Article

In the United States, acne affects 85% of adolescents and can persist into adulthood at a prevalence of 30% to 50% in adult women. ^1,2 The pathogenesis of acne is multifactorial and involves hyperkeratinization of the follicle, bacterial colonization with Cutibacterium acnes , and increased androgen-induced sebum production, which together lead to inflammation. ^3,4 A wide range of treatment guideline–recommended options are available, including benzoyl peroxide (BPO), topical retinoids, topical and oral antibiotics, antiandrogens, and isotretinoin. ⁵ However, these options vary widely in their clinical uses, effectiveness, and costs.

Why Cost-effective Acne Care Matters

Out-of-pocket spending by patients on acne treatments can be substantial, with surveys finding that acne patients often spend hundreds to thousands of dollars per year.^6,7 In a poll conducted in 2019 by the Kaiser Family Foundation, 3 in 10 patients said they had not taken their medicine as prescribed because of costs.⁸ A mixed methods study by Ryskina et al⁹ found that 65% (17/26) of participants who reported primary nonadherence—intended to fill prescriptions but were unable to do so—cited cost or coverage-related barriers as the reason. With the continued rise of dermatologic drug prices and increased prevalence of high-deductible health plans, cost-effective treatment continues to grow in importance. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. We aim to review the cost-effectiveness of current prescription therapies for acne management and highlight the most cost-effective approaches to patients with mild to moderate acne as well as moderate to severe acne.

In this review, we will take a value-oriented framework.¹⁰ Value can be defined as the cost per outcome of interest. Therefore, a treatment does not necessarily need to be inexpensive to provide high value if it delivers outstanding clinical outcomes. In addition, we will focus on incremental cost-effectiveness relative to common alternatives (eg, a retinoid could deliver high value relative to a vehicle but still provide limited value compared to other available retinoids if it is more expensive but not more efficacious). When possible, we present data from cost-effectiveness studies.^11,12 We also use recent available price data obtained from GoodRx on August 11, 2023, to guide this discussion.¹³ However, as comparative-effectiveness and cost-effectiveness studies rarely are performed for acne medications, much of this discussion will be based on expert opinion.

Treatment Categories

Topical Retinoids—There currently are 4 topical retinoids that are approved by the US Food and Drug Administration (FDA) for the treatment of acne: tretinoin, tazarotene, trifarotene, and adapalene. These drugs are vitamin A derivatives that bind retinoic acid receptors and function as comedolytic and anti-inflammatory agents.⁵ In general, generic tretinoin and adapalene products have the lowest cost (Table).

In network meta-analyses, tretinoin and adapalene often are highly ranked topical treatment options with respect to efficacy.¹⁴ Combined with their low cost, generic tretinoin and adapalene likely are excellent initial options for topical therapy from the standpoint of cost-effectiveness.¹⁵ Adapalene may be preferred in many situations because of its better photostability and compatibility with BPO.

Due to the importance of the vehicle in determining retinoid tolerability, efforts have been made to use encapsulation and polymeric emulsion technology to improve tolerability. Recently, polymeric lotion formulations of tretinoin and tazarotene have become available. In a phase 2 study, tazarotene lotion 0.045% was found to have equivalent efficacy and superior tolerability to tazarotene cream 0.1%.¹⁶ Although head-to-head data are not available, it is likely that tretinoin lotion may offer similar tolerability improvements.¹⁷ Although these formulations currently are more costly, this improved tolerability may be critical for some patients to be able to use topical retinoids, and the additional cost may be worthwhile. In addition, as these products lose market exclusivity, they may become more affordable and similarly priced to other topical retinoids. It is important to keep in mind that in clinical trials of tretinoin and adapalene, rates of dropout due to adverse events typically were 1% to 2%; therefore, because many patients can tolerate generic tretinoin and adapalene, at current prices the lotion formulations of retinoids may not be cost-effective relative to these generics.¹⁴

Trifarotene cream 0.005%, a fourth-generation topical retinoid that is highly sensitive for retinoic acid receptor γ, recently was FDA approved for the treatment of acne. Although trifarotene is efficacious for both facial and truncal acne, there is a lack of active comparator data compared to other topical retinoids.¹⁸ In a 2023 network meta-analysis, trifarotene was found to be both less efficacious and less tolerable compared to other topical retinoids.¹⁹ Thus, it is unclear if trifarotene offers any improved efficacy compared to other options, and it comes at a much higher cost (Table). In a tolerability study, trifarotene was found to be significantly more irritating than tazarotene lotion 0.045% and adapalene gel 0.3% (P<.05).²⁰ Therefore, trifarotene cream 0.005% is unlikely to be a cost-effective option; in fact, it may be overall inferior to other topical retinoids, given its potentially lower tolerability.

Topical Antibiotics—There are 4 commonly prescribed topical antibiotics that are approved by the FDA for the treatment of acne: clindamycin, erythromycin, dapsone, and minocycline. The American Academy of Dermatology guidelines for the treatment of acne recommend concomitant use of BPO to prevent antibiotic resistance.⁵ Clindamycin is favored over erythromycin because of increasing antibiotic resistance to erythromycin.²¹ Inexpensive generic options in multiple vehicles (eg, solution, foam, gel) make clindamycin a highly cost-effective option when antibiotic therapy is desired as part of a topical regimen (Table).

The cost-effectiveness of dapsone gel and minocycline foam relative to clindamycin are less certain. Rates of resistance to minocycline are lower than clindamycin, and minocycline foam may be a reasonable alternative in patients who have not had success with other topical antibiotics, such as clindamycin.²² However, given the absence of comparative effectiveness data to suggest minocycline is more effective than clindamycin, it is difficult to justify the substantially higher cost for the typical patient. Although dapsone gel has been suggested as an option for adult women with acne, there are no data to support that it is any more effective than other topical antibiotics in this patient population.²³ As generic dapsone prices decrease, it may become a reasonable alternative to clindamycin. In addition, the antineutrophil properties of dapsone may be useful in other acneform and inflammatory eruptions, such as scalp folliculitis and folliculitis decalvans.²⁴

Combination Topicals—Current combination topical products include antibiotic and BPO, antibiotic and retinoid, and retinoid and BPO. Use of combination agents is recommended to reduce the risk for resistance and to enhance effectiveness. Combination products offer improved convenience, which is associated with better adherence and outcomes.²⁵ Generic fixed-dose adapalene-BPO can be a highly cost-effective option that can sometimes be less expensive than the individual component products (Table). Similarly, fixed-dose clindamycin-BPO also is likely to be highly cost-effective. A network meta-analysis found fixed-dose adapalene-BPO to be the most efficacious topical treatment, though it also was found to be the most irritating—more so than fixed-dose clindamycin-BPO, which may have similar efficacy.^14,26,27 Generic fixed-dose tretinoin-clindamycin offers improved convenience and adherence compared to the individual components, but it is more expensive, and its cost-effectiveness may be influenced by the importance of convenience for the patient.²⁵ An encapsulated, fixed-dose tretinoin 0.1%–BPO 3% cream is FDA approved for acne, but the cost is high and there is a lack of comparative effectiveness data demonstrating advantages over generic fixed-dose adapalene-BPO products.

Topical Antiandrogen—Clascoterone was introduced in 2020 as the first FDA-approved topical medication to target the hormonal pathogenesis of acne, inhibiting the androgen receptors in the sebaceous gland.²⁸ Because it is rapidly metabolized to cortexolone and does not have systemic antiandrogen effects, clascoterone can be used in both men and women with acne. In clinical trials, it had minimal side effects, including no evidence of irritability, which is an advantage over topical retinoids and BPO.²⁹ In addition, a phase 2 study found that clascoterone may have similar to superior efficacy to tretinoin cream 0.05%.³⁰ Although clascoterone has several strengths, including its efficacy, tolerability, and unique mechanism of action, its cost-effectiveness is limited due to its high cost (Table) and the need for twice-daily application, which reduces convenience. Clascoterone likely is best reserved for patients with a strong hormonal pathogenesis of their acne or difficulty tolerating other topicals, or as an additional therapy to complement other topicals.

Oral Antibiotics—Oral antibiotics are the most commonly prescribed systemic treatments for acne, particularly tetracyclines such as doxycycline, minocycline, and sarecycline.^31-34 Doxycycline and minocycline are considered first-line oral antibiotic therapy in the United States and are inexpensive and easily accessible.⁵ Doxycycline generally is recommended over minocycline given lack of evidence of superior efficacy of minocycline and concerns about severe adverse cutaneous reactions and drug-induced lupus with minocycline.³⁵

In recent years, there has been growing concern of the development of antibiotic resistance.⁵ Sarecycline is a narrow-spectrum tetracycline that was FDA approved for acne in 2018. In vitro studies demonstrate sarecycline maintains high efficacy against C acnes with less activity against other bacteria, particularly gram-negative enterobes.³⁶ The selectivity of sarecycline may lessen alterations of the gut microbiome seen with other oral antibiotics and reduce gastrointestinal tract side effects. Although comparative effectiveness studies are lacking, sarecycline was efficacious in phase 3 trials with few side effects compared with placebo.³⁷ However, at this time, given the absence of comparative effectiveness data and its high cost (Table), sarecycline likely is best reserved for patients with comorbidities (eg, gastrointestinal disease), those requiring long-term antibiotic therapy, or those with acne that has failed to respond to other oral antibiotics.

Hormonal Treatments—Hormonal treatments such as combined oral contraceptives (COCs) and spironolactone often are considered second-line options, though they may represent cost-effective and safe alternatives to oral antibiotics for women with moderate to severe acne.^38-41 There currently are 4 COCs approved by the FDA for the treatment of moderate acne in postmenarcheal females: drospirenone-ethinyl estradiol (Yaz [Bayer HealthCare Pharmaceuticals, Inc]), ethinyl estradiol-norgestimate (Ortho Tri-Cyclen [Ortho-McNeil Pharmaceuticals, Inc]), drospirenone-ethinyl estradiol-levomefolate (Beyaz [Bayer HealthCare Pharmaceuticals, Inc]), and ethinyl estradiol-norethindrone acetate-ferrous fumarate (Estrostep Fe [Allergan USA, Inc]).⁵ Treatment with COCs has been shown to cause substantial reductions in lesion counts across all lesion types compared to placebo, and a meta-analysis of 24 randomized trials conducted by Arowojolu et al⁴² demonstrated no consistent differences in acne reduction among different COCs.^43,44 Although oral antibiotics are associated with faster improvement than COCs, there is some evidence that they have similar efficacy at 6 months of therapy.⁴⁵ Combined oral contraceptives are inexpensive and likely reflect a highly cost-effective option (Table).

Spironolactone is an aldosterone inhibitor and androgen receptor blocker that is used off label to treat acne. It is one of the least expensive systemic medications for acne (Table). Although randomized controlled trials are lacking, several large case series support the effectiveness of spironolactone for women with acne.^38,46 In addition, observational data suggest spironolactone may have similar effectiveness to oral antibiotics.⁴¹ Spironolactone generally is well tolerated, with the most common adverse effects being menstrual irregularities, breast tenderness, and diuresis.^47,48 Many of these adverse effects are dose dependent and less likely with the dosing used in acne care. Additionally, menstrual irregularities can be reduced by concomitant use of a COC.⁴⁸

Although frequent potassium monitoring remains common among patients being treated with spironolactone, there is growing evidence to suggest that potassium monitoring is of low value in young healthy women with acne.^49-51 Reducing this laboratory monitoring likely represents an opportunity to provide higher-value care to patients being treated with spironolactone. However, laboratory monitoring should be considered if risk factors for hyperkalemia are present (eg, older age, comorbidities, medications).⁵¹

Isotretinoin—Isotretinoin is the most efficacious treatment available for acne and has the unique property of being able to induce a remission of acne activity for many patients.⁵ Although it remains modestly expensive (Table), it may be less costly overall relative to other treatments that may need continued use over many years because it can induce a remission of acne activity. As with spironolactone, frequent laboratory monitoring remains common among patients being treated with isotretinoin. There is no evidence to support checking complete blood cell counts.⁵² Several observational studies and a Delphi consensus support reduced monitoring, such as checking lipids and alanine aminotransferase at baseline and peak dose in otherwise young healthy patients.^53,54 A recent critically appraised topic published in the British Journal of Dermatology has proposed eliminating laboratory monitoring entirely.⁵⁵ Reducing laboratory monitoring for patients being treated with isotretinoin has been estimated to potentially save $100 million to $200 million per year in the United States.^52-54

Other Strategies to Reduce Patient Costs

Although choosing a cost-effective treatment approach is critical to preventing financial toxicity given poor coverage for acne care and the growth of high-deductible insurance plans, some patients may still experience high treatment costs.⁵⁶ Because pharmacy costs often are inflated, potentially related to practices of pharmacy benefit managers, it often is possible to find better prices than the presented list price, either by using platforms such as GoodRx or through direct-to-patient mail-order pharmacies such as Cost Plus Drug.⁵⁷ For branded medications, some patients may be eligible for patient-assistance programs, though they typically are not available for those with public insurance such as Medicare or Medicaid. Compounding pharmacies offer another approach to reduce cost and improve convenience for patients, but because the vehicle can influence the efficacy and tolerability of some topical medications, it is possible that these compounded formulations may not perform similarly to the original FDA-approved products.

Conclusion

For mild to moderate acne, multimodal topical therapy often is required. Fixed-dose combination adapalene-BPO and clindamycin-BPO are highly cost-effective options for most patients. Lotion formulations of topical retinoids may be useful in patients with difficulty tolerating other formulations. Clascoterone is a novel topical antiandrogen that is more expensive than other topical therapies but can complement other topical therapies and is well tolerated.

For moderate to severe acne, doxycycline or hormonal therapy (ie, COCs, spironolactone) are highly cost-effective options. Isotretinoin is recommended for severe or scarring acne. Reduced laboratory monitoring for spironolactone and isotretinoin is an opportunity to provide higher-value care.

In the United States, acne affects 85% of adolescents and can persist into adulthood at a prevalence of 30% to 50% in adult women. ^1,2 The pathogenesis of acne is multifactorial and involves hyperkeratinization of the follicle, bacterial colonization with Cutibacterium acnes , and increased androgen-induced sebum production, which together lead to inflammation. ^3,4 A wide range of treatment guideline–recommended options are available, including benzoyl peroxide (BPO), topical retinoids, topical and oral antibiotics, antiandrogens, and isotretinoin. ⁵ However, these options vary widely in their clinical uses, effectiveness, and costs.

Why Cost-effective Acne Care Matters

Out-of-pocket spending by patients on acne treatments can be substantial, with surveys finding that acne patients often spend hundreds to thousands of dollars per year.^6,7 In a poll conducted in 2019 by the Kaiser Family Foundation, 3 in 10 patients said they had not taken their medicine as prescribed because of costs.⁸ A mixed methods study by Ryskina et al⁹ found that 65% (17/26) of participants who reported primary nonadherence—intended to fill prescriptions but were unable to do so—cited cost or coverage-related barriers as the reason. With the continued rise of dermatologic drug prices and increased prevalence of high-deductible health plans, cost-effective treatment continues to grow in importance. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. We aim to review the cost-effectiveness of current prescription therapies for acne management and highlight the most cost-effective approaches to patients with mild to moderate acne as well as moderate to severe acne.

In this review, we will take a value-oriented framework.¹⁰ Value can be defined as the cost per outcome of interest. Therefore, a treatment does not necessarily need to be inexpensive to provide high value if it delivers outstanding clinical outcomes. In addition, we will focus on incremental cost-effectiveness relative to common alternatives (eg, a retinoid could deliver high value relative to a vehicle but still provide limited value compared to other available retinoids if it is more expensive but not more efficacious). When possible, we present data from cost-effectiveness studies.^11,12 We also use recent available price data obtained from GoodRx on August 11, 2023, to guide this discussion.¹³ However, as comparative-effectiveness and cost-effectiveness studies rarely are performed for acne medications, much of this discussion will be based on expert opinion.

Treatment Categories

Topical Retinoids—There currently are 4 topical retinoids that are approved by the US Food and Drug Administration (FDA) for the treatment of acne: tretinoin, tazarotene, trifarotene, and adapalene. These drugs are vitamin A derivatives that bind retinoic acid receptors and function as comedolytic and anti-inflammatory agents.⁵ In general, generic tretinoin and adapalene products have the lowest cost (Table).

In network meta-analyses, tretinoin and adapalene often are highly ranked topical treatment options with respect to efficacy.¹⁴ Combined with their low cost, generic tretinoin and adapalene likely are excellent initial options for topical therapy from the standpoint of cost-effectiveness.¹⁵ Adapalene may be preferred in many situations because of its better photostability and compatibility with BPO.

Due to the importance of the vehicle in determining retinoid tolerability, efforts have been made to use encapsulation and polymeric emulsion technology to improve tolerability. Recently, polymeric lotion formulations of tretinoin and tazarotene have become available. In a phase 2 study, tazarotene lotion 0.045% was found to have equivalent efficacy and superior tolerability to tazarotene cream 0.1%.¹⁶ Although head-to-head data are not available, it is likely that tretinoin lotion may offer similar tolerability improvements.¹⁷ Although these formulations currently are more costly, this improved tolerability may be critical for some patients to be able to use topical retinoids, and the additional cost may be worthwhile. In addition, as these products lose market exclusivity, they may become more affordable and similarly priced to other topical retinoids. It is important to keep in mind that in clinical trials of tretinoin and adapalene, rates of dropout due to adverse events typically were 1% to 2%; therefore, because many patients can tolerate generic tretinoin and adapalene, at current prices the lotion formulations of retinoids may not be cost-effective relative to these generics.¹⁴

Trifarotene cream 0.005%, a fourth-generation topical retinoid that is highly sensitive for retinoic acid receptor γ, recently was FDA approved for the treatment of acne. Although trifarotene is efficacious for both facial and truncal acne, there is a lack of active comparator data compared to other topical retinoids.¹⁸ In a 2023 network meta-analysis, trifarotene was found to be both less efficacious and less tolerable compared to other topical retinoids.¹⁹ Thus, it is unclear if trifarotene offers any improved efficacy compared to other options, and it comes at a much higher cost (Table). In a tolerability study, trifarotene was found to be significantly more irritating than tazarotene lotion 0.045% and adapalene gel 0.3% (P<.05).²⁰ Therefore, trifarotene cream 0.005% is unlikely to be a cost-effective option; in fact, it may be overall inferior to other topical retinoids, given its potentially lower tolerability.

Topical Antibiotics—There are 4 commonly prescribed topical antibiotics that are approved by the FDA for the treatment of acne: clindamycin, erythromycin, dapsone, and minocycline. The American Academy of Dermatology guidelines for the treatment of acne recommend concomitant use of BPO to prevent antibiotic resistance.⁵ Clindamycin is favored over erythromycin because of increasing antibiotic resistance to erythromycin.²¹ Inexpensive generic options in multiple vehicles (eg, solution, foam, gel) make clindamycin a highly cost-effective option when antibiotic therapy is desired as part of a topical regimen (Table).

The cost-effectiveness of dapsone gel and minocycline foam relative to clindamycin are less certain. Rates of resistance to minocycline are lower than clindamycin, and minocycline foam may be a reasonable alternative in patients who have not had success with other topical antibiotics, such as clindamycin.²² However, given the absence of comparative effectiveness data to suggest minocycline is more effective than clindamycin, it is difficult to justify the substantially higher cost for the typical patient. Although dapsone gel has been suggested as an option for adult women with acne, there are no data to support that it is any more effective than other topical antibiotics in this patient population.²³ As generic dapsone prices decrease, it may become a reasonable alternative to clindamycin. In addition, the antineutrophil properties of dapsone may be useful in other acneform and inflammatory eruptions, such as scalp folliculitis and folliculitis decalvans.²⁴

Combination Topicals—Current combination topical products include antibiotic and BPO, antibiotic and retinoid, and retinoid and BPO. Use of combination agents is recommended to reduce the risk for resistance and to enhance effectiveness. Combination products offer improved convenience, which is associated with better adherence and outcomes.²⁵ Generic fixed-dose adapalene-BPO can be a highly cost-effective option that can sometimes be less expensive than the individual component products (Table). Similarly, fixed-dose clindamycin-BPO also is likely to be highly cost-effective. A network meta-analysis found fixed-dose adapalene-BPO to be the most efficacious topical treatment, though it also was found to be the most irritating—more so than fixed-dose clindamycin-BPO, which may have similar efficacy.^14,26,27 Generic fixed-dose tretinoin-clindamycin offers improved convenience and adherence compared to the individual components, but it is more expensive, and its cost-effectiveness may be influenced by the importance of convenience for the patient.²⁵ An encapsulated, fixed-dose tretinoin 0.1%–BPO 3% cream is FDA approved for acne, but the cost is high and there is a lack of comparative effectiveness data demonstrating advantages over generic fixed-dose adapalene-BPO products.

Topical Antiandrogen—Clascoterone was introduced in 2020 as the first FDA-approved topical medication to target the hormonal pathogenesis of acne, inhibiting the androgen receptors in the sebaceous gland.²⁸ Because it is rapidly metabolized to cortexolone and does not have systemic antiandrogen effects, clascoterone can be used in both men and women with acne. In clinical trials, it had minimal side effects, including no evidence of irritability, which is an advantage over topical retinoids and BPO.²⁹ In addition, a phase 2 study found that clascoterone may have similar to superior efficacy to tretinoin cream 0.05%.³⁰ Although clascoterone has several strengths, including its efficacy, tolerability, and unique mechanism of action, its cost-effectiveness is limited due to its high cost (Table) and the need for twice-daily application, which reduces convenience. Clascoterone likely is best reserved for patients with a strong hormonal pathogenesis of their acne or difficulty tolerating other topicals, or as an additional therapy to complement other topicals.

Oral Antibiotics—Oral antibiotics are the most commonly prescribed systemic treatments for acne, particularly tetracyclines such as doxycycline, minocycline, and sarecycline.^31-34 Doxycycline and minocycline are considered first-line oral antibiotic therapy in the United States and are inexpensive and easily accessible.⁵ Doxycycline generally is recommended over minocycline given lack of evidence of superior efficacy of minocycline and concerns about severe adverse cutaneous reactions and drug-induced lupus with minocycline.³⁵

In recent years, there has been growing concern of the development of antibiotic resistance.⁵ Sarecycline is a narrow-spectrum tetracycline that was FDA approved for acne in 2018. In vitro studies demonstrate sarecycline maintains high efficacy against C acnes with less activity against other bacteria, particularly gram-negative enterobes.³⁶ The selectivity of sarecycline may lessen alterations of the gut microbiome seen with other oral antibiotics and reduce gastrointestinal tract side effects. Although comparative effectiveness studies are lacking, sarecycline was efficacious in phase 3 trials with few side effects compared with placebo.³⁷ However, at this time, given the absence of comparative effectiveness data and its high cost (Table), sarecycline likely is best reserved for patients with comorbidities (eg, gastrointestinal disease), those requiring long-term antibiotic therapy, or those with acne that has failed to respond to other oral antibiotics.

Hormonal Treatments—Hormonal treatments such as combined oral contraceptives (COCs) and spironolactone often are considered second-line options, though they may represent cost-effective and safe alternatives to oral antibiotics for women with moderate to severe acne.^38-41 There currently are 4 COCs approved by the FDA for the treatment of moderate acne in postmenarcheal females: drospirenone-ethinyl estradiol (Yaz [Bayer HealthCare Pharmaceuticals, Inc]), ethinyl estradiol-norgestimate (Ortho Tri-Cyclen [Ortho-McNeil Pharmaceuticals, Inc]), drospirenone-ethinyl estradiol-levomefolate (Beyaz [Bayer HealthCare Pharmaceuticals, Inc]), and ethinyl estradiol-norethindrone acetate-ferrous fumarate (Estrostep Fe [Allergan USA, Inc]).⁵ Treatment with COCs has been shown to cause substantial reductions in lesion counts across all lesion types compared to placebo, and a meta-analysis of 24 randomized trials conducted by Arowojolu et al⁴² demonstrated no consistent differences in acne reduction among different COCs.^43,44 Although oral antibiotics are associated with faster improvement than COCs, there is some evidence that they have similar efficacy at 6 months of therapy.⁴⁵ Combined oral contraceptives are inexpensive and likely reflect a highly cost-effective option (Table).

Spironolactone is an aldosterone inhibitor and androgen receptor blocker that is used off label to treat acne. It is one of the least expensive systemic medications for acne (Table). Although randomized controlled trials are lacking, several large case series support the effectiveness of spironolactone for women with acne.^38,46 In addition, observational data suggest spironolactone may have similar effectiveness to oral antibiotics.⁴¹ Spironolactone generally is well tolerated, with the most common adverse effects being menstrual irregularities, breast tenderness, and diuresis.^47,48 Many of these adverse effects are dose dependent and less likely with the dosing used in acne care. Additionally, menstrual irregularities can be reduced by concomitant use of a COC.⁴⁸

Although frequent potassium monitoring remains common among patients being treated with spironolactone, there is growing evidence to suggest that potassium monitoring is of low value in young healthy women with acne.^49-51 Reducing this laboratory monitoring likely represents an opportunity to provide higher-value care to patients being treated with spironolactone. However, laboratory monitoring should be considered if risk factors for hyperkalemia are present (eg, older age, comorbidities, medications).⁵¹

Isotretinoin—Isotretinoin is the most efficacious treatment available for acne and has the unique property of being able to induce a remission of acne activity for many patients.⁵ Although it remains modestly expensive (Table), it may be less costly overall relative to other treatments that may need continued use over many years because it can induce a remission of acne activity. As with spironolactone, frequent laboratory monitoring remains common among patients being treated with isotretinoin. There is no evidence to support checking complete blood cell counts.⁵² Several observational studies and a Delphi consensus support reduced monitoring, such as checking lipids and alanine aminotransferase at baseline and peak dose in otherwise young healthy patients.^53,54 A recent critically appraised topic published in the British Journal of Dermatology has proposed eliminating laboratory monitoring entirely.⁵⁵ Reducing laboratory monitoring for patients being treated with isotretinoin has been estimated to potentially save $100 million to $200 million per year in the United States.^52-54

Other Strategies to Reduce Patient Costs

Although choosing a cost-effective treatment approach is critical to preventing financial toxicity given poor coverage for acne care and the growth of high-deductible insurance plans, some patients may still experience high treatment costs.⁵⁶ Because pharmacy costs often are inflated, potentially related to practices of pharmacy benefit managers, it often is possible to find better prices than the presented list price, either by using platforms such as GoodRx or through direct-to-patient mail-order pharmacies such as Cost Plus Drug.⁵⁷ For branded medications, some patients may be eligible for patient-assistance programs, though they typically are not available for those with public insurance such as Medicare or Medicaid. Compounding pharmacies offer another approach to reduce cost and improve convenience for patients, but because the vehicle can influence the efficacy and tolerability of some topical medications, it is possible that these compounded formulations may not perform similarly to the original FDA-approved products.

Conclusion

For mild to moderate acne, multimodal topical therapy often is required. Fixed-dose combination adapalene-BPO and clindamycin-BPO are highly cost-effective options for most patients. Lotion formulations of topical retinoids may be useful in patients with difficulty tolerating other formulations. Clascoterone is a novel topical antiandrogen that is more expensive than other topical therapies but can complement other topical therapies and is well tolerated.

For moderate to severe acne, doxycycline or hormonal therapy (ie, COCs, spironolactone) are highly cost-effective options. Isotretinoin is recommended for severe or scarring acne. Reduced laboratory monitoring for spironolactone and isotretinoin is an opportunity to provide higher-value care.

In the United States, acne affects 85% of adolescents and can persist into adulthood at a prevalence of 30% to 50% in adult women. ^1,2 The pathogenesis of acne is multifactorial and involves hyperkeratinization of the follicle, bacterial colonization with Cutibacterium acnes , and increased androgen-induced sebum production, which together lead to inflammation. ^3,4 A wide range of treatment guideline–recommended options are available, including benzoyl peroxide (BPO), topical retinoids, topical and oral antibiotics, antiandrogens, and isotretinoin. ⁵ However, these options vary widely in their clinical uses, effectiveness, and costs.

Why Cost-effective Acne Care Matters

Out-of-pocket spending by patients on acne treatments can be substantial, with surveys finding that acne patients often spend hundreds to thousands of dollars per year.^6,7 In a poll conducted in 2019 by the Kaiser Family Foundation, 3 in 10 patients said they had not taken their medicine as prescribed because of costs.⁸ A mixed methods study by Ryskina et al⁹ found that 65% (17/26) of participants who reported primary nonadherence—intended to fill prescriptions but were unable to do so—cited cost or coverage-related barriers as the reason. With the continued rise of dermatologic drug prices and increased prevalence of high-deductible health plans, cost-effective treatment continues to grow in importance. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. We aim to review the cost-effectiveness of current prescription therapies for acne management and highlight the most cost-effective approaches to patients with mild to moderate acne as well as moderate to severe acne.

In this review, we will take a value-oriented framework.¹⁰ Value can be defined as the cost per outcome of interest. Therefore, a treatment does not necessarily need to be inexpensive to provide high value if it delivers outstanding clinical outcomes. In addition, we will focus on incremental cost-effectiveness relative to common alternatives (eg, a retinoid could deliver high value relative to a vehicle but still provide limited value compared to other available retinoids if it is more expensive but not more efficacious). When possible, we present data from cost-effectiveness studies.^11,12 We also use recent available price data obtained from GoodRx on August 11, 2023, to guide this discussion.¹³ However, as comparative-effectiveness and cost-effectiveness studies rarely are performed for acne medications, much of this discussion will be based on expert opinion.

Treatment Categories

Topical Retinoids—There currently are 4 topical retinoids that are approved by the US Food and Drug Administration (FDA) for the treatment of acne: tretinoin, tazarotene, trifarotene, and adapalene. These drugs are vitamin A derivatives that bind retinoic acid receptors and function as comedolytic and anti-inflammatory agents.⁵ In general, generic tretinoin and adapalene products have the lowest cost (Table).

In network meta-analyses, tretinoin and adapalene often are highly ranked topical treatment options with respect to efficacy.¹⁴ Combined with their low cost, generic tretinoin and adapalene likely are excellent initial options for topical therapy from the standpoint of cost-effectiveness.¹⁵ Adapalene may be preferred in many situations because of its better photostability and compatibility with BPO.

Due to the importance of the vehicle in determining retinoid tolerability, efforts have been made to use encapsulation and polymeric emulsion technology to improve tolerability. Recently, polymeric lotion formulations of tretinoin and tazarotene have become available. In a phase 2 study, tazarotene lotion 0.045% was found to have equivalent efficacy and superior tolerability to tazarotene cream 0.1%.¹⁶ Although head-to-head data are not available, it is likely that tretinoin lotion may offer similar tolerability improvements.¹⁷ Although these formulations currently are more costly, this improved tolerability may be critical for some patients to be able to use topical retinoids, and the additional cost may be worthwhile. In addition, as these products lose market exclusivity, they may become more affordable and similarly priced to other topical retinoids. It is important to keep in mind that in clinical trials of tretinoin and adapalene, rates of dropout due to adverse events typically were 1% to 2%; therefore, because many patients can tolerate generic tretinoin and adapalene, at current prices the lotion formulations of retinoids may not be cost-effective relative to these generics.¹⁴

Trifarotene cream 0.005%, a fourth-generation topical retinoid that is highly sensitive for retinoic acid receptor γ, recently was FDA approved for the treatment of acne. Although trifarotene is efficacious for both facial and truncal acne, there is a lack of active comparator data compared to other topical retinoids.¹⁸ In a 2023 network meta-analysis, trifarotene was found to be both less efficacious and less tolerable compared to other topical retinoids.¹⁹ Thus, it is unclear if trifarotene offers any improved efficacy compared to other options, and it comes at a much higher cost (Table). In a tolerability study, trifarotene was found to be significantly more irritating than tazarotene lotion 0.045% and adapalene gel 0.3% (P<.05).²⁰ Therefore, trifarotene cream 0.005% is unlikely to be a cost-effective option; in fact, it may be overall inferior to other topical retinoids, given its potentially lower tolerability.

Topical Antibiotics—There are 4 commonly prescribed topical antibiotics that are approved by the FDA for the treatment of acne: clindamycin, erythromycin, dapsone, and minocycline. The American Academy of Dermatology guidelines for the treatment of acne recommend concomitant use of BPO to prevent antibiotic resistance.⁵ Clindamycin is favored over erythromycin because of increasing antibiotic resistance to erythromycin.²¹ Inexpensive generic options in multiple vehicles (eg, solution, foam, gel) make clindamycin a highly cost-effective option when antibiotic therapy is desired as part of a topical regimen (Table).

The cost-effectiveness of dapsone gel and minocycline foam relative to clindamycin are less certain. Rates of resistance to minocycline are lower than clindamycin, and minocycline foam may be a reasonable alternative in patients who have not had success with other topical antibiotics, such as clindamycin.²² However, given the absence of comparative effectiveness data to suggest minocycline is more effective than clindamycin, it is difficult to justify the substantially higher cost for the typical patient. Although dapsone gel has been suggested as an option for adult women with acne, there are no data to support that it is any more effective than other topical antibiotics in this patient population.²³ As generic dapsone prices decrease, it may become a reasonable alternative to clindamycin. In addition, the antineutrophil properties of dapsone may be useful in other acneform and inflammatory eruptions, such as scalp folliculitis and folliculitis decalvans.²⁴

Combination Topicals—Current combination topical products include antibiotic and BPO, antibiotic and retinoid, and retinoid and BPO. Use of combination agents is recommended to reduce the risk for resistance and to enhance effectiveness. Combination products offer improved convenience, which is associated with better adherence and outcomes.²⁵ Generic fixed-dose adapalene-BPO can be a highly cost-effective option that can sometimes be less expensive than the individual component products (Table). Similarly, fixed-dose clindamycin-BPO also is likely to be highly cost-effective. A network meta-analysis found fixed-dose adapalene-BPO to be the most efficacious topical treatment, though it also was found to be the most irritating—more so than fixed-dose clindamycin-BPO, which may have similar efficacy.^14,26,27 Generic fixed-dose tretinoin-clindamycin offers improved convenience and adherence compared to the individual components, but it is more expensive, and its cost-effectiveness may be influenced by the importance of convenience for the patient.²⁵ An encapsulated, fixed-dose tretinoin 0.1%–BPO 3% cream is FDA approved for acne, but the cost is high and there is a lack of comparative effectiveness data demonstrating advantages over generic fixed-dose adapalene-BPO products.

Topical Antiandrogen—Clascoterone was introduced in 2020 as the first FDA-approved topical medication to target the hormonal pathogenesis of acne, inhibiting the androgen receptors in the sebaceous gland.²⁸ Because it is rapidly metabolized to cortexolone and does not have systemic antiandrogen effects, clascoterone can be used in both men and women with acne. In clinical trials, it had minimal side effects, including no evidence of irritability, which is an advantage over topical retinoids and BPO.²⁹ In addition, a phase 2 study found that clascoterone may have similar to superior efficacy to tretinoin cream 0.05%.³⁰ Although clascoterone has several strengths, including its efficacy, tolerability, and unique mechanism of action, its cost-effectiveness is limited due to its high cost (Table) and the need for twice-daily application, which reduces convenience. Clascoterone likely is best reserved for patients with a strong hormonal pathogenesis of their acne or difficulty tolerating other topicals, or as an additional therapy to complement other topicals.

Oral Antibiotics—Oral antibiotics are the most commonly prescribed systemic treatments for acne, particularly tetracyclines such as doxycycline, minocycline, and sarecycline.^31-34 Doxycycline and minocycline are considered first-line oral antibiotic therapy in the United States and are inexpensive and easily accessible.⁵ Doxycycline generally is recommended over minocycline given lack of evidence of superior efficacy of minocycline and concerns about severe adverse cutaneous reactions and drug-induced lupus with minocycline.³⁵

In recent years, there has been growing concern of the development of antibiotic resistance.⁵ Sarecycline is a narrow-spectrum tetracycline that was FDA approved for acne in 2018. In vitro studies demonstrate sarecycline maintains high efficacy against C acnes with less activity against other bacteria, particularly gram-negative enterobes.³⁶ The selectivity of sarecycline may lessen alterations of the gut microbiome seen with other oral antibiotics and reduce gastrointestinal tract side effects. Although comparative effectiveness studies are lacking, sarecycline was efficacious in phase 3 trials with few side effects compared with placebo.³⁷ However, at this time, given the absence of comparative effectiveness data and its high cost (Table), sarecycline likely is best reserved for patients with comorbidities (eg, gastrointestinal disease), those requiring long-term antibiotic therapy, or those with acne that has failed to respond to other oral antibiotics.

Hormonal Treatments—Hormonal treatments such as combined oral contraceptives (COCs) and spironolactone often are considered second-line options, though they may represent cost-effective and safe alternatives to oral antibiotics for women with moderate to severe acne.^38-41 There currently are 4 COCs approved by the FDA for the treatment of moderate acne in postmenarcheal females: drospirenone-ethinyl estradiol (Yaz [Bayer HealthCare Pharmaceuticals, Inc]), ethinyl estradiol-norgestimate (Ortho Tri-Cyclen [Ortho-McNeil Pharmaceuticals, Inc]), drospirenone-ethinyl estradiol-levomefolate (Beyaz [Bayer HealthCare Pharmaceuticals, Inc]), and ethinyl estradiol-norethindrone acetate-ferrous fumarate (Estrostep Fe [Allergan USA, Inc]).⁵ Treatment with COCs has been shown to cause substantial reductions in lesion counts across all lesion types compared to placebo, and a meta-analysis of 24 randomized trials conducted by Arowojolu et al⁴² demonstrated no consistent differences in acne reduction among different COCs.^43,44 Although oral antibiotics are associated with faster improvement than COCs, there is some evidence that they have similar efficacy at 6 months of therapy.⁴⁵ Combined oral contraceptives are inexpensive and likely reflect a highly cost-effective option (Table).

Spironolactone is an aldosterone inhibitor and androgen receptor blocker that is used off label to treat acne. It is one of the least expensive systemic medications for acne (Table). Although randomized controlled trials are lacking, several large case series support the effectiveness of spironolactone for women with acne.^38,46 In addition, observational data suggest spironolactone may have similar effectiveness to oral antibiotics.⁴¹ Spironolactone generally is well tolerated, with the most common adverse effects being menstrual irregularities, breast tenderness, and diuresis.^47,48 Many of these adverse effects are dose dependent and less likely with the dosing used in acne care. Additionally, menstrual irregularities can be reduced by concomitant use of a COC.⁴⁸

Although frequent potassium monitoring remains common among patients being treated with spironolactone, there is growing evidence to suggest that potassium monitoring is of low value in young healthy women with acne.^49-51 Reducing this laboratory monitoring likely represents an opportunity to provide higher-value care to patients being treated with spironolactone. However, laboratory monitoring should be considered if risk factors for hyperkalemia are present (eg, older age, comorbidities, medications).⁵¹

Isotretinoin—Isotretinoin is the most efficacious treatment available for acne and has the unique property of being able to induce a remission of acne activity for many patients.⁵ Although it remains modestly expensive (Table), it may be less costly overall relative to other treatments that may need continued use over many years because it can induce a remission of acne activity. As with spironolactone, frequent laboratory monitoring remains common among patients being treated with isotretinoin. There is no evidence to support checking complete blood cell counts.⁵² Several observational studies and a Delphi consensus support reduced monitoring, such as checking lipids and alanine aminotransferase at baseline and peak dose in otherwise young healthy patients.^53,54 A recent critically appraised topic published in the British Journal of Dermatology has proposed eliminating laboratory monitoring entirely.⁵⁵ Reducing laboratory monitoring for patients being treated with isotretinoin has been estimated to potentially save $100 million to $200 million per year in the United States.^52-54

Other Strategies to Reduce Patient Costs

Although choosing a cost-effective treatment approach is critical to preventing financial toxicity given poor coverage for acne care and the growth of high-deductible insurance plans, some patients may still experience high treatment costs.⁵⁶ Because pharmacy costs often are inflated, potentially related to practices of pharmacy benefit managers, it often is possible to find better prices than the presented list price, either by using platforms such as GoodRx or through direct-to-patient mail-order pharmacies such as Cost Plus Drug.⁵⁷ For branded medications, some patients may be eligible for patient-assistance programs, though they typically are not available for those with public insurance such as Medicare or Medicaid. Compounding pharmacies offer another approach to reduce cost and improve convenience for patients, but because the vehicle can influence the efficacy and tolerability of some topical medications, it is possible that these compounded formulations may not perform similarly to the original FDA-approved products.

Conclusion

For mild to moderate acne, multimodal topical therapy often is required. Fixed-dose combination adapalene-BPO and clindamycin-BPO are highly cost-effective options for most patients. Lotion formulations of topical retinoids may be useful in patients with difficulty tolerating other formulations. Clascoterone is a novel topical antiandrogen that is more expensive than other topical therapies but can complement other topical therapies and is well tolerated.

For moderate to severe acne, doxycycline or hormonal therapy (ie, COCs, spironolactone) are highly cost-effective options. Isotretinoin is recommended for severe or scarring acne. Reduced laboratory monitoring for spironolactone and isotretinoin is an opportunity to provide higher-value care.

There is now an additional option for the prevention of respiratory syncytial virus (RSV), the most common cause of hospitalization among infants and children in the United States. In July, the US Food and Drug Administration (FDA) approved nirsevimab, an RSV preventive monoclonal antibody, for use in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to RSV during their second season.¹ The Advisory Committee on Immunization Practices (ACIP) subsequently made 2 recommendations regarding use of nirsevimab, which I’ll detail in a moment.²

First, a word about RSV. The Centers for Disease Control and Prevention estimates that each year in children younger than 5 years, RSV is responsible for 1.5 million outpatient clinic visits, 520,000 emergency department visits, 58,000 to 80,000 hospitalizations, and 100 to 200 deaths.² The risk for hospitalization from RSV is highest in the second and third months of life and decreases with increasing age.

There are some racial disparities in RSV severity, likely reflecting social drivers of health: ICU admission rates are 1.2 to 1.6 times higher among non-Hispanic Black infants younger than 6 months than among non-Hispanic White infants, and hospitalization rates are up to 5 times higher in American Indian and Alaska Native populations.²

What nirsevimab adds to the toolbox. Until recently, there was only 1 RSV preventive agent available: palivizumab, also a monoclonal antibody. The American Academy of Pediatrics has recommended palivizumab be used only for infants at high risk for RSV infection, due to its high cost and the need for monthly injections for the duration of an RSV season. In addition, the Academy has noted that palivizumab has limited effect on RSV hospitalizations on a population basis and does not appear to affect mortality.³

Nirsevimab has a longer half-life than palivizumab, and only 1 injection is needed for the RSV season. Early studies on nirsevimab demonstrate 79% effectiveness in preventing medical-attended lower respiratory tract infection, 80.6% effectiveness in preventing hospitalization, and 90% effectiveness in preventing ICU admission. The number needed to immunize with nirsevimab to prevent an outpatient visit is estimated to be 17; to prevent an ED visit, 48; and to prevent an inpatient admission, 128. Due to the low RSV death rate, the studies were not able to demonstrate reduced mortality.²

What the ACIP recommends. At a special meeting in July, the ACIP recommended 1 dose of nirsevimab for²:

• all infants younger than 8 months who are born during or entering their first RSV season
• children ages 8 to 19 months who are at increased risk for severe RSV disease and entering their second RSV season.

Those at risk include children with chronic lung disease of prematurity who required medical support any time during the 6-month period before the start of their second RSV season; those with severe immunocompromise; those with cystic fibrosis who have manifestations of severe lung disease or weight-for-length < 10th percentile; and American Indian and Alaska Native children.²

How to administer nirsevimab. The dose of nirsevimab is 50 mg IM for those weighing < 5 kg, 100 mg for those weighing ≥ 5 kg, and 200 mg for high-risk children entering their second RSV season.² Nirsevimab can be co-administered with other recommended vaccines; however, both nirsevimab and palivizumab should not be used in the same child in the same RSV season.

Nirsevimab should be administered in the first week of life for infants born shortly before or during RSV season, and shortly before the season for infants younger than 8 months and those ages 8 to 19 months who are at high risk.⁴ The months of highest RSV transmission in most locations are December through February, but this can vary. Local epidemiology and advice from state and local health departments are the best source of information about when RSV season starts and ends in your area.

On the horizon. Nirsevimab will be included in the Vaccines for Children program and covered by commercial health plans with no cost sharing.⁵ A maternal vaccine to prevent RSV in newborns is likely to be approved by the FDA in the near future.

There is now an additional option for the prevention of respiratory syncytial virus (RSV), the most common cause of hospitalization among infants and children in the United States. In July, the US Food and Drug Administration (FDA) approved nirsevimab, an RSV preventive monoclonal antibody, for use in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to RSV during their second season.¹ The Advisory Committee on Immunization Practices (ACIP) subsequently made 2 recommendations regarding use of nirsevimab, which I’ll detail in a moment.²

First, a word about RSV. The Centers for Disease Control and Prevention estimates that each year in children younger than 5 years, RSV is responsible for 1.5 million outpatient clinic visits, 520,000 emergency department visits, 58,000 to 80,000 hospitalizations, and 100 to 200 deaths.² The risk for hospitalization from RSV is highest in the second and third months of life and decreases with increasing age.

There are some racial disparities in RSV severity, likely reflecting social drivers of health: ICU admission rates are 1.2 to 1.6 times higher among non-Hispanic Black infants younger than 6 months than among non-Hispanic White infants, and hospitalization rates are up to 5 times higher in American Indian and Alaska Native populations.²

What nirsevimab adds to the toolbox. Until recently, there was only 1 RSV preventive agent available: palivizumab, also a monoclonal antibody. The American Academy of Pediatrics has recommended palivizumab be used only for infants at high risk for RSV infection, due to its high cost and the need for monthly injections for the duration of an RSV season. In addition, the Academy has noted that palivizumab has limited effect on RSV hospitalizations on a population basis and does not appear to affect mortality.³

Nirsevimab has a longer half-life than palivizumab, and only 1 injection is needed for the RSV season. Early studies on nirsevimab demonstrate 79% effectiveness in preventing medical-attended lower respiratory tract infection, 80.6% effectiveness in preventing hospitalization, and 90% effectiveness in preventing ICU admission. The number needed to immunize with nirsevimab to prevent an outpatient visit is estimated to be 17; to prevent an ED visit, 48; and to prevent an inpatient admission, 128. Due to the low RSV death rate, the studies were not able to demonstrate reduced mortality.²

What the ACIP recommends. At a special meeting in July, the ACIP recommended 1 dose of nirsevimab for²:

• all infants younger than 8 months who are born during or entering their first RSV season
• children ages 8 to 19 months who are at increased risk for severe RSV disease and entering their second RSV season.

Those at risk include children with chronic lung disease of prematurity who required medical support any time during the 6-month period before the start of their second RSV season; those with severe immunocompromise; those with cystic fibrosis who have manifestations of severe lung disease or weight-for-length < 10th percentile; and American Indian and Alaska Native children.²

How to administer nirsevimab. The dose of nirsevimab is 50 mg IM for those weighing < 5 kg, 100 mg for those weighing ≥ 5 kg, and 200 mg for high-risk children entering their second RSV season.² Nirsevimab can be co-administered with other recommended vaccines; however, both nirsevimab and palivizumab should not be used in the same child in the same RSV season.

Nirsevimab should be administered in the first week of life for infants born shortly before or during RSV season, and shortly before the season for infants younger than 8 months and those ages 8 to 19 months who are at high risk.⁴ The months of highest RSV transmission in most locations are December through February, but this can vary. Local epidemiology and advice from state and local health departments are the best source of information about when RSV season starts and ends in your area.

On the horizon. Nirsevimab will be included in the Vaccines for Children program and covered by commercial health plans with no cost sharing.⁵ A maternal vaccine to prevent RSV in newborns is likely to be approved by the FDA in the near future.

There is now an additional option for the prevention of respiratory syncytial virus (RSV), the most common cause of hospitalization among infants and children in the United States. In July, the US Food and Drug Administration (FDA) approved nirsevimab, an RSV preventive monoclonal antibody, for use in neonates and infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to RSV during their second season.¹ The Advisory Committee on Immunization Practices (ACIP) subsequently made 2 recommendations regarding use of nirsevimab, which I’ll detail in a moment.²

First, a word about RSV. The Centers for Disease Control and Prevention estimates that each year in children younger than 5 years, RSV is responsible for 1.5 million outpatient clinic visits, 520,000 emergency department visits, 58,000 to 80,000 hospitalizations, and 100 to 200 deaths.² The risk for hospitalization from RSV is highest in the second and third months of life and decreases with increasing age.

There are some racial disparities in RSV severity, likely reflecting social drivers of health: ICU admission rates are 1.2 to 1.6 times higher among non-Hispanic Black infants younger than 6 months than among non-Hispanic White infants, and hospitalization rates are up to 5 times higher in American Indian and Alaska Native populations.²

What nirsevimab adds to the toolbox. Until recently, there was only 1 RSV preventive agent available: palivizumab, also a monoclonal antibody. The American Academy of Pediatrics has recommended palivizumab be used only for infants at high risk for RSV infection, due to its high cost and the need for monthly injections for the duration of an RSV season. In addition, the Academy has noted that palivizumab has limited effect on RSV hospitalizations on a population basis and does not appear to affect mortality.³

Nirsevimab has a longer half-life than palivizumab, and only 1 injection is needed for the RSV season. Early studies on nirsevimab demonstrate 79% effectiveness in preventing medical-attended lower respiratory tract infection, 80.6% effectiveness in preventing hospitalization, and 90% effectiveness in preventing ICU admission. The number needed to immunize with nirsevimab to prevent an outpatient visit is estimated to be 17; to prevent an ED visit, 48; and to prevent an inpatient admission, 128. Due to the low RSV death rate, the studies were not able to demonstrate reduced mortality.²

What the ACIP recommends. At a special meeting in July, the ACIP recommended 1 dose of nirsevimab for²:

• all infants younger than 8 months who are born during or entering their first RSV season
• children ages 8 to 19 months who are at increased risk for severe RSV disease and entering their second RSV season.

Those at risk include children with chronic lung disease of prematurity who required medical support any time during the 6-month period before the start of their second RSV season; those with severe immunocompromise; those with cystic fibrosis who have manifestations of severe lung disease or weight-for-length < 10th percentile; and American Indian and Alaska Native children.²

How to administer nirsevimab. The dose of nirsevimab is 50 mg IM for those weighing < 5 kg, 100 mg for those weighing ≥ 5 kg, and 200 mg for high-risk children entering their second RSV season.² Nirsevimab can be co-administered with other recommended vaccines; however, both nirsevimab and palivizumab should not be used in the same child in the same RSV season.

Nirsevimab should be administered in the first week of life for infants born shortly before or during RSV season, and shortly before the season for infants younger than 8 months and those ages 8 to 19 months who are at high risk.⁴ The months of highest RSV transmission in most locations are December through February, but this can vary. Local epidemiology and advice from state and local health departments are the best source of information about when RSV season starts and ends in your area.

On the horizon. Nirsevimab will be included in the Vaccines for Children program and covered by commercial health plans with no cost sharing.⁵ A maternal vaccine to prevent RSV in newborns is likely to be approved by the FDA in the near future.

PURPOSE

To improve germline genetic testing among Veterans with high risk, very high risk and metastatic prostate cancer.

BACKGROUND

During our Commission on Cancer survey in 2021, it was noted that the Detroit VA’s referrals for germline genetic testing and counseling were extremely low. In 2020, only 1 Veteran was referred for prostate germline genetic testing and counseling and only 8 Veterans were referred in 2021. It was felt that the need to refer Veterans outside of the Detroit VA may have contributed to these low numbers. Our Cancer Committee chose prostate cancer as a disease to focus on. We chose a timeline of one year to implement our process.

METHODS

We made testing and counseling locally accessible to Veterans and encouraged medical oncology providers to make it part of the care of Veterans with high risk, very high risk and metastatic prostate cancer. We sought the assistance of the VA’s National Precision Oncology Program and were able to secure financial and logistical support to perform germline molecular prostate panel testing at the Detroit VA. We were also able to identify a cancer genetic specialist at the Ann Arbor VA that would perform genetic counseling among this group of patients based on their test results. Our medical oncology providers identified Veterans meeting the criteria for testing. Education regarding germline testing, its benefits and implications were conducted with Veterans, and performed after obtaining their informed consent in collaboration with our pathology department. The specimen is then sent to a VA central laboratory for processing. Detroit VA providers are alerted by the local laboratory once results are available. Veterans are then referred to the genetic counseling specialist based on the results. Some of these counseling visits are done virtually for the Veteran’s convenience.

DATA ANALYSIS

A retrospective chart analysis was used to collect the data.

RESULTS

After the implementation of our initiative, 97 Veterans with high risk, very high risk or metastatic prostate cancer were educated on the benefits of germline genetic testing, 87 of whom agreed to be tested. As of 4/2/23, 48 tests have already been performed. Pathogenic variants were recorded on 2 Veterans so far. One was for BRCA2 and KDM6A, and the other was for ATM. Data collection and recording is on-going.

IMPLICATIONS

Improving accessibility and incorporating genetic testing and counseling in cancer care can improve their utilization.

PURPOSE

To improve germline genetic testing among Veterans with high risk, very high risk and metastatic prostate cancer.

BACKGROUND

During our Commission on Cancer survey in 2021, it was noted that the Detroit VA’s referrals for germline genetic testing and counseling were extremely low. In 2020, only 1 Veteran was referred for prostate germline genetic testing and counseling and only 8 Veterans were referred in 2021. It was felt that the need to refer Veterans outside of the Detroit VA may have contributed to these low numbers. Our Cancer Committee chose prostate cancer as a disease to focus on. We chose a timeline of one year to implement our process.

METHODS

We made testing and counseling locally accessible to Veterans and encouraged medical oncology providers to make it part of the care of Veterans with high risk, very high risk and metastatic prostate cancer. We sought the assistance of the VA’s National Precision Oncology Program and were able to secure financial and logistical support to perform germline molecular prostate panel testing at the Detroit VA. We were also able to identify a cancer genetic specialist at the Ann Arbor VA that would perform genetic counseling among this group of patients based on their test results. Our medical oncology providers identified Veterans meeting the criteria for testing. Education regarding germline testing, its benefits and implications were conducted with Veterans, and performed after obtaining their informed consent in collaboration with our pathology department. The specimen is then sent to a VA central laboratory for processing. Detroit VA providers are alerted by the local laboratory once results are available. Veterans are then referred to the genetic counseling specialist based on the results. Some of these counseling visits are done virtually for the Veteran’s convenience.

DATA ANALYSIS

A retrospective chart analysis was used to collect the data.

RESULTS

After the implementation of our initiative, 97 Veterans with high risk, very high risk or metastatic prostate cancer were educated on the benefits of germline genetic testing, 87 of whom agreed to be tested. As of 4/2/23, 48 tests have already been performed. Pathogenic variants were recorded on 2 Veterans so far. One was for BRCA2 and KDM6A, and the other was for ATM. Data collection and recording is on-going.

IMPLICATIONS

Improving accessibility and incorporating genetic testing and counseling in cancer care can improve their utilization.

PURPOSE

To improve germline genetic testing among Veterans with high risk, very high risk and metastatic prostate cancer.

BACKGROUND

During our Commission on Cancer survey in 2021, it was noted that the Detroit VA’s referrals for germline genetic testing and counseling were extremely low. In 2020, only 1 Veteran was referred for prostate germline genetic testing and counseling and only 8 Veterans were referred in 2021. It was felt that the need to refer Veterans outside of the Detroit VA may have contributed to these low numbers. Our Cancer Committee chose prostate cancer as a disease to focus on. We chose a timeline of one year to implement our process.

METHODS

We made testing and counseling locally accessible to Veterans and encouraged medical oncology providers to make it part of the care of Veterans with high risk, very high risk and metastatic prostate cancer. We sought the assistance of the VA’s National Precision Oncology Program and were able to secure financial and logistical support to perform germline molecular prostate panel testing at the Detroit VA. We were also able to identify a cancer genetic specialist at the Ann Arbor VA that would perform genetic counseling among this group of patients based on their test results. Our medical oncology providers identified Veterans meeting the criteria for testing. Education regarding germline testing, its benefits and implications were conducted with Veterans, and performed after obtaining their informed consent in collaboration with our pathology department. The specimen is then sent to a VA central laboratory for processing. Detroit VA providers are alerted by the local laboratory once results are available. Veterans are then referred to the genetic counseling specialist based on the results. Some of these counseling visits are done virtually for the Veteran’s convenience.

DATA ANALYSIS

A retrospective chart analysis was used to collect the data.

RESULTS

After the implementation of our initiative, 97 Veterans with high risk, very high risk or metastatic prostate cancer were educated on the benefits of germline genetic testing, 87 of whom agreed to be tested. As of 4/2/23, 48 tests have already been performed. Pathogenic variants were recorded on 2 Veterans so far. One was for BRCA2 and KDM6A, and the other was for ATM. Data collection and recording is on-going.

IMPLICATIONS

Improving accessibility and incorporating genetic testing and counseling in cancer care can improve their utilization.

A leg ulcer may have many causes, including venous stasis, trauma, vasculitis, infection, or (as in this case) squamous cell carcinoma in situ (SCCis), aka Bowen’s Disease.

SCC and SCCis are common skin cancers that occur less frequently than basal cell carcinomas (BCCs).¹ SCCis is normally scaly and hyperkeratotic, but it can manifest in rare cases as a chronic ulcer. Fair skin, long history of sun damage, and immunosuppression are significant risk factors for both SCCis and SCC.

While history and other clinical features may help narrow the diagnosis, a wound that does not heal despite treatments should be biopsied. Shave and punch biopsies are both excellent ways to diagnose an SCCis that has a classic appearance. However, ulcers and blisters can be caused by inflammatory processes (as in pyoderma gangrenosum or a fixed drug eruption) with characteristic findings deeper in the dermis; these lesions are better assessed with a punch biopsy.

In this case, a 4-mm punch biopsy was performed at the tissue edge and showed atypical keratinocytes limited to the epidermis. These atypical keratinocytes are associated with vesicle formation and ulcer, consistent with SCCis.

SCCis transforms into invasive disease in 3% to 5% of cases.² Surgical treatment includes fusiform excision and electrodessication and curettage, both with cure rates that often exceed 90%.^2,3 Nonsurgical options include topical 5-fluorouracil (67%-92% effective), topical imiquimod (75%-93%), and photodynamic therapy (52%-98%).⁴

Treatment choices depend on patient preference and provider capabilities. With surgical options there is the risk of bleeding and the need to care for a healing wound. Nonsurgical treatments can last longer and require topical treatment regimens and medications.

This patient opted for a fusiform excision and linear closure. She will continue to undergo serial skin evaluations twice a year for at least 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.

A leg ulcer may have many causes, including venous stasis, trauma, vasculitis, infection, or (as in this case) squamous cell carcinoma in situ (SCCis), aka Bowen’s Disease.

SCC and SCCis are common skin cancers that occur less frequently than basal cell carcinomas (BCCs).¹ SCCis is normally scaly and hyperkeratotic, but it can manifest in rare cases as a chronic ulcer. Fair skin, long history of sun damage, and immunosuppression are significant risk factors for both SCCis and SCC.

While history and other clinical features may help narrow the diagnosis, a wound that does not heal despite treatments should be biopsied. Shave and punch biopsies are both excellent ways to diagnose an SCCis that has a classic appearance. However, ulcers and blisters can be caused by inflammatory processes (as in pyoderma gangrenosum or a fixed drug eruption) with characteristic findings deeper in the dermis; these lesions are better assessed with a punch biopsy.

In this case, a 4-mm punch biopsy was performed at the tissue edge and showed atypical keratinocytes limited to the epidermis. These atypical keratinocytes are associated with vesicle formation and ulcer, consistent with SCCis.

SCCis transforms into invasive disease in 3% to 5% of cases.² Surgical treatment includes fusiform excision and electrodessication and curettage, both with cure rates that often exceed 90%.^2,3 Nonsurgical options include topical 5-fluorouracil (67%-92% effective), topical imiquimod (75%-93%), and photodynamic therapy (52%-98%).⁴

Treatment choices depend on patient preference and provider capabilities. With surgical options there is the risk of bleeding and the need to care for a healing wound. Nonsurgical treatments can last longer and require topical treatment regimens and medications.

This patient opted for a fusiform excision and linear closure. She will continue to undergo serial skin evaluations twice a year for at least 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.

A leg ulcer may have many causes, including venous stasis, trauma, vasculitis, infection, or (as in this case) squamous cell carcinoma in situ (SCCis), aka Bowen’s Disease.

SCC and SCCis are common skin cancers that occur less frequently than basal cell carcinomas (BCCs).¹ SCCis is normally scaly and hyperkeratotic, but it can manifest in rare cases as a chronic ulcer. Fair skin, long history of sun damage, and immunosuppression are significant risk factors for both SCCis and SCC.

While history and other clinical features may help narrow the diagnosis, a wound that does not heal despite treatments should be biopsied. Shave and punch biopsies are both excellent ways to diagnose an SCCis that has a classic appearance. However, ulcers and blisters can be caused by inflammatory processes (as in pyoderma gangrenosum or a fixed drug eruption) with characteristic findings deeper in the dermis; these lesions are better assessed with a punch biopsy.

In this case, a 4-mm punch biopsy was performed at the tissue edge and showed atypical keratinocytes limited to the epidermis. These atypical keratinocytes are associated with vesicle formation and ulcer, consistent with SCCis.

SCCis transforms into invasive disease in 3% to 5% of cases.² Surgical treatment includes fusiform excision and electrodessication and curettage, both with cure rates that often exceed 90%.^2,3 Nonsurgical options include topical 5-fluorouracil (67%-92% effective), topical imiquimod (75%-93%), and photodynamic therapy (52%-98%).⁴

Treatment choices depend on patient preference and provider capabilities. With surgical options there is the risk of bleeding and the need to care for a healing wound. Nonsurgical treatments can last longer and require topical treatment regimens and medications.

This patient opted for a fusiform excision and linear closure. She will continue to undergo serial skin evaluations twice a year for at least 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, Maine.

The Diagnosis: Papular Acantholytic Dyskeratosis

The shave biopsy revealed suprabasal clefts associated with acantholytic and dyskeratotic cells as well as overlying hyperkeratosis. Direct immunofluorescence (DIF) was negative. Based on the combined clinical and histological findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD), a rare disease that clinically presents as small whitishgreyish papules with the potential to coalesce into larger plaques.^1,2 The condition predominantly manifests without symptoms, though pruritus and burning have been reported in affected sites. Most cases of PAD have been reported in older adults rather than in children or adolescents; it is more prevalent in women than in men. Lesions generally are localized to the penis, vulva, scrotum, inguinal folds, and perianal region.³ More specific terms have been used to describe this presentation such as papular acantholytic dyskeratosis of the anogenital region and papular acantholytic dyskeratosis of the genital-crural region. Histologic findings of PAD include epidermal acantholysis and dyskeratosis with hyperkeratosis and parakeratosis (quiz image).

The histologic differential diagnosis of PAD is broad due to its overlapping features with other diseases such as pemphigus vulgaris, Hailey-Hailey disease (HHD), Darier disease, and Grover disease. The acantholytic pathophysiology of these conditions involves dysfunction in cell adhesion markers. The correct diagnosis can be made by considering both the clinical location of involvement and histopathologic clues.

Pemphigus is a family of disorders involving mucocutaneous blistering of an autoimmune nature (Figure 1). Pemphigus vulgaris is the most prevalent variant of the pemphigus family, with symptomatically painful involvement of mucosal and cutaneous tissue. Autoantibodies to desmoglein 3 alone or both desmoglein 1 and 3 are present. Pemphigus vulgaris displays positive DIF findings with intercellular IgG and C3.

Hailey-Hailey disease (also known as benign familial pemphigus) is an autosomal-dominant disease that shares the acantholytic feature that is common in this class of diseases and caused by a defect in cell-cell adhesion as well as a loss of function in the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Blistering lesions typically appear in the neck, axillary, inguinal, or genital regions, and they can develop into crusted, exudate-filled lesions. No autoimmunity has been associated with this disease, unlike other diseases in the pemphigus family, and mutations in the ATP2C1 gene have been linked with dysregulation of cell-cell adhesion, particularly in cadherins and calcium-dependent cell adhesion processes. Histologically, HHD will show diffuse keratinocyte acantholysis with suprabasal clefting (Figure 2).⁴ Dyskeratosis is mild, if present at all, and dyskeratotic keratinocytes show a well-defined nucleus with cytoplasmic preservation. In contrast to HHD, PAD typically shows more dyskeratosis.

Darier disease (also known as keratosis follicularis) is an autosomal-dominant condition that normally presents with seborrheic eruptions in intertriginous areas, usually with onset during adolescence. Darier disease is caused by a loss-of-function mutation in the ATP2A2 gene found on chromosome 12q23-24.1 that encodes for the sarco(endo)plasmic reticulum calcium ATPase2 (SERCA2) enzymes involved in calcium-dependent transport of the endoplasmic reticulum within the cell. Due to calcium dysregulation, desmosomes are unable to carry out their function in cell-cell adhesion, resulting in keratinocyte acantholysis. Histopathology of Darier disease is identical to HHD but displays more dyskeratosis than HHD (Figure 3), possibly due to the endoplasmic reticulum calcium stores that are affected in Darier disease compared to the Golgi apparatus calcium stores that are implicated in HHD.5 The lowered endoplasmic reticulum calcium stores in Darier-White disease are associated with more pronounced dyskeratosis, which is seen histologically as corps ronds. Suprabasal hyperkeratosis also is found in Darier disease. The histopathologic findings of Darier disease and PAD can be identical, but the clinical presentations are distinct, with Darier disease typically manifesting as seborrheic eruptions appearing in adolescence and PAD presenting as small white papules in the anogenital or crural regions.

Grover disease (also referred to as transient acantholytic dermatosis) has an idiopathic pathophysiology. It clinically manifests with eruptions of erythematous, pruritic, truncal papules on the chest or back. Grover disease has a predilection for White men older than 50 years, and symptoms may be exacerbated in heat and diaphoretic conditions. Histologically, Grover disease may show acantholytic features seen in pemphigus vulgaris, HHD, and Darier disease; the pattern can only follow a specific disease or consist of a combination of all disease features (Figure 4). The acantholytic pattern of Grover disease was found to be similar to pemphigus vulgaris, Darier disease, pemphigus foliaceus, and HHD 47%, 18%, 9%, and 8% of the time, respectively. In 9% of cases, Grover disease will exhibit a mixed histopathology in which its acantholytic pattern will consist of a combination of features seen in the pemphigus family of diseases.6 Biopsy results showing mixed histologic patterns or a combination of different acantholytic features are suggestive of Grover disease over PAD. Moreover, the clinical distribution helps to differentiate Grover disease from PAD.

Because the histologic characteristics of these diseases overlap, certain nuances in clinical correlations and histology allow for distinction. In our patient, the diagnosis was most consistent with PAD based on the clinical manifestation of the disease and the biopsy results. Considering solely the clinical location of the lesions, Grover disease was a less likely diagnosis because our patient’s lesions were observed in the perianal region, not the truncal region as typically seen in Grover disease. Taking into account the DIF assay results in our patient, the pemphigus family of diseases also moved lower on the differential diagnosis. Finally, because the biopsy showed more dyskeratosis than would be present in HHD and also was inconsistent with the location and onset that would be expected to be seen in Darier disease, PAD was the most probable diagnosis. Interestingly, studies have shown mosaic mutations in ATP2A2 and ATP2C1 as possible causes of PAD, suggesting that this may be an allelic variant of Darier disease and HHD.7-9 No genetic testing was performed in our patient.

The Diagnosis: Papular Acantholytic Dyskeratosis

The shave biopsy revealed suprabasal clefts associated with acantholytic and dyskeratotic cells as well as overlying hyperkeratosis. Direct immunofluorescence (DIF) was negative. Based on the combined clinical and histological findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD), a rare disease that clinically presents as small whitishgreyish papules with the potential to coalesce into larger plaques.^1,2 The condition predominantly manifests without symptoms, though pruritus and burning have been reported in affected sites. Most cases of PAD have been reported in older adults rather than in children or adolescents; it is more prevalent in women than in men. Lesions generally are localized to the penis, vulva, scrotum, inguinal folds, and perianal region.³ More specific terms have been used to describe this presentation such as papular acantholytic dyskeratosis of the anogenital region and papular acantholytic dyskeratosis of the genital-crural region. Histologic findings of PAD include epidermal acantholysis and dyskeratosis with hyperkeratosis and parakeratosis (quiz image).

The histologic differential diagnosis of PAD is broad due to its overlapping features with other diseases such as pemphigus vulgaris, Hailey-Hailey disease (HHD), Darier disease, and Grover disease. The acantholytic pathophysiology of these conditions involves dysfunction in cell adhesion markers. The correct diagnosis can be made by considering both the clinical location of involvement and histopathologic clues.

Pemphigus is a family of disorders involving mucocutaneous blistering of an autoimmune nature (Figure 1). Pemphigus vulgaris is the most prevalent variant of the pemphigus family, with symptomatically painful involvement of mucosal and cutaneous tissue. Autoantibodies to desmoglein 3 alone or both desmoglein 1 and 3 are present. Pemphigus vulgaris displays positive DIF findings with intercellular IgG and C3.

Hailey-Hailey disease (also known as benign familial pemphigus) is an autosomal-dominant disease that shares the acantholytic feature that is common in this class of diseases and caused by a defect in cell-cell adhesion as well as a loss of function in the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Blistering lesions typically appear in the neck, axillary, inguinal, or genital regions, and they can develop into crusted, exudate-filled lesions. No autoimmunity has been associated with this disease, unlike other diseases in the pemphigus family, and mutations in the ATP2C1 gene have been linked with dysregulation of cell-cell adhesion, particularly in cadherins and calcium-dependent cell adhesion processes. Histologically, HHD will show diffuse keratinocyte acantholysis with suprabasal clefting (Figure 2).⁴ Dyskeratosis is mild, if present at all, and dyskeratotic keratinocytes show a well-defined nucleus with cytoplasmic preservation. In contrast to HHD, PAD typically shows more dyskeratosis.

Darier disease (also known as keratosis follicularis) is an autosomal-dominant condition that normally presents with seborrheic eruptions in intertriginous areas, usually with onset during adolescence. Darier disease is caused by a loss-of-function mutation in the ATP2A2 gene found on chromosome 12q23-24.1 that encodes for the sarco(endo)plasmic reticulum calcium ATPase2 (SERCA2) enzymes involved in calcium-dependent transport of the endoplasmic reticulum within the cell. Due to calcium dysregulation, desmosomes are unable to carry out their function in cell-cell adhesion, resulting in keratinocyte acantholysis. Histopathology of Darier disease is identical to HHD but displays more dyskeratosis than HHD (Figure 3), possibly due to the endoplasmic reticulum calcium stores that are affected in Darier disease compared to the Golgi apparatus calcium stores that are implicated in HHD.5 The lowered endoplasmic reticulum calcium stores in Darier-White disease are associated with more pronounced dyskeratosis, which is seen histologically as corps ronds. Suprabasal hyperkeratosis also is found in Darier disease. The histopathologic findings of Darier disease and PAD can be identical, but the clinical presentations are distinct, with Darier disease typically manifesting as seborrheic eruptions appearing in adolescence and PAD presenting as small white papules in the anogenital or crural regions.

Grover disease (also referred to as transient acantholytic dermatosis) has an idiopathic pathophysiology. It clinically manifests with eruptions of erythematous, pruritic, truncal papules on the chest or back. Grover disease has a predilection for White men older than 50 years, and symptoms may be exacerbated in heat and diaphoretic conditions. Histologically, Grover disease may show acantholytic features seen in pemphigus vulgaris, HHD, and Darier disease; the pattern can only follow a specific disease or consist of a combination of all disease features (Figure 4). The acantholytic pattern of Grover disease was found to be similar to pemphigus vulgaris, Darier disease, pemphigus foliaceus, and HHD 47%, 18%, 9%, and 8% of the time, respectively. In 9% of cases, Grover disease will exhibit a mixed histopathology in which its acantholytic pattern will consist of a combination of features seen in the pemphigus family of diseases.6 Biopsy results showing mixed histologic patterns or a combination of different acantholytic features are suggestive of Grover disease over PAD. Moreover, the clinical distribution helps to differentiate Grover disease from PAD.

Because the histologic characteristics of these diseases overlap, certain nuances in clinical correlations and histology allow for distinction. In our patient, the diagnosis was most consistent with PAD based on the clinical manifestation of the disease and the biopsy results. Considering solely the clinical location of the lesions, Grover disease was a less likely diagnosis because our patient’s lesions were observed in the perianal region, not the truncal region as typically seen in Grover disease. Taking into account the DIF assay results in our patient, the pemphigus family of diseases also moved lower on the differential diagnosis. Finally, because the biopsy showed more dyskeratosis than would be present in HHD and also was inconsistent with the location and onset that would be expected to be seen in Darier disease, PAD was the most probable diagnosis. Interestingly, studies have shown mosaic mutations in ATP2A2 and ATP2C1 as possible causes of PAD, suggesting that this may be an allelic variant of Darier disease and HHD.7-9 No genetic testing was performed in our patient.

The Diagnosis: Papular Acantholytic Dyskeratosis

The shave biopsy revealed suprabasal clefts associated with acantholytic and dyskeratotic cells as well as overlying hyperkeratosis. Direct immunofluorescence (DIF) was negative. Based on the combined clinical and histological findings, the patient was diagnosed with papular acantholytic dyskeratosis (PAD), a rare disease that clinically presents as small whitishgreyish papules with the potential to coalesce into larger plaques.^1,2 The condition predominantly manifests without symptoms, though pruritus and burning have been reported in affected sites. Most cases of PAD have been reported in older adults rather than in children or adolescents; it is more prevalent in women than in men. Lesions generally are localized to the penis, vulva, scrotum, inguinal folds, and perianal region.³ More specific terms have been used to describe this presentation such as papular acantholytic dyskeratosis of the anogenital region and papular acantholytic dyskeratosis of the genital-crural region. Histologic findings of PAD include epidermal acantholysis and dyskeratosis with hyperkeratosis and parakeratosis (quiz image).

The histologic differential diagnosis of PAD is broad due to its overlapping features with other diseases such as pemphigus vulgaris, Hailey-Hailey disease (HHD), Darier disease, and Grover disease. The acantholytic pathophysiology of these conditions involves dysfunction in cell adhesion markers. The correct diagnosis can be made by considering both the clinical location of involvement and histopathologic clues.

Pemphigus is a family of disorders involving mucocutaneous blistering of an autoimmune nature (Figure 1). Pemphigus vulgaris is the most prevalent variant of the pemphigus family, with symptomatically painful involvement of mucosal and cutaneous tissue. Autoantibodies to desmoglein 3 alone or both desmoglein 1 and 3 are present. Pemphigus vulgaris displays positive DIF findings with intercellular IgG and C3.

Hailey-Hailey disease (also known as benign familial pemphigus) is an autosomal-dominant disease that shares the acantholytic feature that is common in this class of diseases and caused by a defect in cell-cell adhesion as well as a loss of function in the ATPase secretory pathway Ca2+ transporting 1 gene, ATP2C1. Blistering lesions typically appear in the neck, axillary, inguinal, or genital regions, and they can develop into crusted, exudate-filled lesions. No autoimmunity has been associated with this disease, unlike other diseases in the pemphigus family, and mutations in the ATP2C1 gene have been linked with dysregulation of cell-cell adhesion, particularly in cadherins and calcium-dependent cell adhesion processes. Histologically, HHD will show diffuse keratinocyte acantholysis with suprabasal clefting (Figure 2).⁴ Dyskeratosis is mild, if present at all, and dyskeratotic keratinocytes show a well-defined nucleus with cytoplasmic preservation. In contrast to HHD, PAD typically shows more dyskeratosis.

Darier disease (also known as keratosis follicularis) is an autosomal-dominant condition that normally presents with seborrheic eruptions in intertriginous areas, usually with onset during adolescence. Darier disease is caused by a loss-of-function mutation in the ATP2A2 gene found on chromosome 12q23-24.1 that encodes for the sarco(endo)plasmic reticulum calcium ATPase2 (SERCA2) enzymes involved in calcium-dependent transport of the endoplasmic reticulum within the cell. Due to calcium dysregulation, desmosomes are unable to carry out their function in cell-cell adhesion, resulting in keratinocyte acantholysis. Histopathology of Darier disease is identical to HHD but displays more dyskeratosis than HHD (Figure 3), possibly due to the endoplasmic reticulum calcium stores that are affected in Darier disease compared to the Golgi apparatus calcium stores that are implicated in HHD.5 The lowered endoplasmic reticulum calcium stores in Darier-White disease are associated with more pronounced dyskeratosis, which is seen histologically as corps ronds. Suprabasal hyperkeratosis also is found in Darier disease. The histopathologic findings of Darier disease and PAD can be identical, but the clinical presentations are distinct, with Darier disease typically manifesting as seborrheic eruptions appearing in adolescence and PAD presenting as small white papules in the anogenital or crural regions.

Grover disease (also referred to as transient acantholytic dermatosis) has an idiopathic pathophysiology. It clinically manifests with eruptions of erythematous, pruritic, truncal papules on the chest or back. Grover disease has a predilection for White men older than 50 years, and symptoms may be exacerbated in heat and diaphoretic conditions. Histologically, Grover disease may show acantholytic features seen in pemphigus vulgaris, HHD, and Darier disease; the pattern can only follow a specific disease or consist of a combination of all disease features (Figure 4). The acantholytic pattern of Grover disease was found to be similar to pemphigus vulgaris, Darier disease, pemphigus foliaceus, and HHD 47%, 18%, 9%, and 8% of the time, respectively. In 9% of cases, Grover disease will exhibit a mixed histopathology in which its acantholytic pattern will consist of a combination of features seen in the pemphigus family of diseases.6 Biopsy results showing mixed histologic patterns or a combination of different acantholytic features are suggestive of Grover disease over PAD. Moreover, the clinical distribution helps to differentiate Grover disease from PAD.

Because the histologic characteristics of these diseases overlap, certain nuances in clinical correlations and histology allow for distinction. In our patient, the diagnosis was most consistent with PAD based on the clinical manifestation of the disease and the biopsy results. Considering solely the clinical location of the lesions, Grover disease was a less likely diagnosis because our patient’s lesions were observed in the perianal region, not the truncal region as typically seen in Grover disease. Taking into account the DIF assay results in our patient, the pemphigus family of diseases also moved lower on the differential diagnosis. Finally, because the biopsy showed more dyskeratosis than would be present in HHD and also was inconsistent with the location and onset that would be expected to be seen in Darier disease, PAD was the most probable diagnosis. Interestingly, studies have shown mosaic mutations in ATP2A2 and ATP2C1 as possible causes of PAD, suggesting that this may be an allelic variant of Darier disease and HHD.7-9 No genetic testing was performed in our patient.

Educational organizations across several specialties, including internal medicine and obstetrics and gynecology, have formal surveys¹; however, the field of dermatology has been without one. This study aimed to establish a formal survey for dermatology program directors (PDs) and clinician-educators. Because the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Dermatology surveys do not capture all metrics relevant to dermatology residency educators, an annual survey for our specialty may be helpful to compare dermatology-specific data among programs. Responses could provide context and perspective to faculty and residents who respond to the ACGME annual survey, as our Association of Professors of Dermatology (APD) survey asks more in-depth questions, such as how often didactics occur and who leads them. Resident commute time and faculty demographics and training also are covered. Current ad hoc surveys disseminated through listserves of various medical associations contain overlapping questions and reflect relatively low response rates; dermatology PDs may benefit from a survey with a high response rate to which they can contribute future questions and topics that reflect recent trends and current needs in graduate medical education. As future surveys are administered, the results can be captured in a centralized database accessible by dermatology PDs.

Methods

A survey of PDs from 141 ACGME-accredited dermatology residency programs was conducted by the Residency Program Director Steering Committee of the APD from November 2022 to January 2023 using a prevalidated questionnaire. Personalized survey links were created and sent individually to each PD’s email listed in the ACGME accreditation data system. All survey responses were captured anonymously, with a number assigned to keep de-identified responses separate and organized. The survey consisted of 137 survey questions addressing topics that included program characteristics, PD demographics, the impact of the COVID-19 pandemic on clinical rotation and educational conferences, available resident resources, quality improvement, clinical and didactic instruction, research content, diversity and inclusion, wellness, professionalism, evaluation systems, and graduate outcomes.

Data were collected using Qualtrics survey tools. After removing duplicate and incomplete surveys, data were analyzed using Qualtrics reports and Microsoft Excel for data plotting, averages, and range calculations.

Results

One hundred forty-one personalized survey links were created and sent individually to each program’s filed email obtained from the APD listserv. Fifty-three responses were recorded after removing duplicate or incomplete surveys (38% [53/141] response rate). As of May 2023, there were 144 ACGME-accredited dermatology residency programs due to 3 newly accredited programs in 2022-2023 academic year, which were not included in our survey population.

Program Characteristics—Forty-four respondents (83%) were from a university-based program. Fifty respondents (94%) were from programs that were ACGME accredited prior to 2020, while 3 programs (6%) were American Osteopathic Association accredited prior to singular accreditation. Seventy-one percent (38/53) of respondents had 1 or more associate PDs.

PD Demographics—Eighty-seven percent (45/52) of PDs who responded to the survey graduated from a US allopathic medical school (MD), 10% (5/52) graduated from a US osteopathic medical school (DO), and 4% (2/52) graduated from an international medical school. Seventy-four percent (35/47) of respondents were White, 17% (8/47) were Asian, and 2% (1/47) were Black or African American; this data was not provided for 4 respondents. Forty-eight percent (23/48) of PDs identified as cisgender man, 48% (23/48) identified as cisgender woman, and 4% (2/48) preferred not to answer. Eighty-one percent (38/47) of PDs identified as heterosexual or straight, 15% (7/47) identified as gay or lesbian, and 4% (2/47) preferred not to answer.

Impact of COVID-19 Pandemic on Residency Training—Due to the COVID-19 pandemic, 88% (45/51) of respondents incorporated telemedicine into the resident clinical rotation schedule. Moving forward, 75% (38/51) of respondents indicated that their programs plan to continue to incorporate telemedicine into the rotation schedule. Based on 50 responses, the average of educational conferences that became virtual at the start of the COVID-19 pandemic was 87%; based on 46 responses, the percentage of educational conferences that will remain virtual moving forward is 46%, while 90% (46/51) of respondents indicated that their programs plan to use virtual conferences in some capacity moving forward. Seventy-three percent (37/51) of respondents indicated that they plan to use virtual interviews as part of residency recruitment moving forward.

Available Resources—Twenty-four percent (11/46) of respondents indicated that residents in their program do not get protected time or time off for CORE examinations. Seventy-five percent (33/44) of PDs said their program provides funding for residents to participate in board review courses. The chief residents at 63% (31/49) of programs receive additional compensation, and 69% (34/49) provide additional administrative time to chief residents. Seventy-one percent (24/34) of PDs reported their programs have scribes for attendings, and 12% (4/34) have scribes for residents. Support staff help residents with callbacks and in-basket messages according to 76% (35/46) of respondents. The majority (98% [45/46]) of PDs indicated that residents follow-up on results and messages from patients seen in resident clinics, and 43% (20/46) of programs have residents follow-up with patients seen in faculty clinics. Only 15% (7/46) of PDs responded they have schedules with residents dedicated to handle these tasks. According to respondents, 33% (17/52) have residents who are required to travel more than 25 miles to distant clinical sites. Of them, 35% (6/17) provide accommodations.

Quality Improvement—Seventy-one percent (35/49) of respondents indicated their department has a quality improvement/patient safety team or committee, and 94% (33/35) of these teams include residents. A lecture series on quality improvement and patient safety is offered at 67% (33/49) of the respondents’ programs, while morbidity and mortality conferences are offered in 73% (36/49).

Clinical Instruction—Our survey asked PDs how many months each residency year spends on a certain rotational service. Based on 46 respondents, the average number of months dedicated to medical dermatology is 7, 5, and 6 months for postgraduate year (PGY) 2, PGY3, and PGY4, respectively. The average number of months spent in other subspecialties is provided in the Table. On average, PGY2 residents spend 8 half-days per week seeing patients in clinic, while PGY3 and PGY4 residents see patients for 7 half-days. The median and mean number of patients staffed by a single attending per hour in teaching clinics are 6 and 5.88, respectively. Respondents indicated that residents participate in the following specialty clinics: pediatric dermatology (96% [44/46]), laser/cosmetic (87% [40/44]), high-risk skin cancer (ie, immunosuppressed/transplant patient)(65% [30/44]), pigmented lesion/melanoma (52% [24/44]), connective tissue disease (52% [24/44]), teledermatology (50% [23/44]), free clinic for homeless and/or indigent populations (48% [22/44]), contact dermatitis (43% [20/44]), skin of color (43% [20/44]), oncodermatology (41% [19/44]), and bullous disease (33% [15/44]).

Additionally, in 87% (40/46) of programs, residents participate in a dedicated inpatient consultation service. Most respondents (98% [45/46]) responded that they utilize in-person consultations with a teledermatology supplement. Fifteen percent (7/46) utilize virtual teledermatology (live video-based consultations), and 57% (26/46) utilize asynchronous teledermatology (picture-based consultations). All respondents (n=46) indicated that 0% to 25% of patient encounters involving residents are teledermatology visits. Thirty-three percent (6/18) of programs have a global health special training track, 56% (10/18) have a Specialty Training and Advanced Research/Physician-Scientist Research Training track, 28% (5/18) have a diversity training track, and 50% (9/18) have a clinician educator training track.

Didactic Instruction—Five programs have a full day per week dedicated to didactics, while 36 programs have at least one half-day per week for didactics. On average, didactics in 57% (26/46) of programs are led by faculty alone, while 43% (20/46) are led at least in part by residents or fellows.

Research Content—Fifty percent (23/46) of programs have a specific research requirement for residents beyond general ACGME requirements, and 35% (16/46) require residents to participate in a longitudinal research project over the course of residency. There is a dedicated research coordinator for resident support at 63% (29/46) of programs. Dedicated biostatistics research support is available for resident projects at 42% (19/45) of programs. Additionally, at 42% (19/45) of programs, there is a dedicated faculty member for oversight of resident research.

Diversity, Equity, and Inclusion—Seventy-three percent (29/40) of programs have special diversity, equity, and inclusion programs or meetings specific to residency, 60% (24/40) have residency initiatives, and 55% (22/40) have a residency diversity committee. Eighty-six percent (42/49) of respondents strongly agreed that their current residents represent diverse ethnic and racial backgrounds (ie, >15% are not White). eTable 1 shows PD responses to this statement, which were stratified based on self-identified race. eTable 2 shows PD responses to the statement, “Our current residents represent an inclusion of gender/sexual orientation,” which were stratified based on self-identified gender identity/sexual orientation. Lastly, eTable 3 highlights the percentage of residents with an MD and DO degree, stratified based on PD degree.

Wellness—Forty-eight percent (20/42) of respondents indicated they are under stress and do not always have as much energy as before becoming a PD but do not feel burned out. Thirty-one percent (13/42) indicated they have 1 or more symptoms of burnout, such as emotional exhaustion. Eighty-six percent (36/42) are satisfied with their jobs overall (43% agree and 43% strongly agree [18/42 each]).

Evaluation System—Seventy-five percent (33/44) of programs deliver evaluations of residents by faculty online, 86% (38/44) of programs have PDs discuss evaluations in-person, and 20% (9/44) of programs have faculty evaluators discuss evaluations in-person. Seventy-seven percent (34/44) of programs have formal faculty-resident mentor-mentee programs. Clinical competency committee chair positions are filled by PDs, assistant PDs, or core faculty members 47%, 38%, and 16% of the time, respectively.

Graduation Outcomes of PGY4 Residents—About 28% (55/199) of graduating residents applied to a fellowship position, with the majority (15% [29/55]) matching into Mohs micrographic surgery and dermatologic oncology (MSDO) fellowships. Approximately 5% (9/199) and 4% (7/199) of graduates matched into dermatopathology and pediatric dermatology, respectively. The remaining 5% (10/199) of graduating residents applied to a fellowship but did not match. The majority (45% [91/199]) of residency graduates entered private practice after graduation. Approximately 21% (42/199) of graduating residents chose an academic practice with 17% (33/199), 2% (4/199), and 2% (3/199) of those positions being full-time, part-time, and adjunct, respectively.

Comment

The first annual APD survey is a novel data source and provides opportunities for areas of discussion and investigation. Evaluating the similarities and differences among dermatology residency programs across the United States can strengthen individual programs through collaboration and provide areas of cohesion among programs.

Diversity of PDs—An important area of discussion is diversity and PD demographics. Although DO students make up 1 in 4 US graduating medical students, they are not interviewed or ranked as often as MD students.² Diversity in PD race and ethnicity may be worthy of investigation in future studies, as match rates and recruitment of diverse medical school applicants may be impacted by these demographics.

Continued Use of Telemedicine in Training—Since 2020, the benefits of virtual residency recruitment have been debated among PDs across all medical specialties. Points in favor of virtual interviews include cost savings for programs and especially for applicants, as well as time efficiency, reduced burden of travel, and reduced carbon footprint. A problem posed by virtual interviews is that candidates are unable to fully learn institutional cultures and social environments of the programs.³ Likewise, telehealth was an important means of clinical teaching for residents during the height of the COVID-19 pandemic, with benefits that included cost-effectiveness and reduction of disparities in access to dermatologic care.⁴ Seventy-five percent (38/51) of PDs indicated that their program plans to include telemedicine in resident clinical rotation moving forward.

Resources Available—Our survey showed that resources available for residents, delivery of lectures and program time allocated to didactics, protected academic or study time for residents, and allocation of program time for CORE examinations are highly variable across programs. This could inspire future studies to be done to determine the differences in success of the resident on CORE examinations and in digesting material.

Postgraduate Career Plans and Fellowship Matches—Residents of programs that have a home MSDO fellowship are more likely to successfully match into a MSDO fellowship.⁵ Based on this survey, approximately 28% of graduating residents applied to a fellowship position, with 15%, 5%, and 3% matching into desired MSDO, dermatopathology, and pediatric dermatology fellowships, respectively. Additional studies are needed to determine advantages and disadvantages that lead to residents reaching their career goals.

Limitations—Limitations of this study include a small sample size that may not adequately represent all ACGME-accredited dermatology residency programs and selection bias toward respondents who are more likely to participate in survey-based research.

Conclusion

The APD plans to continue to administer this survey on an annual basis, with updates to the content and questions based on input from PDs. This survey will continue to provide valuable information to drive collaboration among residency programs and optimize the learning experience for residents. Our hope is that the response rate will increase in coming years, allowing us to draw more generalizable conclusions. Nonetheless, the survey data allow individual dermatology residency programs to compare their specific characteristics to other programs.

Educational organizations across several specialties, including internal medicine and obstetrics and gynecology, have formal surveys¹; however, the field of dermatology has been without one. This study aimed to establish a formal survey for dermatology program directors (PDs) and clinician-educators. Because the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Dermatology surveys do not capture all metrics relevant to dermatology residency educators, an annual survey for our specialty may be helpful to compare dermatology-specific data among programs. Responses could provide context and perspective to faculty and residents who respond to the ACGME annual survey, as our Association of Professors of Dermatology (APD) survey asks more in-depth questions, such as how often didactics occur and who leads them. Resident commute time and faculty demographics and training also are covered. Current ad hoc surveys disseminated through listserves of various medical associations contain overlapping questions and reflect relatively low response rates; dermatology PDs may benefit from a survey with a high response rate to which they can contribute future questions and topics that reflect recent trends and current needs in graduate medical education. As future surveys are administered, the results can be captured in a centralized database accessible by dermatology PDs.

Methods

A survey of PDs from 141 ACGME-accredited dermatology residency programs was conducted by the Residency Program Director Steering Committee of the APD from November 2022 to January 2023 using a prevalidated questionnaire. Personalized survey links were created and sent individually to each PD’s email listed in the ACGME accreditation data system. All survey responses were captured anonymously, with a number assigned to keep de-identified responses separate and organized. The survey consisted of 137 survey questions addressing topics that included program characteristics, PD demographics, the impact of the COVID-19 pandemic on clinical rotation and educational conferences, available resident resources, quality improvement, clinical and didactic instruction, research content, diversity and inclusion, wellness, professionalism, evaluation systems, and graduate outcomes.

Data were collected using Qualtrics survey tools. After removing duplicate and incomplete surveys, data were analyzed using Qualtrics reports and Microsoft Excel for data plotting, averages, and range calculations.

Results

One hundred forty-one personalized survey links were created and sent individually to each program’s filed email obtained from the APD listserv. Fifty-three responses were recorded after removing duplicate or incomplete surveys (38% [53/141] response rate). As of May 2023, there were 144 ACGME-accredited dermatology residency programs due to 3 newly accredited programs in 2022-2023 academic year, which were not included in our survey population.

Program Characteristics—Forty-four respondents (83%) were from a university-based program. Fifty respondents (94%) were from programs that were ACGME accredited prior to 2020, while 3 programs (6%) were American Osteopathic Association accredited prior to singular accreditation. Seventy-one percent (38/53) of respondents had 1 or more associate PDs.

PD Demographics—Eighty-seven percent (45/52) of PDs who responded to the survey graduated from a US allopathic medical school (MD), 10% (5/52) graduated from a US osteopathic medical school (DO), and 4% (2/52) graduated from an international medical school. Seventy-four percent (35/47) of respondents were White, 17% (8/47) were Asian, and 2% (1/47) were Black or African American; this data was not provided for 4 respondents. Forty-eight percent (23/48) of PDs identified as cisgender man, 48% (23/48) identified as cisgender woman, and 4% (2/48) preferred not to answer. Eighty-one percent (38/47) of PDs identified as heterosexual or straight, 15% (7/47) identified as gay or lesbian, and 4% (2/47) preferred not to answer.

Impact of COVID-19 Pandemic on Residency Training—Due to the COVID-19 pandemic, 88% (45/51) of respondents incorporated telemedicine into the resident clinical rotation schedule. Moving forward, 75% (38/51) of respondents indicated that their programs plan to continue to incorporate telemedicine into the rotation schedule. Based on 50 responses, the average of educational conferences that became virtual at the start of the COVID-19 pandemic was 87%; based on 46 responses, the percentage of educational conferences that will remain virtual moving forward is 46%, while 90% (46/51) of respondents indicated that their programs plan to use virtual conferences in some capacity moving forward. Seventy-three percent (37/51) of respondents indicated that they plan to use virtual interviews as part of residency recruitment moving forward.

Available Resources—Twenty-four percent (11/46) of respondents indicated that residents in their program do not get protected time or time off for CORE examinations. Seventy-five percent (33/44) of PDs said their program provides funding for residents to participate in board review courses. The chief residents at 63% (31/49) of programs receive additional compensation, and 69% (34/49) provide additional administrative time to chief residents. Seventy-one percent (24/34) of PDs reported their programs have scribes for attendings, and 12% (4/34) have scribes for residents. Support staff help residents with callbacks and in-basket messages according to 76% (35/46) of respondents. The majority (98% [45/46]) of PDs indicated that residents follow-up on results and messages from patients seen in resident clinics, and 43% (20/46) of programs have residents follow-up with patients seen in faculty clinics. Only 15% (7/46) of PDs responded they have schedules with residents dedicated to handle these tasks. According to respondents, 33% (17/52) have residents who are required to travel more than 25 miles to distant clinical sites. Of them, 35% (6/17) provide accommodations.

Quality Improvement—Seventy-one percent (35/49) of respondents indicated their department has a quality improvement/patient safety team or committee, and 94% (33/35) of these teams include residents. A lecture series on quality improvement and patient safety is offered at 67% (33/49) of the respondents’ programs, while morbidity and mortality conferences are offered in 73% (36/49).

Clinical Instruction—Our survey asked PDs how many months each residency year spends on a certain rotational service. Based on 46 respondents, the average number of months dedicated to medical dermatology is 7, 5, and 6 months for postgraduate year (PGY) 2, PGY3, and PGY4, respectively. The average number of months spent in other subspecialties is provided in the Table. On average, PGY2 residents spend 8 half-days per week seeing patients in clinic, while PGY3 and PGY4 residents see patients for 7 half-days. The median and mean number of patients staffed by a single attending per hour in teaching clinics are 6 and 5.88, respectively. Respondents indicated that residents participate in the following specialty clinics: pediatric dermatology (96% [44/46]), laser/cosmetic (87% [40/44]), high-risk skin cancer (ie, immunosuppressed/transplant patient)(65% [30/44]), pigmented lesion/melanoma (52% [24/44]), connective tissue disease (52% [24/44]), teledermatology (50% [23/44]), free clinic for homeless and/or indigent populations (48% [22/44]), contact dermatitis (43% [20/44]), skin of color (43% [20/44]), oncodermatology (41% [19/44]), and bullous disease (33% [15/44]).

Additionally, in 87% (40/46) of programs, residents participate in a dedicated inpatient consultation service. Most respondents (98% [45/46]) responded that they utilize in-person consultations with a teledermatology supplement. Fifteen percent (7/46) utilize virtual teledermatology (live video-based consultations), and 57% (26/46) utilize asynchronous teledermatology (picture-based consultations). All respondents (n=46) indicated that 0% to 25% of patient encounters involving residents are teledermatology visits. Thirty-three percent (6/18) of programs have a global health special training track, 56% (10/18) have a Specialty Training and Advanced Research/Physician-Scientist Research Training track, 28% (5/18) have a diversity training track, and 50% (9/18) have a clinician educator training track.

Didactic Instruction—Five programs have a full day per week dedicated to didactics, while 36 programs have at least one half-day per week for didactics. On average, didactics in 57% (26/46) of programs are led by faculty alone, while 43% (20/46) are led at least in part by residents or fellows.

Research Content—Fifty percent (23/46) of programs have a specific research requirement for residents beyond general ACGME requirements, and 35% (16/46) require residents to participate in a longitudinal research project over the course of residency. There is a dedicated research coordinator for resident support at 63% (29/46) of programs. Dedicated biostatistics research support is available for resident projects at 42% (19/45) of programs. Additionally, at 42% (19/45) of programs, there is a dedicated faculty member for oversight of resident research.

Diversity, Equity, and Inclusion—Seventy-three percent (29/40) of programs have special diversity, equity, and inclusion programs or meetings specific to residency, 60% (24/40) have residency initiatives, and 55% (22/40) have a residency diversity committee. Eighty-six percent (42/49) of respondents strongly agreed that their current residents represent diverse ethnic and racial backgrounds (ie, >15% are not White). eTable 1 shows PD responses to this statement, which were stratified based on self-identified race. eTable 2 shows PD responses to the statement, “Our current residents represent an inclusion of gender/sexual orientation,” which were stratified based on self-identified gender identity/sexual orientation. Lastly, eTable 3 highlights the percentage of residents with an MD and DO degree, stratified based on PD degree.

Wellness—Forty-eight percent (20/42) of respondents indicated they are under stress and do not always have as much energy as before becoming a PD but do not feel burned out. Thirty-one percent (13/42) indicated they have 1 or more symptoms of burnout, such as emotional exhaustion. Eighty-six percent (36/42) are satisfied with their jobs overall (43% agree and 43% strongly agree [18/42 each]).

Evaluation System—Seventy-five percent (33/44) of programs deliver evaluations of residents by faculty online, 86% (38/44) of programs have PDs discuss evaluations in-person, and 20% (9/44) of programs have faculty evaluators discuss evaluations in-person. Seventy-seven percent (34/44) of programs have formal faculty-resident mentor-mentee programs. Clinical competency committee chair positions are filled by PDs, assistant PDs, or core faculty members 47%, 38%, and 16% of the time, respectively.

Graduation Outcomes of PGY4 Residents—About 28% (55/199) of graduating residents applied to a fellowship position, with the majority (15% [29/55]) matching into Mohs micrographic surgery and dermatologic oncology (MSDO) fellowships. Approximately 5% (9/199) and 4% (7/199) of graduates matched into dermatopathology and pediatric dermatology, respectively. The remaining 5% (10/199) of graduating residents applied to a fellowship but did not match. The majority (45% [91/199]) of residency graduates entered private practice after graduation. Approximately 21% (42/199) of graduating residents chose an academic practice with 17% (33/199), 2% (4/199), and 2% (3/199) of those positions being full-time, part-time, and adjunct, respectively.

Comment

The first annual APD survey is a novel data source and provides opportunities for areas of discussion and investigation. Evaluating the similarities and differences among dermatology residency programs across the United States can strengthen individual programs through collaboration and provide areas of cohesion among programs.

Diversity of PDs—An important area of discussion is diversity and PD demographics. Although DO students make up 1 in 4 US graduating medical students, they are not interviewed or ranked as often as MD students.² Diversity in PD race and ethnicity may be worthy of investigation in future studies, as match rates and recruitment of diverse medical school applicants may be impacted by these demographics.

Continued Use of Telemedicine in Training—Since 2020, the benefits of virtual residency recruitment have been debated among PDs across all medical specialties. Points in favor of virtual interviews include cost savings for programs and especially for applicants, as well as time efficiency, reduced burden of travel, and reduced carbon footprint. A problem posed by virtual interviews is that candidates are unable to fully learn institutional cultures and social environments of the programs.³ Likewise, telehealth was an important means of clinical teaching for residents during the height of the COVID-19 pandemic, with benefits that included cost-effectiveness and reduction of disparities in access to dermatologic care.⁴ Seventy-five percent (38/51) of PDs indicated that their program plans to include telemedicine in resident clinical rotation moving forward.

Resources Available—Our survey showed that resources available for residents, delivery of lectures and program time allocated to didactics, protected academic or study time for residents, and allocation of program time for CORE examinations are highly variable across programs. This could inspire future studies to be done to determine the differences in success of the resident on CORE examinations and in digesting material.

Postgraduate Career Plans and Fellowship Matches—Residents of programs that have a home MSDO fellowship are more likely to successfully match into a MSDO fellowship.⁵ Based on this survey, approximately 28% of graduating residents applied to a fellowship position, with 15%, 5%, and 3% matching into desired MSDO, dermatopathology, and pediatric dermatology fellowships, respectively. Additional studies are needed to determine advantages and disadvantages that lead to residents reaching their career goals.

Limitations—Limitations of this study include a small sample size that may not adequately represent all ACGME-accredited dermatology residency programs and selection bias toward respondents who are more likely to participate in survey-based research.

Conclusion

The APD plans to continue to administer this survey on an annual basis, with updates to the content and questions based on input from PDs. This survey will continue to provide valuable information to drive collaboration among residency programs and optimize the learning experience for residents. Our hope is that the response rate will increase in coming years, allowing us to draw more generalizable conclusions. Nonetheless, the survey data allow individual dermatology residency programs to compare their specific characteristics to other programs.

Educational organizations across several specialties, including internal medicine and obstetrics and gynecology, have formal surveys¹; however, the field of dermatology has been without one. This study aimed to establish a formal survey for dermatology program directors (PDs) and clinician-educators. Because the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Dermatology surveys do not capture all metrics relevant to dermatology residency educators, an annual survey for our specialty may be helpful to compare dermatology-specific data among programs. Responses could provide context and perspective to faculty and residents who respond to the ACGME annual survey, as our Association of Professors of Dermatology (APD) survey asks more in-depth questions, such as how often didactics occur and who leads them. Resident commute time and faculty demographics and training also are covered. Current ad hoc surveys disseminated through listserves of various medical associations contain overlapping questions and reflect relatively low response rates; dermatology PDs may benefit from a survey with a high response rate to which they can contribute future questions and topics that reflect recent trends and current needs in graduate medical education. As future surveys are administered, the results can be captured in a centralized database accessible by dermatology PDs.

Methods

A survey of PDs from 141 ACGME-accredited dermatology residency programs was conducted by the Residency Program Director Steering Committee of the APD from November 2022 to January 2023 using a prevalidated questionnaire. Personalized survey links were created and sent individually to each PD’s email listed in the ACGME accreditation data system. All survey responses were captured anonymously, with a number assigned to keep de-identified responses separate and organized. The survey consisted of 137 survey questions addressing topics that included program characteristics, PD demographics, the impact of the COVID-19 pandemic on clinical rotation and educational conferences, available resident resources, quality improvement, clinical and didactic instruction, research content, diversity and inclusion, wellness, professionalism, evaluation systems, and graduate outcomes.

Data were collected using Qualtrics survey tools. After removing duplicate and incomplete surveys, data were analyzed using Qualtrics reports and Microsoft Excel for data plotting, averages, and range calculations.

Results

One hundred forty-one personalized survey links were created and sent individually to each program’s filed email obtained from the APD listserv. Fifty-three responses were recorded after removing duplicate or incomplete surveys (38% [53/141] response rate). As of May 2023, there were 144 ACGME-accredited dermatology residency programs due to 3 newly accredited programs in 2022-2023 academic year, which were not included in our survey population.

Program Characteristics—Forty-four respondents (83%) were from a university-based program. Fifty respondents (94%) were from programs that were ACGME accredited prior to 2020, while 3 programs (6%) were American Osteopathic Association accredited prior to singular accreditation. Seventy-one percent (38/53) of respondents had 1 or more associate PDs.

PD Demographics—Eighty-seven percent (45/52) of PDs who responded to the survey graduated from a US allopathic medical school (MD), 10% (5/52) graduated from a US osteopathic medical school (DO), and 4% (2/52) graduated from an international medical school. Seventy-four percent (35/47) of respondents were White, 17% (8/47) were Asian, and 2% (1/47) were Black or African American; this data was not provided for 4 respondents. Forty-eight percent (23/48) of PDs identified as cisgender man, 48% (23/48) identified as cisgender woman, and 4% (2/48) preferred not to answer. Eighty-one percent (38/47) of PDs identified as heterosexual or straight, 15% (7/47) identified as gay or lesbian, and 4% (2/47) preferred not to answer.

Impact of COVID-19 Pandemic on Residency Training—Due to the COVID-19 pandemic, 88% (45/51) of respondents incorporated telemedicine into the resident clinical rotation schedule. Moving forward, 75% (38/51) of respondents indicated that their programs plan to continue to incorporate telemedicine into the rotation schedule. Based on 50 responses, the average of educational conferences that became virtual at the start of the COVID-19 pandemic was 87%; based on 46 responses, the percentage of educational conferences that will remain virtual moving forward is 46%, while 90% (46/51) of respondents indicated that their programs plan to use virtual conferences in some capacity moving forward. Seventy-three percent (37/51) of respondents indicated that they plan to use virtual interviews as part of residency recruitment moving forward.

Available Resources—Twenty-four percent (11/46) of respondents indicated that residents in their program do not get protected time or time off for CORE examinations. Seventy-five percent (33/44) of PDs said their program provides funding for residents to participate in board review courses. The chief residents at 63% (31/49) of programs receive additional compensation, and 69% (34/49) provide additional administrative time to chief residents. Seventy-one percent (24/34) of PDs reported their programs have scribes for attendings, and 12% (4/34) have scribes for residents. Support staff help residents with callbacks and in-basket messages according to 76% (35/46) of respondents. The majority (98% [45/46]) of PDs indicated that residents follow-up on results and messages from patients seen in resident clinics, and 43% (20/46) of programs have residents follow-up with patients seen in faculty clinics. Only 15% (7/46) of PDs responded they have schedules with residents dedicated to handle these tasks. According to respondents, 33% (17/52) have residents who are required to travel more than 25 miles to distant clinical sites. Of them, 35% (6/17) provide accommodations.

Quality Improvement—Seventy-one percent (35/49) of respondents indicated their department has a quality improvement/patient safety team or committee, and 94% (33/35) of these teams include residents. A lecture series on quality improvement and patient safety is offered at 67% (33/49) of the respondents’ programs, while morbidity and mortality conferences are offered in 73% (36/49).

Clinical Instruction—Our survey asked PDs how many months each residency year spends on a certain rotational service. Based on 46 respondents, the average number of months dedicated to medical dermatology is 7, 5, and 6 months for postgraduate year (PGY) 2, PGY3, and PGY4, respectively. The average number of months spent in other subspecialties is provided in the Table. On average, PGY2 residents spend 8 half-days per week seeing patients in clinic, while PGY3 and PGY4 residents see patients for 7 half-days. The median and mean number of patients staffed by a single attending per hour in teaching clinics are 6 and 5.88, respectively. Respondents indicated that residents participate in the following specialty clinics: pediatric dermatology (96% [44/46]), laser/cosmetic (87% [40/44]), high-risk skin cancer (ie, immunosuppressed/transplant patient)(65% [30/44]), pigmented lesion/melanoma (52% [24/44]), connective tissue disease (52% [24/44]), teledermatology (50% [23/44]), free clinic for homeless and/or indigent populations (48% [22/44]), contact dermatitis (43% [20/44]), skin of color (43% [20/44]), oncodermatology (41% [19/44]), and bullous disease (33% [15/44]).

Additionally, in 87% (40/46) of programs, residents participate in a dedicated inpatient consultation service. Most respondents (98% [45/46]) responded that they utilize in-person consultations with a teledermatology supplement. Fifteen percent (7/46) utilize virtual teledermatology (live video-based consultations), and 57% (26/46) utilize asynchronous teledermatology (picture-based consultations). All respondents (n=46) indicated that 0% to 25% of patient encounters involving residents are teledermatology visits. Thirty-three percent (6/18) of programs have a global health special training track, 56% (10/18) have a Specialty Training and Advanced Research/Physician-Scientist Research Training track, 28% (5/18) have a diversity training track, and 50% (9/18) have a clinician educator training track.

Didactic Instruction—Five programs have a full day per week dedicated to didactics, while 36 programs have at least one half-day per week for didactics. On average, didactics in 57% (26/46) of programs are led by faculty alone, while 43% (20/46) are led at least in part by residents or fellows.

Research Content—Fifty percent (23/46) of programs have a specific research requirement for residents beyond general ACGME requirements, and 35% (16/46) require residents to participate in a longitudinal research project over the course of residency. There is a dedicated research coordinator for resident support at 63% (29/46) of programs. Dedicated biostatistics research support is available for resident projects at 42% (19/45) of programs. Additionally, at 42% (19/45) of programs, there is a dedicated faculty member for oversight of resident research.

Diversity, Equity, and Inclusion—Seventy-three percent (29/40) of programs have special diversity, equity, and inclusion programs or meetings specific to residency, 60% (24/40) have residency initiatives, and 55% (22/40) have a residency diversity committee. Eighty-six percent (42/49) of respondents strongly agreed that their current residents represent diverse ethnic and racial backgrounds (ie, >15% are not White). eTable 1 shows PD responses to this statement, which were stratified based on self-identified race. eTable 2 shows PD responses to the statement, “Our current residents represent an inclusion of gender/sexual orientation,” which were stratified based on self-identified gender identity/sexual orientation. Lastly, eTable 3 highlights the percentage of residents with an MD and DO degree, stratified based on PD degree.

Wellness—Forty-eight percent (20/42) of respondents indicated they are under stress and do not always have as much energy as before becoming a PD but do not feel burned out. Thirty-one percent (13/42) indicated they have 1 or more symptoms of burnout, such as emotional exhaustion. Eighty-six percent (36/42) are satisfied with their jobs overall (43% agree and 43% strongly agree [18/42 each]).

Evaluation System—Seventy-five percent (33/44) of programs deliver evaluations of residents by faculty online, 86% (38/44) of programs have PDs discuss evaluations in-person, and 20% (9/44) of programs have faculty evaluators discuss evaluations in-person. Seventy-seven percent (34/44) of programs have formal faculty-resident mentor-mentee programs. Clinical competency committee chair positions are filled by PDs, assistant PDs, or core faculty members 47%, 38%, and 16% of the time, respectively.

Graduation Outcomes of PGY4 Residents—About 28% (55/199) of graduating residents applied to a fellowship position, with the majority (15% [29/55]) matching into Mohs micrographic surgery and dermatologic oncology (MSDO) fellowships. Approximately 5% (9/199) and 4% (7/199) of graduates matched into dermatopathology and pediatric dermatology, respectively. The remaining 5% (10/199) of graduating residents applied to a fellowship but did not match. The majority (45% [91/199]) of residency graduates entered private practice after graduation. Approximately 21% (42/199) of graduating residents chose an academic practice with 17% (33/199), 2% (4/199), and 2% (3/199) of those positions being full-time, part-time, and adjunct, respectively.

Comment

The first annual APD survey is a novel data source and provides opportunities for areas of discussion and investigation. Evaluating the similarities and differences among dermatology residency programs across the United States can strengthen individual programs through collaboration and provide areas of cohesion among programs.

Diversity of PDs—An important area of discussion is diversity and PD demographics. Although DO students make up 1 in 4 US graduating medical students, they are not interviewed or ranked as often as MD students.² Diversity in PD race and ethnicity may be worthy of investigation in future studies, as match rates and recruitment of diverse medical school applicants may be impacted by these demographics.

Continued Use of Telemedicine in Training—Since 2020, the benefits of virtual residency recruitment have been debated among PDs across all medical specialties. Points in favor of virtual interviews include cost savings for programs and especially for applicants, as well as time efficiency, reduced burden of travel, and reduced carbon footprint. A problem posed by virtual interviews is that candidates are unable to fully learn institutional cultures and social environments of the programs.³ Likewise, telehealth was an important means of clinical teaching for residents during the height of the COVID-19 pandemic, with benefits that included cost-effectiveness and reduction of disparities in access to dermatologic care.⁴ Seventy-five percent (38/51) of PDs indicated that their program plans to include telemedicine in resident clinical rotation moving forward.

Resources Available—Our survey showed that resources available for residents, delivery of lectures and program time allocated to didactics, protected academic or study time for residents, and allocation of program time for CORE examinations are highly variable across programs. This could inspire future studies to be done to determine the differences in success of the resident on CORE examinations and in digesting material.

Postgraduate Career Plans and Fellowship Matches—Residents of programs that have a home MSDO fellowship are more likely to successfully match into a MSDO fellowship.⁵ Based on this survey, approximately 28% of graduating residents applied to a fellowship position, with 15%, 5%, and 3% matching into desired MSDO, dermatopathology, and pediatric dermatology fellowships, respectively. Additional studies are needed to determine advantages and disadvantages that lead to residents reaching their career goals.

Limitations—Limitations of this study include a small sample size that may not adequately represent all ACGME-accredited dermatology residency programs and selection bias toward respondents who are more likely to participate in survey-based research.

Conclusion

The APD plans to continue to administer this survey on an annual basis, with updates to the content and questions based on input from PDs. This survey will continue to provide valuable information to drive collaboration among residency programs and optimize the learning experience for residents. Our hope is that the response rate will increase in coming years, allowing us to draw more generalizable conclusions. Nonetheless, the survey data allow individual dermatology residency programs to compare their specific characteristics to other programs.

Over the past decade, a revolution in the treatment of non–small cell lung cancer (NSCLC) has been sparked by the ongoing discovery of targetable oncogenic driver mutations. Because of the growing number of targeted therapies, comprehensive biomarker testing is essential in this patient population to determine the best individualized treatment.  

Dr Thomas Stinchcombe, of Duke Cancer Institute in Durham, North Carolina, discusses the latest standards for identifying the pathology of NSCLC patients as well as the accepted sequence of treatments informed by the presence or absence of mutations. He also reports on new immunotherapy research for this patient population.  

Molecular testing of tumor tissue is the standard of care for genotyping, but gathering and processing the results takes time. Dr Stinchcombe points out that liquid biopsies complement tissue testing by using a patient's blood to identify circulating tumor DNA (ctDNA) in the plasma, helping to determine pathologic diagnosis more quickly. 

--

Thomas E. Stinchcombe, MD, Professor, Department of Medicine, Duke Cancer Institute, Durham, North Carolina 

Thomas E. Stinchcombe, MD, has disclosed the following relevant financial relationships: 

Consulting or Advisory Role: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences 

Member of the data and safety monitoring board for: GlaxoSmithKline; Genentech/Roche 

Received research grant from: AstraZeneca; Seagen; Mirati Therapeutics; Genentech/Roche 

Received income in an amount equal to or greater than $250 from: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences; GlaxoSmithKline 

Over the past decade, a revolution in the treatment of non–small cell lung cancer (NSCLC) has been sparked by the ongoing discovery of targetable oncogenic driver mutations. Because of the growing number of targeted therapies, comprehensive biomarker testing is essential in this patient population to determine the best individualized treatment.  

Dr Thomas Stinchcombe, of Duke Cancer Institute in Durham, North Carolina, discusses the latest standards for identifying the pathology of NSCLC patients as well as the accepted sequence of treatments informed by the presence or absence of mutations. He also reports on new immunotherapy research for this patient population.  

Molecular testing of tumor tissue is the standard of care for genotyping, but gathering and processing the results takes time. Dr Stinchcombe points out that liquid biopsies complement tissue testing by using a patient's blood to identify circulating tumor DNA (ctDNA) in the plasma, helping to determine pathologic diagnosis more quickly. 

--

Thomas E. Stinchcombe, MD, Professor, Department of Medicine, Duke Cancer Institute, Durham, North Carolina 

Thomas E. Stinchcombe, MD, has disclosed the following relevant financial relationships: 

Consulting or Advisory Role: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences 

Member of the data and safety monitoring board for: GlaxoSmithKline; Genentech/Roche 

Received research grant from: AstraZeneca; Seagen; Mirati Therapeutics; Genentech/Roche 

Received income in an amount equal to or greater than $250 from: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences; GlaxoSmithKline 

Over the past decade, a revolution in the treatment of non–small cell lung cancer (NSCLC) has been sparked by the ongoing discovery of targetable oncogenic driver mutations. Because of the growing number of targeted therapies, comprehensive biomarker testing is essential in this patient population to determine the best individualized treatment.  

Dr Thomas Stinchcombe, of Duke Cancer Institute in Durham, North Carolina, discusses the latest standards for identifying the pathology of NSCLC patients as well as the accepted sequence of treatments informed by the presence or absence of mutations. He also reports on new immunotherapy research for this patient population.  

Molecular testing of tumor tissue is the standard of care for genotyping, but gathering and processing the results takes time. Dr Stinchcombe points out that liquid biopsies complement tissue testing by using a patient's blood to identify circulating tumor DNA (ctDNA) in the plasma, helping to determine pathologic diagnosis more quickly. 

--

Thomas E. Stinchcombe, MD, Professor, Department of Medicine, Duke Cancer Institute, Durham, North Carolina 

Thomas E. Stinchcombe, MD, has disclosed the following relevant financial relationships: 

Consulting or Advisory Role: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences 

Member of the data and safety monitoring board for: GlaxoSmithKline; Genentech/Roche 

Received research grant from: AstraZeneca; Seagen; Mirati Therapeutics; Genentech/Roche 

Received income in an amount equal to or greater than $250 from: Janssen Oncology; Genentech/Roche; Daiichi Sankyo/Astra Zeneca; Takeda; Eisai/H3 Biomedicine; G1 Therapeutics; Spectrum Pharmaceuticals; Gilead Sciences; AstraZeneca; Coherus BioSciences; GlaxoSmithKline 

To the Editor:

COVID-19 infection has resulted in 6.9 million deaths worldwide. India has the third highest mortality from COVID-19 infection after the United States and Brazil.¹ Vaccination plays a crucial role in containing COVID-19 infection and reducing its severity. At present, 11 vaccines have been approved by the World Health Organization. India started its vaccination program on January 16, 2021, with approval for use of Covaxin (Bharat Biotech) and Covishield (Oxford/AstraZeneca formulation)(Serum Institute of India). More than 2 billion doses have been administered since then.^2,3

Patients with psoriasis are prone to develop a severe form of COVID-19 due to comorbidities and the intake of immunosuppressive drugs.⁴ These patients often are hesitant to receive the vaccine without an expert opinion. COVID-19 vaccines are considered to increase tumor necrosis factor α (TNF-α) and IFN-γ production by CD4⁺ T cells. Tumor necrosis factor α is a key proinflammatory cytokine implicated in the pathogenesis of psoriasis. COVID-19 messenger RNA vaccines induce elevation of IL-6 and helper T cells (T_H17), which can induce a flare of psoriasis in a subset of patients.⁵The International Psoriasis Council recommends that patients with psoriasis receive one of the vaccines approved to prevent COVID-19 infection as soon as possible.⁶ Reports of new-onset psoriasis and flare of psoriasis after the use of COVID-19 vaccines, such as those manufactured by Pfizer-BioNTech, Moderna, and AstraZeneca, have been published from different parts of the world.⁷ India used locally developed whole virion inactivated BBV152 (Covaxin) and nonreplicating viral vaccine ChAdOx1 nCoV-19 (Covishield) in its vaccination program and exported them to other developing countries. There is a dearth of data on the safety of these vaccines in patients with psoriasis, which needs to be assessed. Later, Covaxin, ZyCoV-D (DNA plasmid vaccine; Cadila Healthcare), and CorbeVax (protein subunit vaccine; Biological E) were approved for usage in children.⁸ We conducted a cross-sectional study using the direct interview method.

Patients with psoriasis who attended the outpatient department of the Postgraduate Institute of Medical Education and Research (Chandigarh, India) from April 2022 to June 2022 were invited to participate in the study after written informed consent was received. Patients 18 years and older with chronic plaque psoriasis who had received a COVID-19 vaccine dose in the last 90 days were enrolled. Data on demographics, comorbidities, treatment received for psoriasis, vaccination concerns, history of COVID-19 infection, type of vaccine received with doses, adverse effects, and psoriasis flare after receiving the vaccine (considered up to 2 weeks from the date of vaccination) were collected. Ordinal logistic regression was used to identify factors associated with a psoriasis flare following vaccination. P<.05 was considered statistically significant.

A total of 202 patients with chronic plaque psoriasis who received either Covaxin or Covishield were enrolled during the study period. The mean age (SD) was 40.3 (13.1) years, and 149 (73.8%) patients were male. One hundred thirty-five (66.8%) patients completed 2 doses of the vaccine. eTable 1 provides the clinicodemographic details of the patients. Eighty-three (41.1%) patients had a fear of psoriasis flare after vaccination. Seventy-two (35.6%) patients received the vaccine after clearance from their treating physician/dermatologist. One hundred sixty-four (81.2%) patients received the Covishield vaccine, and 38 (18.8%) patients received Covaxin. Eighty-three (41.1%) patients reported flulike symptoms, such as fever, myalgia, or body pain, within the first week of vaccination. Sixty-one (30.2%) patients reported a psoriasis flare after vaccination in the form of new lesions or worsening of pre-existing lesions. Of these patients, 51 reported a flare after receiving the first dose of vaccine, 8 patients reported a flare after receiving the second dose of vaccine, and 2 patients reported a flare after receiving both doses of vaccine. The mean (SD) flare onset was 8.1 (3.4) days after the vaccination. Eighteen patients considered the flare to be severe. Seventeen (8.4%) patients reported a positive history of COVID-19 infection before vaccination. None of the patients reported breakthrough COVID-19 infection or pustular aggravation of psoriasis following the vaccination.

The self-reported psoriasis flare after receiving the COVID-19 vaccine was significantly higher in patients who experienced immediate adverse effects (P=.005), which included fever, myalgia, joint pain, and injection-site reaction. The reported postvaccination psoriasis flare was not significantly associated with patient sex, history of COVID-19 infection, type of vaccine received, comorbidities, or therapy for psoriasis (eTable 2).

Nearly 30% of our patients reported a postvaccination psoriasis flare, which was more common after the first vaccine dose. Sotiriou et al⁷ reported 14 cases of psoriasis flare in patients after receiving Pfizer-BioNTech, Moderna, and AstraZeneca COVID-19 vaccines. These patients experienced an exacerbation of disease soon after the second dose of vaccine (mean [SD], 10.36 [7.71] days), and 21% of the 713 enrolled patients wanted to forego the immunization due to concern of a postvaccination psoriasis flare.⁷ In another report, 14 (27%) patients developed a psoriasis flare after COVID-19 vaccination; the mean (SD) flare onset was 9.3 (4.3) days after vaccination.⁹

Data on the safety of the COVID-19 vaccine in patients using immunosuppressive drugs are limited. We did not find a significant association between the psoriasis flare and use of immunosuppressive drugs or type of vaccine received. Huang and Tsai⁹ observed similar results, with no association between psoriasis flare and use of immunosuppressive drugs or biologics, while Damiani et al¹⁰ demonstrated a protective role of biologics in preventing vaccine-induced psoriasis flare.

Similar to another study from India,¹¹ the immediate adverse effects due to immunization with Covaxin and Covishield were mild in our study and resolved within a week. The incidence of psoriasis flare was significantly higher in patients who reported adverse effects (P=.005). Activation of immune response after vaccination leads to the release of proinflammatory and pyrogenic cytokines (ie, IL-1, IL-6, TNF-α), which may explain the higher incidence of psoriasis flare in patients experiencing adverse effects to vaccination.¹²

Our study showed approximately 30% of patients developed a psoriasis flare after COVID-19 vaccination, with no patients experiencing any vaccine-related serious adverse events, which suggests that Covaxin and Covishield are safe for patients with psoriasis in India. Limitations of our study include potential inaccuracy of the patient’s self-assessment of symptoms and disease flare, recall bias that may lead to errors in estimating patient-reported outcomes, the flare of psoriasis potentially being a part of disease fluctuation, and flare being enhanced by the psychological stress of vaccination.

Considering a high risk for severe COVID-19 infection in patients with psoriasis with comorbidities and those using immunosuppressive drugs, Covaxin and Covishield can be safely recommended in India. However, caution needs to be exercised when vaccinating patients with an unstable disease or severe psoriasis.

To the Editor:

COVID-19 infection has resulted in 6.9 million deaths worldwide. India has the third highest mortality from COVID-19 infection after the United States and Brazil.¹ Vaccination plays a crucial role in containing COVID-19 infection and reducing its severity. At present, 11 vaccines have been approved by the World Health Organization. India started its vaccination program on January 16, 2021, with approval for use of Covaxin (Bharat Biotech) and Covishield (Oxford/AstraZeneca formulation)(Serum Institute of India). More than 2 billion doses have been administered since then.^2,3

Patients with psoriasis are prone to develop a severe form of COVID-19 due to comorbidities and the intake of immunosuppressive drugs.⁴ These patients often are hesitant to receive the vaccine without an expert opinion. COVID-19 vaccines are considered to increase tumor necrosis factor α (TNF-α) and IFN-γ production by CD4⁺ T cells. Tumor necrosis factor α is a key proinflammatory cytokine implicated in the pathogenesis of psoriasis. COVID-19 messenger RNA vaccines induce elevation of IL-6 and helper T cells (T_H17), which can induce a flare of psoriasis in a subset of patients.⁵The International Psoriasis Council recommends that patients with psoriasis receive one of the vaccines approved to prevent COVID-19 infection as soon as possible.⁶ Reports of new-onset psoriasis and flare of psoriasis after the use of COVID-19 vaccines, such as those manufactured by Pfizer-BioNTech, Moderna, and AstraZeneca, have been published from different parts of the world.⁷ India used locally developed whole virion inactivated BBV152 (Covaxin) and nonreplicating viral vaccine ChAdOx1 nCoV-19 (Covishield) in its vaccination program and exported them to other developing countries. There is a dearth of data on the safety of these vaccines in patients with psoriasis, which needs to be assessed. Later, Covaxin, ZyCoV-D (DNA plasmid vaccine; Cadila Healthcare), and CorbeVax (protein subunit vaccine; Biological E) were approved for usage in children.⁸ We conducted a cross-sectional study using the direct interview method.

Patients with psoriasis who attended the outpatient department of the Postgraduate Institute of Medical Education and Research (Chandigarh, India) from April 2022 to June 2022 were invited to participate in the study after written informed consent was received. Patients 18 years and older with chronic plaque psoriasis who had received a COVID-19 vaccine dose in the last 90 days were enrolled. Data on demographics, comorbidities, treatment received for psoriasis, vaccination concerns, history of COVID-19 infection, type of vaccine received with doses, adverse effects, and psoriasis flare after receiving the vaccine (considered up to 2 weeks from the date of vaccination) were collected. Ordinal logistic regression was used to identify factors associated with a psoriasis flare following vaccination. P<.05 was considered statistically significant.

A total of 202 patients with chronic plaque psoriasis who received either Covaxin or Covishield were enrolled during the study period. The mean age (SD) was 40.3 (13.1) years, and 149 (73.8%) patients were male. One hundred thirty-five (66.8%) patients completed 2 doses of the vaccine. eTable 1 provides the clinicodemographic details of the patients. Eighty-three (41.1%) patients had a fear of psoriasis flare after vaccination. Seventy-two (35.6%) patients received the vaccine after clearance from their treating physician/dermatologist. One hundred sixty-four (81.2%) patients received the Covishield vaccine, and 38 (18.8%) patients received Covaxin. Eighty-three (41.1%) patients reported flulike symptoms, such as fever, myalgia, or body pain, within the first week of vaccination. Sixty-one (30.2%) patients reported a psoriasis flare after vaccination in the form of new lesions or worsening of pre-existing lesions. Of these patients, 51 reported a flare after receiving the first dose of vaccine, 8 patients reported a flare after receiving the second dose of vaccine, and 2 patients reported a flare after receiving both doses of vaccine. The mean (SD) flare onset was 8.1 (3.4) days after the vaccination. Eighteen patients considered the flare to be severe. Seventeen (8.4%) patients reported a positive history of COVID-19 infection before vaccination. None of the patients reported breakthrough COVID-19 infection or pustular aggravation of psoriasis following the vaccination.

The self-reported psoriasis flare after receiving the COVID-19 vaccine was significantly higher in patients who experienced immediate adverse effects (P=.005), which included fever, myalgia, joint pain, and injection-site reaction. The reported postvaccination psoriasis flare was not significantly associated with patient sex, history of COVID-19 infection, type of vaccine received, comorbidities, or therapy for psoriasis (eTable 2).

Nearly 30% of our patients reported a postvaccination psoriasis flare, which was more common after the first vaccine dose. Sotiriou et al⁷ reported 14 cases of psoriasis flare in patients after receiving Pfizer-BioNTech, Moderna, and AstraZeneca COVID-19 vaccines. These patients experienced an exacerbation of disease soon after the second dose of vaccine (mean [SD], 10.36 [7.71] days), and 21% of the 713 enrolled patients wanted to forego the immunization due to concern of a postvaccination psoriasis flare.⁷ In another report, 14 (27%) patients developed a psoriasis flare after COVID-19 vaccination; the mean (SD) flare onset was 9.3 (4.3) days after vaccination.⁹

Data on the safety of the COVID-19 vaccine in patients using immunosuppressive drugs are limited. We did not find a significant association between the psoriasis flare and use of immunosuppressive drugs or type of vaccine received. Huang and Tsai⁹ observed similar results, with no association between psoriasis flare and use of immunosuppressive drugs or biologics, while Damiani et al¹⁰ demonstrated a protective role of biologics in preventing vaccine-induced psoriasis flare.

Similar to another study from India,¹¹ the immediate adverse effects due to immunization with Covaxin and Covishield were mild in our study and resolved within a week. The incidence of psoriasis flare was significantly higher in patients who reported adverse effects (P=.005). Activation of immune response after vaccination leads to the release of proinflammatory and pyrogenic cytokines (ie, IL-1, IL-6, TNF-α), which may explain the higher incidence of psoriasis flare in patients experiencing adverse effects to vaccination.¹²

Our study showed approximately 30% of patients developed a psoriasis flare after COVID-19 vaccination, with no patients experiencing any vaccine-related serious adverse events, which suggests that Covaxin and Covishield are safe for patients with psoriasis in India. Limitations of our study include potential inaccuracy of the patient’s self-assessment of symptoms and disease flare, recall bias that may lead to errors in estimating patient-reported outcomes, the flare of psoriasis potentially being a part of disease fluctuation, and flare being enhanced by the psychological stress of vaccination.

Considering a high risk for severe COVID-19 infection in patients with psoriasis with comorbidities and those using immunosuppressive drugs, Covaxin and Covishield can be safely recommended in India. However, caution needs to be exercised when vaccinating patients with an unstable disease or severe psoriasis.

To the Editor:

COVID-19 infection has resulted in 6.9 million deaths worldwide. India has the third highest mortality from COVID-19 infection after the United States and Brazil.¹ Vaccination plays a crucial role in containing COVID-19 infection and reducing its severity. At present, 11 vaccines have been approved by the World Health Organization. India started its vaccination program on January 16, 2021, with approval for use of Covaxin (Bharat Biotech) and Covishield (Oxford/AstraZeneca formulation)(Serum Institute of India). More than 2 billion doses have been administered since then.^2,3

Patients with psoriasis are prone to develop a severe form of COVID-19 due to comorbidities and the intake of immunosuppressive drugs.⁴ These patients often are hesitant to receive the vaccine without an expert opinion. COVID-19 vaccines are considered to increase tumor necrosis factor α (TNF-α) and IFN-γ production by CD4⁺ T cells. Tumor necrosis factor α is a key proinflammatory cytokine implicated in the pathogenesis of psoriasis. COVID-19 messenger RNA vaccines induce elevation of IL-6 and helper T cells (T_H17), which can induce a flare of psoriasis in a subset of patients.⁵The International Psoriasis Council recommends that patients with psoriasis receive one of the vaccines approved to prevent COVID-19 infection as soon as possible.⁶ Reports of new-onset psoriasis and flare of psoriasis after the use of COVID-19 vaccines, such as those manufactured by Pfizer-BioNTech, Moderna, and AstraZeneca, have been published from different parts of the world.⁷ India used locally developed whole virion inactivated BBV152 (Covaxin) and nonreplicating viral vaccine ChAdOx1 nCoV-19 (Covishield) in its vaccination program and exported them to other developing countries. There is a dearth of data on the safety of these vaccines in patients with psoriasis, which needs to be assessed. Later, Covaxin, ZyCoV-D (DNA plasmid vaccine; Cadila Healthcare), and CorbeVax (protein subunit vaccine; Biological E) were approved for usage in children.⁸ We conducted a cross-sectional study using the direct interview method.

Patients with psoriasis who attended the outpatient department of the Postgraduate Institute of Medical Education and Research (Chandigarh, India) from April 2022 to June 2022 were invited to participate in the study after written informed consent was received. Patients 18 years and older with chronic plaque psoriasis who had received a COVID-19 vaccine dose in the last 90 days were enrolled. Data on demographics, comorbidities, treatment received for psoriasis, vaccination concerns, history of COVID-19 infection, type of vaccine received with doses, adverse effects, and psoriasis flare after receiving the vaccine (considered up to 2 weeks from the date of vaccination) were collected. Ordinal logistic regression was used to identify factors associated with a psoriasis flare following vaccination. P<.05 was considered statistically significant.

A total of 202 patients with chronic plaque psoriasis who received either Covaxin or Covishield were enrolled during the study period. The mean age (SD) was 40.3 (13.1) years, and 149 (73.8%) patients were male. One hundred thirty-five (66.8%) patients completed 2 doses of the vaccine. eTable 1 provides the clinicodemographic details of the patients. Eighty-three (41.1%) patients had a fear of psoriasis flare after vaccination. Seventy-two (35.6%) patients received the vaccine after clearance from their treating physician/dermatologist. One hundred sixty-four (81.2%) patients received the Covishield vaccine, and 38 (18.8%) patients received Covaxin. Eighty-three (41.1%) patients reported flulike symptoms, such as fever, myalgia, or body pain, within the first week of vaccination. Sixty-one (30.2%) patients reported a psoriasis flare after vaccination in the form of new lesions or worsening of pre-existing lesions. Of these patients, 51 reported a flare after receiving the first dose of vaccine, 8 patients reported a flare after receiving the second dose of vaccine, and 2 patients reported a flare after receiving both doses of vaccine. The mean (SD) flare onset was 8.1 (3.4) days after the vaccination. Eighteen patients considered the flare to be severe. Seventeen (8.4%) patients reported a positive history of COVID-19 infection before vaccination. None of the patients reported breakthrough COVID-19 infection or pustular aggravation of psoriasis following the vaccination.

The self-reported psoriasis flare after receiving the COVID-19 vaccine was significantly higher in patients who experienced immediate adverse effects (P=.005), which included fever, myalgia, joint pain, and injection-site reaction. The reported postvaccination psoriasis flare was not significantly associated with patient sex, history of COVID-19 infection, type of vaccine received, comorbidities, or therapy for psoriasis (eTable 2).

Nearly 30% of our patients reported a postvaccination psoriasis flare, which was more common after the first vaccine dose. Sotiriou et al⁷ reported 14 cases of psoriasis flare in patients after receiving Pfizer-BioNTech, Moderna, and AstraZeneca COVID-19 vaccines. These patients experienced an exacerbation of disease soon after the second dose of vaccine (mean [SD], 10.36 [7.71] days), and 21% of the 713 enrolled patients wanted to forego the immunization due to concern of a postvaccination psoriasis flare.⁷ In another report, 14 (27%) patients developed a psoriasis flare after COVID-19 vaccination; the mean (SD) flare onset was 9.3 (4.3) days after vaccination.⁹

Data on the safety of the COVID-19 vaccine in patients using immunosuppressive drugs are limited. We did not find a significant association between the psoriasis flare and use of immunosuppressive drugs or type of vaccine received. Huang and Tsai⁹ observed similar results, with no association between psoriasis flare and use of immunosuppressive drugs or biologics, while Damiani et al¹⁰ demonstrated a protective role of biologics in preventing vaccine-induced psoriasis flare.

Similar to another study from India,¹¹ the immediate adverse effects due to immunization with Covaxin and Covishield were mild in our study and resolved within a week. The incidence of psoriasis flare was significantly higher in patients who reported adverse effects (P=.005). Activation of immune response after vaccination leads to the release of proinflammatory and pyrogenic cytokines (ie, IL-1, IL-6, TNF-α), which may explain the higher incidence of psoriasis flare in patients experiencing adverse effects to vaccination.¹²

Our study showed approximately 30% of patients developed a psoriasis flare after COVID-19 vaccination, with no patients experiencing any vaccine-related serious adverse events, which suggests that Covaxin and Covishield are safe for patients with psoriasis in India. Limitations of our study include potential inaccuracy of the patient’s self-assessment of symptoms and disease flare, recall bias that may lead to errors in estimating patient-reported outcomes, the flare of psoriasis potentially being a part of disease fluctuation, and flare being enhanced by the psychological stress of vaccination.

Considering a high risk for severe COVID-19 infection in patients with psoriasis with comorbidities and those using immunosuppressive drugs, Covaxin and Covishield can be safely recommended in India. However, caution needs to be exercised when vaccinating patients with an unstable disease or severe psoriasis.

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

Characteristics

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

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

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

Infestation and Transmission

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

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

Clinical Presentation of Infestation

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

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

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

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

Case Report

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

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

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

Identification of Rate Mite Dermatitis

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

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

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

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

Characteristics

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

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

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

Infestation and Transmission

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

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

Clinical Presentation of Infestation

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

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

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

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

Case Report

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

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

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

Identification of Rate Mite Dermatitis

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

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

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

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

Characteristics

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

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

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

Infestation and Transmission

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

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

Clinical Presentation of Infestation

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

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

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

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

Case Report

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

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

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

Identification of Rate Mite Dermatitis

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

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

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

Sarcoidosis is a chronic inflammatory disease characterized by noncaseating granulomas that can affect many organ systems, most commonly the lungs and skin, with cutaneous involvement in 25% to 30% of patients in the United States.¹ The etiology of sarcoidosis largely is unknown and likely is multifactorial; however, specific environmental, infectious, and pharmaceutical triggers may contribute to its pathogenesis. Sarcoidosis secondary to occupational exposures in US Military veterans historically has been discussed and investigated. Still, it was not considered a service-connected disability until the passing of the Promise to Address Comprehensive Toxics (PACT) Act² in 2022. In this article, we review the risk factors and incidence of sarcoidosis in post–9/11 veterans as well as provide recommendations for managing presumptive service-connected sarcoidosis covered under the recently enacted PACT Act.

The PACT Act and Post–9/11 Military Veterans

Veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have a history of occupational exposures to open-air burn pits, gun smoke, and recurrent high-intensity sandstorms that may cause chronic disease.³ Burn pits, which were used to dispose of solid waste on forward operating bases, released antigenic particulate matter that was detectable on air sampling.^4,5 Increased respiratory disease rates in veterans that were deployed post–9/11 are well documented, but a causal relationship has not been established.⁶ Although burn pits cannot be directly associated with any disease at this time,⁵ veterans with assumed exposures can now receive a Veterans Affairs (VA) Disability Rating for presumptive conditions under the PACT Act.² The major points of this legislation include expanding and extending eligibility for veterans with toxic exposures, providing access to toxic exposure screening for all veterans receiving VA health care, and increasing research related to toxic exposures in US servicemembers. The PACT Act expands health care benefits, making it easier for veterans exposed post–9/11 to receive coverage for 24 new presumptive diagnoses.² Of these diagnoses, several are relevant to the practicing dermatologist. Patients with metastasis of primary cancers to the skin as well as melanoma or sarcoidosis may be eligible for coverage depending on the location and time of service. The Table lists service locations where the VA has determined servicemembers may have been exposed to burn pits or other toxins. Servicemembers with a presumptive diagnosis who served in these locations may be eligible for care under the PACT Act. Sarcoidosis is of particular concern due to its increased incidence and prevalence in military veterans compared to civilian populations. An analysis of more than 13 million veterans who received health care benefits through the Veterans Health Administration in 2019 found an annual incidence of sarcoidosis of 52 cases per 100,000 person-years and an annual prevalence of 141 cases per 100,000 individuals.⁷ In contrast, the United States has a reported annual incidence of sarcoidosis of 4.9 cases per 100,000 person-years and an annual prevalence of 60 cases per 100,000 individuals.⁸ Although the increased rates of sarcoidosis in veterans have been noted for decades, only recently have investigations provided insights into the etiology of sarcoidosis in this population.

Sarcoidosis and Environmental Factors

Sarcoidosis is a multisystem granulomatous inflammatory disease that can present in any organ system⁹; however, it most commonly affects the lungs, skin, and eyes—all of which are subjected to direct contact with environmental toxins. The cause of sarcoidosis is unknown, but environmental exposures are theorized to play a role.^9,10 It has been hypothesized that exposure to various immunologically active triggers may invoke the granulomatous inflammatory response that characterizes the disease.¹¹ The World Trade Center disaster on 9/11 has provided insight into the potential environmental component of sarcoidosis. Firefighters who spent extensive amounts of time at the World Trade Center site experienced intense exposure to inorganic particulate matter; it was later found that there was a marked increase in the incidence of sarcoidosis or sarcoidosislike granulomatous pulmonary disease in exposed firefighters. It has been speculated that the elevated exposure to potentially antigenic particulates may have induced granulomatous inflammation, resulting in the manifestation of the disease.¹² Other known occupational exposures associated with an increased risk for sarcoidosis or sarcoidosislike illness include mold, silicates, metal dust, and microbial contaminants.¹¹ Servicemembers commonly are exposed to several of these aerosolized toxins, which theoretically could increase their risk for developing sarcoidosis.

Sarcoidosis in the Military

Servicemembers historically have faced unique environmental hazards that may increase their risk for developing sarcoidosis. Studies of naval veterans have shown relationships between occupational location and increased rates of sarcoidosis. Sailors assigned to aircraft carriers with nonskid coatings containing particulate matter such as aluminum, titanium, and silicates had a higher prevalence of sarcoidosis than those stationed on “clean” ships.^13,14 Although no one trigger was identified, the increased rates of sarcoidosis in populations with extensive exposure to toxins raise concern for the possibility of occupationally induced sarcoidosis in post–9/11 veterans.

Environmental exposures during OIF and OEF may be associated with sarcoidosis. A retrospective review of lung biopsy data collected from Department of Defense military treatment facilities was conducted to identify associations between lung disease and deployment to the Middle East.¹⁵ The study included 391 military patients divided into deployed and nondeployed groups undergoing lung biopsies for various reasons from 2005 to 2012. An analysis of the reported lung histology showed an increased frequency of nonnecrotizing granulomas in those with a history of deployment to the Middle East compared to those who had never been deployed. Development of disease was not associated with confounding factors such as age, ethnicity, sex, or tobacco use, raising suspicion about similar shared toxic exposures among deployed servicemembers.¹⁵ A 2020 study of sarcoidosis in active-duty military personnel reported that the incidence of observed cases was 2-times those seen in civilian Department of Defense employees from 2005 to 2010; however, data collected in this study did not indicate an increased risk for developing sarcoidosis based on deployment to the Middle East. Still, the higher prevalence of sarcoidosis in active-duty military personnel suggests similar shared exposures in this group.¹⁶

Identification of exposures that may potentially trigger sarcoidosis is difficult due to many confounding variables; however, the Airborne Hazards and Open Burn Pit Registry questionnaire has been used to extrapolate prospective hazards of concern. Results from the questionnaire identified that only veterans exposed to convoy activity had a statistically significant (odds ratio, 1.16; 95% CI, 1.00-1.35; P=.046) increased risk for developing sarcoidosis.¹⁷ Interestingly, enlisted personnel had a higher rate of sarcoidosis than officers, comprising upwards of 78% of cases in the Military Health System from 2004 to 2013.⁹ This finding requires further study, but increased exposure to toxins due to occupational specialty may be the cause.

Veterans with sarcoidosis may have a unique pathophysiology, which may point to occupational exposure. Studies show that affected veterans have unique plasma metabolites and metal ions compared to civilians, with lower anti-inflammatory amino acid concentrations and downregulated GABA synthesis. The environmental exposures in OIF and OEF may have primed deployed servicemembers to develop a distinct subtype of sarcoidosis.³ Overall, there is a dearth of literature on post–9/11 veterans with sarcoidosis; therefore, further investigation is necessary to determine the actual risk for developing the disease following exposures related to military service.

Cutaneous sarcoidosis protean morphology is considered an imitator of many other skin diseases. The most common sarcoidosis-specific skin lesions include papules and papulonodules (Figure, A), lupus pernio (Figure, B), plaques (Figure, C), and subcutaneous nodules. Lesions typically present on the face, neck, trunk, and extremities and are associated with a favorable prognosis. Lupus pernio presents as centrofacial, bluish-red or violaceous nodules and can be disfiguring (Figure, B). Subcutaneous nodules occur in the subcutaneous tissue or deep dermis with minimal surface changes. Sarcoidal lesions also can occur at sites of scar tissue or trauma, within tattoos, and around foreign bodies. Other uncommon sarcoidosis-specific skin lesions include ichthyosiform, hypopigmented, atrophic, ulcerative and mucosal lesions; erythroderma; alopecia; and nail sarcoidosis.¹⁸

When cutaneous sarcoidosis is suspected, the skin serves as an easily accessible organ for biopsy to confirm the diagnosis.¹ Sarcoidosis-specific skin lesions are histologically characterized as sarcoidal granulomas with a classic noncaseating naked appearance comprised of epithelioid histocytes with giant cells amidst a mild lymphocytic inflammatory infiltrate. Nonspecific sarcoidosis skin lesions do not contain characteristic noncaseating granulomas. Erythema nodosum is the most common nonspecific lesion and is associated with a favorable prognosis. Other nonspecific sarcoidosis skin findings include calcinosis cutis, clubbing, and vasculitis.¹⁸

Workup

Due to the systemic nature of sarcoidosis, dermatologists should initiate a comprehensive workup upon diagnosis of cutaneous sarcoidosis, which should include the following: a complete in-depth history, including occupational/environmental exposures; a complete review of systems; a military history, including time of service and location of deployments; physical examination; pulmonary function test; high-resolution chest computed tomography¹⁹; pulmonology referral for additional pulmonary function tests, including diffusion capacity for carbon monoxide and 6-minute walk test; ophthalmology referral for full ophthalmologic examination; initial cardiac screening with electrocardiogram; and a review of symptoms including assessment of heart palpitations. Any abnormalities should prompt cardiology referral for evaluation of cardiac involvement with a workup that may include transthoracic echocardiogram, Holter monitor, cardiac magnetic resonance imaging with gadolinium contrast, or cardiac positron emission tomography/computed tomography; a complete blood cell count; comprehensive metabolic panel; urinalysis, with a 24-hour urine calcium if there is a history of a kidney stone; tuberculin skin test or IFN-γ release assay to rule out tuberculosis on a case-by-case basis; thyroid testing; and 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D screening.¹

Treatment

Cutaneous sarcoidosis is treated with topical or intralesional anti-inflammatory medications, immunomodulators, systemic immunosuppressants, and biologic agents. Management of cutaneous sarcoidosis should be done in an escalating approach guided by treatment response, location on the body, and patient preference. Response to therapy can take upwards of 3 months, and appropriate patient counseling is necessary to manage expectations.²⁰ Most cutaneous sarcoidosis treatments are not approved by the US Food and Drug Administration for this purpose, and off-label use is based on available evidence and expert consensus (eTable).

An important consideration for treating sarcoidosis in active-duty servicemembers is the use of immunosuppressants or biologics requiring refrigeration or continuous monitoring. According to Department of Defense retention standards, an active-duty servicemember may be disqualified from future service if their condition persists despite appropriate treatment and impairs their ability to perform required military duties. A medical evaluation board typically is initiated on any servicemember who starts a medication while on active duty that requires frequent monitoring by a medical provider, including immunomodulating and immunosuppressant medications.²¹

Final Thoughts

Military servicemembers put themselves at risk for acute bodily harm during deployment and also expose themselves to occupational hazards that may result in chronic health conditions. The VA’s coverage of new presumptive diagnoses means that veterans will receive extended care for conditions presumptively acquired during military service, including sarcoidosis. Although there are no conclusive data on whether exposure while on deployment overseas causes sarcoidosis, environmental exposures should be considered a potential cause. Patients with confirmed cutaneous sarcoidosis should undergo a complete workup for systemic sarcoidosis and be asked about their history of military service to evaluate for coverage under the PACT Act.

Sarcoidosis is a chronic inflammatory disease characterized by noncaseating granulomas that can affect many organ systems, most commonly the lungs and skin, with cutaneous involvement in 25% to 30% of patients in the United States.¹ The etiology of sarcoidosis largely is unknown and likely is multifactorial; however, specific environmental, infectious, and pharmaceutical triggers may contribute to its pathogenesis. Sarcoidosis secondary to occupational exposures in US Military veterans historically has been discussed and investigated. Still, it was not considered a service-connected disability until the passing of the Promise to Address Comprehensive Toxics (PACT) Act² in 2022. In this article, we review the risk factors and incidence of sarcoidosis in post–9/11 veterans as well as provide recommendations for managing presumptive service-connected sarcoidosis covered under the recently enacted PACT Act.

The PACT Act and Post–9/11 Military Veterans

Veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have a history of occupational exposures to open-air burn pits, gun smoke, and recurrent high-intensity sandstorms that may cause chronic disease.³ Burn pits, which were used to dispose of solid waste on forward operating bases, released antigenic particulate matter that was detectable on air sampling.^4,5 Increased respiratory disease rates in veterans that were deployed post–9/11 are well documented, but a causal relationship has not been established.⁶ Although burn pits cannot be directly associated with any disease at this time,⁵ veterans with assumed exposures can now receive a Veterans Affairs (VA) Disability Rating for presumptive conditions under the PACT Act.² The major points of this legislation include expanding and extending eligibility for veterans with toxic exposures, providing access to toxic exposure screening for all veterans receiving VA health care, and increasing research related to toxic exposures in US servicemembers. The PACT Act expands health care benefits, making it easier for veterans exposed post–9/11 to receive coverage for 24 new presumptive diagnoses.² Of these diagnoses, several are relevant to the practicing dermatologist. Patients with metastasis of primary cancers to the skin as well as melanoma or sarcoidosis may be eligible for coverage depending on the location and time of service. The Table lists service locations where the VA has determined servicemembers may have been exposed to burn pits or other toxins. Servicemembers with a presumptive diagnosis who served in these locations may be eligible for care under the PACT Act. Sarcoidosis is of particular concern due to its increased incidence and prevalence in military veterans compared to civilian populations. An analysis of more than 13 million veterans who received health care benefits through the Veterans Health Administration in 2019 found an annual incidence of sarcoidosis of 52 cases per 100,000 person-years and an annual prevalence of 141 cases per 100,000 individuals.⁷ In contrast, the United States has a reported annual incidence of sarcoidosis of 4.9 cases per 100,000 person-years and an annual prevalence of 60 cases per 100,000 individuals.⁸ Although the increased rates of sarcoidosis in veterans have been noted for decades, only recently have investigations provided insights into the etiology of sarcoidosis in this population.

Sarcoidosis and Environmental Factors

Sarcoidosis is a multisystem granulomatous inflammatory disease that can present in any organ system⁹; however, it most commonly affects the lungs, skin, and eyes—all of which are subjected to direct contact with environmental toxins. The cause of sarcoidosis is unknown, but environmental exposures are theorized to play a role.^9,10 It has been hypothesized that exposure to various immunologically active triggers may invoke the granulomatous inflammatory response that characterizes the disease.¹¹ The World Trade Center disaster on 9/11 has provided insight into the potential environmental component of sarcoidosis. Firefighters who spent extensive amounts of time at the World Trade Center site experienced intense exposure to inorganic particulate matter; it was later found that there was a marked increase in the incidence of sarcoidosis or sarcoidosislike granulomatous pulmonary disease in exposed firefighters. It has been speculated that the elevated exposure to potentially antigenic particulates may have induced granulomatous inflammation, resulting in the manifestation of the disease.¹² Other known occupational exposures associated with an increased risk for sarcoidosis or sarcoidosislike illness include mold, silicates, metal dust, and microbial contaminants.¹¹ Servicemembers commonly are exposed to several of these aerosolized toxins, which theoretically could increase their risk for developing sarcoidosis.

Sarcoidosis in the Military

Servicemembers historically have faced unique environmental hazards that may increase their risk for developing sarcoidosis. Studies of naval veterans have shown relationships between occupational location and increased rates of sarcoidosis. Sailors assigned to aircraft carriers with nonskid coatings containing particulate matter such as aluminum, titanium, and silicates had a higher prevalence of sarcoidosis than those stationed on “clean” ships.^13,14 Although no one trigger was identified, the increased rates of sarcoidosis in populations with extensive exposure to toxins raise concern for the possibility of occupationally induced sarcoidosis in post–9/11 veterans.

Environmental exposures during OIF and OEF may be associated with sarcoidosis. A retrospective review of lung biopsy data collected from Department of Defense military treatment facilities was conducted to identify associations between lung disease and deployment to the Middle East.¹⁵ The study included 391 military patients divided into deployed and nondeployed groups undergoing lung biopsies for various reasons from 2005 to 2012. An analysis of the reported lung histology showed an increased frequency of nonnecrotizing granulomas in those with a history of deployment to the Middle East compared to those who had never been deployed. Development of disease was not associated with confounding factors such as age, ethnicity, sex, or tobacco use, raising suspicion about similar shared toxic exposures among deployed servicemembers.¹⁵ A 2020 study of sarcoidosis in active-duty military personnel reported that the incidence of observed cases was 2-times those seen in civilian Department of Defense employees from 2005 to 2010; however, data collected in this study did not indicate an increased risk for developing sarcoidosis based on deployment to the Middle East. Still, the higher prevalence of sarcoidosis in active-duty military personnel suggests similar shared exposures in this group.¹⁶

Identification of exposures that may potentially trigger sarcoidosis is difficult due to many confounding variables; however, the Airborne Hazards and Open Burn Pit Registry questionnaire has been used to extrapolate prospective hazards of concern. Results from the questionnaire identified that only veterans exposed to convoy activity had a statistically significant (odds ratio, 1.16; 95% CI, 1.00-1.35; P=.046) increased risk for developing sarcoidosis.¹⁷ Interestingly, enlisted personnel had a higher rate of sarcoidosis than officers, comprising upwards of 78% of cases in the Military Health System from 2004 to 2013.⁹ This finding requires further study, but increased exposure to toxins due to occupational specialty may be the cause.

Veterans with sarcoidosis may have a unique pathophysiology, which may point to occupational exposure. Studies show that affected veterans have unique plasma metabolites and metal ions compared to civilians, with lower anti-inflammatory amino acid concentrations and downregulated GABA synthesis. The environmental exposures in OIF and OEF may have primed deployed servicemembers to develop a distinct subtype of sarcoidosis.³ Overall, there is a dearth of literature on post–9/11 veterans with sarcoidosis; therefore, further investigation is necessary to determine the actual risk for developing the disease following exposures related to military service.

Cutaneous sarcoidosis protean morphology is considered an imitator of many other skin diseases. The most common sarcoidosis-specific skin lesions include papules and papulonodules (Figure, A), lupus pernio (Figure, B), plaques (Figure, C), and subcutaneous nodules. Lesions typically present on the face, neck, trunk, and extremities and are associated with a favorable prognosis. Lupus pernio presents as centrofacial, bluish-red or violaceous nodules and can be disfiguring (Figure, B). Subcutaneous nodules occur in the subcutaneous tissue or deep dermis with minimal surface changes. Sarcoidal lesions also can occur at sites of scar tissue or trauma, within tattoos, and around foreign bodies. Other uncommon sarcoidosis-specific skin lesions include ichthyosiform, hypopigmented, atrophic, ulcerative and mucosal lesions; erythroderma; alopecia; and nail sarcoidosis.¹⁸

When cutaneous sarcoidosis is suspected, the skin serves as an easily accessible organ for biopsy to confirm the diagnosis.¹ Sarcoidosis-specific skin lesions are histologically characterized as sarcoidal granulomas with a classic noncaseating naked appearance comprised of epithelioid histocytes with giant cells amidst a mild lymphocytic inflammatory infiltrate. Nonspecific sarcoidosis skin lesions do not contain characteristic noncaseating granulomas. Erythema nodosum is the most common nonspecific lesion and is associated with a favorable prognosis. Other nonspecific sarcoidosis skin findings include calcinosis cutis, clubbing, and vasculitis.¹⁸

Workup

Due to the systemic nature of sarcoidosis, dermatologists should initiate a comprehensive workup upon diagnosis of cutaneous sarcoidosis, which should include the following: a complete in-depth history, including occupational/environmental exposures; a complete review of systems; a military history, including time of service and location of deployments; physical examination; pulmonary function test; high-resolution chest computed tomography¹⁹; pulmonology referral for additional pulmonary function tests, including diffusion capacity for carbon monoxide and 6-minute walk test; ophthalmology referral for full ophthalmologic examination; initial cardiac screening with electrocardiogram; and a review of symptoms including assessment of heart palpitations. Any abnormalities should prompt cardiology referral for evaluation of cardiac involvement with a workup that may include transthoracic echocardiogram, Holter monitor, cardiac magnetic resonance imaging with gadolinium contrast, or cardiac positron emission tomography/computed tomography; a complete blood cell count; comprehensive metabolic panel; urinalysis, with a 24-hour urine calcium if there is a history of a kidney stone; tuberculin skin test or IFN-γ release assay to rule out tuberculosis on a case-by-case basis; thyroid testing; and 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D screening.¹

Treatment

Cutaneous sarcoidosis is treated with topical or intralesional anti-inflammatory medications, immunomodulators, systemic immunosuppressants, and biologic agents. Management of cutaneous sarcoidosis should be done in an escalating approach guided by treatment response, location on the body, and patient preference. Response to therapy can take upwards of 3 months, and appropriate patient counseling is necessary to manage expectations.²⁰ Most cutaneous sarcoidosis treatments are not approved by the US Food and Drug Administration for this purpose, and off-label use is based on available evidence and expert consensus (eTable).

An important consideration for treating sarcoidosis in active-duty servicemembers is the use of immunosuppressants or biologics requiring refrigeration or continuous monitoring. According to Department of Defense retention standards, an active-duty servicemember may be disqualified from future service if their condition persists despite appropriate treatment and impairs their ability to perform required military duties. A medical evaluation board typically is initiated on any servicemember who starts a medication while on active duty that requires frequent monitoring by a medical provider, including immunomodulating and immunosuppressant medications.²¹

Final Thoughts

Military servicemembers put themselves at risk for acute bodily harm during deployment and also expose themselves to occupational hazards that may result in chronic health conditions. The VA’s coverage of new presumptive diagnoses means that veterans will receive extended care for conditions presumptively acquired during military service, including sarcoidosis. Although there are no conclusive data on whether exposure while on deployment overseas causes sarcoidosis, environmental exposures should be considered a potential cause. Patients with confirmed cutaneous sarcoidosis should undergo a complete workup for systemic sarcoidosis and be asked about their history of military service to evaluate for coverage under the PACT Act.

Sarcoidosis is a chronic inflammatory disease characterized by noncaseating granulomas that can affect many organ systems, most commonly the lungs and skin, with cutaneous involvement in 25% to 30% of patients in the United States.¹ The etiology of sarcoidosis largely is unknown and likely is multifactorial; however, specific environmental, infectious, and pharmaceutical triggers may contribute to its pathogenesis. Sarcoidosis secondary to occupational exposures in US Military veterans historically has been discussed and investigated. Still, it was not considered a service-connected disability until the passing of the Promise to Address Comprehensive Toxics (PACT) Act² in 2022. In this article, we review the risk factors and incidence of sarcoidosis in post–9/11 veterans as well as provide recommendations for managing presumptive service-connected sarcoidosis covered under the recently enacted PACT Act.

The PACT Act and Post–9/11 Military Veterans

Veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have a history of occupational exposures to open-air burn pits, gun smoke, and recurrent high-intensity sandstorms that may cause chronic disease.³ Burn pits, which were used to dispose of solid waste on forward operating bases, released antigenic particulate matter that was detectable on air sampling.^4,5 Increased respiratory disease rates in veterans that were deployed post–9/11 are well documented, but a causal relationship has not been established.⁶ Although burn pits cannot be directly associated with any disease at this time,⁵ veterans with assumed exposures can now receive a Veterans Affairs (VA) Disability Rating for presumptive conditions under the PACT Act.² The major points of this legislation include expanding and extending eligibility for veterans with toxic exposures, providing access to toxic exposure screening for all veterans receiving VA health care, and increasing research related to toxic exposures in US servicemembers. The PACT Act expands health care benefits, making it easier for veterans exposed post–9/11 to receive coverage for 24 new presumptive diagnoses.² Of these diagnoses, several are relevant to the practicing dermatologist. Patients with metastasis of primary cancers to the skin as well as melanoma or sarcoidosis may be eligible for coverage depending on the location and time of service. The Table lists service locations where the VA has determined servicemembers may have been exposed to burn pits or other toxins. Servicemembers with a presumptive diagnosis who served in these locations may be eligible for care under the PACT Act. Sarcoidosis is of particular concern due to its increased incidence and prevalence in military veterans compared to civilian populations. An analysis of more than 13 million veterans who received health care benefits through the Veterans Health Administration in 2019 found an annual incidence of sarcoidosis of 52 cases per 100,000 person-years and an annual prevalence of 141 cases per 100,000 individuals.⁷ In contrast, the United States has a reported annual incidence of sarcoidosis of 4.9 cases per 100,000 person-years and an annual prevalence of 60 cases per 100,000 individuals.⁸ Although the increased rates of sarcoidosis in veterans have been noted for decades, only recently have investigations provided insights into the etiology of sarcoidosis in this population.

Sarcoidosis and Environmental Factors

Sarcoidosis is a multisystem granulomatous inflammatory disease that can present in any organ system⁹; however, it most commonly affects the lungs, skin, and eyes—all of which are subjected to direct contact with environmental toxins. The cause of sarcoidosis is unknown, but environmental exposures are theorized to play a role.^9,10 It has been hypothesized that exposure to various immunologically active triggers may invoke the granulomatous inflammatory response that characterizes the disease.¹¹ The World Trade Center disaster on 9/11 has provided insight into the potential environmental component of sarcoidosis. Firefighters who spent extensive amounts of time at the World Trade Center site experienced intense exposure to inorganic particulate matter; it was later found that there was a marked increase in the incidence of sarcoidosis or sarcoidosislike granulomatous pulmonary disease in exposed firefighters. It has been speculated that the elevated exposure to potentially antigenic particulates may have induced granulomatous inflammation, resulting in the manifestation of the disease.¹² Other known occupational exposures associated with an increased risk for sarcoidosis or sarcoidosislike illness include mold, silicates, metal dust, and microbial contaminants.¹¹ Servicemembers commonly are exposed to several of these aerosolized toxins, which theoretically could increase their risk for developing sarcoidosis.

Sarcoidosis in the Military

Servicemembers historically have faced unique environmental hazards that may increase their risk for developing sarcoidosis. Studies of naval veterans have shown relationships between occupational location and increased rates of sarcoidosis. Sailors assigned to aircraft carriers with nonskid coatings containing particulate matter such as aluminum, titanium, and silicates had a higher prevalence of sarcoidosis than those stationed on “clean” ships.^13,14 Although no one trigger was identified, the increased rates of sarcoidosis in populations with extensive exposure to toxins raise concern for the possibility of occupationally induced sarcoidosis in post–9/11 veterans.

Environmental exposures during OIF and OEF may be associated with sarcoidosis. A retrospective review of lung biopsy data collected from Department of Defense military treatment facilities was conducted to identify associations between lung disease and deployment to the Middle East.¹⁵ The study included 391 military patients divided into deployed and nondeployed groups undergoing lung biopsies for various reasons from 2005 to 2012. An analysis of the reported lung histology showed an increased frequency of nonnecrotizing granulomas in those with a history of deployment to the Middle East compared to those who had never been deployed. Development of disease was not associated with confounding factors such as age, ethnicity, sex, or tobacco use, raising suspicion about similar shared toxic exposures among deployed servicemembers.¹⁵ A 2020 study of sarcoidosis in active-duty military personnel reported that the incidence of observed cases was 2-times those seen in civilian Department of Defense employees from 2005 to 2010; however, data collected in this study did not indicate an increased risk for developing sarcoidosis based on deployment to the Middle East. Still, the higher prevalence of sarcoidosis in active-duty military personnel suggests similar shared exposures in this group.¹⁶

Identification of exposures that may potentially trigger sarcoidosis is difficult due to many confounding variables; however, the Airborne Hazards and Open Burn Pit Registry questionnaire has been used to extrapolate prospective hazards of concern. Results from the questionnaire identified that only veterans exposed to convoy activity had a statistically significant (odds ratio, 1.16; 95% CI, 1.00-1.35; P=.046) increased risk for developing sarcoidosis.¹⁷ Interestingly, enlisted personnel had a higher rate of sarcoidosis than officers, comprising upwards of 78% of cases in the Military Health System from 2004 to 2013.⁹ This finding requires further study, but increased exposure to toxins due to occupational specialty may be the cause.

Veterans with sarcoidosis may have a unique pathophysiology, which may point to occupational exposure. Studies show that affected veterans have unique plasma metabolites and metal ions compared to civilians, with lower anti-inflammatory amino acid concentrations and downregulated GABA synthesis. The environmental exposures in OIF and OEF may have primed deployed servicemembers to develop a distinct subtype of sarcoidosis.³ Overall, there is a dearth of literature on post–9/11 veterans with sarcoidosis; therefore, further investigation is necessary to determine the actual risk for developing the disease following exposures related to military service.

Cutaneous sarcoidosis protean morphology is considered an imitator of many other skin diseases. The most common sarcoidosis-specific skin lesions include papules and papulonodules (Figure, A), lupus pernio (Figure, B), plaques (Figure, C), and subcutaneous nodules. Lesions typically present on the face, neck, trunk, and extremities and are associated with a favorable prognosis. Lupus pernio presents as centrofacial, bluish-red or violaceous nodules and can be disfiguring (Figure, B). Subcutaneous nodules occur in the subcutaneous tissue or deep dermis with minimal surface changes. Sarcoidal lesions also can occur at sites of scar tissue or trauma, within tattoos, and around foreign bodies. Other uncommon sarcoidosis-specific skin lesions include ichthyosiform, hypopigmented, atrophic, ulcerative and mucosal lesions; erythroderma; alopecia; and nail sarcoidosis.¹⁸

When cutaneous sarcoidosis is suspected, the skin serves as an easily accessible organ for biopsy to confirm the diagnosis.¹ Sarcoidosis-specific skin lesions are histologically characterized as sarcoidal granulomas with a classic noncaseating naked appearance comprised of epithelioid histocytes with giant cells amidst a mild lymphocytic inflammatory infiltrate. Nonspecific sarcoidosis skin lesions do not contain characteristic noncaseating granulomas. Erythema nodosum is the most common nonspecific lesion and is associated with a favorable prognosis. Other nonspecific sarcoidosis skin findings include calcinosis cutis, clubbing, and vasculitis.¹⁸

Workup

Due to the systemic nature of sarcoidosis, dermatologists should initiate a comprehensive workup upon diagnosis of cutaneous sarcoidosis, which should include the following: a complete in-depth history, including occupational/environmental exposures; a complete review of systems; a military history, including time of service and location of deployments; physical examination; pulmonary function test; high-resolution chest computed tomography¹⁹; pulmonology referral for additional pulmonary function tests, including diffusion capacity for carbon monoxide and 6-minute walk test; ophthalmology referral for full ophthalmologic examination; initial cardiac screening with electrocardiogram; and a review of symptoms including assessment of heart palpitations. Any abnormalities should prompt cardiology referral for evaluation of cardiac involvement with a workup that may include transthoracic echocardiogram, Holter monitor, cardiac magnetic resonance imaging with gadolinium contrast, or cardiac positron emission tomography/computed tomography; a complete blood cell count; comprehensive metabolic panel; urinalysis, with a 24-hour urine calcium if there is a history of a kidney stone; tuberculin skin test or IFN-γ release assay to rule out tuberculosis on a case-by-case basis; thyroid testing; and 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D screening.¹

Treatment

Cutaneous sarcoidosis is treated with topical or intralesional anti-inflammatory medications, immunomodulators, systemic immunosuppressants, and biologic agents. Management of cutaneous sarcoidosis should be done in an escalating approach guided by treatment response, location on the body, and patient preference. Response to therapy can take upwards of 3 months, and appropriate patient counseling is necessary to manage expectations.²⁰ Most cutaneous sarcoidosis treatments are not approved by the US Food and Drug Administration for this purpose, and off-label use is based on available evidence and expert consensus (eTable).

An important consideration for treating sarcoidosis in active-duty servicemembers is the use of immunosuppressants or biologics requiring refrigeration or continuous monitoring. According to Department of Defense retention standards, an active-duty servicemember may be disqualified from future service if their condition persists despite appropriate treatment and impairs their ability to perform required military duties. A medical evaluation board typically is initiated on any servicemember who starts a medication while on active duty that requires frequent monitoring by a medical provider, including immunomodulating and immunosuppressant medications.²¹

Final Thoughts

Military servicemembers put themselves at risk for acute bodily harm during deployment and also expose themselves to occupational hazards that may result in chronic health conditions. The VA’s coverage of new presumptive diagnoses means that veterans will receive extended care for conditions presumptively acquired during military service, including sarcoidosis. Although there are no conclusive data on whether exposure while on deployment overseas causes sarcoidosis, environmental exposures should be considered a potential cause. Patients with confirmed cutaneous sarcoidosis should undergo a complete workup for systemic sarcoidosis and be asked about their history of military service to evaluate for coverage under the PACT Act.