Article

To the Editor:

With a steady increase in dermatology publications over recent decades, there is an expanding pool of evidence to address clinical questions.¹ Residency training is the time when appraising the medical literature and practicing evidence-based medicine is most honed. Evidence-based medicine is an essential component of Practice-based Learning and Improvement, a required core competency of the Accreditation Council for Graduate Medical Education.² Assimilation of new research evidence is traditionally taught through didactics and journal club discussions in residency.

However, at a time when the demand for information overwhelms safeguards that exist to evaluate its quality, it is more important than ever to be equipped with the proper tools to critically appraise novel literature. Beyond accepting a scientific article at face value, physicians must learn to ask targeted questions of the study design, results, and clinical relevance. These questions change based on the type of study, and organizations such as the Oxford Centre for Evidence-Based Medicine provide guidance through critical appraisal worksheets.³

To investigate the utility of using guided questions to evaluate the reliability, significance, and applicability of clinical evidence, we beta tested a novel web-based application in an academic dermatology setting to design and run a journal club for residents. Six dermatology residents participated in this institutional review board–approved study comprised of 3 phases: (1) independent article appraisal through the web-based application, (2) group discussion, and (3) anonymous postsurvey.

Using this platform, we uploaded a recent article into the interactive reader, which contained an integrated tool for appraisal based on specific questions. Because the article described the results of a randomized clinical trial, we used questions from the Centre for Evidence-Based Medicine’s Randomised Controlled Trials Critical Appraisal Worksheet, which has a series of questions to evaluate internal validity, results, and external validity and applicability.³

Residents used the platform to independently read the article, highlight areas of the text that corresponded to 8 critical appraisal questions, and answer yes or no to these questions. Based on residents’ answers, a final appraisal score (on a scale of 1% to 100%) was generated. Simultaneously, the attending dermatologist leading the journal club (C.W.) also completed the assignment to establish an expert score.

Scores from the residents’ independent appraisal ranged from 75% to 100% (mean, 85.4%). Upon discussing the article in a group setting, the residents established a consensus score of 75%. This consensus score matched the expert score, which suggested to us that both independently reviewing the article using guided questions and conducting a group debriefing were necessary to match the expert level of critical appraisal.

Of note, the residents’ average independent appraisal score was higher than both the consensus and expert scores, indicating that the residents evaluated the article less critically on their own. With more practice using this method, it is possible that the precision and accuracy of the residents’ critical appraisal of scientific articles will improve.

In the postsurvey, we asked residents about the critical appraisal of the medical literature. All residents agreed that evaluating the quality of evidence when reading a scientific article was somewhat important or very important to them; however, only 2 of 6 evaluated the quality of evidence all the time, and the other 4 did so half of the time or less than half of the time.

When critically appraising articles, 2 of 6 residents used specific rubrics half of the time; 4 of 6 less than half of the time. Most important, 5 of 6 residents agreed that the quality of evidence affected their management decisions more than half of the time or all of the time. Although it is clear that residents value evidence-based medicine and understand the importance of evaluating the quality of evidence, doing so currently might not be simple or practical.

An organized framework for appraising articles would streamline the process. Five of 6 residents agreed that the use of specific questions as a guide made it easier to appraise an article for the quality of its evidence. Four of 6 residents found that juxtaposing specific questions with the interactive reader was helpful; 5 of 6 agreed that they would use a web-based journal club platform if given the option.

Lastly, 5 of 6 residents agreed that if such a tool were available, a platform containing all major dermatology publications in an interactive reader format, along with relevant appraisal questions on the side, would be useful.

This pilot study augmented the typical journal club experience by emphasizing goal-directed reading and the importance of analyzing the quality of evidence. The combination of independent appraisal of an article using targeted questions and a group debrief led to better understanding of the evidence and its clinical applicability. The COVID-19 pandemic may be a better time than ever to explore innovative ways to teach evidence-based medicine in residency training.

To the Editor:

With a steady increase in dermatology publications over recent decades, there is an expanding pool of evidence to address clinical questions.¹ Residency training is the time when appraising the medical literature and practicing evidence-based medicine is most honed. Evidence-based medicine is an essential component of Practice-based Learning and Improvement, a required core competency of the Accreditation Council for Graduate Medical Education.² Assimilation of new research evidence is traditionally taught through didactics and journal club discussions in residency.

However, at a time when the demand for information overwhelms safeguards that exist to evaluate its quality, it is more important than ever to be equipped with the proper tools to critically appraise novel literature. Beyond accepting a scientific article at face value, physicians must learn to ask targeted questions of the study design, results, and clinical relevance. These questions change based on the type of study, and organizations such as the Oxford Centre for Evidence-Based Medicine provide guidance through critical appraisal worksheets.³

To investigate the utility of using guided questions to evaluate the reliability, significance, and applicability of clinical evidence, we beta tested a novel web-based application in an academic dermatology setting to design and run a journal club for residents. Six dermatology residents participated in this institutional review board–approved study comprised of 3 phases: (1) independent article appraisal through the web-based application, (2) group discussion, and (3) anonymous postsurvey.

Using this platform, we uploaded a recent article into the interactive reader, which contained an integrated tool for appraisal based on specific questions. Because the article described the results of a randomized clinical trial, we used questions from the Centre for Evidence-Based Medicine’s Randomised Controlled Trials Critical Appraisal Worksheet, which has a series of questions to evaluate internal validity, results, and external validity and applicability.³

Residents used the platform to independently read the article, highlight areas of the text that corresponded to 8 critical appraisal questions, and answer yes or no to these questions. Based on residents’ answers, a final appraisal score (on a scale of 1% to 100%) was generated. Simultaneously, the attending dermatologist leading the journal club (C.W.) also completed the assignment to establish an expert score.

Scores from the residents’ independent appraisal ranged from 75% to 100% (mean, 85.4%). Upon discussing the article in a group setting, the residents established a consensus score of 75%. This consensus score matched the expert score, which suggested to us that both independently reviewing the article using guided questions and conducting a group debriefing were necessary to match the expert level of critical appraisal.

Of note, the residents’ average independent appraisal score was higher than both the consensus and expert scores, indicating that the residents evaluated the article less critically on their own. With more practice using this method, it is possible that the precision and accuracy of the residents’ critical appraisal of scientific articles will improve.

In the postsurvey, we asked residents about the critical appraisal of the medical literature. All residents agreed that evaluating the quality of evidence when reading a scientific article was somewhat important or very important to them; however, only 2 of 6 evaluated the quality of evidence all the time, and the other 4 did so half of the time or less than half of the time.

When critically appraising articles, 2 of 6 residents used specific rubrics half of the time; 4 of 6 less than half of the time. Most important, 5 of 6 residents agreed that the quality of evidence affected their management decisions more than half of the time or all of the time. Although it is clear that residents value evidence-based medicine and understand the importance of evaluating the quality of evidence, doing so currently might not be simple or practical.

An organized framework for appraising articles would streamline the process. Five of 6 residents agreed that the use of specific questions as a guide made it easier to appraise an article for the quality of its evidence. Four of 6 residents found that juxtaposing specific questions with the interactive reader was helpful; 5 of 6 agreed that they would use a web-based journal club platform if given the option.

Lastly, 5 of 6 residents agreed that if such a tool were available, a platform containing all major dermatology publications in an interactive reader format, along with relevant appraisal questions on the side, would be useful.

This pilot study augmented the typical journal club experience by emphasizing goal-directed reading and the importance of analyzing the quality of evidence. The combination of independent appraisal of an article using targeted questions and a group debrief led to better understanding of the evidence and its clinical applicability. The COVID-19 pandemic may be a better time than ever to explore innovative ways to teach evidence-based medicine in residency training.

To the Editor:

With a steady increase in dermatology publications over recent decades, there is an expanding pool of evidence to address clinical questions.¹ Residency training is the time when appraising the medical literature and practicing evidence-based medicine is most honed. Evidence-based medicine is an essential component of Practice-based Learning and Improvement, a required core competency of the Accreditation Council for Graduate Medical Education.² Assimilation of new research evidence is traditionally taught through didactics and journal club discussions in residency.

However, at a time when the demand for information overwhelms safeguards that exist to evaluate its quality, it is more important than ever to be equipped with the proper tools to critically appraise novel literature. Beyond accepting a scientific article at face value, physicians must learn to ask targeted questions of the study design, results, and clinical relevance. These questions change based on the type of study, and organizations such as the Oxford Centre for Evidence-Based Medicine provide guidance through critical appraisal worksheets.³

To investigate the utility of using guided questions to evaluate the reliability, significance, and applicability of clinical evidence, we beta tested a novel web-based application in an academic dermatology setting to design and run a journal club for residents. Six dermatology residents participated in this institutional review board–approved study comprised of 3 phases: (1) independent article appraisal through the web-based application, (2) group discussion, and (3) anonymous postsurvey.

Using this platform, we uploaded a recent article into the interactive reader, which contained an integrated tool for appraisal based on specific questions. Because the article described the results of a randomized clinical trial, we used questions from the Centre for Evidence-Based Medicine’s Randomised Controlled Trials Critical Appraisal Worksheet, which has a series of questions to evaluate internal validity, results, and external validity and applicability.³

Residents used the platform to independently read the article, highlight areas of the text that corresponded to 8 critical appraisal questions, and answer yes or no to these questions. Based on residents’ answers, a final appraisal score (on a scale of 1% to 100%) was generated. Simultaneously, the attending dermatologist leading the journal club (C.W.) also completed the assignment to establish an expert score.

Scores from the residents’ independent appraisal ranged from 75% to 100% (mean, 85.4%). Upon discussing the article in a group setting, the residents established a consensus score of 75%. This consensus score matched the expert score, which suggested to us that both independently reviewing the article using guided questions and conducting a group debriefing were necessary to match the expert level of critical appraisal.

Of note, the residents’ average independent appraisal score was higher than both the consensus and expert scores, indicating that the residents evaluated the article less critically on their own. With more practice using this method, it is possible that the precision and accuracy of the residents’ critical appraisal of scientific articles will improve.

In the postsurvey, we asked residents about the critical appraisal of the medical literature. All residents agreed that evaluating the quality of evidence when reading a scientific article was somewhat important or very important to them; however, only 2 of 6 evaluated the quality of evidence all the time, and the other 4 did so half of the time or less than half of the time.

When critically appraising articles, 2 of 6 residents used specific rubrics half of the time; 4 of 6 less than half of the time. Most important, 5 of 6 residents agreed that the quality of evidence affected their management decisions more than half of the time or all of the time. Although it is clear that residents value evidence-based medicine and understand the importance of evaluating the quality of evidence, doing so currently might not be simple or practical.

An organized framework for appraising articles would streamline the process. Five of 6 residents agreed that the use of specific questions as a guide made it easier to appraise an article for the quality of its evidence. Four of 6 residents found that juxtaposing specific questions with the interactive reader was helpful; 5 of 6 agreed that they would use a web-based journal club platform if given the option.

Lastly, 5 of 6 residents agreed that if such a tool were available, a platform containing all major dermatology publications in an interactive reader format, along with relevant appraisal questions on the side, would be useful.

This pilot study augmented the typical journal club experience by emphasizing goal-directed reading and the importance of analyzing the quality of evidence. The combination of independent appraisal of an article using targeted questions and a group debrief led to better understanding of the evidence and its clinical applicability. The COVID-19 pandemic may be a better time than ever to explore innovative ways to teach evidence-based medicine in residency training.

The Diagnosis: Desmoplastic Spitz Nevus

Desmoplastic Spitz nevus is a rare variant of Spitz nevus that commonly presents as a red to brown papule on the head, neck, or extremities. It is pertinent to review the histologic features of this neoplasm, as it can be confused with other more sinister entities such as spitzoid melanoma. Histologically, there is a dermal infiltrate of melanocytes containing eosinophilic cytoplasm and vesicular nuclei. Junctional involvement is rare, and there should be no pagetoid spread.¹ This entity features abundant stromal fibrosis formed by dense collagen bundles, low cellular density, and polygonal-shaped melanocytes, which helps to differentiate it from melanoma.^2,3 In a retrospective study comparing the characteristics of desmoplastic Spitz nevi with desmoplastic melanoma, desmoplastic Spitz nevi histologically were more symmetric and circumscribed with greater melanocytic maturation and adnexal structure involvement.³ Although this entity demonstrates maturation from the superficial to the deep dermis, it also may feature deep dermal vascular proliferation.⁴ S-100 and SRY-related HMG box 10, SOX-10, are noted to be positive in desmoplastic Spitz nevi, which can help to differentiate it from nonmelanocytic entities (Figure 1).

Although spitzoid lesions can be ambiguous and difficult even for experts to classify, spitzoid melanoma tends to have a high Breslow thickness, high cell density, marked atypia, and an increased nucleus to cytoplasm ratio.⁵ Additionally, desmoplastic melanoma was found to more often display “melanocytic junctional nests associated with discohesive cells, variations in size and shape of the nests, lentiginous melanocytic proliferation, actinic elastosis, pagetoid spread, dermal mitosis, perineural involvement and brisk inflammatory infiltrate.”³ Given the challenge of histologically separating desmoplastic Spitz nevi from melanoma, immunostaining can be useful. For example, Hilliard et al⁶ used a p16 antibody to differentiate desmoplastic Spitz nevi from desmoplastic melanoma, finding that most desmoplastic melanomas (81.8%; n=11) were negative for p16, whereas all desmoplastic Spitz nevi were at least moderately positive. However, another study re-evaluated the utility of p16 in desmoplastic melanoma and found that 72.7% (16/22) were at least focally reactive for the immunostain.⁷ Thus, caution must be exercised when using p16.

PReferentially expressed Antigen in MElanoma (PRAME) is a newer nuclear immunohistochemical marker that tends to be positive in melanomas and negative in nevi. Desmoplastic Spitz nevi would be expected to be negative for PRAME, while desmoplastic melanoma may be positive; however, this marker seems to be less effective in desmoplastic melanoma than in most other subtypes of the malignancy. In one study, only 35% (n=20) of desmoplastic melanomas were positive for PRAME.⁸ Likewise, another study showed that some benign Spitz nevi may diffusely express PRAME.⁹ As such, PRAME should be used prudently.

For cases in which immunohistochemistry is equivocal, molecular testing may aid in differentiating Spitz nevi from melanoma. For example, comparative genomic hybridization has revealed an increased copy number of chromosome 11p in approximately 20% of Spitz nevi cases¹⁰; this finding is not seen in melanoma. Mutation analyses of HRas proto-oncogene, GTPase, HRAS; B-Raf proto-oncogene, serine/threonine kinase, BRAF; and NRAS proto-oncogene, GTPase, NRAS, also have shown some promise in distinguishing spitzoid lesions from melanoma, but these analyses may be oversimplified.¹¹ Fluorescence in situ hybridization (FISH) is another diagnostic modality that has been studied to differentiate benign nevi from melanoma. One study challenged the utility of FISH, reporting 7 of 15 desmoplastic melanomas tested positive compared to 0 of 15 sclerotic melanocytic nevi.¹² Thus, negative FISH cannot reliably rule out melanoma. Ultimately, a combination of immunostains along with FISH or another genetic study would prove to be most effective in ruling out melanoma in difficult cases. Even then, a dermatopathologist may be faced with a degree of uncertainty.

Cellular blue nevi predominantly affect adults younger than 40 years and commonly are seen on the buttocks.¹³ This benign neoplasm demonstrates areas that are distinctly sclerotic as well as those that are cellular in nature.¹⁴ This entity demonstrates a well-circumscribed dermal growth pattern with 2 main populations of cells. The sclerotic portion of the cellular blue nevus mimics that of the blue nevus in that it is noted superficially with irregular margins. The cellular aspect of the nevus features spindle cells contained within well-circumscribed nodules (Figure 2). Stromal melanophages are not uncommon, and some can be observed adjacent to nerve fibers. Although this blue nevus variant displays features of the common blue nevus, its melanocytes track along adnexal and neurovascular structures similar to the deep penetrating nevus and the desmoplastic Spitz nevus. However, these melanocytes are variable in morphology and can appear on a spectrum spanning from pale and lightly pigmented to clear.¹⁵

The breast is the most common site of origin of tumor metastasis to the skin. These cutaneous metastases can vary in both their clinical and histological presentations. For example, cutaneous metastatic breast adenocarcinoma often can present clinically as pink-violaceous papules and plaques on the breast or on other parts of the body. Histologically, it can demonstrate a varying degree of patterns such as collagen infiltration by single cells, cords, tubules, and sheets of atypical cells (Figure 3) that can be observed together in areas of mucin or can form glandular structures.16 Metastatic breast carcinoma is noted to be positive for gross cystic disease fluid protein-15, estrogen receptor, and cytokeratin 7, which can help differentiate this entity from other tumors of glandular origin.¹⁶ Although rare, primary melanoma of the breast has been reported in the literature.^17,18 These malignant melanocytic lesions easily could be differentiated from other breast tumors such as adenocarcinoma using immunohistochemical staining patterns.

Deep penetrating nevi most often are observed clinically as blue, brown, or black papules or nodules on the head or neck.¹⁹ Histologically, this lesion features a wedge-shaped infiltrate of deep dermal melanocytes with oval nuclei. It commonly extends to the reticular dermis or further into the subcutis (Figure 4).^20,21 This neoplasm frequently tracks along adnexal and neurovascular structures, resulting in a plexiform appearance.²² The adnexal involvement of deep penetrating nevi is a shared feature with desmoplastic Spitz nevi. The presence of any number of melanophages is characteristic of this lesion.²³ Lastly, there is a well-documented association between β-catenin mutations and deep penetrating nevi.²⁴ Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans cell histiocytosis that has the pathognomonic clinical finding of pink-red papules (coral beading) with a predilection for acral surfaces. Histology of affected skin reveals a dermal infiltrate of ground glass as well as eosinophilic histiocytes that most often stain positive for CD68 and human alveolar macrophage 56 but negative for S-100 and CD1a (Figure 5).²⁵ Although MRH is rare, negative staining for S-100 could serve as a useful diagnostic clue to differentiate it from other entities that are positive for S-100, such as the desmoplastic Spitz nevus. Arthritis mutilans is a potential complication of MRH, but a reported association with an underlying malignancy is seen in approximately 25% of cases.²⁶ Thus, the cutaneous, rheumatologic, and oncologic implications of this disease help to distinguish it from other differential diagnoses that may be considered.

The Diagnosis: Desmoplastic Spitz Nevus

Desmoplastic Spitz nevus is a rare variant of Spitz nevus that commonly presents as a red to brown papule on the head, neck, or extremities. It is pertinent to review the histologic features of this neoplasm, as it can be confused with other more sinister entities such as spitzoid melanoma. Histologically, there is a dermal infiltrate of melanocytes containing eosinophilic cytoplasm and vesicular nuclei. Junctional involvement is rare, and there should be no pagetoid spread.¹ This entity features abundant stromal fibrosis formed by dense collagen bundles, low cellular density, and polygonal-shaped melanocytes, which helps to differentiate it from melanoma.^2,3 In a retrospective study comparing the characteristics of desmoplastic Spitz nevi with desmoplastic melanoma, desmoplastic Spitz nevi histologically were more symmetric and circumscribed with greater melanocytic maturation and adnexal structure involvement.³ Although this entity demonstrates maturation from the superficial to the deep dermis, it also may feature deep dermal vascular proliferation.⁴ S-100 and SRY-related HMG box 10, SOX-10, are noted to be positive in desmoplastic Spitz nevi, which can help to differentiate it from nonmelanocytic entities (Figure 1).

Although spitzoid lesions can be ambiguous and difficult even for experts to classify, spitzoid melanoma tends to have a high Breslow thickness, high cell density, marked atypia, and an increased nucleus to cytoplasm ratio.⁵ Additionally, desmoplastic melanoma was found to more often display “melanocytic junctional nests associated with discohesive cells, variations in size and shape of the nests, lentiginous melanocytic proliferation, actinic elastosis, pagetoid spread, dermal mitosis, perineural involvement and brisk inflammatory infiltrate.”³ Given the challenge of histologically separating desmoplastic Spitz nevi from melanoma, immunostaining can be useful. For example, Hilliard et al⁶ used a p16 antibody to differentiate desmoplastic Spitz nevi from desmoplastic melanoma, finding that most desmoplastic melanomas (81.8%; n=11) were negative for p16, whereas all desmoplastic Spitz nevi were at least moderately positive. However, another study re-evaluated the utility of p16 in desmoplastic melanoma and found that 72.7% (16/22) were at least focally reactive for the immunostain.⁷ Thus, caution must be exercised when using p16.

PReferentially expressed Antigen in MElanoma (PRAME) is a newer nuclear immunohistochemical marker that tends to be positive in melanomas and negative in nevi. Desmoplastic Spitz nevi would be expected to be negative for PRAME, while desmoplastic melanoma may be positive; however, this marker seems to be less effective in desmoplastic melanoma than in most other subtypes of the malignancy. In one study, only 35% (n=20) of desmoplastic melanomas were positive for PRAME.⁸ Likewise, another study showed that some benign Spitz nevi may diffusely express PRAME.⁹ As such, PRAME should be used prudently.

For cases in which immunohistochemistry is equivocal, molecular testing may aid in differentiating Spitz nevi from melanoma. For example, comparative genomic hybridization has revealed an increased copy number of chromosome 11p in approximately 20% of Spitz nevi cases¹⁰; this finding is not seen in melanoma. Mutation analyses of HRas proto-oncogene, GTPase, HRAS; B-Raf proto-oncogene, serine/threonine kinase, BRAF; and NRAS proto-oncogene, GTPase, NRAS, also have shown some promise in distinguishing spitzoid lesions from melanoma, but these analyses may be oversimplified.¹¹ Fluorescence in situ hybridization (FISH) is another diagnostic modality that has been studied to differentiate benign nevi from melanoma. One study challenged the utility of FISH, reporting 7 of 15 desmoplastic melanomas tested positive compared to 0 of 15 sclerotic melanocytic nevi.¹² Thus, negative FISH cannot reliably rule out melanoma. Ultimately, a combination of immunostains along with FISH or another genetic study would prove to be most effective in ruling out melanoma in difficult cases. Even then, a dermatopathologist may be faced with a degree of uncertainty.

Cellular blue nevi predominantly affect adults younger than 40 years and commonly are seen on the buttocks.¹³ This benign neoplasm demonstrates areas that are distinctly sclerotic as well as those that are cellular in nature.¹⁴ This entity demonstrates a well-circumscribed dermal growth pattern with 2 main populations of cells. The sclerotic portion of the cellular blue nevus mimics that of the blue nevus in that it is noted superficially with irregular margins. The cellular aspect of the nevus features spindle cells contained within well-circumscribed nodules (Figure 2). Stromal melanophages are not uncommon, and some can be observed adjacent to nerve fibers. Although this blue nevus variant displays features of the common blue nevus, its melanocytes track along adnexal and neurovascular structures similar to the deep penetrating nevus and the desmoplastic Spitz nevus. However, these melanocytes are variable in morphology and can appear on a spectrum spanning from pale and lightly pigmented to clear.¹⁵

The breast is the most common site of origin of tumor metastasis to the skin. These cutaneous metastases can vary in both their clinical and histological presentations. For example, cutaneous metastatic breast adenocarcinoma often can present clinically as pink-violaceous papules and plaques on the breast or on other parts of the body. Histologically, it can demonstrate a varying degree of patterns such as collagen infiltration by single cells, cords, tubules, and sheets of atypical cells (Figure 3) that can be observed together in areas of mucin or can form glandular structures.16 Metastatic breast carcinoma is noted to be positive for gross cystic disease fluid protein-15, estrogen receptor, and cytokeratin 7, which can help differentiate this entity from other tumors of glandular origin.¹⁶ Although rare, primary melanoma of the breast has been reported in the literature.^17,18 These malignant melanocytic lesions easily could be differentiated from other breast tumors such as adenocarcinoma using immunohistochemical staining patterns.

Deep penetrating nevi most often are observed clinically as blue, brown, or black papules or nodules on the head or neck.¹⁹ Histologically, this lesion features a wedge-shaped infiltrate of deep dermal melanocytes with oval nuclei. It commonly extends to the reticular dermis or further into the subcutis (Figure 4).^20,21 This neoplasm frequently tracks along adnexal and neurovascular structures, resulting in a plexiform appearance.²² The adnexal involvement of deep penetrating nevi is a shared feature with desmoplastic Spitz nevi. The presence of any number of melanophages is characteristic of this lesion.²³ Lastly, there is a well-documented association between β-catenin mutations and deep penetrating nevi.²⁴ Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans cell histiocytosis that has the pathognomonic clinical finding of pink-red papules (coral beading) with a predilection for acral surfaces. Histology of affected skin reveals a dermal infiltrate of ground glass as well as eosinophilic histiocytes that most often stain positive for CD68 and human alveolar macrophage 56 but negative for S-100 and CD1a (Figure 5).²⁵ Although MRH is rare, negative staining for S-100 could serve as a useful diagnostic clue to differentiate it from other entities that are positive for S-100, such as the desmoplastic Spitz nevus. Arthritis mutilans is a potential complication of MRH, but a reported association with an underlying malignancy is seen in approximately 25% of cases.²⁶ Thus, the cutaneous, rheumatologic, and oncologic implications of this disease help to distinguish it from other differential diagnoses that may be considered.

The Diagnosis: Desmoplastic Spitz Nevus

Desmoplastic Spitz nevus is a rare variant of Spitz nevus that commonly presents as a red to brown papule on the head, neck, or extremities. It is pertinent to review the histologic features of this neoplasm, as it can be confused with other more sinister entities such as spitzoid melanoma. Histologically, there is a dermal infiltrate of melanocytes containing eosinophilic cytoplasm and vesicular nuclei. Junctional involvement is rare, and there should be no pagetoid spread.¹ This entity features abundant stromal fibrosis formed by dense collagen bundles, low cellular density, and polygonal-shaped melanocytes, which helps to differentiate it from melanoma.^2,3 In a retrospective study comparing the characteristics of desmoplastic Spitz nevi with desmoplastic melanoma, desmoplastic Spitz nevi histologically were more symmetric and circumscribed with greater melanocytic maturation and adnexal structure involvement.³ Although this entity demonstrates maturation from the superficial to the deep dermis, it also may feature deep dermal vascular proliferation.⁴ S-100 and SRY-related HMG box 10, SOX-10, are noted to be positive in desmoplastic Spitz nevi, which can help to differentiate it from nonmelanocytic entities (Figure 1).

Although spitzoid lesions can be ambiguous and difficult even for experts to classify, spitzoid melanoma tends to have a high Breslow thickness, high cell density, marked atypia, and an increased nucleus to cytoplasm ratio.⁵ Additionally, desmoplastic melanoma was found to more often display “melanocytic junctional nests associated with discohesive cells, variations in size and shape of the nests, lentiginous melanocytic proliferation, actinic elastosis, pagetoid spread, dermal mitosis, perineural involvement and brisk inflammatory infiltrate.”³ Given the challenge of histologically separating desmoplastic Spitz nevi from melanoma, immunostaining can be useful. For example, Hilliard et al⁶ used a p16 antibody to differentiate desmoplastic Spitz nevi from desmoplastic melanoma, finding that most desmoplastic melanomas (81.8%; n=11) were negative for p16, whereas all desmoplastic Spitz nevi were at least moderately positive. However, another study re-evaluated the utility of p16 in desmoplastic melanoma and found that 72.7% (16/22) were at least focally reactive for the immunostain.⁷ Thus, caution must be exercised when using p16.

PReferentially expressed Antigen in MElanoma (PRAME) is a newer nuclear immunohistochemical marker that tends to be positive in melanomas and negative in nevi. Desmoplastic Spitz nevi would be expected to be negative for PRAME, while desmoplastic melanoma may be positive; however, this marker seems to be less effective in desmoplastic melanoma than in most other subtypes of the malignancy. In one study, only 35% (n=20) of desmoplastic melanomas were positive for PRAME.⁸ Likewise, another study showed that some benign Spitz nevi may diffusely express PRAME.⁹ As such, PRAME should be used prudently.

For cases in which immunohistochemistry is equivocal, molecular testing may aid in differentiating Spitz nevi from melanoma. For example, comparative genomic hybridization has revealed an increased copy number of chromosome 11p in approximately 20% of Spitz nevi cases¹⁰; this finding is not seen in melanoma. Mutation analyses of HRas proto-oncogene, GTPase, HRAS; B-Raf proto-oncogene, serine/threonine kinase, BRAF; and NRAS proto-oncogene, GTPase, NRAS, also have shown some promise in distinguishing spitzoid lesions from melanoma, but these analyses may be oversimplified.¹¹ Fluorescence in situ hybridization (FISH) is another diagnostic modality that has been studied to differentiate benign nevi from melanoma. One study challenged the utility of FISH, reporting 7 of 15 desmoplastic melanomas tested positive compared to 0 of 15 sclerotic melanocytic nevi.¹² Thus, negative FISH cannot reliably rule out melanoma. Ultimately, a combination of immunostains along with FISH or another genetic study would prove to be most effective in ruling out melanoma in difficult cases. Even then, a dermatopathologist may be faced with a degree of uncertainty.

Cellular blue nevi predominantly affect adults younger than 40 years and commonly are seen on the buttocks.¹³ This benign neoplasm demonstrates areas that are distinctly sclerotic as well as those that are cellular in nature.¹⁴ This entity demonstrates a well-circumscribed dermal growth pattern with 2 main populations of cells. The sclerotic portion of the cellular blue nevus mimics that of the blue nevus in that it is noted superficially with irregular margins. The cellular aspect of the nevus features spindle cells contained within well-circumscribed nodules (Figure 2). Stromal melanophages are not uncommon, and some can be observed adjacent to nerve fibers. Although this blue nevus variant displays features of the common blue nevus, its melanocytes track along adnexal and neurovascular structures similar to the deep penetrating nevus and the desmoplastic Spitz nevus. However, these melanocytes are variable in morphology and can appear on a spectrum spanning from pale and lightly pigmented to clear.¹⁵

The breast is the most common site of origin of tumor metastasis to the skin. These cutaneous metastases can vary in both their clinical and histological presentations. For example, cutaneous metastatic breast adenocarcinoma often can present clinically as pink-violaceous papules and plaques on the breast or on other parts of the body. Histologically, it can demonstrate a varying degree of patterns such as collagen infiltration by single cells, cords, tubules, and sheets of atypical cells (Figure 3) that can be observed together in areas of mucin or can form glandular structures.16 Metastatic breast carcinoma is noted to be positive for gross cystic disease fluid protein-15, estrogen receptor, and cytokeratin 7, which can help differentiate this entity from other tumors of glandular origin.¹⁶ Although rare, primary melanoma of the breast has been reported in the literature.^17,18 These malignant melanocytic lesions easily could be differentiated from other breast tumors such as adenocarcinoma using immunohistochemical staining patterns.

Deep penetrating nevi most often are observed clinically as blue, brown, or black papules or nodules on the head or neck.¹⁹ Histologically, this lesion features a wedge-shaped infiltrate of deep dermal melanocytes with oval nuclei. It commonly extends to the reticular dermis or further into the subcutis (Figure 4).^20,21 This neoplasm frequently tracks along adnexal and neurovascular structures, resulting in a plexiform appearance.²² The adnexal involvement of deep penetrating nevi is a shared feature with desmoplastic Spitz nevi. The presence of any number of melanophages is characteristic of this lesion.²³ Lastly, there is a well-documented association between β-catenin mutations and deep penetrating nevi.²⁴ Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans cell histiocytosis that has the pathognomonic clinical finding of pink-red papules (coral beading) with a predilection for acral surfaces. Histology of affected skin reveals a dermal infiltrate of ground glass as well as eosinophilic histiocytes that most often stain positive for CD68 and human alveolar macrophage 56 but negative for S-100 and CD1a (Figure 5).²⁵ Although MRH is rare, negative staining for S-100 could serve as a useful diagnostic clue to differentiate it from other entities that are positive for S-100, such as the desmoplastic Spitz nevus. Arthritis mutilans is a potential complication of MRH, but a reported association with an underlying malignancy is seen in approximately 25% of cases.²⁶ Thus, the cutaneous, rheumatologic, and oncologic implications of this disease help to distinguish it from other differential diagnoses that may be considered.

On November 2, 2021, the Centers for Medicare & Medicaid Services (CMS) released its final rule for the 2022 Medicare Physician Fee Schedule (PFS) and the Quality Payment Program (QPP).^1,2 These guidelines contain updates that will remarkably impact the field of medicine—and dermatology in particular—in 2022. This article will walk you through some of the updates most relevant to dermatology and how they may affect your practice.

Process for the Final Rule

The CMS releases an annual rule for the PFS and QPP. The interim rule generally is released over the summer with preliminary guidelines for the upcoming payment year. There is then a period of open comment where those affected by these changes, including physicians and medical associations, can submit comments to support what has been proposed or advocate for any changes. This input is then reviewed, and a final rule generally is published in the fall.

For this calendar year, the interim 2022 rule was released on July 13, 2021,³ and included many of guidelines that will be discussed in more detail in this article. Many associations that represent medicine overall and specifically dermatology, including the American Medical Association and the American Academy of Dermatology, submitted comments in response to these proposals.^4,5

PFS Conversion Factor

The PFS conversion factor is updated annually to ensure budget neutrality in the setting of changes in relative value units. For 2022, the PFS conversion factor is $34.6062, representing a reduction of approximately $0.29 from the 2021 PFS conversion factor of $34.8931.⁶ This reduction does not take into account other payment adjustments due to legislative changes.

In combination, these changes previously were estimated to represent an overall payment cut of 10% or higher for dermatology, with those practitioners doing more procedural work or dermatopathology likely being impacted more heavily. However, with the passing of the Protecting Medicare and American Farmers from Sequester Cuts Act, it is estimated that the reductions in payment to dermatology will begin at 0.75% and reach 2.75% in the second half of the year with the phased-in reinstatement of the Medicare sequester.^4,5,7

Clinical Labor Pricing Updates

Starting in 2022, the CMS will utilize updated wage rates from the US Bureau of Labor Statistics to revise clinical labor costs over a 4-year period. Clinical labor rates are important, as they are used to calculate practice expense within the PFS. These clinical labor rates were last updated in 2002.⁸ Median wage data, as opposed to mean data, from the US Bureau of Labor Statistics will be utilized to calculate the updated clinical labor rates.

A multiyear implementation plan was put into place by CMS due to multiple concerns, including that current wage rates are inadequate and may not reflect current labor rate information. Additionally, comments on this proposal voiced concern that updating the supply and equipment pricing without updating the clinical labor pricing could create distortions in the allocation of direct practice expense, which also factored into the implementation of a multiyear plan.⁸

Evaluation and Management Visits

The biggest update in this area primarily is related to refining policies for split (shared) evaluation and management (E/M) visits and teaching physician activities. Split E/M visits are defined by the CMS as visits provided in the facility setting by a physician and nonphysician practitioner in the same group, with the visit billed by whomever provides the substantive portion of the visit. For 2022, the term substantive portion will be defined by the CMS as history, physical examination, medical decision-making, or more than half of the total time; for 2023, it will be defined as more than half of the total time spent.³ A split visit also can apply to an E/M visit provided in part by both a teaching physician and resident. Split visits can be reported for new or established patients. For proper reimbursement, the 2 practitioners who performed the services must be documented in the medical record, and the practitioner who provided the substantive portion must sign and date the encounter in the medical record. Additionally, the CMS has indicated the modifier FS must be included on the claim to indicate the split visit.⁹

For dermatologists who act as teaching physicians, it is important to note that many of the existing CMS policies for billing E/M services are still in place, specifically that if a resident participates in a service in a teaching setting, the teaching physician can bill for the service only if they are present for the key or critical portion of the service. A primary care exception does exist, in which teaching physicians at certain teaching hospital primary care centers can bill for some services performed independently by a resident without the physical presence of the teaching physician; however, this often is not applicable within dermatology.

With updated outpatient E/M guidelines, if time is being selected to bill, only the time that the teaching physician was present can be included to determine the overall E/M level.

Billing for Physician Assistant Services

Currently Medicare can only make payments to the employer or independent contractor of a physician assistant (PA); however, starting January 1, 2022, the CMS has authorized Medicare to make direct payments to PAs for qualifying professional services, in the same manner that nurse practitioners can currently bill. This also will allow PAs to incorporate as a group and bill Medicare for PA services. This stems from a congressional mandate within the Consolidated Appropriations Act of 2021.⁸ As a result, in states where PAs can practice independently, they can opt out of physician-led care teams and furnish services independently, including dermatologic services.

Several changes were made to the Merit-Based Incentive Payment System (MIPS). Some of these changes include:

• Increase the MIPS performance threshold to 75 points from 60 points.
• Set the performance threshold at 89 points.
• Reduce the quality performance category weight from 40% to 30% of the final MIPS score.
• Increase the cost performance category weight from 20% to 30% of the final MIPS score.
• The extreme and uncontrollable circumstances application also has been extended to the end of 2022, allowing those remarkably impacted by the COVID-19 public health emergency to request for reweighting on any or all MIPS performance categories.

Cost Measures and MIPS Value Pathways

The melanoma resection cost measure will be implemented in 2022, representing the first dermatology cost measure, which will include the cost to Medicare over a 1-year period for all patient care for the excision of a melanoma. Although cost measures will be part of the MIPS value pathways (MVPs) reporting, dermatology currently is not part of the MVP; however, with the CMS moving forward with an initial set of MVPs that physicians can voluntarily report on in 2023, there is a possibility that dermatology will be asked to be part of the program in the future.¹⁰

Final Thoughts

There are many upcoming changes as part of the 2022 final rule, including to the conversion factor, E/M split visits, PA billing, and the QPP. Advocacy in these areas to the CMS and lawmakers, either directly or through dermatologic and other medical societies, is critical to help influence eventual recommendations.

On November 2, 2021, the Centers for Medicare & Medicaid Services (CMS) released its final rule for the 2022 Medicare Physician Fee Schedule (PFS) and the Quality Payment Program (QPP).^1,2 These guidelines contain updates that will remarkably impact the field of medicine—and dermatology in particular—in 2022. This article will walk you through some of the updates most relevant to dermatology and how they may affect your practice.

Process for the Final Rule

The CMS releases an annual rule for the PFS and QPP. The interim rule generally is released over the summer with preliminary guidelines for the upcoming payment year. There is then a period of open comment where those affected by these changes, including physicians and medical associations, can submit comments to support what has been proposed or advocate for any changes. This input is then reviewed, and a final rule generally is published in the fall.

For this calendar year, the interim 2022 rule was released on July 13, 2021,³ and included many of guidelines that will be discussed in more detail in this article. Many associations that represent medicine overall and specifically dermatology, including the American Medical Association and the American Academy of Dermatology, submitted comments in response to these proposals.^4,5

PFS Conversion Factor

The PFS conversion factor is updated annually to ensure budget neutrality in the setting of changes in relative value units. For 2022, the PFS conversion factor is $34.6062, representing a reduction of approximately $0.29 from the 2021 PFS conversion factor of $34.8931.⁶ This reduction does not take into account other payment adjustments due to legislative changes.

In combination, these changes previously were estimated to represent an overall payment cut of 10% or higher for dermatology, with those practitioners doing more procedural work or dermatopathology likely being impacted more heavily. However, with the passing of the Protecting Medicare and American Farmers from Sequester Cuts Act, it is estimated that the reductions in payment to dermatology will begin at 0.75% and reach 2.75% in the second half of the year with the phased-in reinstatement of the Medicare sequester.^4,5,7

Clinical Labor Pricing Updates

Starting in 2022, the CMS will utilize updated wage rates from the US Bureau of Labor Statistics to revise clinical labor costs over a 4-year period. Clinical labor rates are important, as they are used to calculate practice expense within the PFS. These clinical labor rates were last updated in 2002.⁸ Median wage data, as opposed to mean data, from the US Bureau of Labor Statistics will be utilized to calculate the updated clinical labor rates.

A multiyear implementation plan was put into place by CMS due to multiple concerns, including that current wage rates are inadequate and may not reflect current labor rate information. Additionally, comments on this proposal voiced concern that updating the supply and equipment pricing without updating the clinical labor pricing could create distortions in the allocation of direct practice expense, which also factored into the implementation of a multiyear plan.⁸

Evaluation and Management Visits

The biggest update in this area primarily is related to refining policies for split (shared) evaluation and management (E/M) visits and teaching physician activities. Split E/M visits are defined by the CMS as visits provided in the facility setting by a physician and nonphysician practitioner in the same group, with the visit billed by whomever provides the substantive portion of the visit. For 2022, the term substantive portion will be defined by the CMS as history, physical examination, medical decision-making, or more than half of the total time; for 2023, it will be defined as more than half of the total time spent.³ A split visit also can apply to an E/M visit provided in part by both a teaching physician and resident. Split visits can be reported for new or established patients. For proper reimbursement, the 2 practitioners who performed the services must be documented in the medical record, and the practitioner who provided the substantive portion must sign and date the encounter in the medical record. Additionally, the CMS has indicated the modifier FS must be included on the claim to indicate the split visit.⁹

For dermatologists who act as teaching physicians, it is important to note that many of the existing CMS policies for billing E/M services are still in place, specifically that if a resident participates in a service in a teaching setting, the teaching physician can bill for the service only if they are present for the key or critical portion of the service. A primary care exception does exist, in which teaching physicians at certain teaching hospital primary care centers can bill for some services performed independently by a resident without the physical presence of the teaching physician; however, this often is not applicable within dermatology.

With updated outpatient E/M guidelines, if time is being selected to bill, only the time that the teaching physician was present can be included to determine the overall E/M level.

Billing for Physician Assistant Services

Currently Medicare can only make payments to the employer or independent contractor of a physician assistant (PA); however, starting January 1, 2022, the CMS has authorized Medicare to make direct payments to PAs for qualifying professional services, in the same manner that nurse practitioners can currently bill. This also will allow PAs to incorporate as a group and bill Medicare for PA services. This stems from a congressional mandate within the Consolidated Appropriations Act of 2021.⁸ As a result, in states where PAs can practice independently, they can opt out of physician-led care teams and furnish services independently, including dermatologic services.

Several changes were made to the Merit-Based Incentive Payment System (MIPS). Some of these changes include:

• Increase the MIPS performance threshold to 75 points from 60 points.
• Set the performance threshold at 89 points.
• Reduce the quality performance category weight from 40% to 30% of the final MIPS score.
• Increase the cost performance category weight from 20% to 30% of the final MIPS score.
• The extreme and uncontrollable circumstances application also has been extended to the end of 2022, allowing those remarkably impacted by the COVID-19 public health emergency to request for reweighting on any or all MIPS performance categories.

Cost Measures and MIPS Value Pathways

The melanoma resection cost measure will be implemented in 2022, representing the first dermatology cost measure, which will include the cost to Medicare over a 1-year period for all patient care for the excision of a melanoma. Although cost measures will be part of the MIPS value pathways (MVPs) reporting, dermatology currently is not part of the MVP; however, with the CMS moving forward with an initial set of MVPs that physicians can voluntarily report on in 2023, there is a possibility that dermatology will be asked to be part of the program in the future.¹⁰

Final Thoughts

There are many upcoming changes as part of the 2022 final rule, including to the conversion factor, E/M split visits, PA billing, and the QPP. Advocacy in these areas to the CMS and lawmakers, either directly or through dermatologic and other medical societies, is critical to help influence eventual recommendations.

On November 2, 2021, the Centers for Medicare & Medicaid Services (CMS) released its final rule for the 2022 Medicare Physician Fee Schedule (PFS) and the Quality Payment Program (QPP).^1,2 These guidelines contain updates that will remarkably impact the field of medicine—and dermatology in particular—in 2022. This article will walk you through some of the updates most relevant to dermatology and how they may affect your practice.

Process for the Final Rule

The CMS releases an annual rule for the PFS and QPP. The interim rule generally is released over the summer with preliminary guidelines for the upcoming payment year. There is then a period of open comment where those affected by these changes, including physicians and medical associations, can submit comments to support what has been proposed or advocate for any changes. This input is then reviewed, and a final rule generally is published in the fall.

For this calendar year, the interim 2022 rule was released on July 13, 2021,³ and included many of guidelines that will be discussed in more detail in this article. Many associations that represent medicine overall and specifically dermatology, including the American Medical Association and the American Academy of Dermatology, submitted comments in response to these proposals.^4,5

PFS Conversion Factor

The PFS conversion factor is updated annually to ensure budget neutrality in the setting of changes in relative value units. For 2022, the PFS conversion factor is $34.6062, representing a reduction of approximately $0.29 from the 2021 PFS conversion factor of $34.8931.⁶ This reduction does not take into account other payment adjustments due to legislative changes.

In combination, these changes previously were estimated to represent an overall payment cut of 10% or higher for dermatology, with those practitioners doing more procedural work or dermatopathology likely being impacted more heavily. However, with the passing of the Protecting Medicare and American Farmers from Sequester Cuts Act, it is estimated that the reductions in payment to dermatology will begin at 0.75% and reach 2.75% in the second half of the year with the phased-in reinstatement of the Medicare sequester.^4,5,7

Clinical Labor Pricing Updates

Starting in 2022, the CMS will utilize updated wage rates from the US Bureau of Labor Statistics to revise clinical labor costs over a 4-year period. Clinical labor rates are important, as they are used to calculate practice expense within the PFS. These clinical labor rates were last updated in 2002.⁸ Median wage data, as opposed to mean data, from the US Bureau of Labor Statistics will be utilized to calculate the updated clinical labor rates.

A multiyear implementation plan was put into place by CMS due to multiple concerns, including that current wage rates are inadequate and may not reflect current labor rate information. Additionally, comments on this proposal voiced concern that updating the supply and equipment pricing without updating the clinical labor pricing could create distortions in the allocation of direct practice expense, which also factored into the implementation of a multiyear plan.⁸

Evaluation and Management Visits

The biggest update in this area primarily is related to refining policies for split (shared) evaluation and management (E/M) visits and teaching physician activities. Split E/M visits are defined by the CMS as visits provided in the facility setting by a physician and nonphysician practitioner in the same group, with the visit billed by whomever provides the substantive portion of the visit. For 2022, the term substantive portion will be defined by the CMS as history, physical examination, medical decision-making, or more than half of the total time; for 2023, it will be defined as more than half of the total time spent.³ A split visit also can apply to an E/M visit provided in part by both a teaching physician and resident. Split visits can be reported for new or established patients. For proper reimbursement, the 2 practitioners who performed the services must be documented in the medical record, and the practitioner who provided the substantive portion must sign and date the encounter in the medical record. Additionally, the CMS has indicated the modifier FS must be included on the claim to indicate the split visit.⁹

For dermatologists who act as teaching physicians, it is important to note that many of the existing CMS policies for billing E/M services are still in place, specifically that if a resident participates in a service in a teaching setting, the teaching physician can bill for the service only if they are present for the key or critical portion of the service. A primary care exception does exist, in which teaching physicians at certain teaching hospital primary care centers can bill for some services performed independently by a resident without the physical presence of the teaching physician; however, this often is not applicable within dermatology.

With updated outpatient E/M guidelines, if time is being selected to bill, only the time that the teaching physician was present can be included to determine the overall E/M level.

Billing for Physician Assistant Services

Currently Medicare can only make payments to the employer or independent contractor of a physician assistant (PA); however, starting January 1, 2022, the CMS has authorized Medicare to make direct payments to PAs for qualifying professional services, in the same manner that nurse practitioners can currently bill. This also will allow PAs to incorporate as a group and bill Medicare for PA services. This stems from a congressional mandate within the Consolidated Appropriations Act of 2021.⁸ As a result, in states where PAs can practice independently, they can opt out of physician-led care teams and furnish services independently, including dermatologic services.

Several changes were made to the Merit-Based Incentive Payment System (MIPS). Some of these changes include:

• Increase the MIPS performance threshold to 75 points from 60 points.
• Set the performance threshold at 89 points.
• Reduce the quality performance category weight from 40% to 30% of the final MIPS score.
• Increase the cost performance category weight from 20% to 30% of the final MIPS score.
• The extreme and uncontrollable circumstances application also has been extended to the end of 2022, allowing those remarkably impacted by the COVID-19 public health emergency to request for reweighting on any or all MIPS performance categories.

Cost Measures and MIPS Value Pathways

The melanoma resection cost measure will be implemented in 2022, representing the first dermatology cost measure, which will include the cost to Medicare over a 1-year period for all patient care for the excision of a melanoma. Although cost measures will be part of the MIPS value pathways (MVPs) reporting, dermatology currently is not part of the MVP; however, with the CMS moving forward with an initial set of MVPs that physicians can voluntarily report on in 2023, there is a possibility that dermatology will be asked to be part of the program in the future.¹⁰

Final Thoughts

There are many upcoming changes as part of the 2022 final rule, including to the conversion factor, E/M split visits, PA billing, and the QPP. Advocacy in these areas to the CMS and lawmakers, either directly or through dermatologic and other medical societies, is critical to help influence eventual recommendations.

Acne vulgaris is an extremely common dermatologic disease affecting 40 to 50 million individuals in the United States each year, with a prevalence of 85% in adolescents and young adults aged 12 to 24 years. For some patients, the disease may persist well into adulthood, affecting 8% of adults aged 25 and 34 years.¹ Acne negatively impacts patients’ quality of life and productivity, with an estimated direct and indirect cost of over $3 billion per year.²

Oral isotretinoin, a vitamin A derivative, is approved by the US Food and Drug Administration for the treatment of severe nodulocystic acne. Isotretinoin reduces the size and secretions of sebaceous glands, inhibits growth and resulting inflammation of Cutibacterium acnes, and normalizes the differentiation of follicular keratinocytes, resulting in permanent changes in the pathogenesis of acne that may lead to remission.³ The use of oral isotretinoin in the active-duty US Military population may cause service members to be nondeployable or limit their ability to function in special roles (eg, pilot, submariner).⁴ Treatment regimens that minimize the course duration of isotretinoin and reduce the risk for relapse that requires a retrial of isotretinoin may, in turn, increase a service member’s readiness, deployment availability, and ability to perform unique occupational roles.

Additionally, teledermatology has been increasingly utilized to maintain treatment continuity for patients on isotretinoin during the COVID-19 pandemic.⁵ Application of this technology in the military also may be used to facilitate timely isotretinoin treatment regimens in active-duty service members to minimize course duration and increase readiness.

In this article, we discuss an accelerated course of oral isotretinoin as a safe and effective option for military service members bound by duty restrictions and operational timelines and explore the role of teledermatology for the treatment of acne in military service members.

Isotretinoin for Acne

Isotretinoin typically is initiated at a dosage of 0.5 mg/kg daily, increasing to 1 mg/kg daily with a goal cumulative dose between 120 and 150 mg/kg. Relapse may occur after completing a treatment course and is associated with cumulative dosing less than 120 mg/kg.⁶ The average duration of acne treatment with oral isotretinoin is approximately 6 months.⁷ At therapeutic doses, nearly all patients experience side effects, most commonly dryness and desquamation of the skin and mucous membranes, as well as possible involvement of the lips, eyes, and nose. Notable extracutaneous side effects include headache, visual disturbances at night, idiopathic intracranial hypertension, and myalgia. Serum cholesterol, triglycerides, and transaminases may be increased in patients taking isotretinoin, which requires routine monitoring using serum lipid profiles and liver function studies. A potential association between isotretinoin and inflammatory bowel disease and changes in mood have been reported, but current data do not suggest an evidence-based link.^6,8 Isotretinoin is a potent teratogen, and in the United States, all patients are required to enroll in iPLEDGE, a US Food and Drug Administration–approved pregnancy prevention program that monitors prescribing and dispensing of the medication. For patients who can become pregnant, iPLEDGE requires use of 2 forms of contraception as well as monthly pregnancy tests prior to dispensing the medication.

Acne in Military Service Members

Acne is exceedingly common in the active-duty military population. In 2018, more than 40% of soldiers, sailors, airmen, and marines were 25 years or younger, and 75% of all US service members were 35 years or younger, corresponding to acne peak incidences.^1,9 Management of acne in this population requires unique treatment considerations due to distinctive occupational requirements of and hazards faced by military personnel. Use of personal protective equipment, including gas masks, safety restraints, parachute rigging, and flak jackets, may be limiting in individuals with moderate to severe acne.¹⁰ For example, severe nodulocystic acne on the chin and jawline can interfere with proper wear of the chin strap on a Kevlar helmet. The severity of acne often necessitates the use of oral isotretinoin therapy, which is considered disqualifying for many special military assignments, including submarine duty, nuclear field duty, and diving duty.¹¹ In military aviation communities, oral isotretinoin requires grounding for the duration of therapy plus 3 months after cessation. Slit-lamp examination, triglycerides, and transaminase levels must be normal prior to returning to unrestricted duty.¹² Furthermore, use of oral isotretinoin may limit overseas assignments or deployment eligibility.⁴

The high prevalence of acne and the operationally limiting consequences of isotretinoin therapy present a unique challenge for dermatologists treating military personnel. The average duration of isotretinoin treatment is approximately 6 months,⁷ which represents a considerable amount of time during an average 4-year enlistment contract. Therapeutic treatment strategies that (1) reduce the duration of oral isotretinoin therapy, (2) reduce the risk for relapse, and (3) increase medication compliance can reduce the operational impact of this acne treatment. Such treatment strategies are discussed below.

An optimal isotretinoin dosing regimen would achieve swift resolution of acne lesions and reduce the overall relapse rate requiring retrial of isotretinoin, thereby minimizing the operational- and duty-limiting impacts of the medication. Cyrulnik et al¹³ studied treatment outcomes of high-dose isotretinoin for acne vulgaris using a mean dosage of 1.6 mg/kg daily with an average cumulative dosage of 290 mg/kg. They demonstrated 100% clearance of lesions over 6 months, with a 12.5% relapse rate at 3 years. Aside from an increased rate of elevated transaminases, incidence of adverse effects and laboratory abnormalities were not significantly increased compared to conventional dosing regimens.¹³ The goal cumulative dosing of 120 to 150 mg/kg can be achieved 1 to 2 months earlier using a dosage of 1.6 mg/kg daily vs a conventional dosage of 1 mg/kg daily.

It has been hypothesized that higher cumulative doses of oral isotretinoin reduce the risk for relapse of acne and retrial of oral isotretinoin.¹⁴ Blasiak et al¹⁵ studied relapse and retrial of oral isotretinoin in acne patients who received cumulative dosing higher or lower than 220 mg/kg. A clinically but not statistically significant reduced relapse rate was observed in the cohort that received cumulative dosing higher than 220 mg/kg. No statistically significant difference in rates of adverse advents was observed aside from an increase in retinoid dermatitis in the cohort that received cumulative dosing higher than 220 mg/kg. Higher but not statistically significant rates of adverse events were seen in the group that received dosing higher than 220 mg/kg.¹⁵ Cumulative doses of oral isotretinoin higher than the 120 to 150 mg/kg range may decrease the risk for acne relapse and the need for an additional course of oral isotretinoin, which would reduce a service member’s total time away from deployment and full duty.

Relapse requiring a retrial of oral isotretinoin not only increases the operational cost of acne treatment but also considerably increases the monetary cost to the health care system. In a cost-analysis model, cumulative doses of oral isotretinoin higher than 230 mg/kg have a decreased overall cost compared to traditional cumulative dosing of less than 150 mg/kg due to the cost of relapse.¹⁶

Limitations of high daily and cumulative dosing regimens of oral isotretinoin are chiefly the dose-dependent rate of adverse effects. Low-dose regimens are associated with a reduced risk of isotretinoin-related side effects.^6,17 Acute acne flares may be seen following initial administration of oral isotretinoin and are aggravated by increases in dosage.¹⁸ Isotretinoin-induced acne fulminans is a rare but devastating complication observed with high initial doses of oral isotretinoin in patients with severe acne.¹⁹ The risks and benefits of high daily and cumulatively dosed isotretinoin must be carefully considered in patients with severe acne.

Teledermatology: A Force for Readiness

The COVID-19 pandemic drastically changed the dermatology practice landscape with recommendations to cancel all elective outpatient visits in favor of teledermatology encounters.²⁰ This decreased access to care, which resulted in an increase in drug interruption for dermatology patients, including patients on oral isotretinoin.²¹ Teledermatology has been increasingly utilized to maintain continuity of care for the management of patients taking isotretinoin.⁵ Routine utilization of teledermatology evaluation in military practices could expedite care, decrease patient travel time, and allow for in-clinic visits to be utilized for higher-acuity concerns.²²

The use of teledermatology for uncomplicated oral isotretinoin management has the potential to increase medication compliance and decrease the amount of travel time for active-duty service members; for example, consider a military dermatology practice based in San Diego, California, that accepts referrals from military bases 3 hours away by car. After an initial consultation for consideration and initiation of oral isotretinoin, teledermatology appointments can save the active-duty service member 3 hours of travel time for each follow-up visit per month. This ultimately increases operational productivity, reduces barriers to accessing care, and improves patient satisfaction.²³

Although military personnel usually are located at duty stations for 2 to 4 years, training exercises and military vocational schools often temporarily take personnel away from their home station. These temporary-duty assignments have the potential to interrupt medical follow-up appointments and may cause delays in treatment for individuals who miss monthly isotretinoin visits. When deemed appropriate by the prescribing dermatologist, teledermatology allows for increased continuity of care for active-duty service members and maintenance of a therapeutic isotretinoin course despite temporary geographic displacement.

By facilitating regular follow-up appointments, teledermatology can minimize the amount of time an active-duty service member is on a course of oral isotretinoin, thereby reducing the operational and duty-limiting implications of the medication.

Final Thoughts

Acne is a common dermatologic concern within the active-duty military population. Oral isotretinoin is indicated for treatment-resistant moderate or severe acne; however, it limits the ability of service members to deploy and is disqualifying for special military assignments. High daily- and cumulative-dose isotretinoin treatment strategies can reduce the duration of therapy and may be associated with a decrease in acne relapse and the need for retrial. Teledermatology can increase access to care and facilitate the completion of oral isotretinoin courses in a timely manner. These treatment strategies may help mitigate the duty-limiting impact of oral isotretinoin therapy in military service members.

Acne vulgaris is an extremely common dermatologic disease affecting 40 to 50 million individuals in the United States each year, with a prevalence of 85% in adolescents and young adults aged 12 to 24 years. For some patients, the disease may persist well into adulthood, affecting 8% of adults aged 25 and 34 years.¹ Acne negatively impacts patients’ quality of life and productivity, with an estimated direct and indirect cost of over $3 billion per year.²

Oral isotretinoin, a vitamin A derivative, is approved by the US Food and Drug Administration for the treatment of severe nodulocystic acne. Isotretinoin reduces the size and secretions of sebaceous glands, inhibits growth and resulting inflammation of Cutibacterium acnes, and normalizes the differentiation of follicular keratinocytes, resulting in permanent changes in the pathogenesis of acne that may lead to remission.³ The use of oral isotretinoin in the active-duty US Military population may cause service members to be nondeployable or limit their ability to function in special roles (eg, pilot, submariner).⁴ Treatment regimens that minimize the course duration of isotretinoin and reduce the risk for relapse that requires a retrial of isotretinoin may, in turn, increase a service member’s readiness, deployment availability, and ability to perform unique occupational roles.

Additionally, teledermatology has been increasingly utilized to maintain treatment continuity for patients on isotretinoin during the COVID-19 pandemic.⁵ Application of this technology in the military also may be used to facilitate timely isotretinoin treatment regimens in active-duty service members to minimize course duration and increase readiness.

In this article, we discuss an accelerated course of oral isotretinoin as a safe and effective option for military service members bound by duty restrictions and operational timelines and explore the role of teledermatology for the treatment of acne in military service members.

Isotretinoin for Acne

Isotretinoin typically is initiated at a dosage of 0.5 mg/kg daily, increasing to 1 mg/kg daily with a goal cumulative dose between 120 and 150 mg/kg. Relapse may occur after completing a treatment course and is associated with cumulative dosing less than 120 mg/kg.⁶ The average duration of acne treatment with oral isotretinoin is approximately 6 months.⁷ At therapeutic doses, nearly all patients experience side effects, most commonly dryness and desquamation of the skin and mucous membranes, as well as possible involvement of the lips, eyes, and nose. Notable extracutaneous side effects include headache, visual disturbances at night, idiopathic intracranial hypertension, and myalgia. Serum cholesterol, triglycerides, and transaminases may be increased in patients taking isotretinoin, which requires routine monitoring using serum lipid profiles and liver function studies. A potential association between isotretinoin and inflammatory bowel disease and changes in mood have been reported, but current data do not suggest an evidence-based link.^6,8 Isotretinoin is a potent teratogen, and in the United States, all patients are required to enroll in iPLEDGE, a US Food and Drug Administration–approved pregnancy prevention program that monitors prescribing and dispensing of the medication. For patients who can become pregnant, iPLEDGE requires use of 2 forms of contraception as well as monthly pregnancy tests prior to dispensing the medication.

Acne in Military Service Members

Acne is exceedingly common in the active-duty military population. In 2018, more than 40% of soldiers, sailors, airmen, and marines were 25 years or younger, and 75% of all US service members were 35 years or younger, corresponding to acne peak incidences.^1,9 Management of acne in this population requires unique treatment considerations due to distinctive occupational requirements of and hazards faced by military personnel. Use of personal protective equipment, including gas masks, safety restraints, parachute rigging, and flak jackets, may be limiting in individuals with moderate to severe acne.¹⁰ For example, severe nodulocystic acne on the chin and jawline can interfere with proper wear of the chin strap on a Kevlar helmet. The severity of acne often necessitates the use of oral isotretinoin therapy, which is considered disqualifying for many special military assignments, including submarine duty, nuclear field duty, and diving duty.¹¹ In military aviation communities, oral isotretinoin requires grounding for the duration of therapy plus 3 months after cessation. Slit-lamp examination, triglycerides, and transaminase levels must be normal prior to returning to unrestricted duty.¹² Furthermore, use of oral isotretinoin may limit overseas assignments or deployment eligibility.⁴

The high prevalence of acne and the operationally limiting consequences of isotretinoin therapy present a unique challenge for dermatologists treating military personnel. The average duration of isotretinoin treatment is approximately 6 months,⁷ which represents a considerable amount of time during an average 4-year enlistment contract. Therapeutic treatment strategies that (1) reduce the duration of oral isotretinoin therapy, (2) reduce the risk for relapse, and (3) increase medication compliance can reduce the operational impact of this acne treatment. Such treatment strategies are discussed below.

An optimal isotretinoin dosing regimen would achieve swift resolution of acne lesions and reduce the overall relapse rate requiring retrial of isotretinoin, thereby minimizing the operational- and duty-limiting impacts of the medication. Cyrulnik et al¹³ studied treatment outcomes of high-dose isotretinoin for acne vulgaris using a mean dosage of 1.6 mg/kg daily with an average cumulative dosage of 290 mg/kg. They demonstrated 100% clearance of lesions over 6 months, with a 12.5% relapse rate at 3 years. Aside from an increased rate of elevated transaminases, incidence of adverse effects and laboratory abnormalities were not significantly increased compared to conventional dosing regimens.¹³ The goal cumulative dosing of 120 to 150 mg/kg can be achieved 1 to 2 months earlier using a dosage of 1.6 mg/kg daily vs a conventional dosage of 1 mg/kg daily.

It has been hypothesized that higher cumulative doses of oral isotretinoin reduce the risk for relapse of acne and retrial of oral isotretinoin.¹⁴ Blasiak et al¹⁵ studied relapse and retrial of oral isotretinoin in acne patients who received cumulative dosing higher or lower than 220 mg/kg. A clinically but not statistically significant reduced relapse rate was observed in the cohort that received cumulative dosing higher than 220 mg/kg. No statistically significant difference in rates of adverse advents was observed aside from an increase in retinoid dermatitis in the cohort that received cumulative dosing higher than 220 mg/kg. Higher but not statistically significant rates of adverse events were seen in the group that received dosing higher than 220 mg/kg.¹⁵ Cumulative doses of oral isotretinoin higher than the 120 to 150 mg/kg range may decrease the risk for acne relapse and the need for an additional course of oral isotretinoin, which would reduce a service member’s total time away from deployment and full duty.

Relapse requiring a retrial of oral isotretinoin not only increases the operational cost of acne treatment but also considerably increases the monetary cost to the health care system. In a cost-analysis model, cumulative doses of oral isotretinoin higher than 230 mg/kg have a decreased overall cost compared to traditional cumulative dosing of less than 150 mg/kg due to the cost of relapse.¹⁶

Limitations of high daily and cumulative dosing regimens of oral isotretinoin are chiefly the dose-dependent rate of adverse effects. Low-dose regimens are associated with a reduced risk of isotretinoin-related side effects.^6,17 Acute acne flares may be seen following initial administration of oral isotretinoin and are aggravated by increases in dosage.¹⁸ Isotretinoin-induced acne fulminans is a rare but devastating complication observed with high initial doses of oral isotretinoin in patients with severe acne.¹⁹ The risks and benefits of high daily and cumulatively dosed isotretinoin must be carefully considered in patients with severe acne.

Teledermatology: A Force for Readiness

The COVID-19 pandemic drastically changed the dermatology practice landscape with recommendations to cancel all elective outpatient visits in favor of teledermatology encounters.²⁰ This decreased access to care, which resulted in an increase in drug interruption for dermatology patients, including patients on oral isotretinoin.²¹ Teledermatology has been increasingly utilized to maintain continuity of care for the management of patients taking isotretinoin.⁵ Routine utilization of teledermatology evaluation in military practices could expedite care, decrease patient travel time, and allow for in-clinic visits to be utilized for higher-acuity concerns.²²

The use of teledermatology for uncomplicated oral isotretinoin management has the potential to increase medication compliance and decrease the amount of travel time for active-duty service members; for example, consider a military dermatology practice based in San Diego, California, that accepts referrals from military bases 3 hours away by car. After an initial consultation for consideration and initiation of oral isotretinoin, teledermatology appointments can save the active-duty service member 3 hours of travel time for each follow-up visit per month. This ultimately increases operational productivity, reduces barriers to accessing care, and improves patient satisfaction.²³

Although military personnel usually are located at duty stations for 2 to 4 years, training exercises and military vocational schools often temporarily take personnel away from their home station. These temporary-duty assignments have the potential to interrupt medical follow-up appointments and may cause delays in treatment for individuals who miss monthly isotretinoin visits. When deemed appropriate by the prescribing dermatologist, teledermatology allows for increased continuity of care for active-duty service members and maintenance of a therapeutic isotretinoin course despite temporary geographic displacement.

By facilitating regular follow-up appointments, teledermatology can minimize the amount of time an active-duty service member is on a course of oral isotretinoin, thereby reducing the operational and duty-limiting implications of the medication.

Final Thoughts

Acne is a common dermatologic concern within the active-duty military population. Oral isotretinoin is indicated for treatment-resistant moderate or severe acne; however, it limits the ability of service members to deploy and is disqualifying for special military assignments. High daily- and cumulative-dose isotretinoin treatment strategies can reduce the duration of therapy and may be associated with a decrease in acne relapse and the need for retrial. Teledermatology can increase access to care and facilitate the completion of oral isotretinoin courses in a timely manner. These treatment strategies may help mitigate the duty-limiting impact of oral isotretinoin therapy in military service members.

Acne vulgaris is an extremely common dermatologic disease affecting 40 to 50 million individuals in the United States each year, with a prevalence of 85% in adolescents and young adults aged 12 to 24 years. For some patients, the disease may persist well into adulthood, affecting 8% of adults aged 25 and 34 years.¹ Acne negatively impacts patients’ quality of life and productivity, with an estimated direct and indirect cost of over $3 billion per year.²

Oral isotretinoin, a vitamin A derivative, is approved by the US Food and Drug Administration for the treatment of severe nodulocystic acne. Isotretinoin reduces the size and secretions of sebaceous glands, inhibits growth and resulting inflammation of Cutibacterium acnes, and normalizes the differentiation of follicular keratinocytes, resulting in permanent changes in the pathogenesis of acne that may lead to remission.³ The use of oral isotretinoin in the active-duty US Military population may cause service members to be nondeployable or limit their ability to function in special roles (eg, pilot, submariner).⁴ Treatment regimens that minimize the course duration of isotretinoin and reduce the risk for relapse that requires a retrial of isotretinoin may, in turn, increase a service member’s readiness, deployment availability, and ability to perform unique occupational roles.

Additionally, teledermatology has been increasingly utilized to maintain treatment continuity for patients on isotretinoin during the COVID-19 pandemic.⁵ Application of this technology in the military also may be used to facilitate timely isotretinoin treatment regimens in active-duty service members to minimize course duration and increase readiness.

In this article, we discuss an accelerated course of oral isotretinoin as a safe and effective option for military service members bound by duty restrictions and operational timelines and explore the role of teledermatology for the treatment of acne in military service members.

Isotretinoin for Acne

Isotretinoin typically is initiated at a dosage of 0.5 mg/kg daily, increasing to 1 mg/kg daily with a goal cumulative dose between 120 and 150 mg/kg. Relapse may occur after completing a treatment course and is associated with cumulative dosing less than 120 mg/kg.⁶ The average duration of acne treatment with oral isotretinoin is approximately 6 months.⁷ At therapeutic doses, nearly all patients experience side effects, most commonly dryness and desquamation of the skin and mucous membranes, as well as possible involvement of the lips, eyes, and nose. Notable extracutaneous side effects include headache, visual disturbances at night, idiopathic intracranial hypertension, and myalgia. Serum cholesterol, triglycerides, and transaminases may be increased in patients taking isotretinoin, which requires routine monitoring using serum lipid profiles and liver function studies. A potential association between isotretinoin and inflammatory bowel disease and changes in mood have been reported, but current data do not suggest an evidence-based link.^6,8 Isotretinoin is a potent teratogen, and in the United States, all patients are required to enroll in iPLEDGE, a US Food and Drug Administration–approved pregnancy prevention program that monitors prescribing and dispensing of the medication. For patients who can become pregnant, iPLEDGE requires use of 2 forms of contraception as well as monthly pregnancy tests prior to dispensing the medication.

Acne in Military Service Members

Acne is exceedingly common in the active-duty military population. In 2018, more than 40% of soldiers, sailors, airmen, and marines were 25 years or younger, and 75% of all US service members were 35 years or younger, corresponding to acne peak incidences.^1,9 Management of acne in this population requires unique treatment considerations due to distinctive occupational requirements of and hazards faced by military personnel. Use of personal protective equipment, including gas masks, safety restraints, parachute rigging, and flak jackets, may be limiting in individuals with moderate to severe acne.¹⁰ For example, severe nodulocystic acne on the chin and jawline can interfere with proper wear of the chin strap on a Kevlar helmet. The severity of acne often necessitates the use of oral isotretinoin therapy, which is considered disqualifying for many special military assignments, including submarine duty, nuclear field duty, and diving duty.¹¹ In military aviation communities, oral isotretinoin requires grounding for the duration of therapy plus 3 months after cessation. Slit-lamp examination, triglycerides, and transaminase levels must be normal prior to returning to unrestricted duty.¹² Furthermore, use of oral isotretinoin may limit overseas assignments or deployment eligibility.⁴

The high prevalence of acne and the operationally limiting consequences of isotretinoin therapy present a unique challenge for dermatologists treating military personnel. The average duration of isotretinoin treatment is approximately 6 months,⁷ which represents a considerable amount of time during an average 4-year enlistment contract. Therapeutic treatment strategies that (1) reduce the duration of oral isotretinoin therapy, (2) reduce the risk for relapse, and (3) increase medication compliance can reduce the operational impact of this acne treatment. Such treatment strategies are discussed below.

An optimal isotretinoin dosing regimen would achieve swift resolution of acne lesions and reduce the overall relapse rate requiring retrial of isotretinoin, thereby minimizing the operational- and duty-limiting impacts of the medication. Cyrulnik et al¹³ studied treatment outcomes of high-dose isotretinoin for acne vulgaris using a mean dosage of 1.6 mg/kg daily with an average cumulative dosage of 290 mg/kg. They demonstrated 100% clearance of lesions over 6 months, with a 12.5% relapse rate at 3 years. Aside from an increased rate of elevated transaminases, incidence of adverse effects and laboratory abnormalities were not significantly increased compared to conventional dosing regimens.¹³ The goal cumulative dosing of 120 to 150 mg/kg can be achieved 1 to 2 months earlier using a dosage of 1.6 mg/kg daily vs a conventional dosage of 1 mg/kg daily.

It has been hypothesized that higher cumulative doses of oral isotretinoin reduce the risk for relapse of acne and retrial of oral isotretinoin.¹⁴ Blasiak et al¹⁵ studied relapse and retrial of oral isotretinoin in acne patients who received cumulative dosing higher or lower than 220 mg/kg. A clinically but not statistically significant reduced relapse rate was observed in the cohort that received cumulative dosing higher than 220 mg/kg. No statistically significant difference in rates of adverse advents was observed aside from an increase in retinoid dermatitis in the cohort that received cumulative dosing higher than 220 mg/kg. Higher but not statistically significant rates of adverse events were seen in the group that received dosing higher than 220 mg/kg.¹⁵ Cumulative doses of oral isotretinoin higher than the 120 to 150 mg/kg range may decrease the risk for acne relapse and the need for an additional course of oral isotretinoin, which would reduce a service member’s total time away from deployment and full duty.

Relapse requiring a retrial of oral isotretinoin not only increases the operational cost of acne treatment but also considerably increases the monetary cost to the health care system. In a cost-analysis model, cumulative doses of oral isotretinoin higher than 230 mg/kg have a decreased overall cost compared to traditional cumulative dosing of less than 150 mg/kg due to the cost of relapse.¹⁶

Limitations of high daily and cumulative dosing regimens of oral isotretinoin are chiefly the dose-dependent rate of adverse effects. Low-dose regimens are associated with a reduced risk of isotretinoin-related side effects.^6,17 Acute acne flares may be seen following initial administration of oral isotretinoin and are aggravated by increases in dosage.¹⁸ Isotretinoin-induced acne fulminans is a rare but devastating complication observed with high initial doses of oral isotretinoin in patients with severe acne.¹⁹ The risks and benefits of high daily and cumulatively dosed isotretinoin must be carefully considered in patients with severe acne.

Teledermatology: A Force for Readiness

The COVID-19 pandemic drastically changed the dermatology practice landscape with recommendations to cancel all elective outpatient visits in favor of teledermatology encounters.²⁰ This decreased access to care, which resulted in an increase in drug interruption for dermatology patients, including patients on oral isotretinoin.²¹ Teledermatology has been increasingly utilized to maintain continuity of care for the management of patients taking isotretinoin.⁵ Routine utilization of teledermatology evaluation in military practices could expedite care, decrease patient travel time, and allow for in-clinic visits to be utilized for higher-acuity concerns.²²

The use of teledermatology for uncomplicated oral isotretinoin management has the potential to increase medication compliance and decrease the amount of travel time for active-duty service members; for example, consider a military dermatology practice based in San Diego, California, that accepts referrals from military bases 3 hours away by car. After an initial consultation for consideration and initiation of oral isotretinoin, teledermatology appointments can save the active-duty service member 3 hours of travel time for each follow-up visit per month. This ultimately increases operational productivity, reduces barriers to accessing care, and improves patient satisfaction.²³

Although military personnel usually are located at duty stations for 2 to 4 years, training exercises and military vocational schools often temporarily take personnel away from their home station. These temporary-duty assignments have the potential to interrupt medical follow-up appointments and may cause delays in treatment for individuals who miss monthly isotretinoin visits. When deemed appropriate by the prescribing dermatologist, teledermatology allows for increased continuity of care for active-duty service members and maintenance of a therapeutic isotretinoin course despite temporary geographic displacement.

By facilitating regular follow-up appointments, teledermatology can minimize the amount of time an active-duty service member is on a course of oral isotretinoin, thereby reducing the operational and duty-limiting implications of the medication.

Final Thoughts

Acne is a common dermatologic concern within the active-duty military population. Oral isotretinoin is indicated for treatment-resistant moderate or severe acne; however, it limits the ability of service members to deploy and is disqualifying for special military assignments. High daily- and cumulative-dose isotretinoin treatment strategies can reduce the duration of therapy and may be associated with a decrease in acne relapse and the need for retrial. Teledermatology can increase access to care and facilitate the completion of oral isotretinoin courses in a timely manner. These treatment strategies may help mitigate the duty-limiting impact of oral isotretinoin therapy in military service members.

The Diagnosis: Histiocytoid Sweet Syndrome

The patient was admitted for clinical study and treatment monitoring. During the first 72 hours of admittance, the lesions and general malaise further developed along with C-reactive protein elevation (126 mg/L). Administration of intravenous prednisone at a dosage of 1 mg/kg daily was accompanied by substantial improvement after 1 week of treatment, with subsequent follow-up and outpatient monitoring. An underlying neoplasia was ruled out after review of medical history, physical examination, complete blood cell count, chest radiography, abdominal ultrasonography, colonoscopy, and bone marrow aspiration.

A 4-mm skin biopsy was performed from a lesion on the neck (Figure 1). Histology revealed a dermis with prominent edema alongside superficial, deep, and periadnexal perivascular inflammatory infiltrates, as well as predominant lymphocytes and cells with a histiocytoid profile (Figure 2). These findings were accompanied by isolated neutrophil foci. The absence of leukocytoclastic vasculitis was noted. Immunohistochemistry demonstrated that the histiocyte population was positive for myeloperoxidase and CD68, which categorized them as immature cells of myeloid origin (Figure 3). Clinical and histopathologic findings led to a definitive diagnosis of histiocytoid Sweet syndrome (SS). Sweet syndrome consists of a neutrophilic dermatosis profile. Clinically, it manifests as a sudden onset of painful nodules and plaques accompanied by fever, malaise, and leukocytosis.

Histiocytoid SS is a rare histologic variant of SS initially described by Requena et al1 in 2005. In histiocytoid SS, the main inflammatory infiltrates are promyelocytes and myelocytes.² Immunohistochemistry shows positivity for myeloperoxidase, CD15, CD43, CD45, CD68, MAC-386, and HAM56.¹ The diagnosis is determined by exclusion after adequate clinical and histopathologic correlation, which also should exclude other diagnoses such as leukemia cutis and interstitial granulomatous dermatitis.³ Histiocytoid SS may be related to an increased risk for underlying malignancy. Haber et al⁴ performed a systematic review in which they concluded that approximately 40% of patients newly diagnosed with histiocytoid SS subsequently were diagnosed or already were diagnosed with a hematologic or solid cancer vs 21% in the classical neutrophilic infiltrate of SS (NSS). Histiocytoid SS more commonly was associated with myelodysplastic syndrome (46% vs 2.5% in NSS) and hematologic malignancies (42.5% vs 25% in SS).

The initial differential diagnoses include inflammatory dermatoses, infections, neoplasms, and systemic diseases. In exudative erythema multiforme, early lesions are composed of typical target lesions with mucosal involvement in 25% to 60% of patients.⁵ Erythema elevatum diutinum is a chronic dermatosis characterized by asymptomatic papules and red-violet nodules. The most characteristic histologic finding is leukocytoclastic vasculitis.⁶ The absence of vasculitis is part of the major diagnostic criteria for SS.⁷ Wells syndrome is associated with general malaise, and edematous and erythematous-violet plaques or nodules appear on the limbs; however, it frequently is associated with eosinophilia in peripheral blood, and histology shows that the main cell population of the inflammatory infiltrate also is eosinophilic.⁸ Painful, superficial, and erosive blisters appear preferentially on the face and backs of the arms in bullous pyoderma gangrenosum. It usually is not associated with the typical systemic manifestations of SS (ie, fever, arthralgia, damage to target organs). On histopathology, the neutrophilic infiltrate is accompanied by subepidermal vesicles.⁹

Histiocytoid SS responds dramatically to corticosteroids. Other first-line treatments that avoid use of corticosteroids are colchicine, dapsone, and potassium iodide. Multiple treatments were attempted in our patient, including corticosteroids, methotrexate, dapsone, colchicine, and anakinra. Despite patients responding well to treatment, a possible underlying neoplasm, most frequently of hematologic origin, must be excluded.¹⁰

The Diagnosis: Histiocytoid Sweet Syndrome

The patient was admitted for clinical study and treatment monitoring. During the first 72 hours of admittance, the lesions and general malaise further developed along with C-reactive protein elevation (126 mg/L). Administration of intravenous prednisone at a dosage of 1 mg/kg daily was accompanied by substantial improvement after 1 week of treatment, with subsequent follow-up and outpatient monitoring. An underlying neoplasia was ruled out after review of medical history, physical examination, complete blood cell count, chest radiography, abdominal ultrasonography, colonoscopy, and bone marrow aspiration.

A 4-mm skin biopsy was performed from a lesion on the neck (Figure 1). Histology revealed a dermis with prominent edema alongside superficial, deep, and periadnexal perivascular inflammatory infiltrates, as well as predominant lymphocytes and cells with a histiocytoid profile (Figure 2). These findings were accompanied by isolated neutrophil foci. The absence of leukocytoclastic vasculitis was noted. Immunohistochemistry demonstrated that the histiocyte population was positive for myeloperoxidase and CD68, which categorized them as immature cells of myeloid origin (Figure 3). Clinical and histopathologic findings led to a definitive diagnosis of histiocytoid Sweet syndrome (SS). Sweet syndrome consists of a neutrophilic dermatosis profile. Clinically, it manifests as a sudden onset of painful nodules and plaques accompanied by fever, malaise, and leukocytosis.

Histiocytoid SS is a rare histologic variant of SS initially described by Requena et al1 in 2005. In histiocytoid SS, the main inflammatory infiltrates are promyelocytes and myelocytes.² Immunohistochemistry shows positivity for myeloperoxidase, CD15, CD43, CD45, CD68, MAC-386, and HAM56.¹ The diagnosis is determined by exclusion after adequate clinical and histopathologic correlation, which also should exclude other diagnoses such as leukemia cutis and interstitial granulomatous dermatitis.³ Histiocytoid SS may be related to an increased risk for underlying malignancy. Haber et al⁴ performed a systematic review in which they concluded that approximately 40% of patients newly diagnosed with histiocytoid SS subsequently were diagnosed or already were diagnosed with a hematologic or solid cancer vs 21% in the classical neutrophilic infiltrate of SS (NSS). Histiocytoid SS more commonly was associated with myelodysplastic syndrome (46% vs 2.5% in NSS) and hematologic malignancies (42.5% vs 25% in SS).

The initial differential diagnoses include inflammatory dermatoses, infections, neoplasms, and systemic diseases. In exudative erythema multiforme, early lesions are composed of typical target lesions with mucosal involvement in 25% to 60% of patients.⁵ Erythema elevatum diutinum is a chronic dermatosis characterized by asymptomatic papules and red-violet nodules. The most characteristic histologic finding is leukocytoclastic vasculitis.⁶ The absence of vasculitis is part of the major diagnostic criteria for SS.⁷ Wells syndrome is associated with general malaise, and edematous and erythematous-violet plaques or nodules appear on the limbs; however, it frequently is associated with eosinophilia in peripheral blood, and histology shows that the main cell population of the inflammatory infiltrate also is eosinophilic.⁸ Painful, superficial, and erosive blisters appear preferentially on the face and backs of the arms in bullous pyoderma gangrenosum. It usually is not associated with the typical systemic manifestations of SS (ie, fever, arthralgia, damage to target organs). On histopathology, the neutrophilic infiltrate is accompanied by subepidermal vesicles.⁹

Histiocytoid SS responds dramatically to corticosteroids. Other first-line treatments that avoid use of corticosteroids are colchicine, dapsone, and potassium iodide. Multiple treatments were attempted in our patient, including corticosteroids, methotrexate, dapsone, colchicine, and anakinra. Despite patients responding well to treatment, a possible underlying neoplasm, most frequently of hematologic origin, must be excluded.¹⁰

The Diagnosis: Histiocytoid Sweet Syndrome

The patient was admitted for clinical study and treatment monitoring. During the first 72 hours of admittance, the lesions and general malaise further developed along with C-reactive protein elevation (126 mg/L). Administration of intravenous prednisone at a dosage of 1 mg/kg daily was accompanied by substantial improvement after 1 week of treatment, with subsequent follow-up and outpatient monitoring. An underlying neoplasia was ruled out after review of medical history, physical examination, complete blood cell count, chest radiography, abdominal ultrasonography, colonoscopy, and bone marrow aspiration.

A 4-mm skin biopsy was performed from a lesion on the neck (Figure 1). Histology revealed a dermis with prominent edema alongside superficial, deep, and periadnexal perivascular inflammatory infiltrates, as well as predominant lymphocytes and cells with a histiocytoid profile (Figure 2). These findings were accompanied by isolated neutrophil foci. The absence of leukocytoclastic vasculitis was noted. Immunohistochemistry demonstrated that the histiocyte population was positive for myeloperoxidase and CD68, which categorized them as immature cells of myeloid origin (Figure 3). Clinical and histopathologic findings led to a definitive diagnosis of histiocytoid Sweet syndrome (SS). Sweet syndrome consists of a neutrophilic dermatosis profile. Clinically, it manifests as a sudden onset of painful nodules and plaques accompanied by fever, malaise, and leukocytosis.

Histiocytoid SS is a rare histologic variant of SS initially described by Requena et al1 in 2005. In histiocytoid SS, the main inflammatory infiltrates are promyelocytes and myelocytes.² Immunohistochemistry shows positivity for myeloperoxidase, CD15, CD43, CD45, CD68, MAC-386, and HAM56.¹ The diagnosis is determined by exclusion after adequate clinical and histopathologic correlation, which also should exclude other diagnoses such as leukemia cutis and interstitial granulomatous dermatitis.³ Histiocytoid SS may be related to an increased risk for underlying malignancy. Haber et al⁴ performed a systematic review in which they concluded that approximately 40% of patients newly diagnosed with histiocytoid SS subsequently were diagnosed or already were diagnosed with a hematologic or solid cancer vs 21% in the classical neutrophilic infiltrate of SS (NSS). Histiocytoid SS more commonly was associated with myelodysplastic syndrome (46% vs 2.5% in NSS) and hematologic malignancies (42.5% vs 25% in SS).

The initial differential diagnoses include inflammatory dermatoses, infections, neoplasms, and systemic diseases. In exudative erythema multiforme, early lesions are composed of typical target lesions with mucosal involvement in 25% to 60% of patients.⁵ Erythema elevatum diutinum is a chronic dermatosis characterized by asymptomatic papules and red-violet nodules. The most characteristic histologic finding is leukocytoclastic vasculitis.⁶ The absence of vasculitis is part of the major diagnostic criteria for SS.⁷ Wells syndrome is associated with general malaise, and edematous and erythematous-violet plaques or nodules appear on the limbs; however, it frequently is associated with eosinophilia in peripheral blood, and histology shows that the main cell population of the inflammatory infiltrate also is eosinophilic.⁸ Painful, superficial, and erosive blisters appear preferentially on the face and backs of the arms in bullous pyoderma gangrenosum. It usually is not associated with the typical systemic manifestations of SS (ie, fever, arthralgia, damage to target organs). On histopathology, the neutrophilic infiltrate is accompanied by subepidermal vesicles.⁹

Histiocytoid SS responds dramatically to corticosteroids. Other first-line treatments that avoid use of corticosteroids are colchicine, dapsone, and potassium iodide. Multiple treatments were attempted in our patient, including corticosteroids, methotrexate, dapsone, colchicine, and anakinra. Despite patients responding well to treatment, a possible underlying neoplasm, most frequently of hematologic origin, must be excluded.¹⁰

In 2014, amidst stories of delays at Veterans Health Administration facilities, Congress established the Veterans Choice Program, which expanded access to private sector health care practitioners. When the program expired in 2018, lawmakers replaced it with the Veterans Community Care Program (VCCP) as part of the US Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks Act (38 USC § 1703 MISSION Act). Since then, the VCCP has grown exponentially; 34% of current veteran health care visits are with private clinicians.

Along with broader private sector access, the MISSION Act also mandated the creation of quality-of-care standards for both VA and VCCP, and stipulated that data be compiled and made available to “provide covered veterans relevant comparative information to make informed decisions regarding their health care.” Two-and-a-half years later, data about the quality of VCCP care remains largely unknown.

Access to Care Website 

In the lead up to the MISSION Act, the VA launched its Access to Care website, an online tool thatpublishes institutional performance data on key metrics so that veterans can make “more informed choices about where, when, and how they receive their health care.” Following the bill’s passage, the VA added a MISSION Act Quality Standards section, which includes results of 27 conventional quality measures for every VA facility. These scores are posted alongside data of regional facilities.

This trailblazing tool is exceedingly comprehensive. Yet, multiple website gaps compromise its utility for veterans deliberating whether to obtain VCCP care, including:

1. Data isn’t about VCCP care. The hospitals are selected because they are local, not whether they participate in VCCP.  Further, it appears that aggregate scores include non-VCCP facilities.
2. Missing conditions/treatments. While the website contains quality scores for an ample range of procedures, it lacks information for many conditions that disproportionately affect veterans. A veteran with posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI), for example, has no data to check.
3. Skewed comparison population. Private sector practitioners primarily treat nonveteran patients, a population that is, on average, healthier and of higher socioeconomic status when compared with VA patients. Outcomes differ, for example, when patients have coexisting mental illness or homelessness. For VCCP scores to be beneficial for comparisons, they should derive from treated veterans or be accurately risk-adjusted.
4. Tangential measures. The Institute of Medicine defined health care quality as “improvement of outcomes.” Patients considering health care options benefit from information about treatment effectiveness and symptom reduction. But because obtaining that quality data is labor intensive, proxy measures are substituted. For example, the measure advising smokers to quit is the closest the website comes to reporting on the quality of mental health care.

High-Performers

The VA initiated a second means to inform veterans about the quality of furnished care. Specifically, they guided third-party administrators (TPAs)—TriWest Healthcare Alliance and Optum—in creating algorithms designating that VCCP individual clinicians, practice groups, and hospitals can be deemed high performing providers (HPPs). The algorithms are calculated using a mix of Healthcare Effectiveness Data and Information Set (HEDIS), Physician Quality Reporting System (PQRS), and Blue Health Intelligence (BHI) primary and specialty care measures. The designations are intended to be accessible to local VA community care schedulers to connect veterans with HPPs.

Many aspects of the HPP system are not yet public, including the measures that comprise the algorithms and when the designations will become operational. From what is publicly discoverable about HPP designations, there are crucial gaps like those on the Access to Care website. Behavioral and mental health conditions, for instance, are intentionally excluded in HPP monitoring. HPP algorithms draw from care provided to the general population; an HPP’s patient panel may contain no veterans (with their common comorbidities) at all. Most limiting, there’s no expectation that VCCP clinicians be high performing. Of the 1.2 million program clinicians treating veterans as of November 2020, only a nominal 13.4% were HPP.

After studying the HPP system, VA Partnered Evidence-based Policy Resource Center acknowledged that “it remains unclear whether the quality metrics and referral system result in higher quality of care for VA patients or whether the program improves veteran health.”

Quality of VCCP Mental Health Treatment

The MISSION Act mandated the VA to “establish standards and requirements for the provision of care by non-VA health care practitioners in clinical areas for which the Department of Veterans Affairs has special expertise, including PTSD, military sexual trauma-related conditions (MST), and TBI.” This requirement arose from a recognition that mental health care provided in the private sector pales in comparisonto the VA’s rigorous evidence-based training, consultation, case review and care delivery. For example, over 8500 VA clinicians have received training in evidence-based cognitive processing therapy and/or prolonged exposure therapy for PTSD.

The MISSION Act also mandated that VCCP providers must “fulfill training requirements established by the Secretary on how to deliver evidence-based treatments in the clinical areas for which the Department of Veterans Affairs has special expertise” before furnishing care pursuant to a contract with the VA. However, the VA elected to disregard the directive, and left it up to VCCP clinician’s discretion whether to obtain training or proficiency.

Two bills introduced in Congress in 2021 aim to uphold these vital mandates for the VCCP program. The Veterans’ Culturally Competent Care Act requires VCCP mental health practitioners to take courses on the evaluation and management of suicide, PTSD, TBI, and MST. The Lethal Means Safety Training Act aligns VCCP clinicians suicide prevention training with existing VA standards.

Recommendations to Assure the Quality of VCCP Care

With review and revision of VCCP quality standards now underway, the following remedial actions are recommended:

1. VCCP metrics must be compiled using data on veterans’ care, not the general population, and be published on the Access to Care website. This indispensable information is published on the website for VA care but not for VCCP. Unless VCCP is required to track their veterans, apples-to-apples comparisons of quality of care will remain difficult to attain. Supplemental research that directly contrasts quality of VA to VCCP care should be posted. For example, a 2021 study of enrolled veterans brought by ambulance to VA or community emergency rooms found that all 170 VA medical centers had lower comparative death rates.
2. VCCP providers should be held to the same quality standards as those applied to VA clinicians. In a 2020 critical issue update on implementation of the MISSION Act, major veterans service organizations (VSOs) recommended that competency, training, and quality standards for non-VA community clinicians must be equivalent to benchmarks expected of VA clinicians. That includes credentials, initial and follow-up training, diagnostic screening, care-delivery, and documentation standards. Enacting the Veterans’ Culturally Competent Care Act and the Lethal Means Safety Training Act would begin to meet the MISSION Act’s clear statutory language.
3. The VA and VCCP should add quality information about major diagnostic categories. This will allow veterans to make informed decisions about their personal condition. For most health diagnoses, there is no searchable listing by disorder. 
4. Quality assessments should be realigned to focus on outcome measures. For prospective patients, outcome results provide the most meaningful basis for comparing and selecting clinicians. Proxy measures may have little bearing on whether veterans receive effective care. (As Albert Einstein’s famously observed, “Not everything that can be counted counts.”). Also, the specific measures used for a clinician’s HPP designation should be delineated.
5. The VA must enforce the MISSION Act’s instruction to renew or cancel contracts based on demonstrated quality of care. As VSOs emphasized, “if the private sector is unwilling or unable to match the VA’s access and quality standards, the VA must consider whether it needs to find new community partners.”  

Seventeen billion dollars is spent yearly on purchased health care whose quality remains indeterminate. Ironclad commitments are needed from Congress and the VA to ensure that the effectiveness of, and standards for, veterans care options in the private sector match that in the VA.

In 2014, amidst stories of delays at Veterans Health Administration facilities, Congress established the Veterans Choice Program, which expanded access to private sector health care practitioners. When the program expired in 2018, lawmakers replaced it with the Veterans Community Care Program (VCCP) as part of the US Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks Act (38 USC § 1703 MISSION Act). Since then, the VCCP has grown exponentially; 34% of current veteran health care visits are with private clinicians.

Along with broader private sector access, the MISSION Act also mandated the creation of quality-of-care standards for both VA and VCCP, and stipulated that data be compiled and made available to “provide covered veterans relevant comparative information to make informed decisions regarding their health care.” Two-and-a-half years later, data about the quality of VCCP care remains largely unknown.

Access to Care Website 

In the lead up to the MISSION Act, the VA launched its Access to Care website, an online tool thatpublishes institutional performance data on key metrics so that veterans can make “more informed choices about where, when, and how they receive their health care.” Following the bill’s passage, the VA added a MISSION Act Quality Standards section, which includes results of 27 conventional quality measures for every VA facility. These scores are posted alongside data of regional facilities.

This trailblazing tool is exceedingly comprehensive. Yet, multiple website gaps compromise its utility for veterans deliberating whether to obtain VCCP care, including:

1. Data isn’t about VCCP care. The hospitals are selected because they are local, not whether they participate in VCCP.  Further, it appears that aggregate scores include non-VCCP facilities.
2. Missing conditions/treatments. While the website contains quality scores for an ample range of procedures, it lacks information for many conditions that disproportionately affect veterans. A veteran with posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI), for example, has no data to check.
3. Skewed comparison population. Private sector practitioners primarily treat nonveteran patients, a population that is, on average, healthier and of higher socioeconomic status when compared with VA patients. Outcomes differ, for example, when patients have coexisting mental illness or homelessness. For VCCP scores to be beneficial for comparisons, they should derive from treated veterans or be accurately risk-adjusted.
4. Tangential measures. The Institute of Medicine defined health care quality as “improvement of outcomes.” Patients considering health care options benefit from information about treatment effectiveness and symptom reduction. But because obtaining that quality data is labor intensive, proxy measures are substituted. For example, the measure advising smokers to quit is the closest the website comes to reporting on the quality of mental health care.

High-Performers

The VA initiated a second means to inform veterans about the quality of furnished care. Specifically, they guided third-party administrators (TPAs)—TriWest Healthcare Alliance and Optum—in creating algorithms designating that VCCP individual clinicians, practice groups, and hospitals can be deemed high performing providers (HPPs). The algorithms are calculated using a mix of Healthcare Effectiveness Data and Information Set (HEDIS), Physician Quality Reporting System (PQRS), and Blue Health Intelligence (BHI) primary and specialty care measures. The designations are intended to be accessible to local VA community care schedulers to connect veterans with HPPs.

Many aspects of the HPP system are not yet public, including the measures that comprise the algorithms and when the designations will become operational. From what is publicly discoverable about HPP designations, there are crucial gaps like those on the Access to Care website. Behavioral and mental health conditions, for instance, are intentionally excluded in HPP monitoring. HPP algorithms draw from care provided to the general population; an HPP’s patient panel may contain no veterans (with their common comorbidities) at all. Most limiting, there’s no expectation that VCCP clinicians be high performing. Of the 1.2 million program clinicians treating veterans as of November 2020, only a nominal 13.4% were HPP.

After studying the HPP system, VA Partnered Evidence-based Policy Resource Center acknowledged that “it remains unclear whether the quality metrics and referral system result in higher quality of care for VA patients or whether the program improves veteran health.”

Quality of VCCP Mental Health Treatment

The MISSION Act mandated the VA to “establish standards and requirements for the provision of care by non-VA health care practitioners in clinical areas for which the Department of Veterans Affairs has special expertise, including PTSD, military sexual trauma-related conditions (MST), and TBI.” This requirement arose from a recognition that mental health care provided in the private sector pales in comparisonto the VA’s rigorous evidence-based training, consultation, case review and care delivery. For example, over 8500 VA clinicians have received training in evidence-based cognitive processing therapy and/or prolonged exposure therapy for PTSD.

The MISSION Act also mandated that VCCP providers must “fulfill training requirements established by the Secretary on how to deliver evidence-based treatments in the clinical areas for which the Department of Veterans Affairs has special expertise” before furnishing care pursuant to a contract with the VA. However, the VA elected to disregard the directive, and left it up to VCCP clinician’s discretion whether to obtain training or proficiency.

Two bills introduced in Congress in 2021 aim to uphold these vital mandates for the VCCP program. The Veterans’ Culturally Competent Care Act requires VCCP mental health practitioners to take courses on the evaluation and management of suicide, PTSD, TBI, and MST. The Lethal Means Safety Training Act aligns VCCP clinicians suicide prevention training with existing VA standards.

Recommendations to Assure the Quality of VCCP Care

With review and revision of VCCP quality standards now underway, the following remedial actions are recommended:

1. VCCP metrics must be compiled using data on veterans’ care, not the general population, and be published on the Access to Care website. This indispensable information is published on the website for VA care but not for VCCP. Unless VCCP is required to track their veterans, apples-to-apples comparisons of quality of care will remain difficult to attain. Supplemental research that directly contrasts quality of VA to VCCP care should be posted. For example, a 2021 study of enrolled veterans brought by ambulance to VA or community emergency rooms found that all 170 VA medical centers had lower comparative death rates.
2. VCCP providers should be held to the same quality standards as those applied to VA clinicians. In a 2020 critical issue update on implementation of the MISSION Act, major veterans service organizations (VSOs) recommended that competency, training, and quality standards for non-VA community clinicians must be equivalent to benchmarks expected of VA clinicians. That includes credentials, initial and follow-up training, diagnostic screening, care-delivery, and documentation standards. Enacting the Veterans’ Culturally Competent Care Act and the Lethal Means Safety Training Act would begin to meet the MISSION Act’s clear statutory language.
3. The VA and VCCP should add quality information about major diagnostic categories. This will allow veterans to make informed decisions about their personal condition. For most health diagnoses, there is no searchable listing by disorder. 
4. Quality assessments should be realigned to focus on outcome measures. For prospective patients, outcome results provide the most meaningful basis for comparing and selecting clinicians. Proxy measures may have little bearing on whether veterans receive effective care. (As Albert Einstein’s famously observed, “Not everything that can be counted counts.”). Also, the specific measures used for a clinician’s HPP designation should be delineated.
5. The VA must enforce the MISSION Act’s instruction to renew or cancel contracts based on demonstrated quality of care. As VSOs emphasized, “if the private sector is unwilling or unable to match the VA’s access and quality standards, the VA must consider whether it needs to find new community partners.”  

Seventeen billion dollars is spent yearly on purchased health care whose quality remains indeterminate. Ironclad commitments are needed from Congress and the VA to ensure that the effectiveness of, and standards for, veterans care options in the private sector match that in the VA.

In 2014, amidst stories of delays at Veterans Health Administration facilities, Congress established the Veterans Choice Program, which expanded access to private sector health care practitioners. When the program expired in 2018, lawmakers replaced it with the Veterans Community Care Program (VCCP) as part of the US Department of Veterans Affairs (VA) Maintaining Internal Systems and Strengthening Integrated Outside Networks Act (38 USC § 1703 MISSION Act). Since then, the VCCP has grown exponentially; 34% of current veteran health care visits are with private clinicians.

Along with broader private sector access, the MISSION Act also mandated the creation of quality-of-care standards for both VA and VCCP, and stipulated that data be compiled and made available to “provide covered veterans relevant comparative information to make informed decisions regarding their health care.” Two-and-a-half years later, data about the quality of VCCP care remains largely unknown.

Access to Care Website 

In the lead up to the MISSION Act, the VA launched its Access to Care website, an online tool thatpublishes institutional performance data on key metrics so that veterans can make “more informed choices about where, when, and how they receive their health care.” Following the bill’s passage, the VA added a MISSION Act Quality Standards section, which includes results of 27 conventional quality measures for every VA facility. These scores are posted alongside data of regional facilities.

This trailblazing tool is exceedingly comprehensive. Yet, multiple website gaps compromise its utility for veterans deliberating whether to obtain VCCP care, including:

1. Data isn’t about VCCP care. The hospitals are selected because they are local, not whether they participate in VCCP.  Further, it appears that aggregate scores include non-VCCP facilities.
2. Missing conditions/treatments. While the website contains quality scores for an ample range of procedures, it lacks information for many conditions that disproportionately affect veterans. A veteran with posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI), for example, has no data to check.
3. Skewed comparison population. Private sector practitioners primarily treat nonveteran patients, a population that is, on average, healthier and of higher socioeconomic status when compared with VA patients. Outcomes differ, for example, when patients have coexisting mental illness or homelessness. For VCCP scores to be beneficial for comparisons, they should derive from treated veterans or be accurately risk-adjusted.
4. Tangential measures. The Institute of Medicine defined health care quality as “improvement of outcomes.” Patients considering health care options benefit from information about treatment effectiveness and symptom reduction. But because obtaining that quality data is labor intensive, proxy measures are substituted. For example, the measure advising smokers to quit is the closest the website comes to reporting on the quality of mental health care.

High-Performers

The VA initiated a second means to inform veterans about the quality of furnished care. Specifically, they guided third-party administrators (TPAs)—TriWest Healthcare Alliance and Optum—in creating algorithms designating that VCCP individual clinicians, practice groups, and hospitals can be deemed high performing providers (HPPs). The algorithms are calculated using a mix of Healthcare Effectiveness Data and Information Set (HEDIS), Physician Quality Reporting System (PQRS), and Blue Health Intelligence (BHI) primary and specialty care measures. The designations are intended to be accessible to local VA community care schedulers to connect veterans with HPPs.

Many aspects of the HPP system are not yet public, including the measures that comprise the algorithms and when the designations will become operational. From what is publicly discoverable about HPP designations, there are crucial gaps like those on the Access to Care website. Behavioral and mental health conditions, for instance, are intentionally excluded in HPP monitoring. HPP algorithms draw from care provided to the general population; an HPP’s patient panel may contain no veterans (with their common comorbidities) at all. Most limiting, there’s no expectation that VCCP clinicians be high performing. Of the 1.2 million program clinicians treating veterans as of November 2020, only a nominal 13.4% were HPP.

After studying the HPP system, VA Partnered Evidence-based Policy Resource Center acknowledged that “it remains unclear whether the quality metrics and referral system result in higher quality of care for VA patients or whether the program improves veteran health.”

Quality of VCCP Mental Health Treatment

The MISSION Act mandated the VA to “establish standards and requirements for the provision of care by non-VA health care practitioners in clinical areas for which the Department of Veterans Affairs has special expertise, including PTSD, military sexual trauma-related conditions (MST), and TBI.” This requirement arose from a recognition that mental health care provided in the private sector pales in comparisonto the VA’s rigorous evidence-based training, consultation, case review and care delivery. For example, over 8500 VA clinicians have received training in evidence-based cognitive processing therapy and/or prolonged exposure therapy for PTSD.

The MISSION Act also mandated that VCCP providers must “fulfill training requirements established by the Secretary on how to deliver evidence-based treatments in the clinical areas for which the Department of Veterans Affairs has special expertise” before furnishing care pursuant to a contract with the VA. However, the VA elected to disregard the directive, and left it up to VCCP clinician’s discretion whether to obtain training or proficiency.

Two bills introduced in Congress in 2021 aim to uphold these vital mandates for the VCCP program. The Veterans’ Culturally Competent Care Act requires VCCP mental health practitioners to take courses on the evaluation and management of suicide, PTSD, TBI, and MST. The Lethal Means Safety Training Act aligns VCCP clinicians suicide prevention training with existing VA standards.

Recommendations to Assure the Quality of VCCP Care

With review and revision of VCCP quality standards now underway, the following remedial actions are recommended:

1. VCCP metrics must be compiled using data on veterans’ care, not the general population, and be published on the Access to Care website. This indispensable information is published on the website for VA care but not for VCCP. Unless VCCP is required to track their veterans, apples-to-apples comparisons of quality of care will remain difficult to attain. Supplemental research that directly contrasts quality of VA to VCCP care should be posted. For example, a 2021 study of enrolled veterans brought by ambulance to VA or community emergency rooms found that all 170 VA medical centers had lower comparative death rates.
2. VCCP providers should be held to the same quality standards as those applied to VA clinicians. In a 2020 critical issue update on implementation of the MISSION Act, major veterans service organizations (VSOs) recommended that competency, training, and quality standards for non-VA community clinicians must be equivalent to benchmarks expected of VA clinicians. That includes credentials, initial and follow-up training, diagnostic screening, care-delivery, and documentation standards. Enacting the Veterans’ Culturally Competent Care Act and the Lethal Means Safety Training Act would begin to meet the MISSION Act’s clear statutory language.
3. The VA and VCCP should add quality information about major diagnostic categories. This will allow veterans to make informed decisions about their personal condition. For most health diagnoses, there is no searchable listing by disorder. 
4. Quality assessments should be realigned to focus on outcome measures. For prospective patients, outcome results provide the most meaningful basis for comparing and selecting clinicians. Proxy measures may have little bearing on whether veterans receive effective care. (As Albert Einstein’s famously observed, “Not everything that can be counted counts.”). Also, the specific measures used for a clinician’s HPP designation should be delineated.
5. The VA must enforce the MISSION Act’s instruction to renew or cancel contracts based on demonstrated quality of care. As VSOs emphasized, “if the private sector is unwilling or unable to match the VA’s access and quality standards, the VA must consider whether it needs to find new community partners.”  

Seventeen billion dollars is spent yearly on purchased health care whose quality remains indeterminate. Ironclad commitments are needed from Congress and the VA to ensure that the effectiveness of, and standards for, veterans care options in the private sector match that in the VA.

The Diagnosis: Kaposi Sarcoma

A punch biopsy of a lesion on the right side of the back revealed a diffuse, poorly circumscribed, spindle cell neoplasm of the papillary and reticular dermis with associated vascular and pseudovascular spaces distended by erythrocytes (Figure 1). Immunostaining was positive for human herpesvirus 8 (HHV-8)(Figure 2), ETS-related gene, CD31, and CD34 and negative for pan cytokeratin, confirming the diagnosis of Kaposi sarcoma (KS). Bacterial, fungal, and mycobacterial tissue cultures were negative. The patient was tested for HIV and referred to infectious disease and oncology. He subsequently was found to have HIV with a viral load greater than 1 million copies. He was started on antiretroviral therapy and Pneumocystis jirovecii pneumonia prophylaxis. Computed tomography of the chest, abdomen, and pelvis showed bilateral, multifocal, perihilar, flame-shaped consolidations suggestive of KS. The patient later disclosed having an intermittent dry cough of more than a year’s duration with occasional bright red blood per rectum after bowel movements. After workup, the patient was found to have cytomegalovirus esophagitis/gastritis and candidal esophagitis that were treated with valganciclovir and fluconazole, respectively.

Kaposi sarcoma is an angioproliferative, AIDSdefining disease associated with HHV-8. There are 4 types of KS as defined by the populations they affect. AIDS-associated KS occurs in individuals with HIV, as seen in our patient. It often is accompanied by extensive mucocutaneous and visceral lesions, as well as systemic symptoms such as fever, weight loss, and diarrhea.¹ Classic KS is a variant that presents in older men of Mediterranean, Eastern European, and South American descent. Cutaneous lesions typically are distributed on the lower extremities.^2,3 Endemic (African) KS is seen in HIV-negative children and young adults in equatorial Africa. It most commonly affects the lower extremities or lymph nodes and usually follows a more aggressive course.² Lastly, iatrogenic KS is associated with immunosuppressive medications or conditions, such as organ transplantation, chemotherapy, and rheumatologic disorders.^3,4

Kaposi sarcoma commonly presents as violaceous or dark red macules, patches, papules, plaques, and nodules on various parts of the body (Figure 3). Lesions typically begin as macules and progress into plaques or nodules. Our patient presented as a deceptively healthy young man with lesions at various stages of development. In addition to the skin and oral mucosa, the lungs, lymph nodes, and gastrointestinal tract commonly are involved in AIDS-associated KS.⁵ Patients may experience symptoms of internal involvement, including bleeding, hematochezia, odynophagia, or dyspnea.

The differential diagnosis includes conditions that can mimic KS, including bacillary angiomatosis, angioinvasive fungal disease, sarcoid, and other malignancies. A skin biopsy is the gold standard for definitive diagnosis of KS. Histopathology shows a vascular proliferation in the dermis and spindle cell proliferation.⁶ Kaposi sarcoma stains positively for factor VIII–related antigen, CD31, and CD34.² Additionally, staining for HHV-8 gene products, such as latency-associated nuclear antigen 1, is helpful in differentiating KS from other conditions.⁷

In HIV-associated KS, the mainstay of treatment is initiation of highly active antiretroviral therapy. Typically, as the CD4 count rises with treatment, the tumor burden classic KS, effective treatment options include recurrent cryotherapy or intralesional chemotherapeutics, such as vincristine, for localized lesions; for widespread disease, pegylated liposomal doxorubicin or radiation have been found to be effective options. Lastly, for patients with iatrogenic KS, reducing immunosuppressive medications is a reasonable first step in management. If this does not yield adequate improvement, transitioning from calcineurin inhibitors (eg, cyclosporine) to proliferation signal inhibitors (eg, sirolimus) may lead to resolution.⁷

The Diagnosis: Kaposi Sarcoma

A punch biopsy of a lesion on the right side of the back revealed a diffuse, poorly circumscribed, spindle cell neoplasm of the papillary and reticular dermis with associated vascular and pseudovascular spaces distended by erythrocytes (Figure 1). Immunostaining was positive for human herpesvirus 8 (HHV-8)(Figure 2), ETS-related gene, CD31, and CD34 and negative for pan cytokeratin, confirming the diagnosis of Kaposi sarcoma (KS). Bacterial, fungal, and mycobacterial tissue cultures were negative. The patient was tested for HIV and referred to infectious disease and oncology. He subsequently was found to have HIV with a viral load greater than 1 million copies. He was started on antiretroviral therapy and Pneumocystis jirovecii pneumonia prophylaxis. Computed tomography of the chest, abdomen, and pelvis showed bilateral, multifocal, perihilar, flame-shaped consolidations suggestive of KS. The patient later disclosed having an intermittent dry cough of more than a year’s duration with occasional bright red blood per rectum after bowel movements. After workup, the patient was found to have cytomegalovirus esophagitis/gastritis and candidal esophagitis that were treated with valganciclovir and fluconazole, respectively.

Kaposi sarcoma is an angioproliferative, AIDSdefining disease associated with HHV-8. There are 4 types of KS as defined by the populations they affect. AIDS-associated KS occurs in individuals with HIV, as seen in our patient. It often is accompanied by extensive mucocutaneous and visceral lesions, as well as systemic symptoms such as fever, weight loss, and diarrhea.¹ Classic KS is a variant that presents in older men of Mediterranean, Eastern European, and South American descent. Cutaneous lesions typically are distributed on the lower extremities.^2,3 Endemic (African) KS is seen in HIV-negative children and young adults in equatorial Africa. It most commonly affects the lower extremities or lymph nodes and usually follows a more aggressive course.² Lastly, iatrogenic KS is associated with immunosuppressive medications or conditions, such as organ transplantation, chemotherapy, and rheumatologic disorders.^3,4

Kaposi sarcoma commonly presents as violaceous or dark red macules, patches, papules, plaques, and nodules on various parts of the body (Figure 3). Lesions typically begin as macules and progress into plaques or nodules. Our patient presented as a deceptively healthy young man with lesions at various stages of development. In addition to the skin and oral mucosa, the lungs, lymph nodes, and gastrointestinal tract commonly are involved in AIDS-associated KS.⁵ Patients may experience symptoms of internal involvement, including bleeding, hematochezia, odynophagia, or dyspnea.

The differential diagnosis includes conditions that can mimic KS, including bacillary angiomatosis, angioinvasive fungal disease, sarcoid, and other malignancies. A skin biopsy is the gold standard for definitive diagnosis of KS. Histopathology shows a vascular proliferation in the dermis and spindle cell proliferation.⁶ Kaposi sarcoma stains positively for factor VIII–related antigen, CD31, and CD34.² Additionally, staining for HHV-8 gene products, such as latency-associated nuclear antigen 1, is helpful in differentiating KS from other conditions.⁷

In HIV-associated KS, the mainstay of treatment is initiation of highly active antiretroviral therapy. Typically, as the CD4 count rises with treatment, the tumor burden classic KS, effective treatment options include recurrent cryotherapy or intralesional chemotherapeutics, such as vincristine, for localized lesions; for widespread disease, pegylated liposomal doxorubicin or radiation have been found to be effective options. Lastly, for patients with iatrogenic KS, reducing immunosuppressive medications is a reasonable first step in management. If this does not yield adequate improvement, transitioning from calcineurin inhibitors (eg, cyclosporine) to proliferation signal inhibitors (eg, sirolimus) may lead to resolution.⁷

The Diagnosis: Kaposi Sarcoma

A punch biopsy of a lesion on the right side of the back revealed a diffuse, poorly circumscribed, spindle cell neoplasm of the papillary and reticular dermis with associated vascular and pseudovascular spaces distended by erythrocytes (Figure 1). Immunostaining was positive for human herpesvirus 8 (HHV-8)(Figure 2), ETS-related gene, CD31, and CD34 and negative for pan cytokeratin, confirming the diagnosis of Kaposi sarcoma (KS). Bacterial, fungal, and mycobacterial tissue cultures were negative. The patient was tested for HIV and referred to infectious disease and oncology. He subsequently was found to have HIV with a viral load greater than 1 million copies. He was started on antiretroviral therapy and Pneumocystis jirovecii pneumonia prophylaxis. Computed tomography of the chest, abdomen, and pelvis showed bilateral, multifocal, perihilar, flame-shaped consolidations suggestive of KS. The patient later disclosed having an intermittent dry cough of more than a year’s duration with occasional bright red blood per rectum after bowel movements. After workup, the patient was found to have cytomegalovirus esophagitis/gastritis and candidal esophagitis that were treated with valganciclovir and fluconazole, respectively.

Kaposi sarcoma is an angioproliferative, AIDSdefining disease associated with HHV-8. There are 4 types of KS as defined by the populations they affect. AIDS-associated KS occurs in individuals with HIV, as seen in our patient. It often is accompanied by extensive mucocutaneous and visceral lesions, as well as systemic symptoms such as fever, weight loss, and diarrhea.¹ Classic KS is a variant that presents in older men of Mediterranean, Eastern European, and South American descent. Cutaneous lesions typically are distributed on the lower extremities.^2,3 Endemic (African) KS is seen in HIV-negative children and young adults in equatorial Africa. It most commonly affects the lower extremities or lymph nodes and usually follows a more aggressive course.² Lastly, iatrogenic KS is associated with immunosuppressive medications or conditions, such as organ transplantation, chemotherapy, and rheumatologic disorders.^3,4

Kaposi sarcoma commonly presents as violaceous or dark red macules, patches, papules, plaques, and nodules on various parts of the body (Figure 3). Lesions typically begin as macules and progress into plaques or nodules. Our patient presented as a deceptively healthy young man with lesions at various stages of development. In addition to the skin and oral mucosa, the lungs, lymph nodes, and gastrointestinal tract commonly are involved in AIDS-associated KS.⁵ Patients may experience symptoms of internal involvement, including bleeding, hematochezia, odynophagia, or dyspnea.

The differential diagnosis includes conditions that can mimic KS, including bacillary angiomatosis, angioinvasive fungal disease, sarcoid, and other malignancies. A skin biopsy is the gold standard for definitive diagnosis of KS. Histopathology shows a vascular proliferation in the dermis and spindle cell proliferation.⁶ Kaposi sarcoma stains positively for factor VIII–related antigen, CD31, and CD34.² Additionally, staining for HHV-8 gene products, such as latency-associated nuclear antigen 1, is helpful in differentiating KS from other conditions.⁷

In HIV-associated KS, the mainstay of treatment is initiation of highly active antiretroviral therapy. Typically, as the CD4 count rises with treatment, the tumor burden classic KS, effective treatment options include recurrent cryotherapy or intralesional chemotherapeutics, such as vincristine, for localized lesions; for widespread disease, pegylated liposomal doxorubicin or radiation have been found to be effective options. Lastly, for patients with iatrogenic KS, reducing immunosuppressive medications is a reasonable first step in management. If this does not yield adequate improvement, transitioning from calcineurin inhibitors (eg, cyclosporine) to proliferation signal inhibitors (eg, sirolimus) may lead to resolution.⁷

Psoriasis vulgaris is a chronic inflammatory skin condition associated with notable elevation in helper T cell (T_H) production of T_H1/T_H17-mediated inflammatory cytokines, including IL-17A.¹ Upon binding of IL-17A to IL-17 receptors in the skin, an inflammatory cascade is triggered, resulting in the classic clinical appearance of psoriasis. Moderate to severe psoriasis often is managed by suppressing T_H1/T_H17-mediated inflammation using targeted immune therapy such as secukinumab, an IL-17A inhibitor.² Atopic dermatitis (AD), another chronic inflammatory dermatosis, is associated with substantial elevation in T_H2-mediated inflammatory cytokines, such as IL-4.³ Dupilumab, which interacts with IL-4R, disrupts the IL-4 and IL-13 signaling pathways and demonstrates considerable efficacy in the treatment of moderate to severe AD.⁴

A case series has shown that suppression of the T_H1/T_H17-mediated inflammation of psoriasis may paradoxically result in the development of T_H2-mediated AD.⁵ Similarly, a recent case report described a patient who developed psoriasis following treatment of AD with dupilumab.⁶ Herein, we describe a patient with a history of psoriasis that was well controlled with secukinumab who developed severe refractory erythrodermic AD that resolved with dupilumab treatment. Following clearance of AD with dupilumab, he exhibited psoriasis recurrence.

Case Report

A 39-year-old man with a lifelong history of psoriasis was admitted to the hospital for management of severe erythroderma. Four years prior, secukinumab was initiated for treatment of psoriasis, resulting in excellent clinical response. He discontinued secukinumab after 2 years of treatment because of insurance coverage issues and managed his condition with only topical corticosteroids. He restarted secukinumab 10 months before admission because of a psoriasis flare. Shortly after resuming secukinumab, he developed a severe exfoliative erythroderma that was not responsive to corticosteroids, etanercept, methotrexate, or ustekinumab.

On initial presentation, physical examination revealed diffuse erythema and scaling with associated edema of the face, trunk, and extremities (Figure 1). A biopsy from the patient’s right arm demonstrated a superficial perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, and scattered eosinophils consistent with spongiotic dermatitis (Figure 2). Cyclosporine 225 mg twice daily and topical corticosteroids were started.

Over the next several months, the patient had several admissions secondary to recurrent skin abscesses in the setting of refractory erythroderma. He underwent trials of infliximab, corticosteroids, intravenous immunoglobulin, guselkumab, and acitretin with minimal improvement. He underwent an extensive laboratory and radiologic workup, which was notable for cyclical peripheral eosinophilia and elevated IgE levels correlating with the erythroderma flares. A second biopsy was obtained and continued to demonstrate changes consistent with AD.

Four months after the initial hospitalization, all psoriasis medications were stopped, and the patient was started on dupilumab 300 mg/2 mL every 2 weeks and an 8-week oral prednisone taper. This combination led to notable clinical improvement and resolution of peripheral eosinophilia. Several months after disease remission, he began to develop worsening erythema and pruritus on the trunk and extremities, followed by the development of new psoriatic lesions (Figure 3) with a biopsy consistent with psoriasis (Figure 4). The patient was continued on dupilumab, but cyclosporine was added. The patient self-discontinued dupilumab owing to injection-site discomfort and has been slowly weaning off oral cyclosporine with 1 to 2 remaining eczematous plaques and 1 to 2 psoriatic plaques managed by topical corticosteroids.

Comment

We present a patient with psoriasis that was well controlled on secukinumab who developed severe AD following treatment with secukinumab. The AD resolved following treatment with dupilumab and a tapering dose of prednisone. However, after several months of treatment with dupilumab alone, he began to develop psoriatic lesions again. This case supports findings in a case series describing the development of AD in patients with psoriasis treated with IL-17 inhibitors⁵ and a recent case report describing a patient with AD who developed psoriasis following treatment with an IL-4/IL-13 inhibitor.⁶

Recognized adverse effects demonstrate biologic medications’ contributions to both normal as well as aberrant immunologic responses. For example, IL-17 plays an essential role in innate and adaptive immune responses against infections at mucosal and cutaneous interfaces, as demonstrated by chronic mucocutaneous candidiasis in patients with genetic defects in IL-17–related pathways.⁷ Similarly, in patients taking IL-17 antagonists, an increase in the incidence of Candida infections has been observed.⁸ In patients with concurrent psoriasis and inflammatory bowel disease (IBD), treatment with IL-17 inhibitors is contraindicated due to the risk of exacerbating the IBD. This observation is somewhat paradoxical, as increased IL-17 release by T_H17 cells is implicated in the pathogenesis of IBD.⁹ Interestingly, it is now thought that IL-17 may play a protective role in T-cell–driven intestinal inflammation through induction of protective intestinal epithelial gene expression and increased mucosal defense against gut microbes, explaining the worsening of IBD in patients on IL-17 inhibitors.¹⁰ These adverse effects illustrate the complicated and varied roles biologic medications play in immunologic response.

Given that T_H1 and T_H2 exert opposing immune mechanisms, it is uncommon for psoriasis and AD to coexist in a single patient. However, patients who exhibit concurrent findings may represent a unique population in which psoriasis and AD coexist, perhaps because of an underlying genetic predisposition. Moreover, targeted treatment of pathways unique to these disease processes may result in paradoxical flaring of the nontargeted pathway. It also is possible that inhibition of a specific T-cell pathway in a subset of patients will result in an immunologic imbalance, favoring increased activity of the opposing pathway in the absence of coexisting disease. In the case presented here, the findings may be explained by secukinumab’s inhibition of T_H1/T_H17-mediated inflammation, which resulted in a shift to a T_H2-mediated inflammatory response manifesting as AD, as well as dupilumab’s inhibition of T_H2-mediated inflammation, which caused a shift back to T_H1-mediated inflammatory pathways. Additionally, for patients with changing morphologies exacerbated by biologic medications, alternative diagnoses, such as cutaneous T-cell lymphoma, may be considered.

Conclusion

We report an unusual case of secukinumab-induced AD in a patient with psoriasis that resolved following several months of treatment with dupilumab and a tapering dose of prednisone. Subsequently, this same patient developed re-emergence of psoriatic lesions with continued use of dupilumab, which was eventually discontinued by the patient despite appropriate disease control. In addition to illustrating the underlying pathophysiologic mechanisms of 2 common inflammatory dermatologic conditions, this case highlights how pharmacologic interventions targeted at specific immunologic pathways may have unintended consequences. Further investigation into the effects of targeted biologics on the T_H1/T_H2 immune axis is warranted to better understand the mechanism and possible implications of the phenotypic switching presented in this case.

Psoriasis vulgaris is a chronic inflammatory skin condition associated with notable elevation in helper T cell (T_H) production of T_H1/T_H17-mediated inflammatory cytokines, including IL-17A.¹ Upon binding of IL-17A to IL-17 receptors in the skin, an inflammatory cascade is triggered, resulting in the classic clinical appearance of psoriasis. Moderate to severe psoriasis often is managed by suppressing T_H1/T_H17-mediated inflammation using targeted immune therapy such as secukinumab, an IL-17A inhibitor.² Atopic dermatitis (AD), another chronic inflammatory dermatosis, is associated with substantial elevation in T_H2-mediated inflammatory cytokines, such as IL-4.³ Dupilumab, which interacts with IL-4R, disrupts the IL-4 and IL-13 signaling pathways and demonstrates considerable efficacy in the treatment of moderate to severe AD.⁴

A case series has shown that suppression of the T_H1/T_H17-mediated inflammation of psoriasis may paradoxically result in the development of T_H2-mediated AD.⁵ Similarly, a recent case report described a patient who developed psoriasis following treatment of AD with dupilumab.⁶ Herein, we describe a patient with a history of psoriasis that was well controlled with secukinumab who developed severe refractory erythrodermic AD that resolved with dupilumab treatment. Following clearance of AD with dupilumab, he exhibited psoriasis recurrence.

Case Report

A 39-year-old man with a lifelong history of psoriasis was admitted to the hospital for management of severe erythroderma. Four years prior, secukinumab was initiated for treatment of psoriasis, resulting in excellent clinical response. He discontinued secukinumab after 2 years of treatment because of insurance coverage issues and managed his condition with only topical corticosteroids. He restarted secukinumab 10 months before admission because of a psoriasis flare. Shortly after resuming secukinumab, he developed a severe exfoliative erythroderma that was not responsive to corticosteroids, etanercept, methotrexate, or ustekinumab.

On initial presentation, physical examination revealed diffuse erythema and scaling with associated edema of the face, trunk, and extremities (Figure 1). A biopsy from the patient’s right arm demonstrated a superficial perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, and scattered eosinophils consistent with spongiotic dermatitis (Figure 2). Cyclosporine 225 mg twice daily and topical corticosteroids were started.

Over the next several months, the patient had several admissions secondary to recurrent skin abscesses in the setting of refractory erythroderma. He underwent trials of infliximab, corticosteroids, intravenous immunoglobulin, guselkumab, and acitretin with minimal improvement. He underwent an extensive laboratory and radiologic workup, which was notable for cyclical peripheral eosinophilia and elevated IgE levels correlating with the erythroderma flares. A second biopsy was obtained and continued to demonstrate changes consistent with AD.

Four months after the initial hospitalization, all psoriasis medications were stopped, and the patient was started on dupilumab 300 mg/2 mL every 2 weeks and an 8-week oral prednisone taper. This combination led to notable clinical improvement and resolution of peripheral eosinophilia. Several months after disease remission, he began to develop worsening erythema and pruritus on the trunk and extremities, followed by the development of new psoriatic lesions (Figure 3) with a biopsy consistent with psoriasis (Figure 4). The patient was continued on dupilumab, but cyclosporine was added. The patient self-discontinued dupilumab owing to injection-site discomfort and has been slowly weaning off oral cyclosporine with 1 to 2 remaining eczematous plaques and 1 to 2 psoriatic plaques managed by topical corticosteroids.

Comment

We present a patient with psoriasis that was well controlled on secukinumab who developed severe AD following treatment with secukinumab. The AD resolved following treatment with dupilumab and a tapering dose of prednisone. However, after several months of treatment with dupilumab alone, he began to develop psoriatic lesions again. This case supports findings in a case series describing the development of AD in patients with psoriasis treated with IL-17 inhibitors⁵ and a recent case report describing a patient with AD who developed psoriasis following treatment with an IL-4/IL-13 inhibitor.⁶

Recognized adverse effects demonstrate biologic medications’ contributions to both normal as well as aberrant immunologic responses. For example, IL-17 plays an essential role in innate and adaptive immune responses against infections at mucosal and cutaneous interfaces, as demonstrated by chronic mucocutaneous candidiasis in patients with genetic defects in IL-17–related pathways.⁷ Similarly, in patients taking IL-17 antagonists, an increase in the incidence of Candida infections has been observed.⁸ In patients with concurrent psoriasis and inflammatory bowel disease (IBD), treatment with IL-17 inhibitors is contraindicated due to the risk of exacerbating the IBD. This observation is somewhat paradoxical, as increased IL-17 release by T_H17 cells is implicated in the pathogenesis of IBD.⁹ Interestingly, it is now thought that IL-17 may play a protective role in T-cell–driven intestinal inflammation through induction of protective intestinal epithelial gene expression and increased mucosal defense against gut microbes, explaining the worsening of IBD in patients on IL-17 inhibitors.¹⁰ These adverse effects illustrate the complicated and varied roles biologic medications play in immunologic response.

Given that T_H1 and T_H2 exert opposing immune mechanisms, it is uncommon for psoriasis and AD to coexist in a single patient. However, patients who exhibit concurrent findings may represent a unique population in which psoriasis and AD coexist, perhaps because of an underlying genetic predisposition. Moreover, targeted treatment of pathways unique to these disease processes may result in paradoxical flaring of the nontargeted pathway. It also is possible that inhibition of a specific T-cell pathway in a subset of patients will result in an immunologic imbalance, favoring increased activity of the opposing pathway in the absence of coexisting disease. In the case presented here, the findings may be explained by secukinumab’s inhibition of T_H1/T_H17-mediated inflammation, which resulted in a shift to a T_H2-mediated inflammatory response manifesting as AD, as well as dupilumab’s inhibition of T_H2-mediated inflammation, which caused a shift back to T_H1-mediated inflammatory pathways. Additionally, for patients with changing morphologies exacerbated by biologic medications, alternative diagnoses, such as cutaneous T-cell lymphoma, may be considered.

Conclusion

We report an unusual case of secukinumab-induced AD in a patient with psoriasis that resolved following several months of treatment with dupilumab and a tapering dose of prednisone. Subsequently, this same patient developed re-emergence of psoriatic lesions with continued use of dupilumab, which was eventually discontinued by the patient despite appropriate disease control. In addition to illustrating the underlying pathophysiologic mechanisms of 2 common inflammatory dermatologic conditions, this case highlights how pharmacologic interventions targeted at specific immunologic pathways may have unintended consequences. Further investigation into the effects of targeted biologics on the T_H1/T_H2 immune axis is warranted to better understand the mechanism and possible implications of the phenotypic switching presented in this case.

Psoriasis vulgaris is a chronic inflammatory skin condition associated with notable elevation in helper T cell (T_H) production of T_H1/T_H17-mediated inflammatory cytokines, including IL-17A.¹ Upon binding of IL-17A to IL-17 receptors in the skin, an inflammatory cascade is triggered, resulting in the classic clinical appearance of psoriasis. Moderate to severe psoriasis often is managed by suppressing T_H1/T_H17-mediated inflammation using targeted immune therapy such as secukinumab, an IL-17A inhibitor.² Atopic dermatitis (AD), another chronic inflammatory dermatosis, is associated with substantial elevation in T_H2-mediated inflammatory cytokines, such as IL-4.³ Dupilumab, which interacts with IL-4R, disrupts the IL-4 and IL-13 signaling pathways and demonstrates considerable efficacy in the treatment of moderate to severe AD.⁴

A case series has shown that suppression of the T_H1/T_H17-mediated inflammation of psoriasis may paradoxically result in the development of T_H2-mediated AD.⁵ Similarly, a recent case report described a patient who developed psoriasis following treatment of AD with dupilumab.⁶ Herein, we describe a patient with a history of psoriasis that was well controlled with secukinumab who developed severe refractory erythrodermic AD that resolved with dupilumab treatment. Following clearance of AD with dupilumab, he exhibited psoriasis recurrence.

Case Report

A 39-year-old man with a lifelong history of psoriasis was admitted to the hospital for management of severe erythroderma. Four years prior, secukinumab was initiated for treatment of psoriasis, resulting in excellent clinical response. He discontinued secukinumab after 2 years of treatment because of insurance coverage issues and managed his condition with only topical corticosteroids. He restarted secukinumab 10 months before admission because of a psoriasis flare. Shortly after resuming secukinumab, he developed a severe exfoliative erythroderma that was not responsive to corticosteroids, etanercept, methotrexate, or ustekinumab.

On initial presentation, physical examination revealed diffuse erythema and scaling with associated edema of the face, trunk, and extremities (Figure 1). A biopsy from the patient’s right arm demonstrated a superficial perivascular inflammatory infiltrate composed of lymphocytes, histiocytes, and scattered eosinophils consistent with spongiotic dermatitis (Figure 2). Cyclosporine 225 mg twice daily and topical corticosteroids were started.

Over the next several months, the patient had several admissions secondary to recurrent skin abscesses in the setting of refractory erythroderma. He underwent trials of infliximab, corticosteroids, intravenous immunoglobulin, guselkumab, and acitretin with minimal improvement. He underwent an extensive laboratory and radiologic workup, which was notable for cyclical peripheral eosinophilia and elevated IgE levels correlating with the erythroderma flares. A second biopsy was obtained and continued to demonstrate changes consistent with AD.

Four months after the initial hospitalization, all psoriasis medications were stopped, and the patient was started on dupilumab 300 mg/2 mL every 2 weeks and an 8-week oral prednisone taper. This combination led to notable clinical improvement and resolution of peripheral eosinophilia. Several months after disease remission, he began to develop worsening erythema and pruritus on the trunk and extremities, followed by the development of new psoriatic lesions (Figure 3) with a biopsy consistent with psoriasis (Figure 4). The patient was continued on dupilumab, but cyclosporine was added. The patient self-discontinued dupilumab owing to injection-site discomfort and has been slowly weaning off oral cyclosporine with 1 to 2 remaining eczematous plaques and 1 to 2 psoriatic plaques managed by topical corticosteroids.

Comment

We present a patient with psoriasis that was well controlled on secukinumab who developed severe AD following treatment with secukinumab. The AD resolved following treatment with dupilumab and a tapering dose of prednisone. However, after several months of treatment with dupilumab alone, he began to develop psoriatic lesions again. This case supports findings in a case series describing the development of AD in patients with psoriasis treated with IL-17 inhibitors⁵ and a recent case report describing a patient with AD who developed psoriasis following treatment with an IL-4/IL-13 inhibitor.⁶

Recognized adverse effects demonstrate biologic medications’ contributions to both normal as well as aberrant immunologic responses. For example, IL-17 plays an essential role in innate and adaptive immune responses against infections at mucosal and cutaneous interfaces, as demonstrated by chronic mucocutaneous candidiasis in patients with genetic defects in IL-17–related pathways.⁷ Similarly, in patients taking IL-17 antagonists, an increase in the incidence of Candida infections has been observed.⁸ In patients with concurrent psoriasis and inflammatory bowel disease (IBD), treatment with IL-17 inhibitors is contraindicated due to the risk of exacerbating the IBD. This observation is somewhat paradoxical, as increased IL-17 release by T_H17 cells is implicated in the pathogenesis of IBD.⁹ Interestingly, it is now thought that IL-17 may play a protective role in T-cell–driven intestinal inflammation through induction of protective intestinal epithelial gene expression and increased mucosal defense against gut microbes, explaining the worsening of IBD in patients on IL-17 inhibitors.¹⁰ These adverse effects illustrate the complicated and varied roles biologic medications play in immunologic response.

Given that T_H1 and T_H2 exert opposing immune mechanisms, it is uncommon for psoriasis and AD to coexist in a single patient. However, patients who exhibit concurrent findings may represent a unique population in which psoriasis and AD coexist, perhaps because of an underlying genetic predisposition. Moreover, targeted treatment of pathways unique to these disease processes may result in paradoxical flaring of the nontargeted pathway. It also is possible that inhibition of a specific T-cell pathway in a subset of patients will result in an immunologic imbalance, favoring increased activity of the opposing pathway in the absence of coexisting disease. In the case presented here, the findings may be explained by secukinumab’s inhibition of T_H1/T_H17-mediated inflammation, which resulted in a shift to a T_H2-mediated inflammatory response manifesting as AD, as well as dupilumab’s inhibition of T_H2-mediated inflammation, which caused a shift back to T_H1-mediated inflammatory pathways. Additionally, for patients with changing morphologies exacerbated by biologic medications, alternative diagnoses, such as cutaneous T-cell lymphoma, may be considered.

Conclusion

We report an unusual case of secukinumab-induced AD in a patient with psoriasis that resolved following several months of treatment with dupilumab and a tapering dose of prednisone. Subsequently, this same patient developed re-emergence of psoriatic lesions with continued use of dupilumab, which was eventually discontinued by the patient despite appropriate disease control. In addition to illustrating the underlying pathophysiologic mechanisms of 2 common inflammatory dermatologic conditions, this case highlights how pharmacologic interventions targeted at specific immunologic pathways may have unintended consequences. Further investigation into the effects of targeted biologics on the T_H1/T_H2 immune axis is warranted to better understand the mechanism and possible implications of the phenotypic switching presented in this case.

Total knee replacement (TKR) is one of the most common surgeries worldwide, with > 1 million performed last year. Many patients have seen tremendous benefit from TKR; however, studies have shown that up to 20% of patients are not satisfied with the results of this procedure.^1,2 This equates to about 200,000 patients worldwide every year who are dissatisfied. This is a huge concern to patients, surgeons, implant manufacturers, hospitals, and health care payers.

Many attempts to improve satisfaction in TKR have been tried, including computer navigation, minimally invasive surgery, rotating platform prostheses, gender-specific implants, different materials, changes in pain management, and revised postoperative rehabilitation.^3-7 However, these efforts show no significant improvement in satisfaction.

The most common method of TKR today involves using a long rod placed through a drill hole in the femur. Standardized cuts on the femur and tibia are made through metal cutting blocks. Only metal mechanical instruments are used to perform the surgery, and all patients are aligned the same. However, anatomic studies have shown that patient anatomy in 3 dimensions (3D) varies widely from patient to patient.⁸ Our current technique seems far removed from modern engineering, where we now see extensive use of artificial intelligence (AI) to improve outcomes.

Machine learning (ML) is considered a subset of AI that involves the use of various computer algorithms. ML allows the computer to learn and continually improve analysis of data. Large sets of inputs and outputs are used to train the machine to make autonomous recommendations or decisions.^9,10

Seven years ago, our team at the Phoenix Veteran Affairs Medical Center in Arizona published a randomized controlled trial evaluating a new, individualized alignment technique for TKR.¹¹ This method used 3D-printed guides made from an MRI of an individual patient’s knee. Instead of aligning all knee replacements the same, each patient was aligned according to their unique anatomy. Compared with the conventional alignment technique, the newer technique showed significant improvement in all outcome scores and range of motion at 2 years postsurgery. There has been a great deal of interest in individualizing TKR, and many articles and techniques have followed.¹²

Our surgical technique has evolved since publishing our trial. Currently, knee X-rays are digitally templated for each patient. Understanding the patient’s preoperative alignment can then assist in planning a TKR in 3D. A plastic 3D-printed guide is manufactured in Belgium, shipped to the US, sterilized, and used in surgery. These guides fit accurately on the patient’s anatomy and allow precise angles and depth of resection for each surgical bone cut. Our research has shown that these guides are accurate to within 0.5° and 0.5 mm for the bone cuts performed in surgery. After surgery, we track patient-reported outcomes (PROs), which can then be used in ML or logistic regression analysis to determine alignment factors that contribute to the best outcome.¹³

Soon, use of a robot will take the place of the templating and preplanning, allowing the 3D plan to be immediately produced in surgery by the software installed in the robot.^14-16 Each patient’s preoperative alignment can then be immediately compared with the postoperative result, and smartphone technology can allow a patient to input their PRO after the surgery is healed.¹⁷

Collecting all this information in a large database can allow ML analyses of the outcomes and individual alignment.^14-17 As the factors contributing to the best clinical results are determined, the computer can be programmed to learn how to make the best recommendations for alignment of each patient, which can be incorporated into the robotic platform for each surgery. Also pre- and postoperative factors can be added to the ML platform so we can identify the best preoperative patient parameters, anticoagulation program postoperative rehabilitation program, etc, to help drive higher PROs and satisfaction.

Multiple surgical robots for TKR are now on the market. Orthopedic literature includes ML algorithms to improve outcomes after total hip arthroplasty.¹⁸ The EHR can be used to develop models to predict poor outcomes after TKR. Integrating these models into clinical decision support could improve patient selection, education, and satisfaction.¹⁹ AI for adult spinal surgery using predictive analytics can help surgeons better inform patients about outcomes after corrective surgery.^20,21

With worldwide TKRs expected to exceed 3 million over the next decade, ML using large databases, robotic surgery, and PROs could be key to improving our TKR outcomes.²² This form of AI may reduce the large number of patients currently not satisfied with their knee replacement.

Total knee replacement (TKR) is one of the most common surgeries worldwide, with > 1 million performed last year. Many patients have seen tremendous benefit from TKR; however, studies have shown that up to 20% of patients are not satisfied with the results of this procedure.^1,2 This equates to about 200,000 patients worldwide every year who are dissatisfied. This is a huge concern to patients, surgeons, implant manufacturers, hospitals, and health care payers.

Many attempts to improve satisfaction in TKR have been tried, including computer navigation, minimally invasive surgery, rotating platform prostheses, gender-specific implants, different materials, changes in pain management, and revised postoperative rehabilitation.^3-7 However, these efforts show no significant improvement in satisfaction.

The most common method of TKR today involves using a long rod placed through a drill hole in the femur. Standardized cuts on the femur and tibia are made through metal cutting blocks. Only metal mechanical instruments are used to perform the surgery, and all patients are aligned the same. However, anatomic studies have shown that patient anatomy in 3 dimensions (3D) varies widely from patient to patient.⁸ Our current technique seems far removed from modern engineering, where we now see extensive use of artificial intelligence (AI) to improve outcomes.

Machine learning (ML) is considered a subset of AI that involves the use of various computer algorithms. ML allows the computer to learn and continually improve analysis of data. Large sets of inputs and outputs are used to train the machine to make autonomous recommendations or decisions.^9,10

Seven years ago, our team at the Phoenix Veteran Affairs Medical Center in Arizona published a randomized controlled trial evaluating a new, individualized alignment technique for TKR.¹¹ This method used 3D-printed guides made from an MRI of an individual patient’s knee. Instead of aligning all knee replacements the same, each patient was aligned according to their unique anatomy. Compared with the conventional alignment technique, the newer technique showed significant improvement in all outcome scores and range of motion at 2 years postsurgery. There has been a great deal of interest in individualizing TKR, and many articles and techniques have followed.¹²

Our surgical technique has evolved since publishing our trial. Currently, knee X-rays are digitally templated for each patient. Understanding the patient’s preoperative alignment can then assist in planning a TKR in 3D. A plastic 3D-printed guide is manufactured in Belgium, shipped to the US, sterilized, and used in surgery. These guides fit accurately on the patient’s anatomy and allow precise angles and depth of resection for each surgical bone cut. Our research has shown that these guides are accurate to within 0.5° and 0.5 mm for the bone cuts performed in surgery. After surgery, we track patient-reported outcomes (PROs), which can then be used in ML or logistic regression analysis to determine alignment factors that contribute to the best outcome.¹³

Soon, use of a robot will take the place of the templating and preplanning, allowing the 3D plan to be immediately produced in surgery by the software installed in the robot.^14-16 Each patient’s preoperative alignment can then be immediately compared with the postoperative result, and smartphone technology can allow a patient to input their PRO after the surgery is healed.¹⁷

Collecting all this information in a large database can allow ML analyses of the outcomes and individual alignment.^14-17 As the factors contributing to the best clinical results are determined, the computer can be programmed to learn how to make the best recommendations for alignment of each patient, which can be incorporated into the robotic platform for each surgery. Also pre- and postoperative factors can be added to the ML platform so we can identify the best preoperative patient parameters, anticoagulation program postoperative rehabilitation program, etc, to help drive higher PROs and satisfaction.

Multiple surgical robots for TKR are now on the market. Orthopedic literature includes ML algorithms to improve outcomes after total hip arthroplasty.¹⁸ The EHR can be used to develop models to predict poor outcomes after TKR. Integrating these models into clinical decision support could improve patient selection, education, and satisfaction.¹⁹ AI for adult spinal surgery using predictive analytics can help surgeons better inform patients about outcomes after corrective surgery.^20,21

With worldwide TKRs expected to exceed 3 million over the next decade, ML using large databases, robotic surgery, and PROs could be key to improving our TKR outcomes.²² This form of AI may reduce the large number of patients currently not satisfied with their knee replacement.

Total knee replacement (TKR) is one of the most common surgeries worldwide, with > 1 million performed last year. Many patients have seen tremendous benefit from TKR; however, studies have shown that up to 20% of patients are not satisfied with the results of this procedure.^1,2 This equates to about 200,000 patients worldwide every year who are dissatisfied. This is a huge concern to patients, surgeons, implant manufacturers, hospitals, and health care payers.

Many attempts to improve satisfaction in TKR have been tried, including computer navigation, minimally invasive surgery, rotating platform prostheses, gender-specific implants, different materials, changes in pain management, and revised postoperative rehabilitation.^3-7 However, these efforts show no significant improvement in satisfaction.

The most common method of TKR today involves using a long rod placed through a drill hole in the femur. Standardized cuts on the femur and tibia are made through metal cutting blocks. Only metal mechanical instruments are used to perform the surgery, and all patients are aligned the same. However, anatomic studies have shown that patient anatomy in 3 dimensions (3D) varies widely from patient to patient.⁸ Our current technique seems far removed from modern engineering, where we now see extensive use of artificial intelligence (AI) to improve outcomes.

Machine learning (ML) is considered a subset of AI that involves the use of various computer algorithms. ML allows the computer to learn and continually improve analysis of data. Large sets of inputs and outputs are used to train the machine to make autonomous recommendations or decisions.^9,10

Seven years ago, our team at the Phoenix Veteran Affairs Medical Center in Arizona published a randomized controlled trial evaluating a new, individualized alignment technique for TKR.¹¹ This method used 3D-printed guides made from an MRI of an individual patient’s knee. Instead of aligning all knee replacements the same, each patient was aligned according to their unique anatomy. Compared with the conventional alignment technique, the newer technique showed significant improvement in all outcome scores and range of motion at 2 years postsurgery. There has been a great deal of interest in individualizing TKR, and many articles and techniques have followed.¹²

Our surgical technique has evolved since publishing our trial. Currently, knee X-rays are digitally templated for each patient. Understanding the patient’s preoperative alignment can then assist in planning a TKR in 3D. A plastic 3D-printed guide is manufactured in Belgium, shipped to the US, sterilized, and used in surgery. These guides fit accurately on the patient’s anatomy and allow precise angles and depth of resection for each surgical bone cut. Our research has shown that these guides are accurate to within 0.5° and 0.5 mm for the bone cuts performed in surgery. After surgery, we track patient-reported outcomes (PROs), which can then be used in ML or logistic regression analysis to determine alignment factors that contribute to the best outcome.¹³

Soon, use of a robot will take the place of the templating and preplanning, allowing the 3D plan to be immediately produced in surgery by the software installed in the robot.^14-16 Each patient’s preoperative alignment can then be immediately compared with the postoperative result, and smartphone technology can allow a patient to input their PRO after the surgery is healed.¹⁷

Collecting all this information in a large database can allow ML analyses of the outcomes and individual alignment.^14-17 As the factors contributing to the best clinical results are determined, the computer can be programmed to learn how to make the best recommendations for alignment of each patient, which can be incorporated into the robotic platform for each surgery. Also pre- and postoperative factors can be added to the ML platform so we can identify the best preoperative patient parameters, anticoagulation program postoperative rehabilitation program, etc, to help drive higher PROs and satisfaction.

Multiple surgical robots for TKR are now on the market. Orthopedic literature includes ML algorithms to improve outcomes after total hip arthroplasty.¹⁸ The EHR can be used to develop models to predict poor outcomes after TKR. Integrating these models into clinical decision support could improve patient selection, education, and satisfaction.¹⁹ AI for adult spinal surgery using predictive analytics can help surgeons better inform patients about outcomes after corrective surgery.^20,21

With worldwide TKRs expected to exceed 3 million over the next decade, ML using large databases, robotic surgery, and PROs could be key to improving our TKR outcomes.²² This form of AI may reduce the large number of patients currently not satisfied with their knee replacement.

Cutis Reviewers, JANUARY TO DECEMBER 2021

Jennifer L. Adams, MD

Brandon Adler, MD

Iris Ahronowitz, MD

Abdullah Aleisa, MD

Justin Bandino, MD

Robert Baran, MD

Naiara S. Barbosa, MD

Kristina R. Burke, MD

Craig Burkhart, MD

Jeffrey P. Callen, MD

Charles Camisa, MD

Ashley B. Crew, MD

Zoe Diana Draelos, MD

Joseph S. Eastern, MD

Nada Elbuluk, MD, MSc

Joseph C. English III, MD

Tammie C. Ferringer, MD

Bahar F. Firoz, MD, MPH

John R. Griffin, MD

Kristi Hawley, DO

Thomas N. Helm, MD

Stephen Ellsworth Helms, MD

Brian P. Hibler, MD

Ranella J. Hirsch, MD

Jenny Hu, MD, MPH

Erick Jacobson-Dunlop, MD

William D. James, MD

Camilla K. Janniger, MD

Ronald Belle Johnston Jr, MD

Theodora Karagounis, MD

Michael Kasperkiewicz, MD

Brett H. Keeling, MD

Chesahna Kindred, MD, MBA

Christina Nicole Kraus, MD

Eun Ji Kwon, MD

Eden Lake, MD

Nicholas Logemann, DO

Michele S. Maroon, MD

Cathy Massoud, MD

Elizabeth I. McBurney, MD

Lynn J. McKinley-Grant, MD

Amy J. McMichael, MD

Darius R. Mehregan, MD

Jon Hamilton Meyerle, MD

Robert Micheletti, MD

Binh Ngo, MD

Anh Nguyen, MD

Josephine Nguyen, MD, MHCDS

Joe Niamtu III, DMD

Rajiv I. Nijhawan, MD

Michael A. Nowak, MD

Maria T. Ochoa, MD

Chika Ohata, MD

Lawrence C. Parish, MD

Marion Apter Quinn, MD

Phoebe Rich, MD

Maureen Riegert, MD

Bethany Rohr, MD

Lorraine L. Rosamilia, MD

Ted Rosen, MD

Robert I. Rudolph, MD

Elizabeth K. Satter, MD, MPH

Robert A. Schwartz, MD, MPH

Michael J. Scott III, DO, MD, MPH

Jane Scribner, MD

Bridget E. Shields, MD

Daniel Mark Siegel, MD, MS

Nanette B. Silverberg, MD

Steven Brett Sloan, MD

Leonard Sperling, MD

Stephen P. Stone, MD

Brian L. Swick, MD

Susan C. Taylor, MD

Manuel Valdebran, MD

Richard F. Wagner Jr, MD

Emily Wong, MD

Julie Woodward, MD

Scott Worswick, MD

Julia Wu, MD

If you are interested in serving as a reviewer, please email the Editorial Office at [email protected].

Cutis Reviewers, JANUARY TO DECEMBER 2021

Jennifer L. Adams, MD

Brandon Adler, MD

Iris Ahronowitz, MD

Abdullah Aleisa, MD

Justin Bandino, MD

Robert Baran, MD

Naiara S. Barbosa, MD

Kristina R. Burke, MD

Craig Burkhart, MD

Jeffrey P. Callen, MD

Charles Camisa, MD

Ashley B. Crew, MD

Zoe Diana Draelos, MD

Joseph S. Eastern, MD

Nada Elbuluk, MD, MSc

Joseph C. English III, MD

Tammie C. Ferringer, MD

Bahar F. Firoz, MD, MPH

John R. Griffin, MD

Kristi Hawley, DO

Thomas N. Helm, MD

Stephen Ellsworth Helms, MD

Brian P. Hibler, MD

Ranella J. Hirsch, MD

Jenny Hu, MD, MPH

Erick Jacobson-Dunlop, MD

William D. James, MD

Camilla K. Janniger, MD

Ronald Belle Johnston Jr, MD

Theodora Karagounis, MD

Michael Kasperkiewicz, MD

Brett H. Keeling, MD

Chesahna Kindred, MD, MBA

Christina Nicole Kraus, MD

Eun Ji Kwon, MD

Eden Lake, MD

Nicholas Logemann, DO

Michele S. Maroon, MD

Cathy Massoud, MD

Elizabeth I. McBurney, MD

Lynn J. McKinley-Grant, MD

Amy J. McMichael, MD

Darius R. Mehregan, MD

Jon Hamilton Meyerle, MD

Robert Micheletti, MD

Binh Ngo, MD

Anh Nguyen, MD

Josephine Nguyen, MD, MHCDS

Joe Niamtu III, DMD

Rajiv I. Nijhawan, MD

Michael A. Nowak, MD

Maria T. Ochoa, MD

Chika Ohata, MD

Lawrence C. Parish, MD

Marion Apter Quinn, MD

Phoebe Rich, MD

Maureen Riegert, MD

Bethany Rohr, MD

Lorraine L. Rosamilia, MD

Ted Rosen, MD

Robert I. Rudolph, MD

Elizabeth K. Satter, MD, MPH

Robert A. Schwartz, MD, MPH

Michael J. Scott III, DO, MD, MPH

Jane Scribner, MD

Bridget E. Shields, MD

Daniel Mark Siegel, MD, MS

Nanette B. Silverberg, MD

Steven Brett Sloan, MD

Leonard Sperling, MD

Stephen P. Stone, MD

Brian L. Swick, MD

Susan C. Taylor, MD

Manuel Valdebran, MD

Richard F. Wagner Jr, MD

Emily Wong, MD

Julie Woodward, MD

Scott Worswick, MD

Julia Wu, MD

If you are interested in serving as a reviewer, please email the Editorial Office at [email protected].

Cutis Reviewers, JANUARY TO DECEMBER 2021

Jennifer L. Adams, MD

Brandon Adler, MD

Iris Ahronowitz, MD

Abdullah Aleisa, MD

Justin Bandino, MD

Robert Baran, MD

Naiara S. Barbosa, MD

Kristina R. Burke, MD

Craig Burkhart, MD

Jeffrey P. Callen, MD

Charles Camisa, MD

Ashley B. Crew, MD

Zoe Diana Draelos, MD

Joseph S. Eastern, MD

Nada Elbuluk, MD, MSc

Joseph C. English III, MD

Tammie C. Ferringer, MD

Bahar F. Firoz, MD, MPH

John R. Griffin, MD

Kristi Hawley, DO

Thomas N. Helm, MD

Stephen Ellsworth Helms, MD

Brian P. Hibler, MD

Ranella J. Hirsch, MD

Jenny Hu, MD, MPH

Erick Jacobson-Dunlop, MD

William D. James, MD

Camilla K. Janniger, MD

Ronald Belle Johnston Jr, MD

Theodora Karagounis, MD

Michael Kasperkiewicz, MD

Brett H. Keeling, MD

Chesahna Kindred, MD, MBA

Christina Nicole Kraus, MD

Eun Ji Kwon, MD

Eden Lake, MD

Nicholas Logemann, DO

Michele S. Maroon, MD

Cathy Massoud, MD

Elizabeth I. McBurney, MD

Lynn J. McKinley-Grant, MD

Amy J. McMichael, MD

Darius R. Mehregan, MD

Jon Hamilton Meyerle, MD

Robert Micheletti, MD

Binh Ngo, MD

Anh Nguyen, MD

Josephine Nguyen, MD, MHCDS

Joe Niamtu III, DMD

Rajiv I. Nijhawan, MD

Michael A. Nowak, MD

Maria T. Ochoa, MD

Chika Ohata, MD

Lawrence C. Parish, MD

Marion Apter Quinn, MD

Phoebe Rich, MD

Maureen Riegert, MD

Bethany Rohr, MD

Lorraine L. Rosamilia, MD

Ted Rosen, MD

Robert I. Rudolph, MD

Elizabeth K. Satter, MD, MPH

Robert A. Schwartz, MD, MPH

Michael J. Scott III, DO, MD, MPH

Jane Scribner, MD

Bridget E. Shields, MD

Daniel Mark Siegel, MD, MS

Nanette B. Silverberg, MD

Steven Brett Sloan, MD

Leonard Sperling, MD

Stephen P. Stone, MD

Brian L. Swick, MD

Susan C. Taylor, MD

Manuel Valdebran, MD

Richard F. Wagner Jr, MD

Emily Wong, MD

Julie Woodward, MD

Scott Worswick, MD

Julia Wu, MD

If you are interested in serving as a reviewer, please email the Editorial Office at [email protected].