Cutis

The Diagnosis: Endocrine Mucin-Producing Sweat Gland Carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal tumor that characteristically presents as slowgrowing, flesh-colored papules, nodules, or cystic lesions around the periorbital skin in elderly female patients.¹ Histopathology of EMPSGCs reveals well-circumscribed multinodular dermal lesions that can be either cystic or solid and often are arranged in papillary and cribriform patterns (quiz image). Nests of uniform tumor cells are composed of small- to medium-sized epithelial cells with monomorphic nuclei showing fine to stippled chromatin.² Histologically, EMPSGC resembles a solid papillary carcinoma of the breast, which is attributed to their common embryologic origin.³ Intracytoplasmic and extracellular mucin often are seen on hematoxylin and eosin staining.² Variable immunohistochemical stain expression has been reported, including positive staining with synaptophysin and chromogranin. Other markers include cytokeratin CAM 5.2, epithelial membrane antigen, estrogen or progesterone receptors, and cytokeratin 7.⁴ Endocrine mucin-producing sweat gland carcinoma is thought to be a precursor to invasive neuroendocrine-type primary cutaneous mucinous carcinoma. Primary cutaneous mucinous carcinoma has been associated with EMPSGC in approximately 35.7% of cases. Histologically, primary cutaneous mucinous carcinoma that has transformed from EMPSGC would show an infiltration of tumor nests with desmoplastic stroma or mucin pools with clusters of tumor cells.²

Primary cutaneous adenoid cystic carcinoma is a rare malignant tumor that often presents on the head and neck. It usually appears as a single, slowly growing subcutaneous nodule or multinodular plaque.^5,6 Histologic features include basaloid cells in alternating tubular and cribriform patterns. The cribriform areas are composed of pseudoglandular adenoid spaces that contain mucin, basement membrane zone material, and cellular debris from necrotic neoplastic cells (Figure 1).⁷ Primary cutaneous adenoid cystic carcinoma predominantly is dermal with extension to the subcutaneous tissue. True ductal structures that demonstrate decapitation secretion also may be present.⁷

Basal cell carcinoma (adenoid type) presents as a pigmented or nonpigmented nodule or ulcer on sunexposed areas of the head and neck. Histopathology reveals basaloid cells surrounding islands of connective tissue resulting in a lacelike pattern (Figure 2). The lumina may contain a colloidal substance or amorphous granular material.⁸ The characteristic features of basal cell carcinomas, such as nests of basaloid cells with peripheral palisading cells, retraction of adjacent stroma, increased apoptosis and mitotic figures, and connection to the epidermis, can be helpful to distinguish basal cell carcinoma histologically from EMPSGC.²

Apocrine hidrocystomas clinically present as round, flesh-colored, shiny or translucent, dome-shaped papules or nodules near the eyelid margin or lateral canthus.⁹ Histologically, they are composed of proliferating apocrine secretory coils with an epithelial side of cuboidal or columnar cells and a luminal side exhibiting decapitation secretion (Figure 3).² An epidermal connection is absent.⁹ Apocrine hidrocystomas may exhibit complex architecture and papillary ductal hyperplasia that are difficult to distinguish from EMPSGC, especially if EMPSGC presents with cystic morphology. Apocrine cytomorphology and the lack of neuroendocrine marker expression and mucin production distinguish apocrine hidrocystomas. Furthermore, hidrocystomas infrequently demonstrate the nodular, solid, cribriform areas appreciated in EMPSGC.²

Microcystic adnexal carcinoma is a rare, slowly growing, locally aggressive sweat gland tumor that commonly presents as a flesh-colored to yellow papule, nodule, or plaque on the central face.¹⁰ Histopathologic examination reveals both eccrine and follicular differentiation. Keratin cysts, bland keratinocyte cords, and epithelium with ductal differentiation is observed in the superficial layers (Figure 4). Deep invasion into the subcutis and perineural invasion frequently is observed.

The Diagnosis: Endocrine Mucin-Producing Sweat Gland Carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal tumor that characteristically presents as slowgrowing, flesh-colored papules, nodules, or cystic lesions around the periorbital skin in elderly female patients.¹ Histopathology of EMPSGCs reveals well-circumscribed multinodular dermal lesions that can be either cystic or solid and often are arranged in papillary and cribriform patterns (quiz image). Nests of uniform tumor cells are composed of small- to medium-sized epithelial cells with monomorphic nuclei showing fine to stippled chromatin.² Histologically, EMPSGC resembles a solid papillary carcinoma of the breast, which is attributed to their common embryologic origin.³ Intracytoplasmic and extracellular mucin often are seen on hematoxylin and eosin staining.² Variable immunohistochemical stain expression has been reported, including positive staining with synaptophysin and chromogranin. Other markers include cytokeratin CAM 5.2, epithelial membrane antigen, estrogen or progesterone receptors, and cytokeratin 7.⁴ Endocrine mucin-producing sweat gland carcinoma is thought to be a precursor to invasive neuroendocrine-type primary cutaneous mucinous carcinoma. Primary cutaneous mucinous carcinoma has been associated with EMPSGC in approximately 35.7% of cases. Histologically, primary cutaneous mucinous carcinoma that has transformed from EMPSGC would show an infiltration of tumor nests with desmoplastic stroma or mucin pools with clusters of tumor cells.²

Primary cutaneous adenoid cystic carcinoma is a rare malignant tumor that often presents on the head and neck. It usually appears as a single, slowly growing subcutaneous nodule or multinodular plaque.^5,6 Histologic features include basaloid cells in alternating tubular and cribriform patterns. The cribriform areas are composed of pseudoglandular adenoid spaces that contain mucin, basement membrane zone material, and cellular debris from necrotic neoplastic cells (Figure 1).⁷ Primary cutaneous adenoid cystic carcinoma predominantly is dermal with extension to the subcutaneous tissue. True ductal structures that demonstrate decapitation secretion also may be present.⁷

Basal cell carcinoma (adenoid type) presents as a pigmented or nonpigmented nodule or ulcer on sunexposed areas of the head and neck. Histopathology reveals basaloid cells surrounding islands of connective tissue resulting in a lacelike pattern (Figure 2). The lumina may contain a colloidal substance or amorphous granular material.⁸ The characteristic features of basal cell carcinomas, such as nests of basaloid cells with peripheral palisading cells, retraction of adjacent stroma, increased apoptosis and mitotic figures, and connection to the epidermis, can be helpful to distinguish basal cell carcinoma histologically from EMPSGC.²

Apocrine hidrocystomas clinically present as round, flesh-colored, shiny or translucent, dome-shaped papules or nodules near the eyelid margin or lateral canthus.⁹ Histologically, they are composed of proliferating apocrine secretory coils with an epithelial side of cuboidal or columnar cells and a luminal side exhibiting decapitation secretion (Figure 3).² An epidermal connection is absent.⁹ Apocrine hidrocystomas may exhibit complex architecture and papillary ductal hyperplasia that are difficult to distinguish from EMPSGC, especially if EMPSGC presents with cystic morphology. Apocrine cytomorphology and the lack of neuroendocrine marker expression and mucin production distinguish apocrine hidrocystomas. Furthermore, hidrocystomas infrequently demonstrate the nodular, solid, cribriform areas appreciated in EMPSGC.²

Microcystic adnexal carcinoma is a rare, slowly growing, locally aggressive sweat gland tumor that commonly presents as a flesh-colored to yellow papule, nodule, or plaque on the central face.¹⁰ Histopathologic examination reveals both eccrine and follicular differentiation. Keratin cysts, bland keratinocyte cords, and epithelium with ductal differentiation is observed in the superficial layers (Figure 4). Deep invasion into the subcutis and perineural invasion frequently is observed.

The Diagnosis: Endocrine Mucin-Producing Sweat Gland Carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal tumor that characteristically presents as slowgrowing, flesh-colored papules, nodules, or cystic lesions around the periorbital skin in elderly female patients.¹ Histopathology of EMPSGCs reveals well-circumscribed multinodular dermal lesions that can be either cystic or solid and often are arranged in papillary and cribriform patterns (quiz image). Nests of uniform tumor cells are composed of small- to medium-sized epithelial cells with monomorphic nuclei showing fine to stippled chromatin.² Histologically, EMPSGC resembles a solid papillary carcinoma of the breast, which is attributed to their common embryologic origin.³ Intracytoplasmic and extracellular mucin often are seen on hematoxylin and eosin staining.² Variable immunohistochemical stain expression has been reported, including positive staining with synaptophysin and chromogranin. Other markers include cytokeratin CAM 5.2, epithelial membrane antigen, estrogen or progesterone receptors, and cytokeratin 7.⁴ Endocrine mucin-producing sweat gland carcinoma is thought to be a precursor to invasive neuroendocrine-type primary cutaneous mucinous carcinoma. Primary cutaneous mucinous carcinoma has been associated with EMPSGC in approximately 35.7% of cases. Histologically, primary cutaneous mucinous carcinoma that has transformed from EMPSGC would show an infiltration of tumor nests with desmoplastic stroma or mucin pools with clusters of tumor cells.²

Primary cutaneous adenoid cystic carcinoma is a rare malignant tumor that often presents on the head and neck. It usually appears as a single, slowly growing subcutaneous nodule or multinodular plaque.^5,6 Histologic features include basaloid cells in alternating tubular and cribriform patterns. The cribriform areas are composed of pseudoglandular adenoid spaces that contain mucin, basement membrane zone material, and cellular debris from necrotic neoplastic cells (Figure 1).⁷ Primary cutaneous adenoid cystic carcinoma predominantly is dermal with extension to the subcutaneous tissue. True ductal structures that demonstrate decapitation secretion also may be present.⁷

Basal cell carcinoma (adenoid type) presents as a pigmented or nonpigmented nodule or ulcer on sunexposed areas of the head and neck. Histopathology reveals basaloid cells surrounding islands of connective tissue resulting in a lacelike pattern (Figure 2). The lumina may contain a colloidal substance or amorphous granular material.⁸ The characteristic features of basal cell carcinomas, such as nests of basaloid cells with peripheral palisading cells, retraction of adjacent stroma, increased apoptosis and mitotic figures, and connection to the epidermis, can be helpful to distinguish basal cell carcinoma histologically from EMPSGC.²

Apocrine hidrocystomas clinically present as round, flesh-colored, shiny or translucent, dome-shaped papules or nodules near the eyelid margin or lateral canthus.⁹ Histologically, they are composed of proliferating apocrine secretory coils with an epithelial side of cuboidal or columnar cells and a luminal side exhibiting decapitation secretion (Figure 3).² An epidermal connection is absent.⁹ Apocrine hidrocystomas may exhibit complex architecture and papillary ductal hyperplasia that are difficult to distinguish from EMPSGC, especially if EMPSGC presents with cystic morphology. Apocrine cytomorphology and the lack of neuroendocrine marker expression and mucin production distinguish apocrine hidrocystomas. Furthermore, hidrocystomas infrequently demonstrate the nodular, solid, cribriform areas appreciated in EMPSGC.²

Microcystic adnexal carcinoma is a rare, slowly growing, locally aggressive sweat gland tumor that commonly presents as a flesh-colored to yellow papule, nodule, or plaque on the central face.¹⁰ Histopathologic examination reveals both eccrine and follicular differentiation. Keratin cysts, bland keratinocyte cords, and epithelium with ductal differentiation is observed in the superficial layers (Figure 4). Deep invasion into the subcutis and perineural invasion frequently is observed.

Practice Gap

Hemostasis after cutaneous surgery typically can be aided by mechanical occlusion with petrolatum and gauze known as a pressure bandage. However, in certain scenarios such as bone bleeding or irregularly shaped areas (eg, conchal bowl), difficulty applying a pressure bandage necessitates alternative hemostatic measures.¹ In those instances, physical hemostatic agents, such as gelatin, oxidized cellulose, microporous polysaccharide spheres, hydrophilic polymers with potassium salts, microfibrillar collagen, and chitin, also can be used.² However, those agents are expensive and often adhere to wound edges, inducing repeat trauma with removal. To avoid such concerns, we propose the use of bone wax as an effective hemostatic technique.

The Technique

When secondary intention healing is chosen or a temporary bandage needs to be placed, we offer the use of bone wax as an alternative to help achieve hemostasis. Bone wax—a combination of beeswax, isopropyl palmitate, and a stabilizing agent such as almond oils or sterilized salicylic acid³—helps achieve hemostasis by purely mechanical means. It is malleable and can be easily adapted to the architecture of the surgical site (Figure 1). The bone wax can be applied immediately following surgery and removed during bandage change.

Practice Implications

Use of bone wax as a physical hemostatic agent provides a practical alternative to other options commonly used in dermatologic surgery for deep wounds or irregular surfaces. It offers several advantages.

Bone wax is not absorbed and does not adhere to wound surfaces, which makes removal easy and painless. Furthermore, bone wax allows for excellent growth of granulation tissue² (Figure 2), most likely due to the healing and emollient properties of the beeswax and the moist occlusive environment created by the bone wax.

Additional advantages are its low cost, especially compared to other hemostatic agents, and long shelf-life (approximately 5 years).² Furthermore, in scenarios when cutaneous tumors extend into the calvarium, bone wax can prevent air emboli from entering noncollapsible emissary veins.⁴

When bone wax is used as a temporary measure in a dermatologic setting, complications inherent to its use in bone healing (eg, granulomatous reaction, infection)—for which it is left in place indefinitely—are avoided.

Practice Gap

Hemostasis after cutaneous surgery typically can be aided by mechanical occlusion with petrolatum and gauze known as a pressure bandage. However, in certain scenarios such as bone bleeding or irregularly shaped areas (eg, conchal bowl), difficulty applying a pressure bandage necessitates alternative hemostatic measures.¹ In those instances, physical hemostatic agents, such as gelatin, oxidized cellulose, microporous polysaccharide spheres, hydrophilic polymers with potassium salts, microfibrillar collagen, and chitin, also can be used.² However, those agents are expensive and often adhere to wound edges, inducing repeat trauma with removal. To avoid such concerns, we propose the use of bone wax as an effective hemostatic technique.

The Technique

When secondary intention healing is chosen or a temporary bandage needs to be placed, we offer the use of bone wax as an alternative to help achieve hemostasis. Bone wax—a combination of beeswax, isopropyl palmitate, and a stabilizing agent such as almond oils or sterilized salicylic acid³—helps achieve hemostasis by purely mechanical means. It is malleable and can be easily adapted to the architecture of the surgical site (Figure 1). The bone wax can be applied immediately following surgery and removed during bandage change.

Practice Implications

Use of bone wax as a physical hemostatic agent provides a practical alternative to other options commonly used in dermatologic surgery for deep wounds or irregular surfaces. It offers several advantages.

Bone wax is not absorbed and does not adhere to wound surfaces, which makes removal easy and painless. Furthermore, bone wax allows for excellent growth of granulation tissue² (Figure 2), most likely due to the healing and emollient properties of the beeswax and the moist occlusive environment created by the bone wax.

Additional advantages are its low cost, especially compared to other hemostatic agents, and long shelf-life (approximately 5 years).² Furthermore, in scenarios when cutaneous tumors extend into the calvarium, bone wax can prevent air emboli from entering noncollapsible emissary veins.⁴

When bone wax is used as a temporary measure in a dermatologic setting, complications inherent to its use in bone healing (eg, granulomatous reaction, infection)—for which it is left in place indefinitely—are avoided.

Practice Gap

Hemostasis after cutaneous surgery typically can be aided by mechanical occlusion with petrolatum and gauze known as a pressure bandage. However, in certain scenarios such as bone bleeding or irregularly shaped areas (eg, conchal bowl), difficulty applying a pressure bandage necessitates alternative hemostatic measures.¹ In those instances, physical hemostatic agents, such as gelatin, oxidized cellulose, microporous polysaccharide spheres, hydrophilic polymers with potassium salts, microfibrillar collagen, and chitin, also can be used.² However, those agents are expensive and often adhere to wound edges, inducing repeat trauma with removal. To avoid such concerns, we propose the use of bone wax as an effective hemostatic technique.

The Technique

When secondary intention healing is chosen or a temporary bandage needs to be placed, we offer the use of bone wax as an alternative to help achieve hemostasis. Bone wax—a combination of beeswax, isopropyl palmitate, and a stabilizing agent such as almond oils or sterilized salicylic acid³—helps achieve hemostasis by purely mechanical means. It is malleable and can be easily adapted to the architecture of the surgical site (Figure 1). The bone wax can be applied immediately following surgery and removed during bandage change.

Practice Implications

Use of bone wax as a physical hemostatic agent provides a practical alternative to other options commonly used in dermatologic surgery for deep wounds or irregular surfaces. It offers several advantages.

Bone wax is not absorbed and does not adhere to wound surfaces, which makes removal easy and painless. Furthermore, bone wax allows for excellent growth of granulation tissue² (Figure 2), most likely due to the healing and emollient properties of the beeswax and the moist occlusive environment created by the bone wax.

Additional advantages are its low cost, especially compared to other hemostatic agents, and long shelf-life (approximately 5 years).² Furthermore, in scenarios when cutaneous tumors extend into the calvarium, bone wax can prevent air emboli from entering noncollapsible emissary veins.⁴

When bone wax is used as a temporary measure in a dermatologic setting, complications inherent to its use in bone healing (eg, granulomatous reaction, infection)—for which it is left in place indefinitely—are avoided.

To the Editor:

Preprint servers allow researchers to post manuscripts before publication in peer-reviewed journals. As of January 2022, 41 public preprint servers accepted medicine/science submissions.¹ We sought to analyze characteristics of dermatology manuscripts in preprint servers and assess preprint publication policies in top dermatology journals.

Thirty-five biology/health sciences preprint servers¹ were searched (March 3 to March 24, 2021) with keywords dermatology, skin, and cutaneous. Preprint server, preprint post date, location, metrics, journal, impact factor (IF), and journal publication date were recorded. Preprint policies of the top 20 dermatology journals—determined by impact factor of the journal (https://www.scimagojr.com/)—were reviewed. Two-tailed t tests and χ² tests were performed (P<.05).

A total of 1420 articles were posted to 11 preprint servers between June 20, 2007, and February 15, 2021 (Table 1); 377 (27%) were published in peer-reviewed journals, with 350 (93%) of those published within 1 year of preprint post. Preprints were published in 203 journals with a mean IF of 6.2. Growth in preprint posts by year (2007-2020) was exponential (R²=0.78)(Figure). On average, preprints were viewed 424 times (Table 2), with published preprints viewed more often than unpublished preprints (596 vs 362 views)(P<.001). Only 23 of 786 (3%) preprints with comments enabled had feedback. Among the top 20 dermatology journals, 18 (90%) allowed preprints, 1 (5%) evaluated case by case, and 1 (5%) prohibited preprints.

Our study showed exponential growth in dermatology preprints, a low proportion published in peer-reviewed journals with high IFs, and a substantial number of page views for both published and unpublished preprints. Very few preprints had feedback. We found that most of the top 20 dermatology journals accept preprints. An analysis of 61 dermatology articles in medRxiv found only 51% (31/61) of articles were subsequently published.² The low rate of publication may be due to the quality of preprints that do not meet criteria to be published following peer review.

Preprint servers are fairly novel, with a majority launched within the last 5 years.¹ The goal of preprints is to claim conception of an idea, solicit feedback prior to submission for peer review, and expedite research distribution.³ Because preprints are uploaded without peer review, manuscripts may lack quality and accuracy. An analysis of 57 of thelargest preprint servers found that few provided guidelines on authorship, image manipulation, or reporting of study limitations; however, most preprint servers do perform some screening.⁴ medRxiv requires full scientific research reports and absence of obscenity, plagiarism, and patient identifiers. In its first year, medRxiv rejected 34% of 176 submissios; reasons were not disclosed.⁵

The low rate of on-site comments suggests that preprint servers may not be effective for obtaining feedback to improve dermatology manuscripts prior to journal submission. Almost all of the top 20 dermatologyjournals accept preprints. Therefore, dermatologists may use these preprint servers to assert project ideas and disseminate research quickly and freely but may not receive constructive criticism.

Our study is subject to several limitations. Although our search was extensive, it is possible manuscripts were missed. Article metrics also were not available on all servers, and we could not account for accepted articles that were not yet indexed.

There has been a surge in posting of dermatology preprints in recent years. Preprints have not been peer reviewed, and data should be corroborated before incorporating new diagnostics or treatments into clinical practice. Utilization of preprint servers by dermatologists is increasing, but because the impact is still unknown, further studies on accuracy and reliability of preprints are warranted.

To the Editor:

Preprint servers allow researchers to post manuscripts before publication in peer-reviewed journals. As of January 2022, 41 public preprint servers accepted medicine/science submissions.¹ We sought to analyze characteristics of dermatology manuscripts in preprint servers and assess preprint publication policies in top dermatology journals.

Thirty-five biology/health sciences preprint servers¹ were searched (March 3 to March 24, 2021) with keywords dermatology, skin, and cutaneous. Preprint server, preprint post date, location, metrics, journal, impact factor (IF), and journal publication date were recorded. Preprint policies of the top 20 dermatology journals—determined by impact factor of the journal (https://www.scimagojr.com/)—were reviewed. Two-tailed t tests and χ² tests were performed (P<.05).

A total of 1420 articles were posted to 11 preprint servers between June 20, 2007, and February 15, 2021 (Table 1); 377 (27%) were published in peer-reviewed journals, with 350 (93%) of those published within 1 year of preprint post. Preprints were published in 203 journals with a mean IF of 6.2. Growth in preprint posts by year (2007-2020) was exponential (R²=0.78)(Figure). On average, preprints were viewed 424 times (Table 2), with published preprints viewed more often than unpublished preprints (596 vs 362 views)(P<.001). Only 23 of 786 (3%) preprints with comments enabled had feedback. Among the top 20 dermatology journals, 18 (90%) allowed preprints, 1 (5%) evaluated case by case, and 1 (5%) prohibited preprints.

Our study showed exponential growth in dermatology preprints, a low proportion published in peer-reviewed journals with high IFs, and a substantial number of page views for both published and unpublished preprints. Very few preprints had feedback. We found that most of the top 20 dermatology journals accept preprints. An analysis of 61 dermatology articles in medRxiv found only 51% (31/61) of articles were subsequently published.² The low rate of publication may be due to the quality of preprints that do not meet criteria to be published following peer review.

Preprint servers are fairly novel, with a majority launched within the last 5 years.¹ The goal of preprints is to claim conception of an idea, solicit feedback prior to submission for peer review, and expedite research distribution.³ Because preprints are uploaded without peer review, manuscripts may lack quality and accuracy. An analysis of 57 of thelargest preprint servers found that few provided guidelines on authorship, image manipulation, or reporting of study limitations; however, most preprint servers do perform some screening.⁴ medRxiv requires full scientific research reports and absence of obscenity, plagiarism, and patient identifiers. In its first year, medRxiv rejected 34% of 176 submissios; reasons were not disclosed.⁵

The low rate of on-site comments suggests that preprint servers may not be effective for obtaining feedback to improve dermatology manuscripts prior to journal submission. Almost all of the top 20 dermatologyjournals accept preprints. Therefore, dermatologists may use these preprint servers to assert project ideas and disseminate research quickly and freely but may not receive constructive criticism.

Our study is subject to several limitations. Although our search was extensive, it is possible manuscripts were missed. Article metrics also were not available on all servers, and we could not account for accepted articles that were not yet indexed.

There has been a surge in posting of dermatology preprints in recent years. Preprints have not been peer reviewed, and data should be corroborated before incorporating new diagnostics or treatments into clinical practice. Utilization of preprint servers by dermatologists is increasing, but because the impact is still unknown, further studies on accuracy and reliability of preprints are warranted.

To the Editor:

Preprint servers allow researchers to post manuscripts before publication in peer-reviewed journals. As of January 2022, 41 public preprint servers accepted medicine/science submissions.¹ We sought to analyze characteristics of dermatology manuscripts in preprint servers and assess preprint publication policies in top dermatology journals.

Thirty-five biology/health sciences preprint servers¹ were searched (March 3 to March 24, 2021) with keywords dermatology, skin, and cutaneous. Preprint server, preprint post date, location, metrics, journal, impact factor (IF), and journal publication date were recorded. Preprint policies of the top 20 dermatology journals—determined by impact factor of the journal (https://www.scimagojr.com/)—were reviewed. Two-tailed t tests and χ² tests were performed (P<.05).

A total of 1420 articles were posted to 11 preprint servers between June 20, 2007, and February 15, 2021 (Table 1); 377 (27%) were published in peer-reviewed journals, with 350 (93%) of those published within 1 year of preprint post. Preprints were published in 203 journals with a mean IF of 6.2. Growth in preprint posts by year (2007-2020) was exponential (R²=0.78)(Figure). On average, preprints were viewed 424 times (Table 2), with published preprints viewed more often than unpublished preprints (596 vs 362 views)(P<.001). Only 23 of 786 (3%) preprints with comments enabled had feedback. Among the top 20 dermatology journals, 18 (90%) allowed preprints, 1 (5%) evaluated case by case, and 1 (5%) prohibited preprints.

Our study showed exponential growth in dermatology preprints, a low proportion published in peer-reviewed journals with high IFs, and a substantial number of page views for both published and unpublished preprints. Very few preprints had feedback. We found that most of the top 20 dermatology journals accept preprints. An analysis of 61 dermatology articles in medRxiv found only 51% (31/61) of articles were subsequently published.² The low rate of publication may be due to the quality of preprints that do not meet criteria to be published following peer review.

Preprint servers are fairly novel, with a majority launched within the last 5 years.¹ The goal of preprints is to claim conception of an idea, solicit feedback prior to submission for peer review, and expedite research distribution.³ Because preprints are uploaded without peer review, manuscripts may lack quality and accuracy. An analysis of 57 of thelargest preprint servers found that few provided guidelines on authorship, image manipulation, or reporting of study limitations; however, most preprint servers do perform some screening.⁴ medRxiv requires full scientific research reports and absence of obscenity, plagiarism, and patient identifiers. In its first year, medRxiv rejected 34% of 176 submissios; reasons were not disclosed.⁵

The low rate of on-site comments suggests that preprint servers may not be effective for obtaining feedback to improve dermatology manuscripts prior to journal submission. Almost all of the top 20 dermatologyjournals accept preprints. Therefore, dermatologists may use these preprint servers to assert project ideas and disseminate research quickly and freely but may not receive constructive criticism.

Our study is subject to several limitations. Although our search was extensive, it is possible manuscripts were missed. Article metrics also were not available on all servers, and we could not account for accepted articles that were not yet indexed.

There has been a surge in posting of dermatology preprints in recent years. Preprints have not been peer reviewed, and data should be corroborated before incorporating new diagnostics or treatments into clinical practice. Utilization of preprint servers by dermatologists is increasing, but because the impact is still unknown, further studies on accuracy and reliability of preprints are warranted.

Transferring from one residency program to another is rare but not unheard of. According to the most recent Accreditation Council for Graduate Medical Education Data Resource Book, there were 1020 residents who transferred residency programs in the 2020-2021 academic year.¹ With a total of 126,759 active residents in specialty programs, the percentage of transferring residents was less than 1%. The specialties with the highest number of transferring residents included psychiatry, general surgery, internal medicine, and family medicine. In dermatology programs, there were only 2 resident transfers during the 2019-2020 academic year and 6 transfers in the 2020-2021 academic year.^1,2 A resident contemplating transferring training programs must carefully consider the advantages and disadvantages before undertaking the uncertain transfer process, but transferring residency programs can be achieved successfully with planning and luck.

Deciding to Transfer

The decision to transfer residency programs may be a difficult one that is wrought with anxiety. There are many reasons why a trainee may wish to pursue transferring training programs. A transfer to another geographic area may be necessary for personal or family reasons, such as to reunite with a spouse and children or to care for a sick family member. A resident may find their program to be a poor fit and may wish to train in a different educational environment. Occasionally, a program can lose its accreditation, and its residents will be tasked with finding a new position elsewhere. A trainee also may realize that the specialty they matched into initially does not align with their true passions. It is important for the potential transfer applicant to be levelheaded about their decision. Residency is a demanding period for every trainee; switching programs may not be the best solution for every problem and should only be considered if essential.

Transfer Timing

A trainee may have thoughts of leaving a program soon after starting residency or perhaps even before starting if their National Resident Matching Program (NRMP) Match result was a disappointment; however, there are certain rules related to transfer timing. The NRMP Match represents a binding commitment for both the applicant and program. If for any reason an applicant will not honor the binding commitment, the NRMP requires the applicant to initiate a waiver review, which can be requested for unanticipated serious and extreme hardship, change of specialty, or ineligibility. According to the NRMP rules and regulations, applicants cannot apply for, discuss, interview for, or accept a position in another program until a waiver has been granted.³ Waivers based on change of specialty must be requested by mid-January prior to the start of training, which means most applicants who match to positions that begin in the same year of the Match do not qualify for change of specialty waivers. However, those who matched to an advanced position and are doing a preliminary year position may consider this option if they have a change of heart during their internship. The NRMP may consider a 1-year deferral to delay training if mutually agreed upon by both the matched applicant and the program.³ The binding commitment is in place for the first 45 days of training, and applicants who resign within 45 days or a program that tries to solicit the transfer of a resident prior to that date could be in violation of the Match and can face consequences such as being barred from entering the matching process in future cycles. Of the 1020 transfers that occurred among residents in specialty programs during the 2020-2021 academic year, 354 (34.7%) occurred during the first year of the training program; 228 (22.4%) occurred during the second year; 389 (38.1%) occurred during the third year; and 49 (4.8%) occurred in the fourth, fifth, or sixth year of the program.¹ Unlike other jobs/occupations in which one can simply give notice, in medical training even if a transfer position is accepted, the transition date between programs must be mutually agreed upon. Often, this may coincide with the start of the new academic year.

The Transfer Process

Transferring residency programs is a substantial undertaking. Unlike the Match, a trainee seeking to transfer programs does so without a standardized application system or structured support through the process; the transfer applicant must be prepared to navigate the transfer process on their own. The first step after making the decision to transfer is for the resident to meet with the program leadership (ie, program director[s], coordinator, designated official) at their home program to discuss the decision—a nerve-wracking but imperative first step. A receiving program may not favor an applicant secretly applying to a new program without the knowledge of their home program and often will require the home program’s blessing to proceed. The receiving program also would want to ensure the applicant is in good standing and not leaving due to misconduct. Once given the go-ahead, the process is largely in the hands of the applicant. The transfer applicant should identify locations or programs of interest and then take initiative to reach out to potential programs. FREIDA (Fellowship and Residency Electronic Interactive Database Access) is the American Medical Association’s residency and fellowship database that allows vacant position listings to be posted online.⁴ Additionally, the Association of American Medical Colleges’ FindAResident website is a year-round search tool designed to help find open residency and fellowship positions.⁵ Various specialties also may have program director listserves that communicate vacant positions. On occasion, there are spots in the main NRMP Match that are reserved positions (“R”). These are postgraduate year 2 positions in specialty programs that begin in the year of the Match and are reserved for physicians with prior graduate medical education; these also are known as “Physician Positions.”⁶ Ultimately, advertisements for vacancies may be few and far between, requiring the resident to send unsolicited emails with curriculum vitae attached to the program directors at programs of interest to inquire about any vacancies and hope for a favorable response. Even if the transfer applicant is qualified, luck that the right spot will be available at the right time may be the deciding factor in transferring programs.

The next step is interviewing for the position. There likely will be fewer candidates interviewing for an open spot but that does not make the process less competitive. The candidate should highlight their strengths and achievements and discuss why the new program would be a great fit both personally and professionally. Even if an applicant is seeking a transfer due to discontent with a prior program, it is best to act graciously and not speak poorly about another training program.

Prior to selection, the candidate may be asked to provide information such as diplomas, US Medical Licensing Examination Step and residency in-service training examination scores, and academic reviews from their current residency program. The interview process may take several weeks as the graduate medical education office often will need to officially approve of an applicant before a formal offer to transfer is extended.

Finally, once an offer is made and accepted, there still is a great amount of paperwork to complete before the transition. The applicant should stay on track with all off-boarding and on-boarding requirements, such as signing a contract, obtaining background checks, and applying for a new license to ensure the switch is not delayed.

 

 

Disadvantages of Transferring Programs

The transfer process is not easy to navigate and can be a source of stress for the applicant. It is natural to fear resentment from colleagues and co-residents. Although transferring programs might be in the best interest of the trainee, it may leave a large gap in the program that they are leaving, which can place a burden on the remaining residents.

There are many adjustments to be made after transferring programs. The transferring resident will again start from scratch, needing to learn the ropes and adapt to the growing pains of being at a new institution. This may require learning a completely new electronic medical record, adapting to a new culture, and in many cases stepping in as a senior resident without fully knowing the ins and outs of the program.

Advantages of Transferring Programs

Successfully transferring programs is something to celebrate. There may be great benefits to transferring to a program that is better suited to the trainee—either personally or professionally. Ameliorating the adversity that led to the decision to transfer such as reuniting a long-distance family or realizing one’s true passion can allow the resident to thrive as a trainee and maximize their potential. Transferring programs can give a resident a more well-rounded training experience, as different programs may have different strengths, patient populations, and practice settings. Working with different faculty members with varied niches and practice styles can create a more comprehensive residency experience.

Final Thoughts

Ultimately, transferring residency programs is not easy but also is not impossible. Successfully switching residency programs can be a rewarding experience providing greater well-being and fulfillment.

Transferring from one residency program to another is rare but not unheard of. According to the most recent Accreditation Council for Graduate Medical Education Data Resource Book, there were 1020 residents who transferred residency programs in the 2020-2021 academic year.¹ With a total of 126,759 active residents in specialty programs, the percentage of transferring residents was less than 1%. The specialties with the highest number of transferring residents included psychiatry, general surgery, internal medicine, and family medicine. In dermatology programs, there were only 2 resident transfers during the 2019-2020 academic year and 6 transfers in the 2020-2021 academic year.^1,2 A resident contemplating transferring training programs must carefully consider the advantages and disadvantages before undertaking the uncertain transfer process, but transferring residency programs can be achieved successfully with planning and luck.

Deciding to Transfer

The decision to transfer residency programs may be a difficult one that is wrought with anxiety. There are many reasons why a trainee may wish to pursue transferring training programs. A transfer to another geographic area may be necessary for personal or family reasons, such as to reunite with a spouse and children or to care for a sick family member. A resident may find their program to be a poor fit and may wish to train in a different educational environment. Occasionally, a program can lose its accreditation, and its residents will be tasked with finding a new position elsewhere. A trainee also may realize that the specialty they matched into initially does not align with their true passions. It is important for the potential transfer applicant to be levelheaded about their decision. Residency is a demanding period for every trainee; switching programs may not be the best solution for every problem and should only be considered if essential.

Transfer Timing

A trainee may have thoughts of leaving a program soon after starting residency or perhaps even before starting if their National Resident Matching Program (NRMP) Match result was a disappointment; however, there are certain rules related to transfer timing. The NRMP Match represents a binding commitment for both the applicant and program. If for any reason an applicant will not honor the binding commitment, the NRMP requires the applicant to initiate a waiver review, which can be requested for unanticipated serious and extreme hardship, change of specialty, or ineligibility. According to the NRMP rules and regulations, applicants cannot apply for, discuss, interview for, or accept a position in another program until a waiver has been granted.³ Waivers based on change of specialty must be requested by mid-January prior to the start of training, which means most applicants who match to positions that begin in the same year of the Match do not qualify for change of specialty waivers. However, those who matched to an advanced position and are doing a preliminary year position may consider this option if they have a change of heart during their internship. The NRMP may consider a 1-year deferral to delay training if mutually agreed upon by both the matched applicant and the program.³ The binding commitment is in place for the first 45 days of training, and applicants who resign within 45 days or a program that tries to solicit the transfer of a resident prior to that date could be in violation of the Match and can face consequences such as being barred from entering the matching process in future cycles. Of the 1020 transfers that occurred among residents in specialty programs during the 2020-2021 academic year, 354 (34.7%) occurred during the first year of the training program; 228 (22.4%) occurred during the second year; 389 (38.1%) occurred during the third year; and 49 (4.8%) occurred in the fourth, fifth, or sixth year of the program.¹ Unlike other jobs/occupations in which one can simply give notice, in medical training even if a transfer position is accepted, the transition date between programs must be mutually agreed upon. Often, this may coincide with the start of the new academic year.

The Transfer Process

Transferring residency programs is a substantial undertaking. Unlike the Match, a trainee seeking to transfer programs does so without a standardized application system or structured support through the process; the transfer applicant must be prepared to navigate the transfer process on their own. The first step after making the decision to transfer is for the resident to meet with the program leadership (ie, program director[s], coordinator, designated official) at their home program to discuss the decision—a nerve-wracking but imperative first step. A receiving program may not favor an applicant secretly applying to a new program without the knowledge of their home program and often will require the home program’s blessing to proceed. The receiving program also would want to ensure the applicant is in good standing and not leaving due to misconduct. Once given the go-ahead, the process is largely in the hands of the applicant. The transfer applicant should identify locations or programs of interest and then take initiative to reach out to potential programs. FREIDA (Fellowship and Residency Electronic Interactive Database Access) is the American Medical Association’s residency and fellowship database that allows vacant position listings to be posted online.⁴ Additionally, the Association of American Medical Colleges’ FindAResident website is a year-round search tool designed to help find open residency and fellowship positions.⁵ Various specialties also may have program director listserves that communicate vacant positions. On occasion, there are spots in the main NRMP Match that are reserved positions (“R”). These are postgraduate year 2 positions in specialty programs that begin in the year of the Match and are reserved for physicians with prior graduate medical education; these also are known as “Physician Positions.”⁶ Ultimately, advertisements for vacancies may be few and far between, requiring the resident to send unsolicited emails with curriculum vitae attached to the program directors at programs of interest to inquire about any vacancies and hope for a favorable response. Even if the transfer applicant is qualified, luck that the right spot will be available at the right time may be the deciding factor in transferring programs.

The next step is interviewing for the position. There likely will be fewer candidates interviewing for an open spot but that does not make the process less competitive. The candidate should highlight their strengths and achievements and discuss why the new program would be a great fit both personally and professionally. Even if an applicant is seeking a transfer due to discontent with a prior program, it is best to act graciously and not speak poorly about another training program.

Prior to selection, the candidate may be asked to provide information such as diplomas, US Medical Licensing Examination Step and residency in-service training examination scores, and academic reviews from their current residency program. The interview process may take several weeks as the graduate medical education office often will need to officially approve of an applicant before a formal offer to transfer is extended.

Finally, once an offer is made and accepted, there still is a great amount of paperwork to complete before the transition. The applicant should stay on track with all off-boarding and on-boarding requirements, such as signing a contract, obtaining background checks, and applying for a new license to ensure the switch is not delayed.

 

 

Disadvantages of Transferring Programs

The transfer process is not easy to navigate and can be a source of stress for the applicant. It is natural to fear resentment from colleagues and co-residents. Although transferring programs might be in the best interest of the trainee, it may leave a large gap in the program that they are leaving, which can place a burden on the remaining residents.

There are many adjustments to be made after transferring programs. The transferring resident will again start from scratch, needing to learn the ropes and adapt to the growing pains of being at a new institution. This may require learning a completely new electronic medical record, adapting to a new culture, and in many cases stepping in as a senior resident without fully knowing the ins and outs of the program.

Advantages of Transferring Programs

Successfully transferring programs is something to celebrate. There may be great benefits to transferring to a program that is better suited to the trainee—either personally or professionally. Ameliorating the adversity that led to the decision to transfer such as reuniting a long-distance family or realizing one’s true passion can allow the resident to thrive as a trainee and maximize their potential. Transferring programs can give a resident a more well-rounded training experience, as different programs may have different strengths, patient populations, and practice settings. Working with different faculty members with varied niches and practice styles can create a more comprehensive residency experience.

Final Thoughts

Ultimately, transferring residency programs is not easy but also is not impossible. Successfully switching residency programs can be a rewarding experience providing greater well-being and fulfillment.

Transferring from one residency program to another is rare but not unheard of. According to the most recent Accreditation Council for Graduate Medical Education Data Resource Book, there were 1020 residents who transferred residency programs in the 2020-2021 academic year.¹ With a total of 126,759 active residents in specialty programs, the percentage of transferring residents was less than 1%. The specialties with the highest number of transferring residents included psychiatry, general surgery, internal medicine, and family medicine. In dermatology programs, there were only 2 resident transfers during the 2019-2020 academic year and 6 transfers in the 2020-2021 academic year.^1,2 A resident contemplating transferring training programs must carefully consider the advantages and disadvantages before undertaking the uncertain transfer process, but transferring residency programs can be achieved successfully with planning and luck.

Deciding to Transfer

The decision to transfer residency programs may be a difficult one that is wrought with anxiety. There are many reasons why a trainee may wish to pursue transferring training programs. A transfer to another geographic area may be necessary for personal or family reasons, such as to reunite with a spouse and children or to care for a sick family member. A resident may find their program to be a poor fit and may wish to train in a different educational environment. Occasionally, a program can lose its accreditation, and its residents will be tasked with finding a new position elsewhere. A trainee also may realize that the specialty they matched into initially does not align with their true passions. It is important for the potential transfer applicant to be levelheaded about their decision. Residency is a demanding period for every trainee; switching programs may not be the best solution for every problem and should only be considered if essential.

Transfer Timing

A trainee may have thoughts of leaving a program soon after starting residency or perhaps even before starting if their National Resident Matching Program (NRMP) Match result was a disappointment; however, there are certain rules related to transfer timing. The NRMP Match represents a binding commitment for both the applicant and program. If for any reason an applicant will not honor the binding commitment, the NRMP requires the applicant to initiate a waiver review, which can be requested for unanticipated serious and extreme hardship, change of specialty, or ineligibility. According to the NRMP rules and regulations, applicants cannot apply for, discuss, interview for, or accept a position in another program until a waiver has been granted.³ Waivers based on change of specialty must be requested by mid-January prior to the start of training, which means most applicants who match to positions that begin in the same year of the Match do not qualify for change of specialty waivers. However, those who matched to an advanced position and are doing a preliminary year position may consider this option if they have a change of heart during their internship. The NRMP may consider a 1-year deferral to delay training if mutually agreed upon by both the matched applicant and the program.³ The binding commitment is in place for the first 45 days of training, and applicants who resign within 45 days or a program that tries to solicit the transfer of a resident prior to that date could be in violation of the Match and can face consequences such as being barred from entering the matching process in future cycles. Of the 1020 transfers that occurred among residents in specialty programs during the 2020-2021 academic year, 354 (34.7%) occurred during the first year of the training program; 228 (22.4%) occurred during the second year; 389 (38.1%) occurred during the third year; and 49 (4.8%) occurred in the fourth, fifth, or sixth year of the program.¹ Unlike other jobs/occupations in which one can simply give notice, in medical training even if a transfer position is accepted, the transition date between programs must be mutually agreed upon. Often, this may coincide with the start of the new academic year.

The Transfer Process

Transferring residency programs is a substantial undertaking. Unlike the Match, a trainee seeking to transfer programs does so without a standardized application system or structured support through the process; the transfer applicant must be prepared to navigate the transfer process on their own. The first step after making the decision to transfer is for the resident to meet with the program leadership (ie, program director[s], coordinator, designated official) at their home program to discuss the decision—a nerve-wracking but imperative first step. A receiving program may not favor an applicant secretly applying to a new program without the knowledge of their home program and often will require the home program’s blessing to proceed. The receiving program also would want to ensure the applicant is in good standing and not leaving due to misconduct. Once given the go-ahead, the process is largely in the hands of the applicant. The transfer applicant should identify locations or programs of interest and then take initiative to reach out to potential programs. FREIDA (Fellowship and Residency Electronic Interactive Database Access) is the American Medical Association’s residency and fellowship database that allows vacant position listings to be posted online.⁴ Additionally, the Association of American Medical Colleges’ FindAResident website is a year-round search tool designed to help find open residency and fellowship positions.⁵ Various specialties also may have program director listserves that communicate vacant positions. On occasion, there are spots in the main NRMP Match that are reserved positions (“R”). These are postgraduate year 2 positions in specialty programs that begin in the year of the Match and are reserved for physicians with prior graduate medical education; these also are known as “Physician Positions.”⁶ Ultimately, advertisements for vacancies may be few and far between, requiring the resident to send unsolicited emails with curriculum vitae attached to the program directors at programs of interest to inquire about any vacancies and hope for a favorable response. Even if the transfer applicant is qualified, luck that the right spot will be available at the right time may be the deciding factor in transferring programs.

The next step is interviewing for the position. There likely will be fewer candidates interviewing for an open spot but that does not make the process less competitive. The candidate should highlight their strengths and achievements and discuss why the new program would be a great fit both personally and professionally. Even if an applicant is seeking a transfer due to discontent with a prior program, it is best to act graciously and not speak poorly about another training program.

Prior to selection, the candidate may be asked to provide information such as diplomas, US Medical Licensing Examination Step and residency in-service training examination scores, and academic reviews from their current residency program. The interview process may take several weeks as the graduate medical education office often will need to officially approve of an applicant before a formal offer to transfer is extended.

Finally, once an offer is made and accepted, there still is a great amount of paperwork to complete before the transition. The applicant should stay on track with all off-boarding and on-boarding requirements, such as signing a contract, obtaining background checks, and applying for a new license to ensure the switch is not delayed.

 

 

Disadvantages of Transferring Programs

The transfer process is not easy to navigate and can be a source of stress for the applicant. It is natural to fear resentment from colleagues and co-residents. Although transferring programs might be in the best interest of the trainee, it may leave a large gap in the program that they are leaving, which can place a burden on the remaining residents.

There are many adjustments to be made after transferring programs. The transferring resident will again start from scratch, needing to learn the ropes and adapt to the growing pains of being at a new institution. This may require learning a completely new electronic medical record, adapting to a new culture, and in many cases stepping in as a senior resident without fully knowing the ins and outs of the program.

Advantages of Transferring Programs

Successfully transferring programs is something to celebrate. There may be great benefits to transferring to a program that is better suited to the trainee—either personally or professionally. Ameliorating the adversity that led to the decision to transfer such as reuniting a long-distance family or realizing one’s true passion can allow the resident to thrive as a trainee and maximize their potential. Transferring programs can give a resident a more well-rounded training experience, as different programs may have different strengths, patient populations, and practice settings. Working with different faculty members with varied niches and practice styles can create a more comprehensive residency experience.

Final Thoughts

Ultimately, transferring residency programs is not easy but also is not impossible. Successfully switching residency programs can be a rewarding experience providing greater well-being and fulfillment.

To the Editor:

Hemorrhagic lacrimation and epistaxis are dramatic presentations with a narrow differential diagnosis. It rarely has been reported to present alongside the more typical features of acute hemorrhagic edema of infancy (AHEI), which is a benign self-limited leukocytoclastic vasculitis most often seen in children aged 4 months to 2 years. Extracutaneous involvement rarely is seen in AHEI, though joint, gastrointestinal tract, and renal involvement have been reported.¹ Most patients present with edematous, annular, or cockade purpuric vasculitic lesions classically involving the face and distal extremities with relative sparing of the trunk. We present a case of a well-appearing, 10-month-old infant boy with hemorrhagic vasculitic lesions, acral edema, and an associated episode of hemorrhagic lacrimation and epistaxis.

A 10-month-old infant boy who was otherwise healthy presented to the emergency department (ED) with an acute-onset, progressively worsening cutaneous eruption of 2 days’ duration. A thorough history revealed that the eruption initially had presented as several small, bright-red papules on the thighs. The eruption subsequently spread to involve the buttocks, legs, and arms (Figures 1 and 2). The parents also noted that the patient had experienced an episode of bloody tears and epistaxis that lasted a few minutes at the pediatrician’s office earlier that morning, a finding that prompted the urgent referral to the ED.

Dermatology was then consulted. A review of systems was notable for rhinorrhea and diarrhea during the week leading to the eruption. The patient’s parents denied fevers, decreased oral intake, or a recent course of antibiotics. The patient’s medical history was notable only for atopic dermatitis treated with emollients and occasional topical steroids. The parents denied recent travel or vaccinations. Physical examination showed an afebrile, well-appearing infant with multiple nontender, slightly edematous, circular, purpuric papules and plaques scattered on the buttocks and extremities with edema on the dorsal feet. The remainder of the patient’s workup in the ED was notable for mild elevations in C-reactive protein levels (1.4 mg/dL [reference range, 0–1.2 mg/dL]) and an elevated erythrocyte sedimentation rate (22 mm/h [reference range, 2–12 mm/h]). A complete blood cell count; liver function tests; urinalysis; and coagulation studies, including prothrombin, partial thromboplastin time, and international normalized ratio, were unremarkable. Acute hemorrhagic edema of infancy was diagnosed based on the clinical manifestations.

Acute hemorrhagic edema of infancy (also known as Finkelstein disease, medallionlike purpura, Seidemayer syndrome, infantile postinfectious irislike purpura and edema, and purpura en cocarde avec oedeme) is believed to result from an immune complex–related reaction, often in the setting of an upper respiratory tract infection; medications, especially antibiotics; or vaccinations. The condition previously was considered a benign form of Henoch-Schönlein purpura; however, it is now recognized as its own clinical entity. Acute hemorrhagic edema of infancy commonly affects children between the ages of 4 months and 2 years. The incidence peaks in the winter months, and males tend to be more affected than females.¹

Acute hemorrhagic edema of infancy is clinically characterized by a triad of large purpuric lesions, low-grade fever, and peripheral acral edema. Edema can develop on the hands, feet, and genitalia. Importantly, facial edema has been noted to precede skin lesions.² Coin-shaped or targetoid hemorrhagic and purpuric lesions in a cockade or rosette pattern with scalloped margins typically begin on the distal extremities and tend to spread proximally. The lesions are variable in size but have been reported to be as large as 5 cm in diameter. Although joint pain, bloody diarrhea, hematuria, and proteinuria can accompany AHEI, most cases are devoid of systemic symptoms.³ Hemorrhagic lacrimation and epistaxis—both present in our patient—are rare findings with AHEI. It is likely that most providers, including dermatologists, may be unfamiliar with these striking clinical findings. Although the pathophysiology of hemorrhagic lacrimation and epistaxis has not been formally investigated, we postulate that it likely is related to the formation of immune complexes that lead to small vessel vasculitis, underpinning the characteristic findings in AHEI.^4,5 This reasoning is supported by the complete resolution of symptoms corresponding with clinical clearance of the cutaneous vasculitis in 2 prior cases^4,5 as well as in our patient who did not have a relapse of symptoms following cessation of the cutaneous eruption at a pediatric follow-up appointment 2 weeks later.

Acute hemorrhagic edema of infancy is a clinical diagnosis; however, a skin biopsy can be performed to confirm the clinical suspicion and rule out more serious conditions. Histopathologic examination reveals a leukocytoclastic vasculitis involving the capillaries and postcapillary venules of the upper and mid dermis. Laboratory test results usually are nonspecific but can help distinguish AHEI from more serious diseases. The erythrocyte sedimentation rate and C-reactive protein level may be slightly elevated in infants with AHEI. Urinalysis and stool guaiac tests also can be performed to evaluate for any renal or gastrointestinal involvement.⁶

The differential diagnosis includes IgA vasculitis, erythema multiforme, acute meningococcemia, urticarial vasculitis, Kawasaki disease, and child abuse. IgA vasculitis often presents with more systemic involvement, with abdominal pain, vomiting, hematemesis, diarrhea, and hematochezia occurring in up to 50% of patients. The cutaneous findings of erythema multiforme classically are confined to the limbs and face, and edema of the extremities typically is not seen. Patients with acute meningococcemia appear toxic with high fevers, malaise, and possible septic shock.⁵

Acute hemorrhagic edema of infancy is a self-limited condition typically lasting 1 to 3 weeks and requires only supportive care.⁷ Antibiotics should be given to treat concurrent bacterial infections, and antihistamines and steroids may be useful for symptomatic relief. Importantly, however, systemic corticosteroids do not appear to conclusively alter the disease course.⁸

Acute hemorrhagic edema of infancy is a rare benign leukocytoclastic vasculitis with a striking presentation often seen following an upper respiratory tract infection or course of antibiotics. Our case demonstrates that on rare occasions, AHEI may be accompanied by hemorrhagic lacrimation and epistaxis—findings that can be quite alarming to both parents and medical providers. Nonetheless, patients and their caretakers should be assured that the condition is self-limited and resolves without permanent sequalae.

To the Editor:

Hemorrhagic lacrimation and epistaxis are dramatic presentations with a narrow differential diagnosis. It rarely has been reported to present alongside the more typical features of acute hemorrhagic edema of infancy (AHEI), which is a benign self-limited leukocytoclastic vasculitis most often seen in children aged 4 months to 2 years. Extracutaneous involvement rarely is seen in AHEI, though joint, gastrointestinal tract, and renal involvement have been reported.¹ Most patients present with edematous, annular, or cockade purpuric vasculitic lesions classically involving the face and distal extremities with relative sparing of the trunk. We present a case of a well-appearing, 10-month-old infant boy with hemorrhagic vasculitic lesions, acral edema, and an associated episode of hemorrhagic lacrimation and epistaxis.

A 10-month-old infant boy who was otherwise healthy presented to the emergency department (ED) with an acute-onset, progressively worsening cutaneous eruption of 2 days’ duration. A thorough history revealed that the eruption initially had presented as several small, bright-red papules on the thighs. The eruption subsequently spread to involve the buttocks, legs, and arms (Figures 1 and 2). The parents also noted that the patient had experienced an episode of bloody tears and epistaxis that lasted a few minutes at the pediatrician’s office earlier that morning, a finding that prompted the urgent referral to the ED.

Dermatology was then consulted. A review of systems was notable for rhinorrhea and diarrhea during the week leading to the eruption. The patient’s parents denied fevers, decreased oral intake, or a recent course of antibiotics. The patient’s medical history was notable only for atopic dermatitis treated with emollients and occasional topical steroids. The parents denied recent travel or vaccinations. Physical examination showed an afebrile, well-appearing infant with multiple nontender, slightly edematous, circular, purpuric papules and plaques scattered on the buttocks and extremities with edema on the dorsal feet. The remainder of the patient’s workup in the ED was notable for mild elevations in C-reactive protein levels (1.4 mg/dL [reference range, 0–1.2 mg/dL]) and an elevated erythrocyte sedimentation rate (22 mm/h [reference range, 2–12 mm/h]). A complete blood cell count; liver function tests; urinalysis; and coagulation studies, including prothrombin, partial thromboplastin time, and international normalized ratio, were unremarkable. Acute hemorrhagic edema of infancy was diagnosed based on the clinical manifestations.

Acute hemorrhagic edema of infancy (also known as Finkelstein disease, medallionlike purpura, Seidemayer syndrome, infantile postinfectious irislike purpura and edema, and purpura en cocarde avec oedeme) is believed to result from an immune complex–related reaction, often in the setting of an upper respiratory tract infection; medications, especially antibiotics; or vaccinations. The condition previously was considered a benign form of Henoch-Schönlein purpura; however, it is now recognized as its own clinical entity. Acute hemorrhagic edema of infancy commonly affects children between the ages of 4 months and 2 years. The incidence peaks in the winter months, and males tend to be more affected than females.¹

Acute hemorrhagic edema of infancy is clinically characterized by a triad of large purpuric lesions, low-grade fever, and peripheral acral edema. Edema can develop on the hands, feet, and genitalia. Importantly, facial edema has been noted to precede skin lesions.² Coin-shaped or targetoid hemorrhagic and purpuric lesions in a cockade or rosette pattern with scalloped margins typically begin on the distal extremities and tend to spread proximally. The lesions are variable in size but have been reported to be as large as 5 cm in diameter. Although joint pain, bloody diarrhea, hematuria, and proteinuria can accompany AHEI, most cases are devoid of systemic symptoms.³ Hemorrhagic lacrimation and epistaxis—both present in our patient—are rare findings with AHEI. It is likely that most providers, including dermatologists, may be unfamiliar with these striking clinical findings. Although the pathophysiology of hemorrhagic lacrimation and epistaxis has not been formally investigated, we postulate that it likely is related to the formation of immune complexes that lead to small vessel vasculitis, underpinning the characteristic findings in AHEI.^4,5 This reasoning is supported by the complete resolution of symptoms corresponding with clinical clearance of the cutaneous vasculitis in 2 prior cases^4,5 as well as in our patient who did not have a relapse of symptoms following cessation of the cutaneous eruption at a pediatric follow-up appointment 2 weeks later.

Acute hemorrhagic edema of infancy is a clinical diagnosis; however, a skin biopsy can be performed to confirm the clinical suspicion and rule out more serious conditions. Histopathologic examination reveals a leukocytoclastic vasculitis involving the capillaries and postcapillary venules of the upper and mid dermis. Laboratory test results usually are nonspecific but can help distinguish AHEI from more serious diseases. The erythrocyte sedimentation rate and C-reactive protein level may be slightly elevated in infants with AHEI. Urinalysis and stool guaiac tests also can be performed to evaluate for any renal or gastrointestinal involvement.⁶

The differential diagnosis includes IgA vasculitis, erythema multiforme, acute meningococcemia, urticarial vasculitis, Kawasaki disease, and child abuse. IgA vasculitis often presents with more systemic involvement, with abdominal pain, vomiting, hematemesis, diarrhea, and hematochezia occurring in up to 50% of patients. The cutaneous findings of erythema multiforme classically are confined to the limbs and face, and edema of the extremities typically is not seen. Patients with acute meningococcemia appear toxic with high fevers, malaise, and possible septic shock.⁵

Acute hemorrhagic edema of infancy is a self-limited condition typically lasting 1 to 3 weeks and requires only supportive care.⁷ Antibiotics should be given to treat concurrent bacterial infections, and antihistamines and steroids may be useful for symptomatic relief. Importantly, however, systemic corticosteroids do not appear to conclusively alter the disease course.⁸

Acute hemorrhagic edema of infancy is a rare benign leukocytoclastic vasculitis with a striking presentation often seen following an upper respiratory tract infection or course of antibiotics. Our case demonstrates that on rare occasions, AHEI may be accompanied by hemorrhagic lacrimation and epistaxis—findings that can be quite alarming to both parents and medical providers. Nonetheless, patients and their caretakers should be assured that the condition is self-limited and resolves without permanent sequalae.

To the Editor:

Hemorrhagic lacrimation and epistaxis are dramatic presentations with a narrow differential diagnosis. It rarely has been reported to present alongside the more typical features of acute hemorrhagic edema of infancy (AHEI), which is a benign self-limited leukocytoclastic vasculitis most often seen in children aged 4 months to 2 years. Extracutaneous involvement rarely is seen in AHEI, though joint, gastrointestinal tract, and renal involvement have been reported.¹ Most patients present with edematous, annular, or cockade purpuric vasculitic lesions classically involving the face and distal extremities with relative sparing of the trunk. We present a case of a well-appearing, 10-month-old infant boy with hemorrhagic vasculitic lesions, acral edema, and an associated episode of hemorrhagic lacrimation and epistaxis.

A 10-month-old infant boy who was otherwise healthy presented to the emergency department (ED) with an acute-onset, progressively worsening cutaneous eruption of 2 days’ duration. A thorough history revealed that the eruption initially had presented as several small, bright-red papules on the thighs. The eruption subsequently spread to involve the buttocks, legs, and arms (Figures 1 and 2). The parents also noted that the patient had experienced an episode of bloody tears and epistaxis that lasted a few minutes at the pediatrician’s office earlier that morning, a finding that prompted the urgent referral to the ED.

Dermatology was then consulted. A review of systems was notable for rhinorrhea and diarrhea during the week leading to the eruption. The patient’s parents denied fevers, decreased oral intake, or a recent course of antibiotics. The patient’s medical history was notable only for atopic dermatitis treated with emollients and occasional topical steroids. The parents denied recent travel or vaccinations. Physical examination showed an afebrile, well-appearing infant with multiple nontender, slightly edematous, circular, purpuric papules and plaques scattered on the buttocks and extremities with edema on the dorsal feet. The remainder of the patient’s workup in the ED was notable for mild elevations in C-reactive protein levels (1.4 mg/dL [reference range, 0–1.2 mg/dL]) and an elevated erythrocyte sedimentation rate (22 mm/h [reference range, 2–12 mm/h]). A complete blood cell count; liver function tests; urinalysis; and coagulation studies, including prothrombin, partial thromboplastin time, and international normalized ratio, were unremarkable. Acute hemorrhagic edema of infancy was diagnosed based on the clinical manifestations.

Acute hemorrhagic edema of infancy (also known as Finkelstein disease, medallionlike purpura, Seidemayer syndrome, infantile postinfectious irislike purpura and edema, and purpura en cocarde avec oedeme) is believed to result from an immune complex–related reaction, often in the setting of an upper respiratory tract infection; medications, especially antibiotics; or vaccinations. The condition previously was considered a benign form of Henoch-Schönlein purpura; however, it is now recognized as its own clinical entity. Acute hemorrhagic edema of infancy commonly affects children between the ages of 4 months and 2 years. The incidence peaks in the winter months, and males tend to be more affected than females.¹

Acute hemorrhagic edema of infancy is clinically characterized by a triad of large purpuric lesions, low-grade fever, and peripheral acral edema. Edema can develop on the hands, feet, and genitalia. Importantly, facial edema has been noted to precede skin lesions.² Coin-shaped or targetoid hemorrhagic and purpuric lesions in a cockade or rosette pattern with scalloped margins typically begin on the distal extremities and tend to spread proximally. The lesions are variable in size but have been reported to be as large as 5 cm in diameter. Although joint pain, bloody diarrhea, hematuria, and proteinuria can accompany AHEI, most cases are devoid of systemic symptoms.³ Hemorrhagic lacrimation and epistaxis—both present in our patient—are rare findings with AHEI. It is likely that most providers, including dermatologists, may be unfamiliar with these striking clinical findings. Although the pathophysiology of hemorrhagic lacrimation and epistaxis has not been formally investigated, we postulate that it likely is related to the formation of immune complexes that lead to small vessel vasculitis, underpinning the characteristic findings in AHEI.^4,5 This reasoning is supported by the complete resolution of symptoms corresponding with clinical clearance of the cutaneous vasculitis in 2 prior cases^4,5 as well as in our patient who did not have a relapse of symptoms following cessation of the cutaneous eruption at a pediatric follow-up appointment 2 weeks later.

Acute hemorrhagic edema of infancy is a clinical diagnosis; however, a skin biopsy can be performed to confirm the clinical suspicion and rule out more serious conditions. Histopathologic examination reveals a leukocytoclastic vasculitis involving the capillaries and postcapillary venules of the upper and mid dermis. Laboratory test results usually are nonspecific but can help distinguish AHEI from more serious diseases. The erythrocyte sedimentation rate and C-reactive protein level may be slightly elevated in infants with AHEI. Urinalysis and stool guaiac tests also can be performed to evaluate for any renal or gastrointestinal involvement.⁶

The differential diagnosis includes IgA vasculitis, erythema multiforme, acute meningococcemia, urticarial vasculitis, Kawasaki disease, and child abuse. IgA vasculitis often presents with more systemic involvement, with abdominal pain, vomiting, hematemesis, diarrhea, and hematochezia occurring in up to 50% of patients. The cutaneous findings of erythema multiforme classically are confined to the limbs and face, and edema of the extremities typically is not seen. Patients with acute meningococcemia appear toxic with high fevers, malaise, and possible septic shock.⁵

Acute hemorrhagic edema of infancy is a self-limited condition typically lasting 1 to 3 weeks and requires only supportive care.⁷ Antibiotics should be given to treat concurrent bacterial infections, and antihistamines and steroids may be useful for symptomatic relief. Importantly, however, systemic corticosteroids do not appear to conclusively alter the disease course.⁸

Acute hemorrhagic edema of infancy is a rare benign leukocytoclastic vasculitis with a striking presentation often seen following an upper respiratory tract infection or course of antibiotics. Our case demonstrates that on rare occasions, AHEI may be accompanied by hemorrhagic lacrimation and epistaxis—findings that can be quite alarming to both parents and medical providers. Nonetheless, patients and their caretakers should be assured that the condition is self-limited and resolves without permanent sequalae.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

To the Editor:

A 44-year-old woman presented with a low-grade fever (temperature, 38.0 °C) and painful acral lesions of 1 week’s duration. She had a history of hepatitis C viral infection and intravenous (IV) drug use, as well as polymicrobial infective endocarditis that involved the tricuspid and aortic valves; pathogenic organisms were identified via blood culture as Enterococcus faecalis, Serratia species, Streptococcus viridans, and Candida albicans. The patient had received a mechanical aortic valve and bioprosthetic tricuspid valve replacement 5 months prior with warfarin therapy and had completed a postsurgical 6-week course of high-dose micafungin. She reported that she had developed painful, violaceous, thin papules on the plantar surface of the left foot 2 weeks prior to presentation. Her symptoms improved with a short systemic steroid taper; however, within a week she developed new tender, erythematous, thin papules on the plantar surface of the right foot and the palmar surface of the left hand with associated lower extremity swelling. She denied other symptoms, including fever, chills, neurologic symptoms, shortness of breath, chest pain, nausea, vomiting, hematuria, and hematochezia. Due to worsening cutaneous findings, the patient presented to the emergency department, prompting hospital admission for empiric antibacterial therapy with vancomycin and piperacillin-tazobactam for suspected infectious endocarditis. Dermatology was consulted after 1 day of antibacterial therapy without improvement to determine the etiology of the patient’s skin findings.

Physical examination revealed the patient was afebrile with partially blanching violaceous to purpuric, tender, edematous papules on the left fourth and fifth finger pads, as well as scattered, painful, purpuric patches with stellate borders on the right plantar foot (Figure 1). Laboratory test results revealed mild anemia (hemoglobin, 11.9 g/dL [reference range, 12.0–15.0 g/dL], mild neutrophilia (neutrophils, 8.4×10⁹/L [reference range, 1.9–7.9×10⁹/L], elevated acute-phase reactants (erythrocyte sedimentation rate, 71 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 5.7 mg/dL [reference range, 0.0–0.5 mg/dL]), and positive hepatitis C virus antibody with an undetectable viral load. At the time of dermatologic evaluation, admission blood cultures and transthoracic echocardiogram were negative. Additionally, a transesophageal echocardiogram, limited by artifact from the mechanical aortic valve, was equivocal for valvular pathology. Subsequent ophthalmologic evaluation was negative for lesions associated with endocarditis, such as retinal hemorrhages.

Punch biopsies of the left fourth finger pad were submitted for histopathologic analysis and tissue cultures. Histopathology demonstrated deep dermal perivascular neutrophilic inflammation with multiple intravascular thrombi, perivascular fibrin, and karyorrhectic debris (Figure 2). Periodic acid–Schiff and Grocott-Gomori methenamine-silver stains revealed fungal spores with rare pseudohyphae within the thrombosed vascular spaces and the perivascular dermis, consistent with fungal septic emboli (Figure 3).

Empiric systemic antifungal coverage composed of IV liposomal amphotericin B and oral flucytosine was initiated, and the patient’s tender acral papules rapidly improved. Within 48 hours of biopsy, skin tissue culture confirmed the presence of C albicans. Four days after the preliminary dermatopathology report, confirmatory blood cultures resulted with pansensitive C albicans. Final tissue and blood cultures were negative for bacteria including mycobacteria. In addition to a 6-week course of IV amphotericin B and flucytosine, repeat surgical intervention was considered, and lifelong suppressive antifungal oral therapy was recommended. Unfortunately, the patient did not present for follow-up. Three months later, she presented to the emergency department with peritonitis; in the operating room, she was found to have ischemia of the entirety of the small and large intestines and died shortly thereafter.

Fungal endocarditis is rare, tending to develop in patient populations with particular risk factors such as immune compromise, structural heart defects or prosthetic valves, and IV drug use. Candida infective endocarditis (CIE) represents less than 2% of infective endocarditis cases and carries a high mortality rate (30%–80%).^1-3 Diagnosis may be challenging, as the clinical presentation varies widely. Although some patients may present with classic features of infective endocarditis, including fever, cardiac murmurs, and positive blood cultures, many cases of infective endocarditis present with nonspecific symptoms, raising a broad clinical differential diagnosis. Delay in diagnosis, which is seen in 82% of patients with fungal endocarditis, may be attributed to the slow progression of symptoms, inconclusive cardiac imaging, or negative blood cultures seen in almost one-third of cases.^2,3 The feared complication of systemic embolization via infective endocarditis may occur in up to one-half of cases, with the highest rates associated with staphylococcal or fungal pathogens.² The risk for embolization in fungal endocarditis is independent of the size of the cardiac valve vegetations; accordingly, sequelae of embolic complications may arise despite negative cardiac imaging.⁴ Embolic complications, which typically are seen within the first 2 to 4 weeks of treatment, may serve as the presenting feature of endocarditis and may even occur after completion of antimicrobial therapy.

Detection of cutaneous manifestations of infective endocarditis, including Janeway lesions, Osler nodes, and splinter hemorrhages, may allow for earlier diagnosis. Despite eponymous recognition, Janeway lesions and Osler nodes are relatively uncommon manifestations of infective endocarditis and may be found in only 5% to 15% of cases.⁵ Biopsies of suspected Janeway lesions and Osler nodes may allow for recognition of relevant vascular pathology, identification of the causative pathogen, and strong support for the diagnosis of infective endocarditis.^4-7

The initial photomicrograph of corresponding Janeway lesion histopathology was published by Kerr in 1955 and revealed dermal microabscesses posited to be secondary to bacterial emboli.^8,9 Additional cases through the years have reported overlapping histopathologic features of Janeway lesions and Osler nodes, with the latter often defined by the presence of vasculitis.⁴ Although there appears to be ongoing debate and overlap between the 2 integumentary findings, a general consensus on differentiation takes into account both the clinical signs and symptoms as well as the histopathologic findings.^10,11

Osler nodes present as tender, violaceous, subcutaneous nodules on the acral surfaces, usually on the pads of the fingers and toes.⁵ The pathogenesis involves the deposition of immune complexes as a sequela of vascular occlusion by microthrombi classically seen in the late phase of subacute endocarditis. Janeway lesions present as nontender erythematous macules on the acral surfaces and are thought to represent microthrombi with dermal microabscesses, more common in acute endocarditis. Our patient demonstrated features of both Osler nodes and Janeway lesions. Despite the presence of fungal thrombi—a pathophysiology closer to that of Janeway lesions—the clinical presentation of painful acral nodules affecting finger pads and histologic features of vasculitis may be better characterized as Osler nodes. Regardless of pathogenesis, these cutaneous findings serve as a minor clinical criterion in the Duke criteria for the diagnosis of infective endocarditis when present.¹²

Candida infective endocarditis should be suspected in a patient with a history of valvular disease or prior infective endocarditis with fungemia, unexplained neurologic signs, or manifestations of peripheral embolization despite negative blood cultures.³ Particularly in the setting of negative cardiac imaging, recognition of CIE requires heightened diagnostic acumen and clinicopathologic correlation. Although culture and pathologic examination of valvular vegetations represents the gold standard for diagnosis of CIE, aspiration and culture of easily accessible septic emboli may provide rapid identification of the etiologic pathogen. In 1976, Alpert et al¹³ identified C albicans from an aspirated Osler node. Postmortem examination revealed extensive involvement of the homograft valve and aortic root with C albicans.¹³ Many other examples exist in the literature demonstrating matching pathogenic isolates from microbiologic cultures of skin and blood.^4,9,14,15 Thadepalli and Francis⁷ investigated 26 cases of endocarditis in heroin users in which the admitting diagnosis was endocarditis in only 4 cases. The etiologic pathogen was aspirated from secondary sites of localized infections secondary to emboli, including cutaneous lesions in 10 of the cases. Gram stain and culture revealed the causative organism leading to the ultimate diagnosis and management in 17 of 26 patients with endocarditis.⁷

The incidence of fungal endocarditis is increasing, with a reported 67% of cases caused by nosocomial infection.¹ Given the rising incidence of fungal endocarditis and its accompanying diagnostic difficulties, including frequently negative blood cultures and cardiac imaging, clinicians must perform careful skin examinations, employ judicious use of skin biopsy, and carefully correlate clinical and pathologic findings to improve recognition of this disease and guide patient care.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Generalized pustular psoriasis (GPP) is a rare but severe subtype of psoriasis that can present with systemic symptoms and organ failure, sometimes leading to hospitalization and even death.^1,2 Due to the rarity of this subtype and GPP being excluded from clinical trials for plaque psoriasis, there is limited information on the optimal treatment of this disease.

More than 20 systemic medications have been described in the literature for treating GPP, including systemic steroids, traditional immunosuppressants, retinoids, and biologics, which often are used in combination; none have been consistently effective.³ Among biologic therapies, the use of tumor necrosis factor α as well as IL-12/23 and IL-17 inhibitors has been reported, with the least amount of experience with IL-17 inhibitors.⁴

A 53-year-old Korean woman presented to the dermatology clinic for evaluation of a widespread painful rash involving the face, neck, torso, arms, and legs that had been treated intermittently with systemic steroids by her primary care physician for several months before presentation. She had no relevant medical or dermatologic history. She denied taking prescription or over-the-counter medications.

Physical examination revealed the patient was afebrile, but she reported general malaise and chills. She had widespread erythematous, annular, scaly plaques that coalesced into polycyclic plaques studded with nonfollicular-based pustules on the forehead, frontal hairline, neck, chest, abdomen, back, arms, and legs (Figure 1).

Two 4-mm punch biopsies were performed for hematoxylin and eosin staining and direct immunofluorescence. Histopathologic analysis showed prominent subcorneal neutrophilic pustules and spongiform collections of neutrophils in the spinous layer without notable eosinophils (Figure 2). Direct immunofluorescence was negative.

Based on the clinical history, physical examination, histopathology, and unremarkable drug history, a diagnosis of GPP was made. Initially, acitretin 25 mg/d was prescribed, but the patient was unable to start treatment because the cost of the drug was prohibitive. Her condition worsened, and she returned to the clinic 2 days later. Based on knowledge of an ongoing phase 3, open-label study for risankizumab in GPP, a sample of risankizumab 150 mg was administered subcutaneously in this patient. Three days later, most of the pustules on the upper half of the patient’s body had dried up and she began to desquamate from head to toe (Figure 3).The patient developed notable edema of the lower extremities, which required furosemide 20 mg/d andibuprofen 600 mg every 6 hours for symptom relief.

Ten days after the initial dose of risankizumab, the patient continued to steadily improve. All the pustules had dried up and she was already showing signs of re-epithelialization. Edema and pain also had notably improved. She received 2 additional samples of risankizumab 150 mg at weeks 4 and 16, at which point she was able to receive compassionate care through the drug manufacturer’s program. At follow-up 151 days after the initial dose of risankizumab, the patient’s skin was completely clear.

Generalized pustular psoriasis remains a difficult disease to study, given its rarity and unpredictable course. Spesolimab, a humanized anti–IL-36 receptor monoclonal antibody, was recently approved by the US Food and Drug Administration (FDA) for the treatment of GPP.⁵ In the pivotal trial (ClinicalTrials.gov Identifier NCT03782792),⁵ an astonishingly high 54% of patients (19/35) given a single dose of intravenous spesolimab reached the primary end point of no pustules at day 7. However, safety concerns, such as serious infections and severe cutaneous adverse reactions, as well as logistical challenges that come with intravenous administration for an acute disease, may prevent widespread adoption by community dermatologists.

Tumor necrosis factor α, IL-17, and IL-23 inhibitors currently are approved for the treatment of GPP in Japan, Thailand, and Taiwan based on small, nonrandomized, open-label studies.^6-10 More recently, results from a phase 3, randomized, open-label study to assess the efficacy and safety of 2 different dosing regimens of risankizumab with 8 Japanese patients with GPP were published.¹¹ However, there currently is only a single approved medication for GPP in Europe and the United States. Therefore, additional therapies, particularly those that have already been established in dermatology, would be welcome in treating this disease.

A number of questions still need to be answered regarding treating GPP with risankizumab:

• What is the optimal dose and schedule of this drug? Our patient received the standard 150-mg dose that is FDA approved for moderate to severe plaque psoriasis; would a higher dose, such as the FDA-approved 600-mg dosing used to treat Crohn disease, have led to a more rapid and durable response?¹²

• For how long should these patients be treated? Will their disease follow the same course as psoriasis vulgaris, requiring long-term, continuous treatment?

• An ongoing 5-year, open-label extension study of spesolimab might eventually answer that question and currently is recruiting participants (NCT03886246).

• Is there a way to predict a priori which patients will be responders? Biomarkers—especially through the use of tape stripping—are promising, but validation studies are still needed.¹³

• Because 69% (24/35) of enrolled patients in the treatment group of the spesolimab trial did not harbor a mutation of the IL36RN gene, how reliable is mutation status in predicting treatment response?⁵

Of note, some of these questions also apply to guttate psoriasis, a far more common subtype of psoriasis that also is worth exploring.

Nevertheless, these are exciting times for patients with GPP. What was once considered an obscure orphan disease is the focus of major recent publications³ and phase 3, randomized, placebo-controlled studies.⁵ We can be cautiously optimistic that in the next few years we will be in a better position to care for patients with GPP.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

To the Editor:

Because the SARS-CoV-2 virus is constantly changing, routine vaccination to prevent COVID-19 infection is recommended. The messenger RNA (mRNA) vaccines from Pfizer-BioNTech and Moderna as well as the Ad26.COV2.S (Johnson & Johnson) and NVX-CoV2373 (Novavax) vaccines are the most commonly used COVID-19 vaccines in the United States. Adverse effects following vaccination against SARS-CoV-2 are well documented; recent studies report a small incidence of adverse effects in the general population, with most being minor (eg, headache, fever, muscle pain).^1,2 Interestingly, reports of exacerbation of psoriasis and new-onset psoriasis following COVID-19 vaccination suggest a potential association.^3,4 However, the literature investigating the vaccine adverse effect profile in this demographic is scarce. We examined the incidence of adverse effects from SARS-CoV-2 vaccines in patients with psoriasis.

This retrospective cohort study used the COVID-19 Research Database (https://covid19researchdatabase.org/) to examine the adverse effects following the first and second doses of the mRNA vaccines in patients with and without psoriasis. The sample size for the Ad26.COV2.S vaccine was too small to analyze.

Claims were evaluated from August to October 2021 for 2 diagnoses of psoriasis prior to January 1, 2020, using the International Classification of Diseases, Tenth Revision (ICD-10) code L40.9 to increase the positive predictive value and ensure that the diagnosis preceded the COVID-19 pandemic. Patients younger than 18 years and those who did not receive 2 doses of a SARS-CoV-2 vaccine were excluded. Controls who did not have a diagnosis of psoriasis were matched for age, sex, and hypertension at a 4:1 ratio. Hypertension represented the most common comorbidity that could feasibly be controlled for in this study population. Other comorbidities recorded included obesity, type 2 diabetes mellitus, congestive heart failure, asthma, chronic obstructive pulmonary disease, chronic ischemic heart disease, rhinitis, and chronic kidney disease.

Common adverse effects as long as 30 days after vaccination were identified using ICD-10 codes. Adverse effects of interest were anaphylactic reaction, initial encounter of adverse effect of viral vaccines, fever, allergic urticaria, weakness, altered mental status, malaise, allergic reaction, chest pain, symptoms involving circulatory or respiratory systems, localized rash, axillary lymphadenopathy, infection, and myocarditis.⁵ Poisson regression was performed using Stata 17 analytical software.

We identified 4273 patients with psoriasis and 17,092 controls who received mRNA COVID-19 vaccines (Table). Adjusted odds ratios (aORs) for doses 1 and 2 were calculated for each vaccine (eTable). Adverse effects with sufficient data to generate an aOR included weakness, altered mental status, malaise, chest pain, and symptoms involving the circulatory or respiratory system. The aORs for allergic urticaria and initial encounter of adverse effect of viral vaccines were only calculated for the Moderna mRNA vaccine due to low sample size.

This study demonstrated that patients with psoriasis do not appear to have a significantly increased risk of adverse effects from mRNA SARS-CoV-2 vaccines. Although the ORs in this study were not significant, most recorded adverse effects demonstrated an aOR less than 1, suggesting that there might be a lower risk of certain adverse effects in psoriasis patients. This could be explained by the immunomodulatory effects of certain systemic psoriasis treatments that might influence the adverse effect presentation.

The study is limited by the lack of treatment data, small sample size, and the fact that it did not assess flares or worsening of psoriasis with the vaccines. Underreporting of adverse effects by patients and underdiagnosis of adverse effects secondary to SARS-CoV-2 vaccines due to its novel nature, incompletely understood consequences, and limited ICD-10 codes associated with adverse effects all contributed to the small sample size.

Our findings suggest that the risk for immediate adverse effects from the mRNA SARS-CoV-2 vaccines is not increased among psoriasis patients. However, the impact of immunomodulatory agents on vaccine efficacy and expected adverse effects should be investigated. As more individuals receive the COVID-19 vaccine, the adverse effect profile in patients with psoriasis is an important area of investigation.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.

Consultations and referrals are an important component of many dermatology practices. There are several families of consultation codes that can be utilized based on the setting and format of the patient encounter. In this article, I describe appropriate use of 3 families of consultation codes and recent updates in these areas.

Consultation Definitions

For all of these code sets, the same definition of consultationapplies—namely that the encounter is provided at the request of another physician, other qualified health care professional, or other appropriate source (eg, nonclinical social worker, educator, lawyer, insurance company) for a specific condition or problem. Importantly, a consultation initiated by a patient or family, or both, and not requested by one of the professionals listed above is not reported using a consultation code.¹

The consultant’s opinion and any services that were ordered or performed also must be communicated to the requesting provider. The type of communication required varies based on the consultation code set in question.

Outpatient Consultation Codes

Outpatient consultation CPT (Current Procedural Terminology) codes (99241-99245) are a family of codes that can be utilized for evaluation of a new patient or an existing patient with a new problem in the outpatient setting. These codes are not reimbursed by the Centers for Medicare & Medicaid Services, but some private payers do recognize and reimburse for them.²

The consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹ Modifier -32 should not be used for a second request by a patient or a patient’s family.¹

This family of codes has been revised in tandem with other evaluation and management (E/M) code sets; changes went into effect January 1, 2023. These updates are part of the ongoing effort to update code wording and structures to reflect guiding principles of the American Medical Association when redesigning E/M codes. These principles include decreasing administrative burden and the need for audits, decreasing unnecessary documentation that is not needed for patient care, and ensuring that payment for E/M is resource based.³ Updated code language and payment structure is found in Table 1.^1,2 The main updates to these codes include:

• Code 99241 was deleted. This was in line with removal of 99201 from the outpatient E/M family set.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 99417 can be utilized.

Inpatient Consultation Codes

Similar to the outpatient consultation codes, the inpatient consultation codes also have been revised as part of E/M updates; revisions went into effect January 1, 2023. Also, as with the outpatient consultation codes, the consultant’s opinion and any services that were ordered or performed must be communicated by written report to the requesting physician, other qualified health care professional, or other appropriate source. If a consultation is mandated (eg, by a third-party payer), then modifier -32 also should be reported.¹

When inpatient consultations are performed, 2 code families generally are utilized. For initial consultation, initial inpatient consultation codes (99251-99255) are used; for any follow-up encounters performed while the patient is an inpatient, subsequent inpatient consultation codes (99231-99233) are used. The subsequent code family is the same that is utilized for all subsequent care within the inpatient or observation care setting, regardless of how the care was initiated.¹

“Initial service” is when the patient has not received any professional services from either the physician or other qualified health care professional or from another physician or other qualified health care professional ofthe exact same specialty and subspecialty who belongs to the same group practice during the inpatient, observation, or nursing facility admission and stay. “Subsequent service” is when the patient has received professional service(s) from either the physician or other qualified health care professional or from another physician or other qualified health care professional.¹ Updated code language and payment structure is found in Table 2.^1,2 Major changes include:

• Code 99251 was deleted. This is in line with deletion of a new low-level patient encounter in the outpatient E/M family set and consultation code family set, as noted above.

• Level of service is now based solely on either time on the date of encounter or medical decision-making.

• Definitions regarding medical decision-making are in line with those utilized for outpatient E/M codes.

• If coding by time and the maximum amount of time has been exceeded by 15 or more minutes, prolonged services code 993X0 can be utilized.

Interprofessional Consultation Codes

An additional code family that can be utilized for consultations is the interprofessional consultation codes. These codes can be utilized when assisting in the diagnosis or management, or both, of a patient without face-to-face contact. These codes are listed in Table 3.^2,4 For all of these codes, the consultation is performed by telephone, internet or electronic health record, or a combination of these means. The consultation can be for a new problem or a worsening existing problem. The patient can be a new or established patient to the consultant. Documentation should be performed in the patient’s medical record, including the reason for the request.

To bill for interprofessional consultation, the consultant should not have seen the patient in a face-to-face encounter within the prior 14 days or see them in the following 14 days. The codes should not be reported more than once in a 7-day period or more than once in a 14-day period in the case of code 99452.⁴ For codes 99446 to 99449, more than 50% of the time spent by the consulting physician must be devoted to verbal or internet discussion, or both, with the referring physician. For code 99451, service time is based on total review and interprofessional communication time.⁴ The correct code is chosen based on the following parameters:

• 99446-99449: Describes interprofessional consultation services, which include both a written and a verbal report to the patient’s treating or requesting physician or qualified health care professional. These codes can be utilized by a consulting physician. The correct code is chosen based on time spent by the consulting physician.

• 99451: Describes an interprofessional consultation service, which includes a written report to the patient’s treating or requesting physician or qualified health care professional. This code can be utilized by a consulting physician once 5 minutes of consultative discussion and review has been performed.

• 99452: Describes an interprofessional consultation service provided by the requesting physician. This code can be utilized when a requesting physician spends 16 to 30 minutes in medical consultative discussion and review.

Final Thoughts

Consultation codes can be an important part of a dermatologist’s practice. Differences exist between consultation code sets based on the encounter setting and whether the encounter was performed with or without face-to-face contact. In addition, updates to the E/M inpatient and outpatient consultation codes went into effect January 1, 2023. It is important to understand those changes to correctly bill for these encounters.