Commentary

What evidence exists on the impact of systemic immunosuppressants, biologics, and small-molecule inhibitors on patch test sensitivity and specificity?

DR. ATWATER: Guidance on this topic recently was published by the North American Contact Dermatitis Group (NACDG) in the Journal of the American Academy of Dermatology in June 2025. The article outlined expert recommendations on whether systemic immunosuppressants, biologics, and small-molecule inhibitors should be held before patch testing, how long they should be withheld, and the maximum recommended doses that can be used during testing.

How can dermatologists perform patch testing or use alternative diagnostic strategies when systemic therapy cannot safely be withheld?

DR. ATWATER: When systemic therapy cannot safely be withheld and patch testing is needed for diagnostic purposes, I typically proceed with the understanding that there is risk of false-negative reactions. If the patient has dermatitis on systemic therapy, it suggests that an allergic response on patch testing is also possible. I generally follow the NACDG guidelines mentioned above, and I hold systemic medications during the week of testing, when possible. If the patient has diffuse dermatitis on systemic therapy and their skin is not clear enough to proceed, I prescribe a prednisone taper and patch test on 10 mg per day for the entire week of testing. In patients taking systemic medications, I typically consider doubtful (+/−) patch test reactions to be the equivalent of a positive (1+) reaction.

One alternative diagnostic strategy is to create a safe list that avoids common allergens and have the patient use only products on this list. If their skin clears with avoidance, it suggests that they may have a contact allergy, and you can proceed with patch testing.

In patients with a convincing history of contact dermatitis but a negative patch test, what are the most common causes of false negatives, and how do you distinguish those from true negatives?

DR. ATWATER: In this setting, the most common cause of a false-negative patch test is not testing the correct allergens. This may occur when too few allergens are tested or when relevant allergens are not tested. Other potential causes of false negatives are incorrect timing of allergen exposure and readings, inadequate allergen adherence, expired allergens, and testing with the incorrect vehicle or concentration of allergen. Some immunosuppressant medications also can cause a false-negative patch test. The only way to distinguish false negatives from true negatives is to be aware of these potential pitfalls and continuously work to avoid errors whenever possible.

What technical and practical factors most influence false negatives/positives, and what steps do you recommend to standardize and improve test yield?

DR. ATWATER: Not testing the correct allergens is a potential pitfall in patch testing. For example, when comparing the 35 allergens in the T.R.U.E. Test (thin layer rapid-use epicutaneous test) to the 80 allergens tested by the NACDG in 2021 to 2022, up to 48% of NACDG allergens are missed when testing with only the T.R.U.E. Test. This argues for comprehensive patch testing and testing of at least 80 to 90 allergens whenever possible. Another example is failure to test allergens relevant to occupational exposures, such as in the case of a hairdresser or nail technician. When patches are not applied for the correct period (48 hours) and the final reading isn’t completed in the recommended timeframe (96 to 168 hours), there is increased risk for false negatives and positives. Both false negatives and positives can occur if you complete your final reading too early, whereas false negatives may be more likely if you complete your final reading late. Poor allergen adherence, which can be caused by hair, sweat, poor tape application, water, and exercise, also can result in false negatives. Allergen concentration that is too low to elicit a reaction, as well as too little allergen placed into the chamber, also could increase the risk of false negatives. Too much allergen in the chamber or too high a concentration of the allergen can result in false positives.

Topical medications applied to the patch test site prior to or during patch testing, as well as phototherapy, sun exposure, intramuscular triamcinolone, immunosuppressants, biologics, and small-molecule inhibitors can suppress the immune response to allergen exposure.

To identify true positive patch test reactions, use side lighting and palpate the skin. Be aware of the appearance of irritant reactions, patch test reaction variants such as follicular reactions, and the poral reaction, which can be seen with cobalt. Strong knowledge of how to read patch test reactions will decrease your risk of false-positive and -negative reactions. Training and protocols are vital for standardization and accurate patch testing. We train our staff on the technicalities of patch testing and utilize patch test orders and checklists in our office. We take photos to confirm application sites and visually track reactions between visits. We also provide verbal and written patch test care instructions for our patients and reinforce instructions at each clinic visit.

What are your top practical tips for dermatologists to maximize diagnostic accuracy and patient safety?

DR. ATWATER: My first tip is to develop patch test protocols that are followed by staff and physicians—every time—for every patient. My second tip is to make sure you understand and are comfortable with the patch test process. There are several great patch test resources that can help, including Introduction to Patch Testing, a recently developed CME module in the AAD Learning Center (https://learning.aad.org/Listing/Introduction-to-Patch- Testing-20366). There also are patch test training courses and other resources offered by the American Contact Dermatitis Society (https://www.contactderm.org/).

What single guideline change would most improve patch testing?

DR. ATWATER: The single guideline change that would most improve the practice of patch testing is removal of payer limitations on the number of patches that can be applied per day. For many payers in the United States, this limit is 80 to 90 allergens, and it is sometimes lower. Limits on the number of allergens that can be applied per day may result in false-negative patch testing (when limits are applied), patient inconvenience (if testing is completed over 2 different application days), and insufficient reimbursement (if more allergens are tested than the limit allows).

What evidence exists on the impact of systemic immunosuppressants, biologics, and small-molecule inhibitors on patch test sensitivity and specificity?

DR. ATWATER: Guidance on this topic recently was published by the North American Contact Dermatitis Group (NACDG) in the Journal of the American Academy of Dermatology in June 2025. The article outlined expert recommendations on whether systemic immunosuppressants, biologics, and small-molecule inhibitors should be held before patch testing, how long they should be withheld, and the maximum recommended doses that can be used during testing.

How can dermatologists perform patch testing or use alternative diagnostic strategies when systemic therapy cannot safely be withheld?

DR. ATWATER: When systemic therapy cannot safely be withheld and patch testing is needed for diagnostic purposes, I typically proceed with the understanding that there is risk of false-negative reactions. If the patient has dermatitis on systemic therapy, it suggests that an allergic response on patch testing is also possible. I generally follow the NACDG guidelines mentioned above, and I hold systemic medications during the week of testing, when possible. If the patient has diffuse dermatitis on systemic therapy and their skin is not clear enough to proceed, I prescribe a prednisone taper and patch test on 10 mg per day for the entire week of testing. In patients taking systemic medications, I typically consider doubtful (+/−) patch test reactions to be the equivalent of a positive (1+) reaction.

One alternative diagnostic strategy is to create a safe list that avoids common allergens and have the patient use only products on this list. If their skin clears with avoidance, it suggests that they may have a contact allergy, and you can proceed with patch testing.

In patients with a convincing history of contact dermatitis but a negative patch test, what are the most common causes of false negatives, and how do you distinguish those from true negatives?

DR. ATWATER: In this setting, the most common cause of a false-negative patch test is not testing the correct allergens. This may occur when too few allergens are tested or when relevant allergens are not tested. Other potential causes of false negatives are incorrect timing of allergen exposure and readings, inadequate allergen adherence, expired allergens, and testing with the incorrect vehicle or concentration of allergen. Some immunosuppressant medications also can cause a false-negative patch test. The only way to distinguish false negatives from true negatives is to be aware of these potential pitfalls and continuously work to avoid errors whenever possible.

What technical and practical factors most influence false negatives/positives, and what steps do you recommend to standardize and improve test yield?

DR. ATWATER: Not testing the correct allergens is a potential pitfall in patch testing. For example, when comparing the 35 allergens in the T.R.U.E. Test (thin layer rapid-use epicutaneous test) to the 80 allergens tested by the NACDG in 2021 to 2022, up to 48% of NACDG allergens are missed when testing with only the T.R.U.E. Test. This argues for comprehensive patch testing and testing of at least 80 to 90 allergens whenever possible. Another example is failure to test allergens relevant to occupational exposures, such as in the case of a hairdresser or nail technician. When patches are not applied for the correct period (48 hours) and the final reading isn’t completed in the recommended timeframe (96 to 168 hours), there is increased risk for false negatives and positives. Both false negatives and positives can occur if you complete your final reading too early, whereas false negatives may be more likely if you complete your final reading late. Poor allergen adherence, which can be caused by hair, sweat, poor tape application, water, and exercise, also can result in false negatives. Allergen concentration that is too low to elicit a reaction, as well as too little allergen placed into the chamber, also could increase the risk of false negatives. Too much allergen in the chamber or too high a concentration of the allergen can result in false positives.

Topical medications applied to the patch test site prior to or during patch testing, as well as phototherapy, sun exposure, intramuscular triamcinolone, immunosuppressants, biologics, and small-molecule inhibitors can suppress the immune response to allergen exposure.

To identify true positive patch test reactions, use side lighting and palpate the skin. Be aware of the appearance of irritant reactions, patch test reaction variants such as follicular reactions, and the poral reaction, which can be seen with cobalt. Strong knowledge of how to read patch test reactions will decrease your risk of false-positive and -negative reactions. Training and protocols are vital for standardization and accurate patch testing. We train our staff on the technicalities of patch testing and utilize patch test orders and checklists in our office. We take photos to confirm application sites and visually track reactions between visits. We also provide verbal and written patch test care instructions for our patients and reinforce instructions at each clinic visit.

What are your top practical tips for dermatologists to maximize diagnostic accuracy and patient safety?

DR. ATWATER: My first tip is to develop patch test protocols that are followed by staff and physicians—every time—for every patient. My second tip is to make sure you understand and are comfortable with the patch test process. There are several great patch test resources that can help, including Introduction to Patch Testing, a recently developed CME module in the AAD Learning Center (https://learning.aad.org/Listing/Introduction-to-Patch- Testing-20366). There also are patch test training courses and other resources offered by the American Contact Dermatitis Society (https://www.contactderm.org/).

What single guideline change would most improve patch testing?

DR. ATWATER: The single guideline change that would most improve the practice of patch testing is removal of payer limitations on the number of patches that can be applied per day. For many payers in the United States, this limit is 80 to 90 allergens, and it is sometimes lower. Limits on the number of allergens that can be applied per day may result in false-negative patch testing (when limits are applied), patient inconvenience (if testing is completed over 2 different application days), and insufficient reimbursement (if more allergens are tested than the limit allows).

What evidence exists on the impact of systemic immunosuppressants, biologics, and small-molecule inhibitors on patch test sensitivity and specificity?

DR. ATWATER: Guidance on this topic recently was published by the North American Contact Dermatitis Group (NACDG) in the Journal of the American Academy of Dermatology in June 2025. The article outlined expert recommendations on whether systemic immunosuppressants, biologics, and small-molecule inhibitors should be held before patch testing, how long they should be withheld, and the maximum recommended doses that can be used during testing.

How can dermatologists perform patch testing or use alternative diagnostic strategies when systemic therapy cannot safely be withheld?

DR. ATWATER: When systemic therapy cannot safely be withheld and patch testing is needed for diagnostic purposes, I typically proceed with the understanding that there is risk of false-negative reactions. If the patient has dermatitis on systemic therapy, it suggests that an allergic response on patch testing is also possible. I generally follow the NACDG guidelines mentioned above, and I hold systemic medications during the week of testing, when possible. If the patient has diffuse dermatitis on systemic therapy and their skin is not clear enough to proceed, I prescribe a prednisone taper and patch test on 10 mg per day for the entire week of testing. In patients taking systemic medications, I typically consider doubtful (+/−) patch test reactions to be the equivalent of a positive (1+) reaction.

One alternative diagnostic strategy is to create a safe list that avoids common allergens and have the patient use only products on this list. If their skin clears with avoidance, it suggests that they may have a contact allergy, and you can proceed with patch testing.

In patients with a convincing history of contact dermatitis but a negative patch test, what are the most common causes of false negatives, and how do you distinguish those from true negatives?

DR. ATWATER: In this setting, the most common cause of a false-negative patch test is not testing the correct allergens. This may occur when too few allergens are tested or when relevant allergens are not tested. Other potential causes of false negatives are incorrect timing of allergen exposure and readings, inadequate allergen adherence, expired allergens, and testing with the incorrect vehicle or concentration of allergen. Some immunosuppressant medications also can cause a false-negative patch test. The only way to distinguish false negatives from true negatives is to be aware of these potential pitfalls and continuously work to avoid errors whenever possible.

What technical and practical factors most influence false negatives/positives, and what steps do you recommend to standardize and improve test yield?

DR. ATWATER: Not testing the correct allergens is a potential pitfall in patch testing. For example, when comparing the 35 allergens in the T.R.U.E. Test (thin layer rapid-use epicutaneous test) to the 80 allergens tested by the NACDG in 2021 to 2022, up to 48% of NACDG allergens are missed when testing with only the T.R.U.E. Test. This argues for comprehensive patch testing and testing of at least 80 to 90 allergens whenever possible. Another example is failure to test allergens relevant to occupational exposures, such as in the case of a hairdresser or nail technician. When patches are not applied for the correct period (48 hours) and the final reading isn’t completed in the recommended timeframe (96 to 168 hours), there is increased risk for false negatives and positives. Both false negatives and positives can occur if you complete your final reading too early, whereas false negatives may be more likely if you complete your final reading late. Poor allergen adherence, which can be caused by hair, sweat, poor tape application, water, and exercise, also can result in false negatives. Allergen concentration that is too low to elicit a reaction, as well as too little allergen placed into the chamber, also could increase the risk of false negatives. Too much allergen in the chamber or too high a concentration of the allergen can result in false positives.

Topical medications applied to the patch test site prior to or during patch testing, as well as phototherapy, sun exposure, intramuscular triamcinolone, immunosuppressants, biologics, and small-molecule inhibitors can suppress the immune response to allergen exposure.

To identify true positive patch test reactions, use side lighting and palpate the skin. Be aware of the appearance of irritant reactions, patch test reaction variants such as follicular reactions, and the poral reaction, which can be seen with cobalt. Strong knowledge of how to read patch test reactions will decrease your risk of false-positive and -negative reactions. Training and protocols are vital for standardization and accurate patch testing. We train our staff on the technicalities of patch testing and utilize patch test orders and checklists in our office. We take photos to confirm application sites and visually track reactions between visits. We also provide verbal and written patch test care instructions for our patients and reinforce instructions at each clinic visit.

What are your top practical tips for dermatologists to maximize diagnostic accuracy and patient safety?

DR. ATWATER: My first tip is to develop patch test protocols that are followed by staff and physicians—every time—for every patient. My second tip is to make sure you understand and are comfortable with the patch test process. There are several great patch test resources that can help, including Introduction to Patch Testing, a recently developed CME module in the AAD Learning Center (https://learning.aad.org/Listing/Introduction-to-Patch- Testing-20366). There also are patch test training courses and other resources offered by the American Contact Dermatitis Society (https://www.contactderm.org/).

What single guideline change would most improve patch testing?

DR. ATWATER: The single guideline change that would most improve the practice of patch testing is removal of payer limitations on the number of patches that can be applied per day. For many payers in the United States, this limit is 80 to 90 allergens, and it is sometimes lower. Limits on the number of allergens that can be applied per day may result in false-negative patch testing (when limits are applied), patient inconvenience (if testing is completed over 2 different application days), and insufficient reimbursement (if more allergens are tested than the limit allows).

Bullous pemphigoid (BP) is a chronic autoimmune skin condition characterized by large, fluid-filled blisters (bullae) on the skin. There usually is severe itching, which may antedate the bullae by several weeks. Bullous pemphigoid most commonly affects adults aged 60 years and older with comorbidities such as metabolic syndrome or other autoimmune diseases. The typical blistering is subepidermal, and its occurrence seems to be driven by autoantibodies targeting the epidermal basement membrane zone.

Conventional treatment for BP has long included systemic corticosteroids and immunosuppressants; this combination of drugs effectively controls inflammation but also is associated with considerable risks such as infection, hyperglycemia with worsening diabetes, hypertension, osteoporosis and fracture risk, and delirium, particularly in older patients. Recent developments in biologic therapy have supported the utilization of potentially safer alternatives. Specifically, dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. Case reports and small research studies included in a recent review have suggested that dupilumab could be effective in managing BP, potentially offering a safer treatment option.¹ Importantly, dupilumab recently was approved for BP by the US Food and Drug Administration, making it the first biologic approved for treating this condition.² In this article, we discuss dupilumab as an option for clinicians to prescribe as an initial therapy for BP.

Pathophysiology of Bullous Pemphigoid and Dupilumab

Bullous pemphigoid pathophysiology is driven by 2 main components: immunologic and inflammatory processes. The immune-mediated attack consists of autoantibodies against the hemidesmosomal proteins BP180 and BP230 in the basement membrane zone, which anchor the epidermis to the dermis.¹ When these proteins are targeted, a cascade of responses is triggered, including the release of inflammatory cells, particularly eosinophils and neutrophils, into the skin. These cells release inflammatory mediators that break down the basement membrane, resulting in the separation of the epidermis from the dermis and leading to subepidermal blister formation.

The inflammation associated with BP largely is driven by a T helper 2–dominant immune response, with increased levels of cytokines such as interleukin (IL) 4 and IL-13.¹ The chronic inflammation contributes to the characteristic blisters and intense pruritus seen in patients with BP. Traditional treatments such as corticosteroids work broadly to suppress this inflammation by reducing the production of all proinflammatory cytokines; however, they lack specificity, which dampens the targeted immune response against BP and broadly suppresses the immune system, increasing the risk for infection and other adverse effects. For older patients with multiple health conditions, these adverse effects can impact quality of life and pose health risks.

Interleukin 4 and IL-13 contribute to eosinophilia by upregulating the expression of eosinophil chemoattractant cytokines that promote eosinophil migration and adhesion.¹ This is where dupilumab presents a promising alternative. Dupilumab is a monoclonal antibody that selectively targets the key cytokines implicated in BP. It binds to the IL-4 receptor alpha subunit, which IL-4 and IL-13 share, thereby inhibiting the signaling of both cytokines.¹

Dupilumab Reports and Case Series

Current evidence supporting the use of dupilumab for BP consists primarily of case series and uncontrolled clinical observations, both of which are useful to formulate but not to test hypotheses.³ One case series of 13 patients diagnosed with BP reported that 92.3% (12/13) of patients achieved disease clearance or satisfactory control, with 53.8% (7/13) achieving total lesion clearance and no adverse events observed.⁴ In a larger case series, 87.0% of 146 patients achieved disease control with an initial dose of dupilumab 600 mg followed by 300 mg every 2 weeks for 4 weeks, though the study also looked at secondary outcomes for up to 64 weeks.⁵ Both these findings are compatible with the idea that dupilumab has efficacy in BP, but they cannot be used to test hypotheses.^3,4

In a single case report of refractory BP, the combination of dupilumab and omalizumab—a monoclonal antibody that blocks the binding of IgE to mast cells, basophils, and dendritic cells—has shown efficacy, particularly when BP is unresponsive to standard therapies.⁶ The case involved a 72-year-old woman with unresponsive BP who was treated with a combination of dupilumab and omalizumab. She experienced marked improvement in pruritus and bullae accompanied by normalization of anti-BP180 autoantibody levels. This result points to the possibility that IL-4 and IL-13 blockade could influence autoantibody production. The authors attributed the reduction in pruritus to dupilumab, although the drug was administered in combination with omalizumab.⁶

Small Randomized Trial of Dupilumab

In addition to these uncontrolled clinical observations, dupilumab recently demonstrated positive results in a small randomized trial.⁷ Patients who were assigned to receive dupilumab were 5 times more likely to achieve sustained remission compared to those assigned to a placebo. All randomized patients also were treated with a standard-of-care oral corticosteroid regimen, which complicated the ability to isolate the specific effects of dupilumab.⁷ Finally, a completed totality of evidence on the prescription of dupilumab for refractory BP should include more reliable results from larger randomized trials.⁸

Final Thoughts

Dupilumab is now approved by the US Food and Drug Administration for the treatment of BP, marking an important milestone as the first targeted biologic therapy for this condition. While the totality of evidence is still evolving, the available data indicate both efficacy and a favorable safety profile when compared to traditional corticosteroids and immunosuppressants. Based on the available data, we suggest that health care providers consider dupilumab as a first-line monotherapy in appropriate patients with BP without specific contraindications, particularly as a practical and safe alternative to corticosteroids and immunosuppressive therapies in older adults with comorbidities. If the patient demonstrates clinical improvement in symptom relief, the therapy can be continued. This strategy minimizes initial exposure to more potent biologics or therapies with higher toxicity profiles. For patients without adequate disease control or with severe initial presentations requiring rapid improvement, clinicians may consider escalation to adjunctive or alternative therapies, such as rituximab, omalizumab, or a short course of systemic corticosteroids for acute management.

Emerging data suggest that dupilumab is a promising therapy for BP. We suggest that it may be a safer targeted alternative to traditional corticosteroids and immunosuppressive therapies. The ability of dupilumab to mitigate inflammation without broadly suppressing the immune system suggests that it may turn out to be an especially valuable option for older patients and those with comorbid conditions.

Acknowledgement—The authors thank Jodi Fiedler, MD (Boca Raton, FL), for her expert advice and assistance.

Bullous pemphigoid (BP) is a chronic autoimmune skin condition characterized by large, fluid-filled blisters (bullae) on the skin. There usually is severe itching, which may antedate the bullae by several weeks. Bullous pemphigoid most commonly affects adults aged 60 years and older with comorbidities such as metabolic syndrome or other autoimmune diseases. The typical blistering is subepidermal, and its occurrence seems to be driven by autoantibodies targeting the epidermal basement membrane zone.

Conventional treatment for BP has long included systemic corticosteroids and immunosuppressants; this combination of drugs effectively controls inflammation but also is associated with considerable risks such as infection, hyperglycemia with worsening diabetes, hypertension, osteoporosis and fracture risk, and delirium, particularly in older patients. Recent developments in biologic therapy have supported the utilization of potentially safer alternatives. Specifically, dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. Case reports and small research studies included in a recent review have suggested that dupilumab could be effective in managing BP, potentially offering a safer treatment option.¹ Importantly, dupilumab recently was approved for BP by the US Food and Drug Administration, making it the first biologic approved for treating this condition.² In this article, we discuss dupilumab as an option for clinicians to prescribe as an initial therapy for BP.

Pathophysiology of Bullous Pemphigoid and Dupilumab

Bullous pemphigoid pathophysiology is driven by 2 main components: immunologic and inflammatory processes. The immune-mediated attack consists of autoantibodies against the hemidesmosomal proteins BP180 and BP230 in the basement membrane zone, which anchor the epidermis to the dermis.¹ When these proteins are targeted, a cascade of responses is triggered, including the release of inflammatory cells, particularly eosinophils and neutrophils, into the skin. These cells release inflammatory mediators that break down the basement membrane, resulting in the separation of the epidermis from the dermis and leading to subepidermal blister formation.

The inflammation associated with BP largely is driven by a T helper 2–dominant immune response, with increased levels of cytokines such as interleukin (IL) 4 and IL-13.¹ The chronic inflammation contributes to the characteristic blisters and intense pruritus seen in patients with BP. Traditional treatments such as corticosteroids work broadly to suppress this inflammation by reducing the production of all proinflammatory cytokines; however, they lack specificity, which dampens the targeted immune response against BP and broadly suppresses the immune system, increasing the risk for infection and other adverse effects. For older patients with multiple health conditions, these adverse effects can impact quality of life and pose health risks.

Interleukin 4 and IL-13 contribute to eosinophilia by upregulating the expression of eosinophil chemoattractant cytokines that promote eosinophil migration and adhesion.¹ This is where dupilumab presents a promising alternative. Dupilumab is a monoclonal antibody that selectively targets the key cytokines implicated in BP. It binds to the IL-4 receptor alpha subunit, which IL-4 and IL-13 share, thereby inhibiting the signaling of both cytokines.¹

Dupilumab Reports and Case Series

Current evidence supporting the use of dupilumab for BP consists primarily of case series and uncontrolled clinical observations, both of which are useful to formulate but not to test hypotheses.³ One case series of 13 patients diagnosed with BP reported that 92.3% (12/13) of patients achieved disease clearance or satisfactory control, with 53.8% (7/13) achieving total lesion clearance and no adverse events observed.⁴ In a larger case series, 87.0% of 146 patients achieved disease control with an initial dose of dupilumab 600 mg followed by 300 mg every 2 weeks for 4 weeks, though the study also looked at secondary outcomes for up to 64 weeks.⁵ Both these findings are compatible with the idea that dupilumab has efficacy in BP, but they cannot be used to test hypotheses.^3,4

In a single case report of refractory BP, the combination of dupilumab and omalizumab—a monoclonal antibody that blocks the binding of IgE to mast cells, basophils, and dendritic cells—has shown efficacy, particularly when BP is unresponsive to standard therapies.⁶ The case involved a 72-year-old woman with unresponsive BP who was treated with a combination of dupilumab and omalizumab. She experienced marked improvement in pruritus and bullae accompanied by normalization of anti-BP180 autoantibody levels. This result points to the possibility that IL-4 and IL-13 blockade could influence autoantibody production. The authors attributed the reduction in pruritus to dupilumab, although the drug was administered in combination with omalizumab.⁶

Small Randomized Trial of Dupilumab

In addition to these uncontrolled clinical observations, dupilumab recently demonstrated positive results in a small randomized trial.⁷ Patients who were assigned to receive dupilumab were 5 times more likely to achieve sustained remission compared to those assigned to a placebo. All randomized patients also were treated with a standard-of-care oral corticosteroid regimen, which complicated the ability to isolate the specific effects of dupilumab.⁷ Finally, a completed totality of evidence on the prescription of dupilumab for refractory BP should include more reliable results from larger randomized trials.⁸

Final Thoughts

Dupilumab is now approved by the US Food and Drug Administration for the treatment of BP, marking an important milestone as the first targeted biologic therapy for this condition. While the totality of evidence is still evolving, the available data indicate both efficacy and a favorable safety profile when compared to traditional corticosteroids and immunosuppressants. Based on the available data, we suggest that health care providers consider dupilumab as a first-line monotherapy in appropriate patients with BP without specific contraindications, particularly as a practical and safe alternative to corticosteroids and immunosuppressive therapies in older adults with comorbidities. If the patient demonstrates clinical improvement in symptom relief, the therapy can be continued. This strategy minimizes initial exposure to more potent biologics or therapies with higher toxicity profiles. For patients without adequate disease control or with severe initial presentations requiring rapid improvement, clinicians may consider escalation to adjunctive or alternative therapies, such as rituximab, omalizumab, or a short course of systemic corticosteroids for acute management.

Emerging data suggest that dupilumab is a promising therapy for BP. We suggest that it may be a safer targeted alternative to traditional corticosteroids and immunosuppressive therapies. The ability of dupilumab to mitigate inflammation without broadly suppressing the immune system suggests that it may turn out to be an especially valuable option for older patients and those with comorbid conditions.

Acknowledgement—The authors thank Jodi Fiedler, MD (Boca Raton, FL), for her expert advice and assistance.

Bullous pemphigoid (BP) is a chronic autoimmune skin condition characterized by large, fluid-filled blisters (bullae) on the skin. There usually is severe itching, which may antedate the bullae by several weeks. Bullous pemphigoid most commonly affects adults aged 60 years and older with comorbidities such as metabolic syndrome or other autoimmune diseases. The typical blistering is subepidermal, and its occurrence seems to be driven by autoantibodies targeting the epidermal basement membrane zone.

Conventional treatment for BP has long included systemic corticosteroids and immunosuppressants; this combination of drugs effectively controls inflammation but also is associated with considerable risks such as infection, hyperglycemia with worsening diabetes, hypertension, osteoporosis and fracture risk, and delirium, particularly in older patients. Recent developments in biologic therapy have supported the utilization of potentially safer alternatives. Specifically, dupilumab has demonstrated efficacy in the treatment of atopic dermatitis. Case reports and small research studies included in a recent review have suggested that dupilumab could be effective in managing BP, potentially offering a safer treatment option.¹ Importantly, dupilumab recently was approved for BP by the US Food and Drug Administration, making it the first biologic approved for treating this condition.² In this article, we discuss dupilumab as an option for clinicians to prescribe as an initial therapy for BP.

Pathophysiology of Bullous Pemphigoid and Dupilumab

Bullous pemphigoid pathophysiology is driven by 2 main components: immunologic and inflammatory processes. The immune-mediated attack consists of autoantibodies against the hemidesmosomal proteins BP180 and BP230 in the basement membrane zone, which anchor the epidermis to the dermis.¹ When these proteins are targeted, a cascade of responses is triggered, including the release of inflammatory cells, particularly eosinophils and neutrophils, into the skin. These cells release inflammatory mediators that break down the basement membrane, resulting in the separation of the epidermis from the dermis and leading to subepidermal blister formation.

The inflammation associated with BP largely is driven by a T helper 2–dominant immune response, with increased levels of cytokines such as interleukin (IL) 4 and IL-13.¹ The chronic inflammation contributes to the characteristic blisters and intense pruritus seen in patients with BP. Traditional treatments such as corticosteroids work broadly to suppress this inflammation by reducing the production of all proinflammatory cytokines; however, they lack specificity, which dampens the targeted immune response against BP and broadly suppresses the immune system, increasing the risk for infection and other adverse effects. For older patients with multiple health conditions, these adverse effects can impact quality of life and pose health risks.

Interleukin 4 and IL-13 contribute to eosinophilia by upregulating the expression of eosinophil chemoattractant cytokines that promote eosinophil migration and adhesion.¹ This is where dupilumab presents a promising alternative. Dupilumab is a monoclonal antibody that selectively targets the key cytokines implicated in BP. It binds to the IL-4 receptor alpha subunit, which IL-4 and IL-13 share, thereby inhibiting the signaling of both cytokines.¹

Dupilumab Reports and Case Series

Current evidence supporting the use of dupilumab for BP consists primarily of case series and uncontrolled clinical observations, both of which are useful to formulate but not to test hypotheses.³ One case series of 13 patients diagnosed with BP reported that 92.3% (12/13) of patients achieved disease clearance or satisfactory control, with 53.8% (7/13) achieving total lesion clearance and no adverse events observed.⁴ In a larger case series, 87.0% of 146 patients achieved disease control with an initial dose of dupilumab 600 mg followed by 300 mg every 2 weeks for 4 weeks, though the study also looked at secondary outcomes for up to 64 weeks.⁵ Both these findings are compatible with the idea that dupilumab has efficacy in BP, but they cannot be used to test hypotheses.^3,4

In a single case report of refractory BP, the combination of dupilumab and omalizumab—a monoclonal antibody that blocks the binding of IgE to mast cells, basophils, and dendritic cells—has shown efficacy, particularly when BP is unresponsive to standard therapies.⁶ The case involved a 72-year-old woman with unresponsive BP who was treated with a combination of dupilumab and omalizumab. She experienced marked improvement in pruritus and bullae accompanied by normalization of anti-BP180 autoantibody levels. This result points to the possibility that IL-4 and IL-13 blockade could influence autoantibody production. The authors attributed the reduction in pruritus to dupilumab, although the drug was administered in combination with omalizumab.⁶

Small Randomized Trial of Dupilumab

In addition to these uncontrolled clinical observations, dupilumab recently demonstrated positive results in a small randomized trial.⁷ Patients who were assigned to receive dupilumab were 5 times more likely to achieve sustained remission compared to those assigned to a placebo. All randomized patients also were treated with a standard-of-care oral corticosteroid regimen, which complicated the ability to isolate the specific effects of dupilumab.⁷ Finally, a completed totality of evidence on the prescription of dupilumab for refractory BP should include more reliable results from larger randomized trials.⁸

Final Thoughts

Dupilumab is now approved by the US Food and Drug Administration for the treatment of BP, marking an important milestone as the first targeted biologic therapy for this condition. While the totality of evidence is still evolving, the available data indicate both efficacy and a favorable safety profile when compared to traditional corticosteroids and immunosuppressants. Based on the available data, we suggest that health care providers consider dupilumab as a first-line monotherapy in appropriate patients with BP without specific contraindications, particularly as a practical and safe alternative to corticosteroids and immunosuppressive therapies in older adults with comorbidities. If the patient demonstrates clinical improvement in symptom relief, the therapy can be continued. This strategy minimizes initial exposure to more potent biologics or therapies with higher toxicity profiles. For patients without adequate disease control or with severe initial presentations requiring rapid improvement, clinicians may consider escalation to adjunctive or alternative therapies, such as rituximab, omalizumab, or a short course of systemic corticosteroids for acute management.

Emerging data suggest that dupilumab is a promising therapy for BP. We suggest that it may be a safer targeted alternative to traditional corticosteroids and immunosuppressive therapies. The ability of dupilumab to mitigate inflammation without broadly suppressing the immune system suggests that it may turn out to be an especially valuable option for older patients and those with comorbid conditions.

Acknowledgement—The authors thank Jodi Fiedler, MD (Boca Raton, FL), for her expert advice and assistance.

Choosing an electronic medical record (EMR) is one of the most important clinical and financial decisions a dermatology practice will make. An effective system can help streamline workflows, support high-quality patient care, and protect revenue, while the wrong choice can slow clinicians down and add to the administrative burden.

Dermatology workflows involve unique documentation, imaging, and billing needs that are not always well served by generic EMR platforms. To help guide the selection of an EMR, the following framework outlines key features and practice considerations specific to dermatology practices.

Dermatology-Specific Charting

While many general EMRs offer customization, dermatology practices benefit greatly from ready-built, specialty-specific documentation tools. Key elements to evaluate include the following:

• Preconfigured dermatology templates for common conditions and procedures (eg, acne, psoriasis, melanoma, biopsies, cosmetic treatments)
• Smart-phrase libraries tailored to dermatologic language and examinations
• Ability to create, modify, and share custom templates across providers

Why It Matters—Efficient charting reduces documentation time, improves consistency, and supports accurate coding.

Clinical Photography and Imaging

Dermatology is a highly visual specialty, making clinical photography and image management essential. Important capabilities of an EMR include the following:

• Easy capture, annotation, and longitudinal tracking of clinical images
• Seamless embedding of photographs directly into the patient chart
• Side-by-side comparison of current and prior images
• Secure image storage and camera integration
• Body-mapping tools to mark and track lesion locations visually

Why It Matters—A high-quality image workflow supports diagnosis, treatment planning, patient education, and medicolegal documentation.

Coding, Billing, and Revenue Cycle Support

For insurance-based practices, robust billing and revenue cycle management (RCM) tools are critical. For direct-care models, some of these items may be prioritized lower. Key features to compare include the following:

• Support for International Classification of Diseases, 10th Revision, Clinical Modification; Current Procedural Terminology; and dermatology-specific code sets
• Automated coding suggestions tied to clinical documentation
• Reviewing claims for errors and inconsistencies prior to submitting to payers’ insurance eligibility verification
• Electronic Remittance Advice/Explanation of Benefits posting and denial management workflows
• Support for cosmetic and self-pay billing
• Ability to generate superbills (itemized receipts for medical services that include International Classification of Diseases Tenth Revision and Current Procedural Terminology codes; patients can submit these directly to their insurance company for reimbursement) for direct-pay practices

Why It Matters—Strong RCM functionality protects revenue, reduces denials, and minimizes staff workload.

Scheduling and Practice Integration

The most effective EMRs tightly integrate clinical charting with daily practice operations. Features to evaluate include the following:

• Integrated scheduling with color-coded calendars
• Appointment-type templates and block scheduling
• Automated patient reminders via text or email
• Support for multiprovider and multilocation practices
• Integration with outside pathology or lab services

Why It Matters—Clear and templated scheduling and practice integration help practices run more smoothly by reducing administrative workload and errors and coordinating communication between providers and even ancillary services.

Telehealth and Patient Communication Tools

Patient communication and virtual care are increasingly important in dermatology. When evaluating EMRs, compare the following:

• Built-in telehealth functionality vs third-party integrations
• Automated appointment reminders
• Patient portal features (forms, messaging, results)
• Online booking capabilities

Why It Matters—Integrated telehealth and patient communication tools improve access to care, enhance patient engagement, and streamline scheduling, messaging, and virtual visits within dermatology workflows.

Reporting and Analytics

Reporting capabilities support clinical quality, compliance, and business decision-making. Key reporting areas include the following:

• Clinical reports (outcomes, lesion tracking, disease management)
• Financial reports (revenue per provider, payer mix, visit types)
• Customizable or exportable reporting tools

Why It Matters—Robust reporting and analytics help dermatology practices track clinical outcomes, monitor financial performance, and make data-driven decisions to improve both patient care and practice management.

Support, Training, and User Community

The user experience after implementation of the EMR is just as important as the software itself. Evaluate the following after the EMR is implemented:

• Initial training and onboarding resources
• Availability of dermatology-specific support teams
• Ongoing education, help centers, or user communities
• Access to dedicated implementation or success managers

Why It Matters—Strong training and support resources help ensure a smoother EMR implementation, faster staff adoption, and ongoing optimization of the system for dermatology workflows.

Cost and Overall Value

Finally, look beyond the sticker price. The total cost of ownership includes far more than monthly fees. Compare the following:

• Upfront costs (implementation, data migration, training)
• Subscription pricing (per provider or per user)
• Billing or RCM fees (including percentages of collections if applicable) and payment processing fees
• Costs for add-on modules (telehealth, imaging, analytics)
• Contract length and termination terms

Why It Matters—Understanding the full cost of ownership helps dermatology practices choose an EMR that fits their budget long-term while avoiding unexpected fees and contractual limitations.

Final Thoughts

There is no single “best” EMR for every dermatology practice. The right choice depends on your practice model, payer mix, clinical focus, and growth plans. By evaluating EMRs through a dermatology-specific lens and asking the right questions, you can choose a system that supports both excellent patient care and long-term practice success.

Choosing an electronic medical record (EMR) is one of the most important clinical and financial decisions a dermatology practice will make. An effective system can help streamline workflows, support high-quality patient care, and protect revenue, while the wrong choice can slow clinicians down and add to the administrative burden.

Dermatology workflows involve unique documentation, imaging, and billing needs that are not always well served by generic EMR platforms. To help guide the selection of an EMR, the following framework outlines key features and practice considerations specific to dermatology practices.

Dermatology-Specific Charting

While many general EMRs offer customization, dermatology practices benefit greatly from ready-built, specialty-specific documentation tools. Key elements to evaluate include the following:

• Preconfigured dermatology templates for common conditions and procedures (eg, acne, psoriasis, melanoma, biopsies, cosmetic treatments)
• Smart-phrase libraries tailored to dermatologic language and examinations
• Ability to create, modify, and share custom templates across providers

Why It Matters—Efficient charting reduces documentation time, improves consistency, and supports accurate coding.

Clinical Photography and Imaging

Dermatology is a highly visual specialty, making clinical photography and image management essential. Important capabilities of an EMR include the following:

• Easy capture, annotation, and longitudinal tracking of clinical images
• Seamless embedding of photographs directly into the patient chart
• Side-by-side comparison of current and prior images
• Secure image storage and camera integration
• Body-mapping tools to mark and track lesion locations visually

Why It Matters—A high-quality image workflow supports diagnosis, treatment planning, patient education, and medicolegal documentation.

Coding, Billing, and Revenue Cycle Support

For insurance-based practices, robust billing and revenue cycle management (RCM) tools are critical. For direct-care models, some of these items may be prioritized lower. Key features to compare include the following:

• Support for International Classification of Diseases, 10th Revision, Clinical Modification; Current Procedural Terminology; and dermatology-specific code sets
• Automated coding suggestions tied to clinical documentation
• Reviewing claims for errors and inconsistencies prior to submitting to payers’ insurance eligibility verification
• Electronic Remittance Advice/Explanation of Benefits posting and denial management workflows
• Support for cosmetic and self-pay billing
• Ability to generate superbills (itemized receipts for medical services that include International Classification of Diseases Tenth Revision and Current Procedural Terminology codes; patients can submit these directly to their insurance company for reimbursement) for direct-pay practices

Why It Matters—Strong RCM functionality protects revenue, reduces denials, and minimizes staff workload.

Scheduling and Practice Integration

The most effective EMRs tightly integrate clinical charting with daily practice operations. Features to evaluate include the following:

• Integrated scheduling with color-coded calendars
• Appointment-type templates and block scheduling
• Automated patient reminders via text or email
• Support for multiprovider and multilocation practices
• Integration with outside pathology or lab services

Why It Matters—Clear and templated scheduling and practice integration help practices run more smoothly by reducing administrative workload and errors and coordinating communication between providers and even ancillary services.

Telehealth and Patient Communication Tools

Patient communication and virtual care are increasingly important in dermatology. When evaluating EMRs, compare the following:

• Built-in telehealth functionality vs third-party integrations
• Automated appointment reminders
• Patient portal features (forms, messaging, results)
• Online booking capabilities

Why It Matters—Integrated telehealth and patient communication tools improve access to care, enhance patient engagement, and streamline scheduling, messaging, and virtual visits within dermatology workflows.

Reporting and Analytics

Reporting capabilities support clinical quality, compliance, and business decision-making. Key reporting areas include the following:

• Clinical reports (outcomes, lesion tracking, disease management)
• Financial reports (revenue per provider, payer mix, visit types)
• Customizable or exportable reporting tools

Why It Matters—Robust reporting and analytics help dermatology practices track clinical outcomes, monitor financial performance, and make data-driven decisions to improve both patient care and practice management.

Support, Training, and User Community

The user experience after implementation of the EMR is just as important as the software itself. Evaluate the following after the EMR is implemented:

• Initial training and onboarding resources
• Availability of dermatology-specific support teams
• Ongoing education, help centers, or user communities
• Access to dedicated implementation or success managers

Why It Matters—Strong training and support resources help ensure a smoother EMR implementation, faster staff adoption, and ongoing optimization of the system for dermatology workflows.

Cost and Overall Value

Finally, look beyond the sticker price. The total cost of ownership includes far more than monthly fees. Compare the following:

• Upfront costs (implementation, data migration, training)
• Subscription pricing (per provider or per user)
• Billing or RCM fees (including percentages of collections if applicable) and payment processing fees
• Costs for add-on modules (telehealth, imaging, analytics)
• Contract length and termination terms

Why It Matters—Understanding the full cost of ownership helps dermatology practices choose an EMR that fits their budget long-term while avoiding unexpected fees and contractual limitations.

Final Thoughts

There is no single “best” EMR for every dermatology practice. The right choice depends on your practice model, payer mix, clinical focus, and growth plans. By evaluating EMRs through a dermatology-specific lens and asking the right questions, you can choose a system that supports both excellent patient care and long-term practice success.

Choosing an electronic medical record (EMR) is one of the most important clinical and financial decisions a dermatology practice will make. An effective system can help streamline workflows, support high-quality patient care, and protect revenue, while the wrong choice can slow clinicians down and add to the administrative burden.

Dermatology workflows involve unique documentation, imaging, and billing needs that are not always well served by generic EMR platforms. To help guide the selection of an EMR, the following framework outlines key features and practice considerations specific to dermatology practices.

Dermatology-Specific Charting

While many general EMRs offer customization, dermatology practices benefit greatly from ready-built, specialty-specific documentation tools. Key elements to evaluate include the following:

• Preconfigured dermatology templates for common conditions and procedures (eg, acne, psoriasis, melanoma, biopsies, cosmetic treatments)
• Smart-phrase libraries tailored to dermatologic language and examinations
• Ability to create, modify, and share custom templates across providers

Why It Matters—Efficient charting reduces documentation time, improves consistency, and supports accurate coding.

Clinical Photography and Imaging

Dermatology is a highly visual specialty, making clinical photography and image management essential. Important capabilities of an EMR include the following:

• Easy capture, annotation, and longitudinal tracking of clinical images
• Seamless embedding of photographs directly into the patient chart
• Side-by-side comparison of current and prior images
• Secure image storage and camera integration
• Body-mapping tools to mark and track lesion locations visually

Why It Matters—A high-quality image workflow supports diagnosis, treatment planning, patient education, and medicolegal documentation.

Coding, Billing, and Revenue Cycle Support

For insurance-based practices, robust billing and revenue cycle management (RCM) tools are critical. For direct-care models, some of these items may be prioritized lower. Key features to compare include the following:

• Support for International Classification of Diseases, 10th Revision, Clinical Modification; Current Procedural Terminology; and dermatology-specific code sets
• Automated coding suggestions tied to clinical documentation
• Reviewing claims for errors and inconsistencies prior to submitting to payers’ insurance eligibility verification
• Electronic Remittance Advice/Explanation of Benefits posting and denial management workflows
• Support for cosmetic and self-pay billing
• Ability to generate superbills (itemized receipts for medical services that include International Classification of Diseases Tenth Revision and Current Procedural Terminology codes; patients can submit these directly to their insurance company for reimbursement) for direct-pay practices

Why It Matters—Strong RCM functionality protects revenue, reduces denials, and minimizes staff workload.

Scheduling and Practice Integration

The most effective EMRs tightly integrate clinical charting with daily practice operations. Features to evaluate include the following:

• Integrated scheduling with color-coded calendars
• Appointment-type templates and block scheduling
• Automated patient reminders via text or email
• Support for multiprovider and multilocation practices
• Integration with outside pathology or lab services

Why It Matters—Clear and templated scheduling and practice integration help practices run more smoothly by reducing administrative workload and errors and coordinating communication between providers and even ancillary services.

Telehealth and Patient Communication Tools

Patient communication and virtual care are increasingly important in dermatology. When evaluating EMRs, compare the following:

• Built-in telehealth functionality vs third-party integrations
• Automated appointment reminders
• Patient portal features (forms, messaging, results)
• Online booking capabilities

Why It Matters—Integrated telehealth and patient communication tools improve access to care, enhance patient engagement, and streamline scheduling, messaging, and virtual visits within dermatology workflows.

Reporting and Analytics

Reporting capabilities support clinical quality, compliance, and business decision-making. Key reporting areas include the following:

• Clinical reports (outcomes, lesion tracking, disease management)
• Financial reports (revenue per provider, payer mix, visit types)
• Customizable or exportable reporting tools

Why It Matters—Robust reporting and analytics help dermatology practices track clinical outcomes, monitor financial performance, and make data-driven decisions to improve both patient care and practice management.

Support, Training, and User Community

The user experience after implementation of the EMR is just as important as the software itself. Evaluate the following after the EMR is implemented:

• Initial training and onboarding resources
• Availability of dermatology-specific support teams
• Ongoing education, help centers, or user communities
• Access to dedicated implementation or success managers

Why It Matters—Strong training and support resources help ensure a smoother EMR implementation, faster staff adoption, and ongoing optimization of the system for dermatology workflows.

Cost and Overall Value

Finally, look beyond the sticker price. The total cost of ownership includes far more than monthly fees. Compare the following:

• Upfront costs (implementation, data migration, training)
• Subscription pricing (per provider or per user)
• Billing or RCM fees (including percentages of collections if applicable) and payment processing fees
• Costs for add-on modules (telehealth, imaging, analytics)
• Contract length and termination terms

Why It Matters—Understanding the full cost of ownership helps dermatology practices choose an EMR that fits their budget long-term while avoiding unexpected fees and contractual limitations.

Final Thoughts

There is no single “best” EMR for every dermatology practice. The right choice depends on your practice model, payer mix, clinical focus, and growth plans. By evaluating EMRs through a dermatology-specific lens and asking the right questions, you can choose a system that supports both excellent patient care and long-term practice success.

Melasma is a chronic hyperpigmentation disorder with a high recurrence rate. Advances in pathogenesis, diagnosis, and treatment have shifted dermatologic approaches for both initial management and long-term care. These advances highlight the need to move beyond conventional paradigms for melasma to adopt a more comprehensive and holistic approach to evaluation and management.

Diagnosis: Beyond the Wood Lamp

Diagnosis of melasma is primarily clinical, based on visual examination, with tools such as a Wood lamp (320-400 nm) aiding in classification as epidermal, dermal, or mixed types.¹ Dermoscopy is another useful tool that commonly demonstrates a brown reticular pseudonetwork, vascular patterns, and brown clods.² Reflectance confocal microscopy allows detailed assessment of pigment distribution across skin layers and may serve as a useful diagnostic adjunct.³ Two-photon excitation microscopy also has shown concordance with reflectance confocal microscopy in identifying key pathologic features of melasma and allows quantitative assessment of pigment burden.^4,5 Biopsy remains warranted in cases when the diagnosis is unclear.^6,7 These advanced tools provide additional options for noninvasive imaging of melasma, which may be useful during both diagnosis and treatment.

Pathogenesis: Beyond the Melanocyte

Recent insights into pathogenesis have shifted the view of melasma from a purely melanocyte-driven disorder to one involving complex epidermal-dermal interactions influenced by chronic UV and visible light exposure and sustained cutaneous inflammation. Evidence suggests involvement of additional cell types and structural components, including epidermal barrier dysfunction, basement membrane alterations, senescent fibroblasts, mast cell activity, vascular remodeling, and dermal solar elastosis. Senescent fibroblasts secrete melanogenic and angiogenic mediators (including stem cell factor, vascular endothelial growth factor, endothelin 1, and matrix metalloproteinases) while mast cell degranulation releases histamine, tryptase, and other proteases that drive melanocyte activation, extracellular matrix degradation, and persistent hyperpigmentation.⁸ New research highlights the importance of epidermal-dermal communication in melasma disease activity.^8,9 Exposure to UV and visible light leads to keratinocyte injury and fibroblast dysfunction, promoting the release of inflammatory and melanogenic mediators that stimulate melanocytes and weaken the basement membrane.⁸ Mast cell activation and vascular signaling also have been implicated, reinforcing the contribution of inflammation and dermal remodeling to ongoing pigmentation.⁹ This broader understanding helps explain the difficulty of sustaining long-term remission.^8,9 The multifaceted and evolving understanding of melasma’s complex pathogenesis highlights areas for future therapeutic targets beyond melanin, which may help lead to greater clearance and remission periods.

Treatment: Beyond Hydroquinone

Melasma treatment has shifted toward a longitudinal approach reflecting its chronic relapsing nature. Effective management should include combination therapy of broad-spectrum photoprotection, topical therapies, systemic therapies (when appropriate), and adjunctive procedural modalities, while emphasizing the importance of maintenance therapy and relapse prevention.^10,11 Growing evidence demonstrates that UV and visible light contribute to melanogenesis and prolonged pigmentation, particularly in individuals with skin of color.^12,13 Visible light, particularly within the high-energy blue wavelength spectrum (400-500 nm), induces reactive oxygen species and stimulates melanogenesis, resulting in persistent hyperpigmentation and exacerbation of melasma in darker skin types.¹³ Iron oxide, a mineral-based physical filter commonly used in tinted mineral sunscreens, enhances protection from visible light, thus improving melasma outcomes.^12,13 In a randomized double-blind placebo-controlled trial, oral polypodium leucotomos extract, an antioxidant with photoprotective effects, improved Melasma Area and Severity Index (MASI)/modified MASI (mMASI) scores and melasma-rated quality of life measures when used as an adjunct to sunscreen with or without topical hydroquinone.¹⁴

Topical therapy serves as the mainstay of melasma treatment. Hydroquinone- and retinoid-based regimens including triple-combination therapy remain an effective gold standard for active disease; however, there still are concerns about irritant dermatitis with both as well as ochronosis with long-term use of hydroquinone.¹⁵ Recent studies highlight the efficacy of nonhydroquinone topical therapies such as azelaic acid, tranexamic acid (TXA), thiamidol, cysteamine, metformin, malassezin, ­2-mercaptonicotinoyl glycine, niacinamide, kojic acid, ascorbic acid, and botanical-derived compounds, many of which demonstrate reductions in disease severity and more favorable tolerability profiles.^16-19 Combinations of these ingredients can allow for addressing the various pathogenic factors of melasma beyond pigmentation, including vascularity, inflammation, and solar damage.

Systemic therapy, particularly oral TXA, has emerged as an option for patients with moderate to severe or refractory melasma. Clinical trials and observational studies demonstrate improvement with oral TXA; however, relapse after discontinuation is common, emphasizing the importance of careful patient selection, established treatment duration, and concurrent maintenance therapy.^16,20 Although it is well tolerated, adverse effects include gastrointestinal discomfort, menstrual irregularities, and headache. Additionally, prescreening for contraindications and clotting risk factors is needed to avoid thromboembolic events.²¹

Procedural interventions are best used as adjunctive therapies rather than primary treatment. Superficial and medium peels can be used depending on baseline skin type.²² Platelet-rich plasma is a promising adjunctive therapy for melasma, demonstrating reductions in MASI scores following intradermal or microneedling-assisted delivery, likely mediated through growth factor–driven inhibition of melanogenesis and modulation of tyrosinase activity. Platelet-rich plasma promotes dermal remodeling through angiogenesis, collagen synthesis, and extracellular matrix production improving skin texture and pigmentation.²³ Botulinum toxin A may improve pigmentation by modulating melanogenesis as well as inflammatory and vascular pathways.²⁴

Radiofrequency microneedling provides a dermal-targeting therapeutic approach, with some evidence showing that monthly treatments can help maintain improvements achieved with conventional therapy by modulating photoaged dermal structures impacted by melanogenic signaling.²⁵ Histopathologic correlation studies suggest that microneedling used alone or as a delivery platform alongside topical agents may be beneficial in dermal-predominant disease, while laser-based therapies should be reserved for recalcitrant cases due to the risk for postinflammatory hyperpigmentation and melasma recurrence, particularly in those with darker skin types.²⁶ Lasers such as Q-switched 1064-nm Nd:YAG as well as nonablative lasers used in conservative settings are options for melasma treatment, including in patients with skin of color.^26,27 Laser toning with serial low-fluence (<3 J/cm²), large-spot 1064-nm Nd:YAG has been used to reduce inflammation and risk for postinflammatory hyperpigmentation.²⁸ Additionally, randomized split-face data demonstrate that picosecond 1064-nm devices achieve comparable reductions in mMASI scores to traditional nanosecond devices, and combination strategies incorporating intense pulsed light (IPL) have shown greater MASI improvement compared with IPL alone.^28,29 However, IPL generally is limited to lighter skin phototypes due to the risk for postinflammatory hyperpigmentation in darker skin.³⁰

Lastly, long-term management requires patient education on the importance of year-round maintenance therapy, consistency, and compliance. Reinforcing adherence to photoprotection, supporting barrier repair, and setting expectations regarding prognosis are essential components to optimizing melasma treatment outcomes.¹²

Future Insights: Beyond the Current State of Melasma Research and Treatment

Future advances in melasma management likely will focus on improving disease assessment and long-term treatment durability. Tools such as the MASI and mMASI are widely used but are limited by interobserver variability and reduced sensitivity in darker skin types, highlighting the need to incorporate objective measures such as colorimetry.^10,26 There also is a need for studies that relate clinical improvement to underlying pathology. Histopathologic correlation remains limited across most therapeutic trials, and more studies should assess long-term outcomes and quality-of-life measures given the relapsing nature of melasma.²⁶

Future interventions will continue to move past the treatment of pigment alone. Increasing recognition of vascular, inflammatory, and barrier-related contributions to melasma, as well as targeting of other cell types affected by melasma, will be important considerations in future treatment innovations.^8,11 In summary, improved inclusion of patients with skin of color in clinical trials, expansion of clinical outcomes measures and objective parameters of disease evaluation, novel approaches to treatment and relapse prevention, and greater attention to patient adherence and education will be essential to achieving advancements in melasma care.¹²

Melasma is a chronic hyperpigmentation disorder with a high recurrence rate. Advances in pathogenesis, diagnosis, and treatment have shifted dermatologic approaches for both initial management and long-term care. These advances highlight the need to move beyond conventional paradigms for melasma to adopt a more comprehensive and holistic approach to evaluation and management.

Diagnosis: Beyond the Wood Lamp

Diagnosis of melasma is primarily clinical, based on visual examination, with tools such as a Wood lamp (320-400 nm) aiding in classification as epidermal, dermal, or mixed types.¹ Dermoscopy is another useful tool that commonly demonstrates a brown reticular pseudonetwork, vascular patterns, and brown clods.² Reflectance confocal microscopy allows detailed assessment of pigment distribution across skin layers and may serve as a useful diagnostic adjunct.³ Two-photon excitation microscopy also has shown concordance with reflectance confocal microscopy in identifying key pathologic features of melasma and allows quantitative assessment of pigment burden.^4,5 Biopsy remains warranted in cases when the diagnosis is unclear.^6,7 These advanced tools provide additional options for noninvasive imaging of melasma, which may be useful during both diagnosis and treatment.

Pathogenesis: Beyond the Melanocyte

Recent insights into pathogenesis have shifted the view of melasma from a purely melanocyte-driven disorder to one involving complex epidermal-dermal interactions influenced by chronic UV and visible light exposure and sustained cutaneous inflammation. Evidence suggests involvement of additional cell types and structural components, including epidermal barrier dysfunction, basement membrane alterations, senescent fibroblasts, mast cell activity, vascular remodeling, and dermal solar elastosis. Senescent fibroblasts secrete melanogenic and angiogenic mediators (including stem cell factor, vascular endothelial growth factor, endothelin 1, and matrix metalloproteinases) while mast cell degranulation releases histamine, tryptase, and other proteases that drive melanocyte activation, extracellular matrix degradation, and persistent hyperpigmentation.⁸ New research highlights the importance of epidermal-dermal communication in melasma disease activity.^8,9 Exposure to UV and visible light leads to keratinocyte injury and fibroblast dysfunction, promoting the release of inflammatory and melanogenic mediators that stimulate melanocytes and weaken the basement membrane.⁸ Mast cell activation and vascular signaling also have been implicated, reinforcing the contribution of inflammation and dermal remodeling to ongoing pigmentation.⁹ This broader understanding helps explain the difficulty of sustaining long-term remission.^8,9 The multifaceted and evolving understanding of melasma’s complex pathogenesis highlights areas for future therapeutic targets beyond melanin, which may help lead to greater clearance and remission periods.

Treatment: Beyond Hydroquinone

Melasma treatment has shifted toward a longitudinal approach reflecting its chronic relapsing nature. Effective management should include combination therapy of broad-spectrum photoprotection, topical therapies, systemic therapies (when appropriate), and adjunctive procedural modalities, while emphasizing the importance of maintenance therapy and relapse prevention.^10,11 Growing evidence demonstrates that UV and visible light contribute to melanogenesis and prolonged pigmentation, particularly in individuals with skin of color.^12,13 Visible light, particularly within the high-energy blue wavelength spectrum (400-500 nm), induces reactive oxygen species and stimulates melanogenesis, resulting in persistent hyperpigmentation and exacerbation of melasma in darker skin types.¹³ Iron oxide, a mineral-based physical filter commonly used in tinted mineral sunscreens, enhances protection from visible light, thus improving melasma outcomes.^12,13 In a randomized double-blind placebo-controlled trial, oral polypodium leucotomos extract, an antioxidant with photoprotective effects, improved Melasma Area and Severity Index (MASI)/modified MASI (mMASI) scores and melasma-rated quality of life measures when used as an adjunct to sunscreen with or without topical hydroquinone.¹⁴

Topical therapy serves as the mainstay of melasma treatment. Hydroquinone- and retinoid-based regimens including triple-combination therapy remain an effective gold standard for active disease; however, there still are concerns about irritant dermatitis with both as well as ochronosis with long-term use of hydroquinone.¹⁵ Recent studies highlight the efficacy of nonhydroquinone topical therapies such as azelaic acid, tranexamic acid (TXA), thiamidol, cysteamine, metformin, malassezin, ­2-mercaptonicotinoyl glycine, niacinamide, kojic acid, ascorbic acid, and botanical-derived compounds, many of which demonstrate reductions in disease severity and more favorable tolerability profiles.^16-19 Combinations of these ingredients can allow for addressing the various pathogenic factors of melasma beyond pigmentation, including vascularity, inflammation, and solar damage.

Systemic therapy, particularly oral TXA, has emerged as an option for patients with moderate to severe or refractory melasma. Clinical trials and observational studies demonstrate improvement with oral TXA; however, relapse after discontinuation is common, emphasizing the importance of careful patient selection, established treatment duration, and concurrent maintenance therapy.^16,20 Although it is well tolerated, adverse effects include gastrointestinal discomfort, menstrual irregularities, and headache. Additionally, prescreening for contraindications and clotting risk factors is needed to avoid thromboembolic events.²¹

Procedural interventions are best used as adjunctive therapies rather than primary treatment. Superficial and medium peels can be used depending on baseline skin type.²² Platelet-rich plasma is a promising adjunctive therapy for melasma, demonstrating reductions in MASI scores following intradermal or microneedling-assisted delivery, likely mediated through growth factor–driven inhibition of melanogenesis and modulation of tyrosinase activity. Platelet-rich plasma promotes dermal remodeling through angiogenesis, collagen synthesis, and extracellular matrix production improving skin texture and pigmentation.²³ Botulinum toxin A may improve pigmentation by modulating melanogenesis as well as inflammatory and vascular pathways.²⁴

Radiofrequency microneedling provides a dermal-targeting therapeutic approach, with some evidence showing that monthly treatments can help maintain improvements achieved with conventional therapy by modulating photoaged dermal structures impacted by melanogenic signaling.²⁵ Histopathologic correlation studies suggest that microneedling used alone or as a delivery platform alongside topical agents may be beneficial in dermal-predominant disease, while laser-based therapies should be reserved for recalcitrant cases due to the risk for postinflammatory hyperpigmentation and melasma recurrence, particularly in those with darker skin types.²⁶ Lasers such as Q-switched 1064-nm Nd:YAG as well as nonablative lasers used in conservative settings are options for melasma treatment, including in patients with skin of color.^26,27 Laser toning with serial low-fluence (<3 J/cm²), large-spot 1064-nm Nd:YAG has been used to reduce inflammation and risk for postinflammatory hyperpigmentation.²⁸ Additionally, randomized split-face data demonstrate that picosecond 1064-nm devices achieve comparable reductions in mMASI scores to traditional nanosecond devices, and combination strategies incorporating intense pulsed light (IPL) have shown greater MASI improvement compared with IPL alone.^28,29 However, IPL generally is limited to lighter skin phototypes due to the risk for postinflammatory hyperpigmentation in darker skin.³⁰

Lastly, long-term management requires patient education on the importance of year-round maintenance therapy, consistency, and compliance. Reinforcing adherence to photoprotection, supporting barrier repair, and setting expectations regarding prognosis are essential components to optimizing melasma treatment outcomes.¹²

Future Insights: Beyond the Current State of Melasma Research and Treatment

Future advances in melasma management likely will focus on improving disease assessment and long-term treatment durability. Tools such as the MASI and mMASI are widely used but are limited by interobserver variability and reduced sensitivity in darker skin types, highlighting the need to incorporate objective measures such as colorimetry.^10,26 There also is a need for studies that relate clinical improvement to underlying pathology. Histopathologic correlation remains limited across most therapeutic trials, and more studies should assess long-term outcomes and quality-of-life measures given the relapsing nature of melasma.²⁶

Future interventions will continue to move past the treatment of pigment alone. Increasing recognition of vascular, inflammatory, and barrier-related contributions to melasma, as well as targeting of other cell types affected by melasma, will be important considerations in future treatment innovations.^8,11 In summary, improved inclusion of patients with skin of color in clinical trials, expansion of clinical outcomes measures and objective parameters of disease evaluation, novel approaches to treatment and relapse prevention, and greater attention to patient adherence and education will be essential to achieving advancements in melasma care.¹²

Melasma is a chronic hyperpigmentation disorder with a high recurrence rate. Advances in pathogenesis, diagnosis, and treatment have shifted dermatologic approaches for both initial management and long-term care. These advances highlight the need to move beyond conventional paradigms for melasma to adopt a more comprehensive and holistic approach to evaluation and management.

Diagnosis: Beyond the Wood Lamp

Diagnosis of melasma is primarily clinical, based on visual examination, with tools such as a Wood lamp (320-400 nm) aiding in classification as epidermal, dermal, or mixed types.¹ Dermoscopy is another useful tool that commonly demonstrates a brown reticular pseudonetwork, vascular patterns, and brown clods.² Reflectance confocal microscopy allows detailed assessment of pigment distribution across skin layers and may serve as a useful diagnostic adjunct.³ Two-photon excitation microscopy also has shown concordance with reflectance confocal microscopy in identifying key pathologic features of melasma and allows quantitative assessment of pigment burden.^4,5 Biopsy remains warranted in cases when the diagnosis is unclear.^6,7 These advanced tools provide additional options for noninvasive imaging of melasma, which may be useful during both diagnosis and treatment.

Pathogenesis: Beyond the Melanocyte

Recent insights into pathogenesis have shifted the view of melasma from a purely melanocyte-driven disorder to one involving complex epidermal-dermal interactions influenced by chronic UV and visible light exposure and sustained cutaneous inflammation. Evidence suggests involvement of additional cell types and structural components, including epidermal barrier dysfunction, basement membrane alterations, senescent fibroblasts, mast cell activity, vascular remodeling, and dermal solar elastosis. Senescent fibroblasts secrete melanogenic and angiogenic mediators (including stem cell factor, vascular endothelial growth factor, endothelin 1, and matrix metalloproteinases) while mast cell degranulation releases histamine, tryptase, and other proteases that drive melanocyte activation, extracellular matrix degradation, and persistent hyperpigmentation.⁸ New research highlights the importance of epidermal-dermal communication in melasma disease activity.^8,9 Exposure to UV and visible light leads to keratinocyte injury and fibroblast dysfunction, promoting the release of inflammatory and melanogenic mediators that stimulate melanocytes and weaken the basement membrane.⁸ Mast cell activation and vascular signaling also have been implicated, reinforcing the contribution of inflammation and dermal remodeling to ongoing pigmentation.⁹ This broader understanding helps explain the difficulty of sustaining long-term remission.^8,9 The multifaceted and evolving understanding of melasma’s complex pathogenesis highlights areas for future therapeutic targets beyond melanin, which may help lead to greater clearance and remission periods.

Treatment: Beyond Hydroquinone

Melasma treatment has shifted toward a longitudinal approach reflecting its chronic relapsing nature. Effective management should include combination therapy of broad-spectrum photoprotection, topical therapies, systemic therapies (when appropriate), and adjunctive procedural modalities, while emphasizing the importance of maintenance therapy and relapse prevention.^10,11 Growing evidence demonstrates that UV and visible light contribute to melanogenesis and prolonged pigmentation, particularly in individuals with skin of color.^12,13 Visible light, particularly within the high-energy blue wavelength spectrum (400-500 nm), induces reactive oxygen species and stimulates melanogenesis, resulting in persistent hyperpigmentation and exacerbation of melasma in darker skin types.¹³ Iron oxide, a mineral-based physical filter commonly used in tinted mineral sunscreens, enhances protection from visible light, thus improving melasma outcomes.^12,13 In a randomized double-blind placebo-controlled trial, oral polypodium leucotomos extract, an antioxidant with photoprotective effects, improved Melasma Area and Severity Index (MASI)/modified MASI (mMASI) scores and melasma-rated quality of life measures when used as an adjunct to sunscreen with or without topical hydroquinone.¹⁴

Topical therapy serves as the mainstay of melasma treatment. Hydroquinone- and retinoid-based regimens including triple-combination therapy remain an effective gold standard for active disease; however, there still are concerns about irritant dermatitis with both as well as ochronosis with long-term use of hydroquinone.¹⁵ Recent studies highlight the efficacy of nonhydroquinone topical therapies such as azelaic acid, tranexamic acid (TXA), thiamidol, cysteamine, metformin, malassezin, ­2-mercaptonicotinoyl glycine, niacinamide, kojic acid, ascorbic acid, and botanical-derived compounds, many of which demonstrate reductions in disease severity and more favorable tolerability profiles.^16-19 Combinations of these ingredients can allow for addressing the various pathogenic factors of melasma beyond pigmentation, including vascularity, inflammation, and solar damage.

Systemic therapy, particularly oral TXA, has emerged as an option for patients with moderate to severe or refractory melasma. Clinical trials and observational studies demonstrate improvement with oral TXA; however, relapse after discontinuation is common, emphasizing the importance of careful patient selection, established treatment duration, and concurrent maintenance therapy.^16,20 Although it is well tolerated, adverse effects include gastrointestinal discomfort, menstrual irregularities, and headache. Additionally, prescreening for contraindications and clotting risk factors is needed to avoid thromboembolic events.²¹

Procedural interventions are best used as adjunctive therapies rather than primary treatment. Superficial and medium peels can be used depending on baseline skin type.²² Platelet-rich plasma is a promising adjunctive therapy for melasma, demonstrating reductions in MASI scores following intradermal or microneedling-assisted delivery, likely mediated through growth factor–driven inhibition of melanogenesis and modulation of tyrosinase activity. Platelet-rich plasma promotes dermal remodeling through angiogenesis, collagen synthesis, and extracellular matrix production improving skin texture and pigmentation.²³ Botulinum toxin A may improve pigmentation by modulating melanogenesis as well as inflammatory and vascular pathways.²⁴

Radiofrequency microneedling provides a dermal-targeting therapeutic approach, with some evidence showing that monthly treatments can help maintain improvements achieved with conventional therapy by modulating photoaged dermal structures impacted by melanogenic signaling.²⁵ Histopathologic correlation studies suggest that microneedling used alone or as a delivery platform alongside topical agents may be beneficial in dermal-predominant disease, while laser-based therapies should be reserved for recalcitrant cases due to the risk for postinflammatory hyperpigmentation and melasma recurrence, particularly in those with darker skin types.²⁶ Lasers such as Q-switched 1064-nm Nd:YAG as well as nonablative lasers used in conservative settings are options for melasma treatment, including in patients with skin of color.^26,27 Laser toning with serial low-fluence (<3 J/cm²), large-spot 1064-nm Nd:YAG has been used to reduce inflammation and risk for postinflammatory hyperpigmentation.²⁸ Additionally, randomized split-face data demonstrate that picosecond 1064-nm devices achieve comparable reductions in mMASI scores to traditional nanosecond devices, and combination strategies incorporating intense pulsed light (IPL) have shown greater MASI improvement compared with IPL alone.^28,29 However, IPL generally is limited to lighter skin phototypes due to the risk for postinflammatory hyperpigmentation in darker skin.³⁰

Lastly, long-term management requires patient education on the importance of year-round maintenance therapy, consistency, and compliance. Reinforcing adherence to photoprotection, supporting barrier repair, and setting expectations regarding prognosis are essential components to optimizing melasma treatment outcomes.¹²

Future Insights: Beyond the Current State of Melasma Research and Treatment

Future advances in melasma management likely will focus on improving disease assessment and long-term treatment durability. Tools such as the MASI and mMASI are widely used but are limited by interobserver variability and reduced sensitivity in darker skin types, highlighting the need to incorporate objective measures such as colorimetry.^10,26 There also is a need for studies that relate clinical improvement to underlying pathology. Histopathologic correlation remains limited across most therapeutic trials, and more studies should assess long-term outcomes and quality-of-life measures given the relapsing nature of melasma.²⁶

Future interventions will continue to move past the treatment of pigment alone. Increasing recognition of vascular, inflammatory, and barrier-related contributions to melasma, as well as targeting of other cell types affected by melasma, will be important considerations in future treatment innovations.^8,11 In summary, improved inclusion of patients with skin of color in clinical trials, expansion of clinical outcomes measures and objective parameters of disease evaluation, novel approaches to treatment and relapse prevention, and greater attention to patient adherence and education will be essential to achieving advancements in melasma care.¹²

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.

Mostly it is loss that teaches us about the worth of things.
Arthur Schopenhauer¹

One of the leaders I most respected in my US Department of Veterans Affairs (VA) career was a man who had worked his way up through the ranks to become a medical center director. Usually calm, cool, and collected, he would wax poetic when discussing the hero of the VA Health Care System revolution, Ken Kizer, MD, MPH.

In this issue of Federal Practitioner, journalist Randy Dotinga interviews Kizer about the current challenges facing the VA. Though many readers will have participated in or at least know about Kizer’s unprecedented overhaul of the agency, many others, especially those new to VA, may not. It seemed a fitting time to offer an outline of the immense and positive accomplishments that occurred in the agency during his tenure, especially as, under the current administration, many of his most forward-thinking initiatives seem to be moving backward.²

When President Clinton nominated Kizer to serve as the Under Secretary for Health for the Veterans Health Administration in 1994, the poor quality care the agency delivered was castigated in popular movies like Born on the Fourth of July. Veterans who were seen in that era, and who eventually returned to a far better, kinder VA thanks to Kizer, would often tell me, “Doc, the VA was really bad then, and I was afraid to come back.” The critique of VA health care in the mid-1990s sounds like a bureaucratic déjà vu of many of the concerns Kizer raised in his interview, including fragmentation of care, access barriers, and poor coordination of treatment.³

If anyone was prepared and qualified to take on this seeming mission impossible, it was Kizer. A US Navy veteran with 6 board certifications, he came to the VA following a brave and innovative stint as the top health official in California, where he successfully took on the tobacco lobby and dramatically reduced the state’s rates of smoking and related diseases.⁴

Long before it was the subject of reality TV shows, Kizer dubbed his major renovation of the VA’s antiquated structure an “extreme makeover.”³ Though this description is an oversimplification of Kizer’s monumental efforts, the makeover can be considered in 4 to 6 buckets, depending on how various health policy experts parse the re-engineering efforts.^5-7

Decentralization. Kizer instituted the Veterans Integrated Service Network (VISN) system to coordinate the management and operations of all the hospitals, clinics, and other VA health care entities in what is roughly a region. The locus of decision-making shifted from the VA Central Office to the VISNs, intended to promote more efficient, economical, and streamlined health care delivery.

Capitation. Accompanying this restructuring was a shift to a capitated system focused on preventive care. The Veterans Equitable Resource Allocation system was designed to logically link workload and funding. This was a major shift away from VA’s previous emphasis on inpatient and specialty care and resulted in the closing of multiple hospitals.⁴

Information Systems. I can still remember the first time I sat down at a prehistoric computer to use the Computerized Patient Record System (CPRS). Though now much maligned, then it was like something out of Star Trek, at a time when almost every other health care institution was buried in paper charts. With CPRS, VA suddenly had a pioneering and much-envied electronic medical record that facilitated continuity of care, communication between professionals, and accuracy and completeness of documentation.

Data Driven Performance Improvement. The VISNs and information systems inaugurated a new era of data-driven quality improvement. The assembly and analysis of data enabled VISNs to have real-time input about comparative facility performance.

Performance Measures. The data enabled evidence-based performance measures to be developed and monitored. Though these have now become the bane of many Federal Practitioner readers’ existence, they were originally intended for VISN directors and members of the senior executive service at VA central office. These were tied to incentives that, though recently the subject of watchdog investigation, were intended to motivate and reward high-quality care.⁶

Even this cursory look at Kizer’s accomplishments is more than enough to demonstrate the magnitude of the makeover, and when the time frame of the achievements is factored in, the transformation is the equivalent of a planet changing its orbit at light speed. Rhetoric aside, there are now hundreds of research articles published in top medical and health policy journals, many of them authored by Kizer,^7,8 that have amply demonstrated that when he departed the VA in 1999, it had become “the best care anywhere.” ⁹ For example, a 2000 New England Journal of Medicine article found that from 1994 to 2000, the percentage of veterans whose care met ≥ 90% of 9 of 17 quality standards was > 70% for 13 of the measures, outperforming fee-for-service Medicare.¹⁰

There had been uncertainty about whether Kizer would seek a second term as Under Secretary when he announced that he was leaving. With concise modesty, Kizer said he had met his charge to, “re-engineer the veterans’ health care system so that it could effectively function in the 21^st century.”¹¹

Despite openly and critically discussing the many difficulties the VA currently confronts, Kizer ends his interview on a note of hope. Since he likely knows more about VA than any person alive, we need to trust his judgment that his legacy, which currently seems more in jeopardy than ever before, will somehow prevail. Perhaps I am too melancholic, but I believe it will take a professional of the stature of Dr. Kizer to take us back to that future, and I fear we will not see his likes again.