natural selection. Individuals with darker skin pigment required higher levels of UVR to synthesize vitamin D. According to Beleza et al,1 as humans migrated to areas of higher latitudes with lower levels of UVR, natural selection favored the development of lighter skin to maximize vitamin D production. Vitamin D is linked to calcium metabolism, and its deficiency can lead to bone malformations and poor immune function.³⁵ Several genes affecting melanogenesis and skin pigment have been found to have geospatial patterns that map to different geographic locations of various populations, indicating how human migration patterns out of Africa created this natural selection for skin lightening. The gene KITLG—associated with lighter skin pigmentation—has been found in high frequencies in both European and East Asian populations and is proposed to have increased in frequency after the migration out of Africa. However, the genes TYRP1, SLC24A5, and SLC45A2 were found at high frequencies only in European populations, and this selection occurred 11,000 to 19,000 years ago during the Last Glacial Maximum (15,000–20,000 years ago), demonstrating the selection for European over East Asian characteristics. During this period, seasonal changes increased the risk for vitamin D deficiency and provided an urgency for selection to a lighter skin pigment.¹

The migration of H sapiens to northern latitudes prompted the selection of alleles that would increasevitamin D synthesis to counteract the reduced UV exposure. Genetic analysis studies have found key associations between genes encoding for the metabolism of vitamin D and pigmentation. Among this complex network are the essential downstream enzymes in the melanocortin receptor 1 pathway, including TYR and TYRP1. Forty-six of 960 single-nucleotide polymorphisms located in 29 different genes involved in skin pigmentation that were analyzed in a cohort of 2970 individuals were significantly associated with serum vitamin D levels (P<.05). The exocyst complex component 2 (EXOC2), TYR, and TYRP1 gene variants were shown to have the greatest influence on vitamin D status.⁹ These data reveal how pigment genotypes are predictive of vitamin D levels and the epistatic potential among many genes in this complex network. 

Gene variation plays an important role in vitamin D status when comparing genetic polymorphisms in populations in northern latitudes to African populations. Vitamin D₃ precursor availability is decreased by 7-DHCR catalyzing the precursors substrate to cholesterol. In a study using GWAS, it was found that “variations in DHCR7 may aid vitamin D production by conserving cutaneous 7-DHC levels. A high prevalence of DHCR7 variants were found in European and Northeast Asian populations but not in African populations, suggesting that selection occurred for these DHCR7 mutations in populations who migrated to more northern latitudes.⁵ Multilocus networks have been established between the VDR promotor and skin color genes (Table 2) that exhibit a strong in-Africa vs out-of-Africa frequency pattern. It also has been shown that genetic variation (suggesting a long-term evolutionary inclination) and epigenetic modification (indicative of short-term exposure) of VDR lends support to the vitamin D hypothesis. As latitude decreases, prevalence of VDR FokI (F allele), BsmI (B allele), ApaI (A allele), and TaqI (T allele) also decreases in a linear manner, linking latitude to VDR polymorphisms. Plasma vitamin D levels and photoperiod of conception—UV exposure during the periconceptional period—also were extrapolative of VDR methylation in a study involving 80 participants, where these 2 factors accounted for 17% of variance in methylation.⁶

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wrehoswojospiswodenabrudephedorimuhedaciuihu

Other noteworthy genes included HERC2, which has implications in the expression of OCA2 (melanocyte-specific transporter protein), and IRF4, which encodes for an important enzyme in folate-dependent melanin production. In an Australian cross-sectional study that analyzed vitamin D and pigmentation gene polymorphisms in conjunction with plasma vitamin D levels, the most notable rate of vitamin D loss occurred in individuals with the darkest pigmentation HERC2 (AA) genotype.³¹ In contrast, the lightest pigmentation HERC2 (GG) genotypes had increased vitamin D₃ photosynthesis. Interestingly, the lightest interferon regulatory factor 4 (IRF4) TT genotype and the darkest HERC2 AA genotype, rendering the greatest folate loss and largest synthesis of vitamin D₃, were not seen in combination in any of the participants.³⁰ In addition to HERC2, derived alleles from pigment-associated genes SLC24A5*A and SLC45A2*G demonstrated greater frequencies in Europeans (>90%) compared to Africans and East Asians, where the allelic frequencies were either rare or absent.1 This evidence delineates not only the complexity but also the strong relationship between skin pigmentation, latitude, and vitamin D status. The GWAS also have supported this concept. In comparing European populations to African populations, there was a 4-fold increase in the frequencies of “derived alleles of the vitamin D transport protein (GC, rs3755967), the 25(OH)D₃ synthesizing enzyme (CYP2R1, rs10741657), VDR (rs2228570 (commonly known as FokI polymorphism), rs1544410 (Bsm1), and rs731236 (Taq1) and the VDR target genes CYP24A1 (rs17216707), CD14 (rs2569190), and CARD9 (rs4077515).”³²

Articles With Evidence Against the Vitamin D Theory—This review analyzed the level of support for the theory that vitamin D was the main driver for skin lightening. Although most articles supported this theory, there were articles that listed other plausible counterarguments. Jablonski and Chaplin3 suggested that humans living in higher latitudes compensated for increased demand of vitamin D by placing cultural importance on a diet of vitamin D–rich foods and thus would not have experienced decreased vitamin D levels, which we hypothesize were the driver for skin lightening. Elias et al³⁹ argued that initial pigment dilution may have instead served to improve metabolic conservation, as the authors found no evidence of rickets—the sequelae of vitamin D deficiency—in pre–industrial age human fossils. Elias and Williams3⁸ proposed that differences in skin pigment are due to a more intact skin permeability barrier as “a requirement for life in a desiccating terrestrial environment,” which is seen in darker skin tones compared to lighter skin tones and thus can survive better in warmer climates with less risk of infections or dehydration.

Articles With Neutral Evidence for the Vitamin D Theory—Greaves⁴¹ argued against the idea that skin evolved to become lighter to protect against vitamin D deficiency. They proposed that the chimpanzee, which is the human’s most closely related species, had light skin covered by hair, and the loss of this hair led to exposed pale skin that created a need for increased melanin production for protection from UVR. Greaves⁴¹ stated that the MC1R gene (associated with darker pigmentation) was selected for in African populations, and those with pale skin retained their original pigment as they migrated to higher latitudes. Further research has demonstrated that the genetic natural selection for skin pigment is a complex process that involves multiple gene variants found throughout cultures across the globe.

sobrochugiphipro

Conclusion

Skin pigmentation has continuously evolved alongside humans. Genetic selection for lighter skin coincides with a favorable selection for genes involved in vitamin D synthesis as humans migrated to northern latitudes, which enabled humans to produce adequate levels of exogenous vitamin D in low-UVR areas and in turn promoted survival. Early humans without access to supplementation or foods rich in vitamin D acquired vitamin D primarily through sunlight. In comparison to modern society, where vitamin D supplementation is accessible and human lifespans are prolonged, lighter skin tone is now a risk factor for malignant cancers of the skin rather than being a protective adaptation. Current sun behavior recommendations conclude that the body’s need for vitamin D is satisfied by UV exposure to the arms, legs, hands, and/or face for only 5 to 30 minutes between 10 am and 4 pm daily without sunscreen.^42-44 Approximately 600 IU of vitamin D supplementation daily is recommended in a typical adult younger than 70 years to avoid deficiency. In adults 70 years and older who are not receiving adequate sunlight exposure, 800 IU of daily vitamin D supplementation is recommended.⁴⁵

The hypothesis that skin lightening primarily was driven by the need for vitamin D can only be partially supported by our review. Studies have shown that there is a corresponding complex network of genes that determines skin pigmentation as well as vitamin D synthesis and conservation. However, there is sufficient evidence that skin lightening is multifactorial in nature, and vitamin D alone may not be the sole driver. The information in this review can be used by health care providers to educate patients on sun protection, given the lesser threat of severe vitamin D deficiency in developed communities today that have access to adequate nutrition and supplementation.

Skin lightening and its coinciding evolutionary drivers are a rather neglected area of research. Due to heterogeneous cohorts and conservative data analysis, GWAS studies run the risk of type II error, yielding a limitation in our data analysis.⁹ Furthermore, the data regarding specific time frames in evolutionary skin lightening as well as the intensity of gene polymorphisms are limited.1 Further studies are needed to determine the interconnectedness of the current skin-lightening theories to identify other important factors that may play a role in the process. Determining the key event can help us better understand skin-adaptation mechanisms and create a framework for understanding the vital process involved in adaptation, survival, and disease manifestation in different patient populations.

The risk for developing skin cancer can be somewhat attributed to variations in skin pigmentation. Historically, lighter skin pigmentation has been observed in populations living in higher latitudes and darker pigmentation in populations near the equator. Although skin pigmentation is a conglomeration of genetic and environmental factors, anthropologic studies have demonstrated an association of human skin lightening with historic human migratory patterns.¹ It is postulated that migration to latitudes with less UVB light penetration has resulted in a compensatory natural selection of lighter skin types. Furthermore, the driving force behind this migration-associated skin lightening has remained unclear.¹

The need for folate metabolism, vitamin D synthesis, and barrier protection, as well as cultural practices, has been postulated as driving factors for skin pigmentation variation. Synthesis of vitamin D is a UV radiation (UVR)–dependent process and has remained a prominent theoretical driver for the basis of evolutionary skin lightening. Vitamin D can be acquired both exogenously or endogenously via dietary supplementation or sunlight; however, historically it has been obtained through UVB exposure primarily. Once UVB is absorbed by the skin, it catalyzes conversion of 7-dehydrocholesterol to previtamin D₃, which is converted to vitamin D in the kidneys.^2,3 It is suggested that lighter skin tones have an advantage over darker skin tones in synthesizing vitamin D at higher latitudes where there is less UVB, thus leading to the adaptation process.1 In this systematic review, we analyzed the evolutionary vitamin D adaptation hypothesis and assessed the validity of evidence supporting this theory in the literature.

Methods

A search of PubMed, Embase, and the Cochrane Reviews database was conducted using the terms evolution, vitamin D, and skin to generate articles published from 2010 to 2022 that evaluated the influence of UVR-dependent production of vitamin D on skin pigmentation through historical migration patterns (Figure). Studies were excluded during an initial screening of abstracts followed by full-text assessment if they only had abstracts and if articles were inaccessible for review or in the form of case reports and commentaries.

The following data were extracted from each included study: reference citation, affiliated institutions of authors, author specialties, journal name, year of publication, study period, type of article, type of study, mechanism of adaptation, data concluding or supporting vitamin D as the driver, and data concluding or suggesting against vitamin D as the driver. Data concluding or supporting vitamin D as the driver were recorded from statistically significant results, study conclusions, and direct quotations. Data concluding or suggesting against vitamin D as the driver also were recorded from significant results, study conclusions, and direct quotes. The mechanism of adaptation was based on vitamin D synthesis modulation, melanin upregulation, genetic selections, genetic drift, mating patterns, increased vitamin D sensitivity, interbreeding, and diet.

Studies included in the analysis were placed into 1 of 3 categories: supporting, neutral, and against. Strength of Recommendation Taxonomy (SORT) criteria were used to classify the level of evidence of each article.⁴ Each article’s level of evidence was then graded (Table 1). The SORT grading levels were based on quality and evidence type: level 1 signified good-quality, patient-oriented evidence; level 2 signified limited-quality, patient-oriented evidence; and level 3 signified other evidence.⁴

Results

Article Selection—A total of 229 articles were identified for screening, and 39 studies met inclusion criteria.^1-3,5-40 Systematic and retrospective reviews were the most common types of studies. Genomic analysis/sequencing/genome-wide association studies (GWAS) were the most common methods of analysis. Of these 39 articles, 26 were classified as supporting the evolutionary vitamin D adaptation hypothesis, 10 were classified as neutral, and 3 were classified as against (Table 1). 

Of the articles classified as supporting the vitamin D hypothesis, 13 articles were level 1 evidence, 9 were level 2, and 4 were level 3. Key findings supporting the vitamin D hypothesis included genetic natural selection favoring vitamin D synthesis genes at higher latitudes with lower UVR and the skin lightening that occurred to protect against vitamin D deficiency (Table 1). Specific genes supporting these findings included 7-dehydrocholesterol reductase (DHCR7), vitamin D receptor (VDR), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), oculocutaneous albinism type 2 melanosomal transmembrane protein (OCA2), solute carrier family 45 member 2 (SLC45A2), solute carrier family 4 member 5 (SLC24A5), Kit ligand (KITLG), melanocortin 1 receptor (MC1R), and HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2)(Table 2).

uolaslecluveclojibratigudrojimashedespehafrefregicubrivedesofrispeswajoswavatrulostikuspabroshiboswonewrusharuwrusokustetuchauokuuepavawrowrephikakideswijugidrupijechawatorophufruvecegonibroraprubestidramusp

Comment

The importance of appropriate vitamin D levels is hypothesized as a potent driver in skin lightening because the vitamin is essential for many biochemical processes within the human body. Proper calcification of bones requires activated vitamin D to prevent rickets in childhood. Pelvic deformation in women with rickets can obstruct childbirth in primitive medical environments.¹⁵ This direct reproductive impairment suggests a strong selective pressure for skin lightening in populations that migrated northward to enhance vitamin D synthesis. 

Of the 39 articles that we reviewed, the majority (n=26 [66.7%]) supported the hypothesis that vitamin D synthesis was the main driver behind skin lightening, whereas 3 (7.7%) did not support the hypothesis and 10 (25.6%) were neutral. Other leading theories explaining skin lightening included the idea that enhanced melanogenesis protected against folate degradation; genetic selection for light-skin alleles due to genetic drift; skin lightening being the result of sexual selection; and a combination of factors, including dietary choices, clothing preferences, and skin permeability barriers. 

Articles With Supporting Evidence for the Vitamin D Theory—As Homo sapiens migrated out of Africa, migration patterns demonstrated the correlation between distance from the equator and skin pigmentation from natural selection. Individuals with darker skin pigment required higher levels of UVR to synthesize vitamin D. According to Beleza et al,1 as humans migrated to areas of higher latitudes with lower levels of UVR, natural selection favored the development of lighter skin to maximize vitamin D production. Vitamin D is linked to calcium metabolism, and its deficiency can lead to bone malformations and poor immune function.³⁵ Several genes affecting melanogenesis and skin pigment have been found to have geospatial patterns that map to different geographic locations of various populations, indicating how human migration patterns out of Africa created this natural selection for skin lightening. The gene KITLG—associated with lighter skin pigmentation—has been found in high frequencies in both European and East Asian populations and is proposed to have increased in frequency after the migration out of Africa. However, the genes TYRP1, SLC24A5, and SLC45A2 were found at high frequencies only in European populations, and this selection occurred 11,000 to 19,000 years ago during the Last Glacial Maximum (15,000–20,000 years ago), demonstrating the selection for European over East Asian characteristics. During this period, seasonal changes increased the risk for vitamin D deficiency and provided an urgency for selection to a lighter skin pigment.¹

The migration of H sapiens to northern latitudes prompted the selection of alleles that would increasevitamin D synthesis to counteract the reduced UV exposure. Genetic analysis studies have found key associations between genes encoding for the metabolism of vitamin D and pigmentation. Among this complex network are the essential downstream enzymes in the melanocortin receptor 1 pathway, including TYR and TYRP1. Forty-six of 960 single-nucleotide polymorphisms located in 29 different genes involved in skin pigmentation that were analyzed in a cohort of 2970 individuals were significantly associated with serum vitamin D levels (P<.05). The exocyst complex component 2 (EXOC2), TYR, and TYRP1 gene variants were shown to have the greatest influence on vitamin D status.⁹ These data reveal how pigment genotypes are predictive of vitamin D levels and the epistatic potential among many genes in this complex network. 

Gene variation plays an important role in vitamin D status when comparing genetic polymorphisms in populations in northern latitudes to African populations. Vitamin D₃ precursor availability is decreased by 7-DHCR catalyzing the precursors substrate to cholesterol. In a study using GWAS, it was found that “variations in DHCR7 may aid vitamin D production by conserving cutaneous 7-DHC levels. A high prevalence of DHCR7 variants were found in European and Northeast Asian populations but not in African populations, suggesting that selection occurred for these DHCR7 mutations in populations who migrated to more northern latitudes.⁵ Multilocus networks have been established between the VDR promotor and skin color genes (Table 2) that exhibit a strong in-Africa vs out-of-Africa frequency pattern. It also has been shown that genetic variation (suggesting a long-term evolutionary inclination) and epigenetic modification (indicative of short-term exposure) of VDR lends support to the vitamin D hypothesis. As latitude decreases, prevalence of VDR FokI (F allele), BsmI (B allele), ApaI (A allele), and TaqI (T allele) also decreases in a linear manner, linking latitude to VDR polymorphisms. Plasma vitamin D levels and photoperiod of conception—UV exposure during the periconceptional period—also were extrapolative of VDR methylation in a study involving 80 participants, where these 2 factors accounted for 17% of variance in methylation.⁶

vephachiprobetrelisutruspishouishophipiphucluchegobesodroswodrasluchachukoprotecishustephocherotropruhiphigechacauojobrephufraswawracheslewechiwrispuspebelidrephegabrithuphoruphathaceboliw

wrehoswojospiswodenabrudephedorimuhedaciuihu

Other noteworthy genes included HERC2, which has implications in the expression of OCA2 (melanocyte-specific transporter protein), and IRF4, which encodes for an important enzyme in folate-dependent melanin production. In an Australian cross-sectional study that analyzed vitamin D and pigmentation gene polymorphisms in conjunction with plasma vitamin D levels, the most notable rate of vitamin D loss occurred in individuals with the darkest pigmentation HERC2 (AA) genotype.³¹ In contrast, the lightest pigmentation HERC2 (GG) genotypes had increased vitamin D₃ photosynthesis. Interestingly, the lightest interferon regulatory factor 4 (IRF4) TT genotype and the darkest HERC2 AA genotype, rendering the greatest folate loss and largest synthesis of vitamin D₃, were not seen in combination in any of the participants.³⁰ In addition to HERC2, derived alleles from pigment-associated genes SLC24A5*A and SLC45A2*G demonstrated greater frequencies in Europeans (>90%) compared to Africans and East Asians, where the allelic frequencies were either rare or absent.1 This evidence delineates not only the complexity but also the strong relationship between skin pigmentation, latitude, and vitamin D status. The GWAS also have supported this concept. In comparing European populations to African populations, there was a 4-fold increase in the frequencies of “derived alleles of the vitamin D transport protein (GC, rs3755967), the 25(OH)D₃ synthesizing enzyme (CYP2R1, rs10741657), VDR (rs2228570 (commonly known as FokI polymorphism), rs1544410 (Bsm1), and rs731236 (Taq1) and the VDR target genes CYP24A1 (rs17216707), CD14 (rs2569190), and CARD9 (rs4077515).”³²

Articles With Evidence Against the Vitamin D Theory—This review analyzed the level of support for the theory that vitamin D was the main driver for skin lightening. Although most articles supported this theory, there were articles that listed other plausible counterarguments. Jablonski and Chaplin3 suggested that humans living in higher latitudes compensated for increased demand of vitamin D by placing cultural importance on a diet of vitamin D–rich foods and thus would not have experienced decreased vitamin D levels, which we hypothesize were the driver for skin lightening. Elias et al³⁹ argued that initial pigment dilution may have instead served to improve metabolic conservation, as the authors found no evidence of rickets—the sequelae of vitamin D deficiency—in pre–industrial age human fossils. Elias and Williams3⁸ proposed that differences in skin pigment are due to a more intact skin permeability barrier as “a requirement for life in a desiccating terrestrial environment,” which is seen in darker skin tones compared to lighter skin tones and thus can survive better in warmer climates with less risk of infections or dehydration.

Articles With Neutral Evidence for the Vitamin D Theory—Greaves⁴¹ argued against the idea that skin evolved to become lighter to protect against vitamin D deficiency. They proposed that the chimpanzee, which is the human’s most closely related species, had light skin covered by hair, and the loss of this hair led to exposed pale skin that created a need for increased melanin production for protection from UVR. Greaves⁴¹ stated that the MC1R gene (associated with darker pigmentation) was selected for in African populations, and those with pale skin retained their original pigment as they migrated to higher latitudes. Further research has demonstrated that the genetic natural selection for skin pigment is a complex process that involves multiple gene variants found throughout cultures across the globe.

sobrochugiphipro

Conclusion

Skin pigmentation has continuously evolved alongside humans. Genetic selection for lighter skin coincides with a favorable selection for genes involved in vitamin D synthesis as humans migrated to northern latitudes, which enabled humans to produce adequate levels of exogenous vitamin D in low-UVR areas and in turn promoted survival. Early humans without access to supplementation or foods rich in vitamin D acquired vitamin D primarily through sunlight. In comparison to modern society, where vitamin D supplementation is accessible and human lifespans are prolonged, lighter skin tone is now a risk factor for malignant cancers of the skin rather than being a protective adaptation. Current sun behavior recommendations conclude that the body’s need for vitamin D is satisfied by UV exposure to the arms, legs, hands, and/or face for only 5 to 30 minutes between 10 am and 4 pm daily without sunscreen.^42-44 Approximately 600 IU of vitamin D supplementation daily is recommended in a typical adult younger than 70 years to avoid deficiency. In adults 70 years and older who are not receiving adequate sunlight exposure, 800 IU of daily vitamin D supplementation is recommended.⁴⁵

The hypothesis that skin lightening primarily was driven by the need for vitamin D can only be partially supported by our review. Studies have shown that there is a corresponding complex network of genes that determines skin pigmentation as well as vitamin D synthesis and conservation. However, there is sufficient evidence that skin lightening is multifactorial in nature, and vitamin D alone may not be the sole driver. The information in this review can be used by health care providers to educate patients on sun protection, given the lesser threat of severe vitamin D deficiency in developed communities today that have access to adequate nutrition and supplementation.

Skin lightening and its coinciding evolutionary drivers are a rather neglected area of research. Due to heterogeneous cohorts and conservative data analysis, GWAS studies run the risk of type II error, yielding a limitation in our data analysis.⁹ Furthermore, the data regarding specific time frames in evolutionary skin lightening as well as the intensity of gene polymorphisms are limited.1 Further studies are needed to determine the interconnectedness of the current skin-lightening theories to identify other important factors that may play a role in the process. Determining the key event can help us better understand skin-adaptation mechanisms and create a framework for understanding the vital process involved in adaptation, survival, and disease manifestation in different patient populations.

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

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The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.

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bu

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

cliprustiwistavadrecokuthivishoslusheswusocepristoceprepushusofrotreceprahebrawrufrebr

ragubipeclenothaspibetrehuclaphoclochicuuohefratrapopravidacrocedrushohochesijaswefrichofropucliprowijebrethadreshesicleclosuphecaueshinanosluswethuchoueclesteclacruchowrobespekach

The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.

tasumileneshosichinoslugechokanepobrihushepuhoswujesuchegotethouofremeciluboniuefreluwotratrothenuphethogekupawrustacuclaphawruspashisoclubrurohilatefrishucruwephustechispohorip

bu

To the Editor:

The term palisaded neutrophilic and granulomatous dermatitis (PNGD) has been proposed to encompass various conditions, including Winkelmann granuloma and superficial ulcerating rheumatoid necrobiosis. More recently, PNGD has been classified along with interstitial granulomatous dermatitis and interstitial granulomatous drug reaction under a unifying rubric of reactive granulomatous dermatitis (RGD).^1-4 The diagnosis of RGD can be challenging because of a range of clinical and histopathologic features as well as variable nomenclature.^1-3,5

Palisaded neutrophilic and granulomatous dermatitis classically manifests with papules and small plaques on the extensor extremities, with histopathology showing characteristic necrobiosis with both neutrophils and histiocytes.^1,2,6 We report 6 cases of RGD, including an index case in which a predominance of neutrophils in the infiltrate impeded the diagnosis.

An 85-year-old woman (the index patient) presented with a several-week history of asymmetric crusted papules on the right upper extremity—3 lesions on the elbow and forearm and 1 lesion on a finger. She was an avid gardener with severe rheumatoid arthritis treated with Janus kinase (JAK) inhibitor therapy. An initial biopsy of the elbow revealed a dense infiltrate of neutrophils and sparse eosinophils within the dermis. Special stains for bacterial, fungal, and acid-fast organisms were negative.

Because infection with sporotrichoid spread remained high in the differential diagnosis, the JAK inhibitor was discontinued and an antifungal agent was initiated. Given the persistence of the lesions, a subsequent biopsy of the right finger revealed scarce neutrophils and predominant histiocytes with rare foci of degenerated collagen. Sporotrichosis remained the leading diagnosis for these unilateral lesions. The patient subsequently developed additional crusted papules on the left arm (Figure 1). A biopsy of a left elbow lesion revealed palisades of histiocytes around degenerated collagen and collections of neutrophils compatible with RGD (Figures 2 and 3). Incidentally, the patient also presented with bilateral lower extremity palpable purpura, with a biopsy showing leukocytoclastic vasculitis. Antifungal therapy was discontinued and JAK inhibitor therapy resumed, with partial resolution of both the arm and right finger lesions and complete resolution of the lower extremity palpable purpura over several months.

cliprustiwistavadrecokuthivishoslusheswusocepristoceprepushusofrotreceprahebrawrufrebr

ragubipeclenothaspibetrehuclaphoclochicuuohefratrapopravidacrocedrushohochesijaswefrichofropucliprowijebrethadreshesicleclosuphecaueshinanosluswethuchoueclesteclacruchowrobespekach

The dense neutrophilic infiltrate and asymmetric presentation seen in our index patient’s initial biopsy hindered categorization of the cutaneous findings as RGD in association with her rheumatoid arthritis rather than as an infectious process. To ascertain whether diagnosis also was difficult in other cases of RGD, we conducted a search of the Yale Dermatopathology database for the diagnosis palisaded neutrophilic and granulomatous dermatitis, a term consistently used at our institution over the past decade. This study was approved by the institutional review board of Yale University (New Haven, Connecticut), and informed consent was waived. The search covered a 10-year period; 13 patients were found. Eight patients were eliminated because further clinical information or follow-up could not be obtained, leaving 5 additional cases (Table). The 8 eliminated cases were consultations submitted to the laboratory by outside pathologists from other institutions.

tasumileneshosichinoslugechokanepobrihushepuhoswujesuchegotethouofremeciluboniuefreluwotratrothenuphethogekupawrustacuclaphawruspashisoclubrurohilatefrishucruwephustechispohorip

bu

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

stoslodephetonafruspashocacrucuslauubirestetoladruchogupruphivimauespagitacudrivumastetregutostetracliveshimetetegecladromegiwushitretuslucratriclashohuswewetucocrodofroprisuphashohosludroswapogarutheprastaswugafrobrivospupredruvophasudru

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

wrokidaricrawraphuthiphicledestisletrashestuclospidrekepiwroslakanestastabrobodrimewribuprustespevostejutacliwechushadreswiduthuporudovistushuclotroswehoswovifrafrufriclusespowrustiwufrimiruguphovustetrikudivuchufruwrespatrenochusw

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

bruspitusawibrigimeuejecibrelukadrastoclethevashafrejivophuluthelihokidratriswedrigolochinedebrejiswitonitastadristucujecabadriprihutrutredreprafrigoriceueprobrahuslapri

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

stoslodephetonafruspashocacrucuslauubirestetoladruchogupruphivimauespagitacudrivumastetregutostetracliveshimetetegecladromegiwushitretuslucratriclashohuswewetucocrodofroprisuphashohosludroswapogarutheprastaswugafrobrivospupredruvophasudru

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

wrokidaricrawraphuthiphicledestisletrashestuclospidrekepiwroslakanestastabrobodrimewribuprustespevostejutacliwechushadreswiduthuporudovistushuclotroswehoswovifrafrufriclusespowrustiwufrimiruguphovustetrikudivuchufruwrespatrenochusw

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

bruspitusawibrigimeuejecibrelukadrastoclethevashafrejivophuluthelihokidratriswedrigolochinedebrejiswitonitastadristucujecabadriprihutrutredreprafrigoriceueprobrahuslapri

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.

To the Editor:

Pseudoxanthoma elasticum (PXE) is a genetic perforating dermatosis characterized by fragmentation and calcification of elastic fibers that most commonly manifests on the skin, eyes, gastrointestinal tract, or cardiovascular system.¹ Classic skin findings include multiple symmetric yellowish papules favoring the flexural surfaces of the body and neck as well as the periumbilical and inguinal regions.^1,2 Many life-threatening complications from this disease can occur due to calcification of elastic fibers in other parts of the body, such as the internal elastic lamina of arteries, which can cause gastrointestinal tract bleeding and accelerated cardiovascular disease including valvular disease.^2,3 If PXE is localized to the skin only without systemic involvement or a family history, a diagnosis of perforating calcific elastosis (PCE) can be made. We report a case of PCE in a patient with a growing umbilical lesion.

stoslodephetonafruspashocacrucuslauubirestetoladruchogupruphivimauespagitacudrivumastetregutostetracliveshimetetegecladromegiwushitretuslucratriclashohuswewetucocrodofroprisuphashohosludroswapogarutheprastaswugafrobrivospupredruvophasudru

A 49-year-old multiparous (gravida 3, para 3) woman presented for evaluation of an evolving periumbilical lesion of 4 months’ duration. She denied pain, bleeding, or drainage from the area, as well as any systemic symptoms. The patient had a surgical history of a laparoscopic hysterectomy 7 years prior to the current presentation due to uterine fibroids, which resulted in a periumbilical scar. At the current presentation, physical examination revealed 2 hyperpigmented to violaceous periumbilical papules coalescing into a plaque with overlying hyperkeratosis and crusting (Figure 1). A punch biopsy was performed and histopathology showed diffuse dermal collections of degenerated eosinophilic distorted elastic fibers with calcification (Figure 2). Further sections showed a transepidermal channel in which the elastic fibers extruded from the dermis through the epidermis (Figure 3). The diagnosis of acquired PCE was made based on the clinical presentation, relevant medical history, and lack of underlying medical conditions or family history of PXE. No further workup was needed, and the patient reported no further progression and rather some improvement (decrease in size) of the lesion at 3-month follow-up.

wrokidaricrawraphuthiphicledestisletrashestuclospidrekepiwroslakanestastabrobodrimewribuprustespevostejutacliwechushadreswiduthuporudovistushuclotroswehoswovifrafrufriclusespowrustiwufrimiruguphovustetrikudivuchufruwrespatrenochusw

Perforating calcific elastosis (also known as periumbilical perforating PXE) is a rare acquired condition that is seen predominantly in multiparous middle-aged women.^4-6 This diagnosis consists of degenerated calcified elastic fibers that may perforate the skin of the abdominal or periumbilical region. It clinically manifests as multiple painless hyperkeratotic papules surrounding the periumbilical region.^4-6

bruspitusawibrigimeuejecibrelukadrastoclethevashafrejivophuluthelihokidratriswedrigolochinedebrejiswitonitastadristucujecabadriprihutrutredreprafrigoriceueprobrahuslapri

The etiology and pathogenesis of PCE have not been defined but have been attributed to recurrent stressing of elastic fibers due to repeat traumas,¹ which is proposed to lead to degeneration of elastic fibers and calcification of damaged tissue.^4-7 As a result, PCE most commonly manifests in multiparous, obese, middle-aged women and patients with multiple abdominal surgeries or ascites.¹ It also has been reported in patients with renal failure due to deposition of abnormal calcium phosphate products onto elastic fibers.⁴ In our patient, the development of PCE was related to both multiparity and trauma from prior surgery.

The histopathologic findings of PCE and PXE are similar, warranting differentiation via thorough clinical examination as well as further investigation of the patient’s medical and family history. Both show degenerated, fragmented, curly elastic fibers with calcium deposition throughout the dermis and a transepidermal channel extruding these elastic fibers.^7,8 The biopsies stain positive for elastic fibers and calcium deposition. Calcium staining can help to differentiate these entities from elastosis perforans serpiginosa, which lacks the presence of calcium staining.⁷

There are no definitive treatments for PCE. A single case report of a patient with PCE and renal failure showed regression with hemodialysis.⁹ In a study evaluating patients with inherited PXE, notable improvement was seen in skin lesions treated with bisphosphonates, possibly suggesting that regulating serum calcium may contribute to improvement of the disease.³ Most cases spontaneously resolve with atrophic plaques. Our patient required no additional treatment with no further progression and reported improvement of the lesion with spontaneous decrease in size.