Article

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

A 70-year-old veteran with a history notable for type 2 diabetes mellitus, complicated by peripheral neuropathy and bilateral foot ulceration, and previous pulmonary tuberculosis (treated in June 2013) presented to an outside medical facility with bilateral worsening foot pain, swelling, and drainage of preexisting ulcers. He received a diagnosis of bilateral fifth toe osteomyelitis and was discharged with a 6-week course of IV daptomycin 600 mg (8 mg/kg) and ertapenem 1 g/d. At discharge, the patient was in stable condition. Follow-up was done by our outpatient parenteral antimicrobial therapy (OPAT) team, which consists of an infectious disease pharmacist and the physician director of antimicrobial stewardship who monitor veterans receiving outpatient IV antibiotic therapy.¹

Three weeks later as part of the regular OPAT surveillance, the patient reported via telephone that his foot osteomyelitis was stable, but he had a 101 °F fever and a new cough. He was instructed to come to the emergency department (ED) immediately. On arrival,

• What is your diagnosis?
• How would you treat this patient?

In the ED, the patient was given a provisional diagnosis of multifocal bacterial pneumonia and was admitted to the hospital for further management. His outpatient regimen of IV daptomycin and ertapenem was adjusted to IV vancomycin and meropenem. The infectious disease service was consulted within 24 hours of admission, and based on the new onset chest infiltrates, therapy with daptomycin and notable peripheral blood eosinophilia, a presumptive diagnosis of daptomycin-related acute eosinophilic pneumonia was made. A medication list review yielded no other potential etiologic agents for drug-related eosinophilia, and the patient did not have any remote or recent pertinent travel history concerning for parasitic disease.

The patient was treated with oral prednisone 40 mg (0.5 mg/kg) daily and the daptomycin was not restarted. Within 24 hours, the patient’s fevers, oxygen requirements, and cough subsided. Laboratory values

Discussion

Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.² The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).³ Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.^4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.

Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.⁷ The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.³ Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.^7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.⁹ However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.¹⁰ Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.¹⁰ However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.

Conclusions

As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

This Veterans Day we honor the passing of the largest expansion of veterans benefits and services in history. On August 10, 2022, President Biden signed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act. This act was named for a combat medic who died of a rare form of lung cancer believed to be the result of a toxic military exposure. His widow was present during the President's State of the Union address that urged Congress to pass the legislation.² 

Like all other congressional bills and government regulations, the PACT Act is complex in its details and still a work in progress. Simply put, the PACT Act expands and/or extends enrollment for a group of previously ineligible veterans. Eligibility will no longer require that veterans demonstrate a service-connected disability due to toxic exposure, including those from burn pits. This has long been a barrier for many veterans seeking benefits and not just related to toxic exposures. Logistical barriers and documentary losses have prevented many service members from establishing a clean chain of evidence for the injuries or illnesses they sustained while in uniform.
 
The new process is a massive step forward by the US Department of Veterans Affairs (VA) to establish high standards of procedural justice for settling beneficiary claims. The PACT Act removes the burden from the shoulders of the veteran and places it squarely on the VA to demonstrate that > 20 different medical conditions--primarily cancers and respiratory illnesses--are linked to toxic exposure. The VA must establish that exposure occurred to cohorts of service members in specific theaters and time frames. A veteran who served in that area and period and has one of the indexed illnesses is presumed to have been exposed in the line of duty.^3,4

As a result, the VA instituted a new screening process to determine that toxic military exposures (a) led to illness; and (b) both exposure and illness are connected to service. According to the VA, the new process is evidence based, transparent, and allows the VA to fast-track policy decisions related to exposures. The PACT Act includes a provision intended to promote sustained implementation and prevent the program from succumbing as so many new initiatives have to inadequate adoption. VA is required to deploy its considerable internal research capacity to collaborate with external partners in and outside government to study military members with toxic exposures.⁴ 

Congress had initially proposed that the provisions of the PACT ACT would take effect in 2026, providing time to ramp up the process. The White House and VA telescoped that time line so veterans can begin now to apply for benefits that they could foreseeably receive in 2023. However, a long-standing problem for the VA has been unfunded agency or congressional mandates. These have often end in undermining the legislative intention or policy purpose of the program undermining their legislative intention or policy purpose through staffing shortages, leading to lack of or delayed access. The PACT Act promises to eschew the infamous Phoenix problem by providing increased personnel, training infrastructure, and technology resources for both the Veterans Benefit Administration and the Veterans Health Administration. Ironically, many seasoned VA observers expect the PACT expansion will lead to even larger backlogs of claims as hundreds of newly eligible veterans are added to the extant rolls of those seeking benefits.⁵ 

An estimated 1 in 5 veterans may be entitled to PACT benefits. The PACT Act is the latest of a long uneven movement toward distributive justice for veteran benefits and services. It is fitting in the month of Veterans Day 2022 to trace that trajectory. Congress first passed veteran benefits legislation in 1917, focused on soldiers with disabilities. This resulted in a massive investment in building hospitals. Ironically, part of the impetus for VA health care was an earlier toxic military exposure. World War I service members suffered from the detrimental effects of mustard gas among other chemical byproducts. In 1924, VA benefits and services underwent a momentous opening to include individuals with non-service-connected disabilities. Four years later, the VA tent became even bigger, welcoming women, National Guard, and militia members to receive care under its auspices.⁶ 

The PACT Act is a fitting memorial for Veterans Day as an increasingly divided country presents a unified response to veterans and their survivors exposed to a variety of toxins across multiple wars. The PACT Act was hard won with veterans and their advocates having to fight years of political bickering, government abdication of accountability, and scientific sparring before this bipartisan legislation passed.⁷ It covers Vietnam War veterans with several conditions due to Agent Orange exposure; Gulf War and post-9/11 veterans with cancer and respiratory conditions; and the service members deployed to Afghanistan and Iraq afflicted with illnesses due to the smoke of burn pits and other toxins. 

As many areas of the country roll back LGBTQ+ rights to health care and social services, the VA has emerged as a leader in the movement for diversity and inclusion. VA Secretary McDonough provided a pathway to VA eligibility for other than honorably discharged veterans, including those LGBTQ+ persons discharged under Don't Ask, Don't Tell.⁸ Lest we take this new inclusivity for granted, we should never forget that this journey toward equity for the military and VA has been long, slow, and uneven. There are many difficult miles yet to travel if we are to achieve liberty and justice for veteran members of racial minorities, women, and other marginalized populations. Even the PACT Act does not cover all putative exposures to toxins.⁹ Yet it is a significant step closer to fulfilling the motto of the VA LGBTQ+ program: to serve all who served.¹⁰ 

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.¹ Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.² Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.³

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.⁴

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.⁵ Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.⁶ Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.⁷ Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.⁸

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.¹ Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.² Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.³

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.⁴

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.⁵ Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.⁶ Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.⁷ Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.⁸

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.¹ Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.² Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.³

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.⁴

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.⁵ Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.⁶ Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.⁷ Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.⁸

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

The US Department of Veterans Affairs (VA) is the largest integrated health care system in the United States, providing care for more than 9 million veterans.¹ With veterans experiencing mental health conditions like posttraumatic stress disorder (PTSD), substance use disorders, and other serious mental illnesses (SMI) at higher rates compared with the general population, the VA plays an important role in the provision of mental health services.^2-5 Since the implementation of its Mental Health Strategic Plan in 2004, the VA has overseen the development of a wide array of mental health programs geared toward the complex needs of veterans. Research has demonstrated VA care outperforming Medicaid-reimbursed services in terms of the percentage of veterans filling antidepressants for at least 12 weeks after initiation of treatment for major depressive disorder (MDD), as well as posthospitalization follow-up.⁶

Eligible veterans enrolled in the VA often also seek non-VA care. Medicaid covers nearly 10% of all nonelderly veterans, and of these veterans, 39% rely solely on Medicaid for health care access.⁷ Today, Medicaid is the largest payer for mental health services in the US, providing coverage for approximately 27% of Americans who have SMI and helping fulfill unmet mental health needs.^8,9 Understanding which of these systems veterans choose to use, and under which circumstances, is essential in guiding the allocation of limited health care resources.¹⁰

Beyond Medicaid, alternatives to VA care may include TRICARE, Medicare, Indian Health Services, and employer-based or self-purchased private insurance. While these options potentially increase convenience, choice, and access to health care practitioners (HCPs) and services not available at local VA systems, cross-system utilization with poor integration may cause care coordination and continuity problems, such as medication mismanagement and opioid overdose, unnecessary duplicate utilization, and possible increased mortality.^11-15 As recent national legislative changes, such as the Patient Protection and Affordable Care Act (ACA), Veterans Access, Choice and Accountability Act, and the VA MISSION Act, continue to shift the health care landscape for veterans, questions surrounding how veterans are changing their health care use become significant.^16,17

Here, we approach the impacts of Medicaid expansion on veterans’ reliance on the VA for mental health services with a unique lens. We leverage a difference-in-difference design to study 2 historical Medicaid expansions in Arizona (AZ) and New York (NY), which extended eligibility to childless adults in 2001. Prior Medicaid dual-eligible mental health research investigated reliance shifts during the immediate postenrollment year in a subset of veterans newly enrolled in Medicaid.¹⁸ However, this study took place in a period of relative policy stability. In contrast, we investigate the potential effects of a broad policy shift by analyzing state-level changes in veterans’ reliance over 6 years after a statewide Medicaid expansion. We match expansion states with demographically similar nonexpansion states to account for unobserved trends and confounding effects. Prior studies have used this method to evaluate post-Medicaid expansion mortality changes and changes in veteran dual enrollment and hospitalizations.^10,19 While a study of ACA Medicaid expansion states would be ideal, Medicaid data from most states were only available through 2014 at the time of this analysis. Our study offers a quasi-experimental framework leveraging longitudinal data that can be applied as more post-ACA data become available.

Given the rising incidence of suicide among veterans, understanding care-seeking behaviors for depression among veterans is important as it is the most common psychiatric condition found in those who died by suicide.^20,21 Furthermore, depression may be useful as a clinical proxy for mental health policy impacts, given that the Patient Health Questionnaire-9 (PHQ-9) screening tool is well validated and increasingly research accessible, and it is a chronic condition responsive to both well-managed pharmacologic treatment and psychotherapeutic interventions.^22,23

In this study, we quantify the change in care-seeking behavior for depression among veterans after Medicaid expansion, using a quasi-experimental design. We hypothesize that new access to Medicaid would be associated with a shift away from using VA services for depression. Given the income-dependent eligibility requirements of Medicaid, we also hypothesize that veterans who qualified for VA coverage due to low income, determined by a regional means test (Priority group 5, “income-eligible”), would be more likely to shift care compared with those whose serviced-connected conditions related to their military service (Priority groups 1-4, “service-connected”) provide VA access.

Methods

To investigate the relative changes in veterans’ reliance on the VA for depression care after the 2001 NY and AZ Medicaid expansions We used a retrospective, difference-in-difference analysis. Our comparison pairings, based on prior demographic analyses were as follows: NY with Pennsylvania(PA); AZ with New Mexico and Nevada (NM/NV).¹⁹ The time frame of our analysis was 1999 to 2006, with pre- and postexpansion periods defined as 1999 to 2000 and 2001 to 2006, respectively.

Data

We included veterans aged 18 to 64 years, seeking care for depression from 1999 to 2006, who were also VA-enrolled and residing in our states of interest. We counted veterans as enrolled in Medicaid if they were enrolled at least 1 month in a given year.

Using similar methods like those used in prior studies, we selected patients with encounters documenting depression as the primary outpatient or inpatient diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 296.2x for a single episode of major depressive disorder, 296.3x for a recurrent episode of MDD, 300.4 for dysthymia, and 311.0 for depression not otherwise specified.^18,24 We used data from the Medicaid Analytic eXtract files (MAX) for Medicaid data and the VA Corporate Data Warehouse (CDW) for VA data. We chose 1999 as the first study year because it was the earliest year MAX data were available.

Our final sample included 1833 person-years pre-expansion and 7157 postexpansion in our inpatient analysis, as well as 31,767 person-years pre-expansion and 130,382 postexpansion in our outpatient analysis.

Outcomes and Variables

Our primary outcomes were comparative shifts in VA reliance between expansion and nonexpansion states after Medicaid expansion for both inpatient and outpatient depression care. For each year of study, we calculated a veteran’s VA reliance by aggregating the number of days with depression-related encounters at the VA and dividing by the total number of days with a VA or Medicaid depression-related encounters for the year. To provide context to these shifts in VA reliance, we further analyzed the changes in the proportion of annual VA-Medicaid dual users and annual per capita utilization of depression care across the VA and Medicaid. Changes in the proportion would indicate a relative shift in usage between the VA and Medicaid. Annual per capita changes demonstrate changes in the volume of usage. Understanding how proportion and volume interact is critical to understanding likely ramifications for resource management and cost. For example, a relative shift in the proportion of care toward Medicaid might be explained by a substitution effect of increased Medicaid usage and lower VA per capita usage, or an additive (or complementary) effect, with more Medicaid services coming on top of the current VA services.

We conducted subanalyses by income-eligible and service-connected veterans and adjusted our models for age, non-White race, sex, distances to the nearest inpatient and outpatient VA facilities, and VA Relative Risk Score, which is a measure of disease burden and clinical complexity validated specifically for veterans.²⁵

Statistical Analysis

We used fractional logistic regression to model the adjusted effect of Medicaid expansion on VA reliance for depression care. In parallel, we leveraged ordered logit regression and negative binomial regression models to examine the proportion of VA-Medicaid dual users and the per capita utilization of Medicaid and VA depression care, respectively. To estimate the difference-in-difference effects, we used the interaction term of 2 categorical variables—expansion vs nonexpansion states and pre- vs postexpansion status—as the independent variable. We then calculated the average marginal effects with 95% CIs to estimate the differences in outcomes between expansion and nonexpansion states from pre- to postexpansion periods, as well as year-by-year shifts as a robustness check. We conducted these analyses using Stata MP, version 15.

This project was approved by the Baylor College of Medicine Institutional Review Board (IRB # H-40441) and the Michael E. Debakey Veterans Affairs Medical Center Research and Development Committee.

Results

Baseline and postexpansion characteristics

VA Reliance

Overall, we observed postexpansion decreases in VA reliance for depression care

At the state level, reliance on the VA for inpatient depression care in NY decreased by 13.53 pp (95% CI, -22.58 to -4.49) for income-eligible veterans and 16.67 pp (95% CI, -24.53 to -8.80) for service-connected veterans. No relative differences were observed in the outpatient comparisons for both income-eligible (-0.58 pp; 95% CI, -2.13 to 0.98) and service-connected (0.05 pp; 95% CI, -1.00 to 1.10) veterans. In AZ, Medicaid expansion was associated with decreased VA reliance for outpatient depression care among income-eligible veterans (-8.60 pp; 95% CI, -10.60 to -6.61), greater than that for service-connected veterans (-2.89 pp; 95% CI, -4.02 to -1.77). This decrease in VA reliance was significant in the inpatient context only for service-connected veterans (-4.55 pp; 95% CI, -8.14 to -0.97), not income-eligible veterans (-8.38 pp; 95% CI, -17.91 to 1.16).

By applying the aggregate pp changes toward the postexpansion number of visits across both expansion and nonexpansion states, we found that expansion of Medicaid across all our study states would have resulted in 996 fewer hospitalizations and 10,109 fewer outpatient visits for depression at VA in the postexpansion period vs if no states had chosen to expand Medicaid.

Dual Use/Per Capita Utilization

Overall, Medicaid expansion was associated with greater dual use for inpatient depression care—a 0.97-pp (95% CI, 0.46 to 1.48) increase among service-connected veterans and a 0.64-pp (95% CI, 0.35 to 0.94) increase among income-eligible veterans.
At the state level, NY similarly showed increases in dual use among both service-connected (1.48 pp; 95% CI, 0.80 to 2.16) and income-eligible veterans (0.73 pp; 95% CI, 0.39 to 1.07) after Medicaid expansion. However, dual use in AZ increased significantly only among service-connected veterans (0.70 pp; 95% CI, 0.03 to 1.38), not income-eligible veterans (0.31 pp; 95% CI, -0.17 to 0.78).

Among outpatient visits, Medicaid expansion was associated with increased dual use only for income-eligible veterans (0.16 pp; 95% CI, 0.03-0.29), and not service-connected veterans (0.09 pp; 95% CI, -0.04 to 0.21). State-level analyses showed that Medicaid expansion in NY was not associated with changes in dual use for either service-connected (0.01 pp; 95% CI, -0.16 to 0.17) or income-eligible veterans (0.03 pp; 95% CI, -0.12 to 0.18), while expansion in AZ was associated with increases in dual use among both service-connected (0.42 pp; 95% CI, 0.23 to 0.61) and income-eligible veterans (0.83 pp; 95% CI, 0.59 to 1.07).

Concerning per capita utilization of depression care after Medicaid expansion, analyses showed no detectable changes for either inpatient or outpatient services, among both service-connected and income-eligible veterans. However, while this pattern held at the state level among hospitalizations, outpatient visit results showed divergent trends between AZ and NY. In NY, Medicaid expansion was associated with decreased per capita utilization of outpatient depression care among both service-connected (-0.25 visits annually; 95% CI, -0.48 to -0.01) and income-eligible veterans (-0.64 visits annually; 95% CI, -0.93 to -0.35). In AZ, Medicaid expansion was associated with increased per capita utilization of outpatient depression care among both service-connected (0.62 visits annually; 95% CI, 0.32-0.91) and income-eligible veterans (2.32 visits annually; 95% CI, 1.99-2.65).

Discussion

Our study quantified changes in depression-related health care utilization after Medicaid expansions in NY and AZ in 2001. Overall, the balance of evidence indicated that Medicaid expansion was associated with decreased reliance on the VA for depression-related services. There was an exception: income-eligible veterans in AZ did not shift their hospital care away from the VA in a statistically discernible way, although the point estimate was lower. More broadly, these findings concerning veterans’ reliance varied not only in inpatient vs outpatient services and income- vs service-connected eligibility, but also in the state-level contexts of veteran dual users and per capita utilization.

Given that the overall per capita utilization of depression care was unchanged from pre- to postexpansion periods, one might interpret the decreases in VA reliance and increases in Medicaid-VA dual users as a substitution effect from VA care to non-VA care. This could be plausible for hospitalizations where state-level analyses showed similarly stable levels of per capita utilization. However, state-level trends in our outpatient utilization analysis, especially with a substantial 2.32 pp increase in annual per capita visits among income-eligible veterans in AZ, leave open the possibility that in some cases veterans may be complementing VA care with Medicaid-reimbursed services.

The causes underlying these differences in reliance shifts between NY and AZ are likely also influenced by the policy contexts of their respective Medicaid expansions. For example, in 1999, NY passed Kendra’s Law, which established a procedure for obtaining court orders for assisted outpatient mental health treatment for individuals deemed unlikely to survive safely in the community.²⁶ A reasonable inference is that there was less unfulfilled outpatient mental health need in NY under the existing accessibility provisioned by Kendra’s Law. In addition, while both states extended coverage to childless adults under 100% of the Federal Poverty level (FPL), the AZ Medicaid expansion was via a voters’ initiative and extended family coverage to 200% FPL vs 150% FPL for families in NY. Given that the AZ Medicaid expansion enjoyed both broader public participation and generosity in terms of eligibility, its uptake and therefore effect size may have been larger than in NY for nonacute outpatient care.

Our findings contribute to the growing body of literature surrounding the changes in health care utilization after Medicaid expansion, specifically for a newly dual-eligible population of veterans seeking mental health services for depression. While prior research concerning Medicare dual-enrolled veterans has shown high reliance on the VA for both mental health diagnoses and services, scholars have established the association of Medicaid enrollment with decreased VA reliance.^27-29 Our analysis is the first to investigate state-level effects of Medicaid expansion on VA reliance for a single mental health condition using a natural experimental framework. We focus on a population that includes a large portion of veterans who are newly Medicaid-eligible due to a sweeping policy change and use demographically matched nonexpansion states to draw comparisons in VA reliance for depression care. Our findings of Medicaid expansion–associated decreases in VA reliance for depression care complement prior literature that describe Medicaid enrollment–associated decreases in VA reliance for overall mental health care.

Implications

From a systems-level perspective, the implications of shifting services away from the VA are complex and incompletely understood. The VA lacks interoperability with the electronic health records (EHRs) used by Medicaid clinicians. Consequently, significant issues of service duplication and incomplete clinical data exist for veterans seeking treatment outside of the VA system, posing health care quality and safety concerns.³⁰ On one hand, Medicaid access is associated with increased health care utilization attributed to filling unmet needs for Medicare dual enrollees, as well as increased prescription filling for psychiatric medications.^31,32 Furthermore, the only randomized control trial of Medicaid expansion to date was associated with a 9-pp decrease in positive screening rates for depression among those who received access at around 2 years postexpansion.³³ On the other hand, the VA has developed a mental health system tailored to the particular needs of veterans, and health care practitioners at the VA have significantly greater rates of military cultural competency compared to those in nonmilitary settings (70% vs 24% in the TRICARE network and 8% among those with no military or TRICARE affiliation).³⁴ Compared to individuals seeking mental health services with private insurance plans, veterans were about twice as likely to receive appropriate treatment for schizophrenia and depression at the VA.³⁵ These documented strengths of VA mental health care may together help explain the small absolute number of visits that were associated with shifts away from VA overall after Medicaid expansion.

Finally, it is worth considering extrinsic factors that influence utilization among newly dual-eligible veterans. For example, hospitalizations are less likely to be planned than outpatient services, translating to a greater importance of proximity to a nearby medical facility than a veteran’s preference of where to seek care. In the same vein, major VA medical centers are fewer and more distant on average than VA outpatient clinics, therefore reducing the advantage of a Medicaid-reimbursed outpatient clinic in terms of distance.³⁶ These realities may partially explain the proportionally larger shifts away from the VA for hospitalizations compared to outpatient care for depression.

These shifts in utilization after Medicaid expansion may have important implications for VA policymakers. First, more study is needed to know which types of veterans are more likely to use Medicaid instead of VA services—or use both Medicaid and VA services. Our research indicates unsurprisingly that veterans without service-connected disability ratings and eligible for VA services due to low income are more likely to use at least some Medicaid services. Further understanding of who switches will be useful for the VA both tailoring its services to those who prefer VA and for reaching out to specific types of patients who might be better served by staying within the VA system. Finally, VA clinicians and administrators can prioritize improving care coordination for those who chose to use both Medicaid and VA services.

Limitations and Future Directions

Our results should be interpreted within methodological and data limitations. With only 2 states in our sample, NY demonstrably skewed overall results, contributing 1.7 to 3 times more observations than AZ across subanalyses—a challenge also cited by Sommers and colleagues.¹⁹ Our veteran groupings were also unable to distinguish those veterans classified as service-connected who may also have qualified by income-eligible criteria (which would tend to understate the size of results) and those veterans who gained and then lost Medicaid coverage in a given year. Our study also faces limitations in generalizability and establishing causality. First, we included only 2 historical state Medicaid expansions, compared with the 38 states and Washington, DC, that have now expanded Medicaid to date under the ACA. Just in the 2 states from our study, we noted significant heterogeneity in the shifts associated with Medicaid expansion, which makes extrapolating specific trends difficult. Differences in underlying health care resources, legislation, and other external factors may limit the applicability of Medicaid expansion in the era of the ACA, as well as the Veterans Choice and MISSION acts. Second, while we leveraged a difference-in-difference analysis using demographically matched, neighboring comparison states, our findings are nevertheless drawn from observational data obviating causality. VA data for other sources of coverage such as private insurance are limited and not included in our study, and MAX datasets vary by quality across states, translating to potential gaps in our study cohort.²⁸Finally, as in any study using diagnoses, visits addressing care for depression may have been missed if other diagnoses were noted as primary (eg, VA clinicians carrying forward old diagnoses, like PTSD, on the problem list) or nondepression care visits may have been captured if a depression diagnosis was used by default.

Moving forward, our study demonstrates the potential for applying a natural experimental approach to studying dual-eligible veterans at the interface of Medicaid expansion. We focused on changes in VA reliance for the specific condition of depression and, in doing so, invite further inquiry into the impact of state mental health policy on outcomes more proximate to veterans’ outcomes. Clinical indicators, such as rates of antidepressant filling, utilization and duration of psychotherapy, and PHQ-9 scores, can similarly be investigated by natural experimental design. While current limits of administrative data and the siloing of EHRs may pose barriers to some of these avenues of research, multidisciplinary methodologies and data querying innovations such as natural language processing algorithms for clinical notes hold exciting opportunities to bridge the gap between policy and clinical efficacy.

Conclusions

This study applied a difference-in-difference analysis and found that Medicaid expansion is associated with decreases in VA reliance for both inpatient and outpatient services for depression. As additional data are generated from the Medicaid expansions of the ACA, similarly robust methods should be applied to further explore the impacts associated with such policy shifts and open the door to a better understanding of implications at the clinical level.

Acknowledgments

We acknowledge the efforts of Janine Wong, who proofread and formatted the manuscript.

The US Department of Veterans Affairs (VA) is the largest integrated health care system in the United States, providing care for more than 9 million veterans.¹ With veterans experiencing mental health conditions like posttraumatic stress disorder (PTSD), substance use disorders, and other serious mental illnesses (SMI) at higher rates compared with the general population, the VA plays an important role in the provision of mental health services.^2-5 Since the implementation of its Mental Health Strategic Plan in 2004, the VA has overseen the development of a wide array of mental health programs geared toward the complex needs of veterans. Research has demonstrated VA care outperforming Medicaid-reimbursed services in terms of the percentage of veterans filling antidepressants for at least 12 weeks after initiation of treatment for major depressive disorder (MDD), as well as posthospitalization follow-up.⁶

Eligible veterans enrolled in the VA often also seek non-VA care. Medicaid covers nearly 10% of all nonelderly veterans, and of these veterans, 39% rely solely on Medicaid for health care access.⁷ Today, Medicaid is the largest payer for mental health services in the US, providing coverage for approximately 27% of Americans who have SMI and helping fulfill unmet mental health needs.^8,9 Understanding which of these systems veterans choose to use, and under which circumstances, is essential in guiding the allocation of limited health care resources.¹⁰

Beyond Medicaid, alternatives to VA care may include TRICARE, Medicare, Indian Health Services, and employer-based or self-purchased private insurance. While these options potentially increase convenience, choice, and access to health care practitioners (HCPs) and services not available at local VA systems, cross-system utilization with poor integration may cause care coordination and continuity problems, such as medication mismanagement and opioid overdose, unnecessary duplicate utilization, and possible increased mortality.^11-15 As recent national legislative changes, such as the Patient Protection and Affordable Care Act (ACA), Veterans Access, Choice and Accountability Act, and the VA MISSION Act, continue to shift the health care landscape for veterans, questions surrounding how veterans are changing their health care use become significant.^16,17

Here, we approach the impacts of Medicaid expansion on veterans’ reliance on the VA for mental health services with a unique lens. We leverage a difference-in-difference design to study 2 historical Medicaid expansions in Arizona (AZ) and New York (NY), which extended eligibility to childless adults in 2001. Prior Medicaid dual-eligible mental health research investigated reliance shifts during the immediate postenrollment year in a subset of veterans newly enrolled in Medicaid.¹⁸ However, this study took place in a period of relative policy stability. In contrast, we investigate the potential effects of a broad policy shift by analyzing state-level changes in veterans’ reliance over 6 years after a statewide Medicaid expansion. We match expansion states with demographically similar nonexpansion states to account for unobserved trends and confounding effects. Prior studies have used this method to evaluate post-Medicaid expansion mortality changes and changes in veteran dual enrollment and hospitalizations.^10,19 While a study of ACA Medicaid expansion states would be ideal, Medicaid data from most states were only available through 2014 at the time of this analysis. Our study offers a quasi-experimental framework leveraging longitudinal data that can be applied as more post-ACA data become available.

Given the rising incidence of suicide among veterans, understanding care-seeking behaviors for depression among veterans is important as it is the most common psychiatric condition found in those who died by suicide.^20,21 Furthermore, depression may be useful as a clinical proxy for mental health policy impacts, given that the Patient Health Questionnaire-9 (PHQ-9) screening tool is well validated and increasingly research accessible, and it is a chronic condition responsive to both well-managed pharmacologic treatment and psychotherapeutic interventions.^22,23

In this study, we quantify the change in care-seeking behavior for depression among veterans after Medicaid expansion, using a quasi-experimental design. We hypothesize that new access to Medicaid would be associated with a shift away from using VA services for depression. Given the income-dependent eligibility requirements of Medicaid, we also hypothesize that veterans who qualified for VA coverage due to low income, determined by a regional means test (Priority group 5, “income-eligible”), would be more likely to shift care compared with those whose serviced-connected conditions related to their military service (Priority groups 1-4, “service-connected”) provide VA access.

Methods

To investigate the relative changes in veterans’ reliance on the VA for depression care after the 2001 NY and AZ Medicaid expansions We used a retrospective, difference-in-difference analysis. Our comparison pairings, based on prior demographic analyses were as follows: NY with Pennsylvania(PA); AZ with New Mexico and Nevada (NM/NV).¹⁹ The time frame of our analysis was 1999 to 2006, with pre- and postexpansion periods defined as 1999 to 2000 and 2001 to 2006, respectively.

Data

We included veterans aged 18 to 64 years, seeking care for depression from 1999 to 2006, who were also VA-enrolled and residing in our states of interest. We counted veterans as enrolled in Medicaid if they were enrolled at least 1 month in a given year.

Using similar methods like those used in prior studies, we selected patients with encounters documenting depression as the primary outpatient or inpatient diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 296.2x for a single episode of major depressive disorder, 296.3x for a recurrent episode of MDD, 300.4 for dysthymia, and 311.0 for depression not otherwise specified.^18,24 We used data from the Medicaid Analytic eXtract files (MAX) for Medicaid data and the VA Corporate Data Warehouse (CDW) for VA data. We chose 1999 as the first study year because it was the earliest year MAX data were available.

Our final sample included 1833 person-years pre-expansion and 7157 postexpansion in our inpatient analysis, as well as 31,767 person-years pre-expansion and 130,382 postexpansion in our outpatient analysis.

Outcomes and Variables

Our primary outcomes were comparative shifts in VA reliance between expansion and nonexpansion states after Medicaid expansion for both inpatient and outpatient depression care. For each year of study, we calculated a veteran’s VA reliance by aggregating the number of days with depression-related encounters at the VA and dividing by the total number of days with a VA or Medicaid depression-related encounters for the year. To provide context to these shifts in VA reliance, we further analyzed the changes in the proportion of annual VA-Medicaid dual users and annual per capita utilization of depression care across the VA and Medicaid. Changes in the proportion would indicate a relative shift in usage between the VA and Medicaid. Annual per capita changes demonstrate changes in the volume of usage. Understanding how proportion and volume interact is critical to understanding likely ramifications for resource management and cost. For example, a relative shift in the proportion of care toward Medicaid might be explained by a substitution effect of increased Medicaid usage and lower VA per capita usage, or an additive (or complementary) effect, with more Medicaid services coming on top of the current VA services.

We conducted subanalyses by income-eligible and service-connected veterans and adjusted our models for age, non-White race, sex, distances to the nearest inpatient and outpatient VA facilities, and VA Relative Risk Score, which is a measure of disease burden and clinical complexity validated specifically for veterans.²⁵

Statistical Analysis

We used fractional logistic regression to model the adjusted effect of Medicaid expansion on VA reliance for depression care. In parallel, we leveraged ordered logit regression and negative binomial regression models to examine the proportion of VA-Medicaid dual users and the per capita utilization of Medicaid and VA depression care, respectively. To estimate the difference-in-difference effects, we used the interaction term of 2 categorical variables—expansion vs nonexpansion states and pre- vs postexpansion status—as the independent variable. We then calculated the average marginal effects with 95% CIs to estimate the differences in outcomes between expansion and nonexpansion states from pre- to postexpansion periods, as well as year-by-year shifts as a robustness check. We conducted these analyses using Stata MP, version 15.

This project was approved by the Baylor College of Medicine Institutional Review Board (IRB # H-40441) and the Michael E. Debakey Veterans Affairs Medical Center Research and Development Committee.

Results

Baseline and postexpansion characteristics

VA Reliance

Overall, we observed postexpansion decreases in VA reliance for depression care

At the state level, reliance on the VA for inpatient depression care in NY decreased by 13.53 pp (95% CI, -22.58 to -4.49) for income-eligible veterans and 16.67 pp (95% CI, -24.53 to -8.80) for service-connected veterans. No relative differences were observed in the outpatient comparisons for both income-eligible (-0.58 pp; 95% CI, -2.13 to 0.98) and service-connected (0.05 pp; 95% CI, -1.00 to 1.10) veterans. In AZ, Medicaid expansion was associated with decreased VA reliance for outpatient depression care among income-eligible veterans (-8.60 pp; 95% CI, -10.60 to -6.61), greater than that for service-connected veterans (-2.89 pp; 95% CI, -4.02 to -1.77). This decrease in VA reliance was significant in the inpatient context only for service-connected veterans (-4.55 pp; 95% CI, -8.14 to -0.97), not income-eligible veterans (-8.38 pp; 95% CI, -17.91 to 1.16).

By applying the aggregate pp changes toward the postexpansion number of visits across both expansion and nonexpansion states, we found that expansion of Medicaid across all our study states would have resulted in 996 fewer hospitalizations and 10,109 fewer outpatient visits for depression at VA in the postexpansion period vs if no states had chosen to expand Medicaid.

Dual Use/Per Capita Utilization

Overall, Medicaid expansion was associated with greater dual use for inpatient depression care—a 0.97-pp (95% CI, 0.46 to 1.48) increase among service-connected veterans and a 0.64-pp (95% CI, 0.35 to 0.94) increase among income-eligible veterans.
At the state level, NY similarly showed increases in dual use among both service-connected (1.48 pp; 95% CI, 0.80 to 2.16) and income-eligible veterans (0.73 pp; 95% CI, 0.39 to 1.07) after Medicaid expansion. However, dual use in AZ increased significantly only among service-connected veterans (0.70 pp; 95% CI, 0.03 to 1.38), not income-eligible veterans (0.31 pp; 95% CI, -0.17 to 0.78).

Among outpatient visits, Medicaid expansion was associated with increased dual use only for income-eligible veterans (0.16 pp; 95% CI, 0.03-0.29), and not service-connected veterans (0.09 pp; 95% CI, -0.04 to 0.21). State-level analyses showed that Medicaid expansion in NY was not associated with changes in dual use for either service-connected (0.01 pp; 95% CI, -0.16 to 0.17) or income-eligible veterans (0.03 pp; 95% CI, -0.12 to 0.18), while expansion in AZ was associated with increases in dual use among both service-connected (0.42 pp; 95% CI, 0.23 to 0.61) and income-eligible veterans (0.83 pp; 95% CI, 0.59 to 1.07).

Concerning per capita utilization of depression care after Medicaid expansion, analyses showed no detectable changes for either inpatient or outpatient services, among both service-connected and income-eligible veterans. However, while this pattern held at the state level among hospitalizations, outpatient visit results showed divergent trends between AZ and NY. In NY, Medicaid expansion was associated with decreased per capita utilization of outpatient depression care among both service-connected (-0.25 visits annually; 95% CI, -0.48 to -0.01) and income-eligible veterans (-0.64 visits annually; 95% CI, -0.93 to -0.35). In AZ, Medicaid expansion was associated with increased per capita utilization of outpatient depression care among both service-connected (0.62 visits annually; 95% CI, 0.32-0.91) and income-eligible veterans (2.32 visits annually; 95% CI, 1.99-2.65).

Discussion

Our study quantified changes in depression-related health care utilization after Medicaid expansions in NY and AZ in 2001. Overall, the balance of evidence indicated that Medicaid expansion was associated with decreased reliance on the VA for depression-related services. There was an exception: income-eligible veterans in AZ did not shift their hospital care away from the VA in a statistically discernible way, although the point estimate was lower. More broadly, these findings concerning veterans’ reliance varied not only in inpatient vs outpatient services and income- vs service-connected eligibility, but also in the state-level contexts of veteran dual users and per capita utilization.

Given that the overall per capita utilization of depression care was unchanged from pre- to postexpansion periods, one might interpret the decreases in VA reliance and increases in Medicaid-VA dual users as a substitution effect from VA care to non-VA care. This could be plausible for hospitalizations where state-level analyses showed similarly stable levels of per capita utilization. However, state-level trends in our outpatient utilization analysis, especially with a substantial 2.32 pp increase in annual per capita visits among income-eligible veterans in AZ, leave open the possibility that in some cases veterans may be complementing VA care with Medicaid-reimbursed services.

The causes underlying these differences in reliance shifts between NY and AZ are likely also influenced by the policy contexts of their respective Medicaid expansions. For example, in 1999, NY passed Kendra’s Law, which established a procedure for obtaining court orders for assisted outpatient mental health treatment for individuals deemed unlikely to survive safely in the community.²⁶ A reasonable inference is that there was less unfulfilled outpatient mental health need in NY under the existing accessibility provisioned by Kendra’s Law. In addition, while both states extended coverage to childless adults under 100% of the Federal Poverty level (FPL), the AZ Medicaid expansion was via a voters’ initiative and extended family coverage to 200% FPL vs 150% FPL for families in NY. Given that the AZ Medicaid expansion enjoyed both broader public participation and generosity in terms of eligibility, its uptake and therefore effect size may have been larger than in NY for nonacute outpatient care.

Our findings contribute to the growing body of literature surrounding the changes in health care utilization after Medicaid expansion, specifically for a newly dual-eligible population of veterans seeking mental health services for depression. While prior research concerning Medicare dual-enrolled veterans has shown high reliance on the VA for both mental health diagnoses and services, scholars have established the association of Medicaid enrollment with decreased VA reliance.^27-29 Our analysis is the first to investigate state-level effects of Medicaid expansion on VA reliance for a single mental health condition using a natural experimental framework. We focus on a population that includes a large portion of veterans who are newly Medicaid-eligible due to a sweeping policy change and use demographically matched nonexpansion states to draw comparisons in VA reliance for depression care. Our findings of Medicaid expansion–associated decreases in VA reliance for depression care complement prior literature that describe Medicaid enrollment–associated decreases in VA reliance for overall mental health care.

Implications

From a systems-level perspective, the implications of shifting services away from the VA are complex and incompletely understood. The VA lacks interoperability with the electronic health records (EHRs) used by Medicaid clinicians. Consequently, significant issues of service duplication and incomplete clinical data exist for veterans seeking treatment outside of the VA system, posing health care quality and safety concerns.³⁰ On one hand, Medicaid access is associated with increased health care utilization attributed to filling unmet needs for Medicare dual enrollees, as well as increased prescription filling for psychiatric medications.^31,32 Furthermore, the only randomized control trial of Medicaid expansion to date was associated with a 9-pp decrease in positive screening rates for depression among those who received access at around 2 years postexpansion.³³ On the other hand, the VA has developed a mental health system tailored to the particular needs of veterans, and health care practitioners at the VA have significantly greater rates of military cultural competency compared to those in nonmilitary settings (70% vs 24% in the TRICARE network and 8% among those with no military or TRICARE affiliation).³⁴ Compared to individuals seeking mental health services with private insurance plans, veterans were about twice as likely to receive appropriate treatment for schizophrenia and depression at the VA.³⁵ These documented strengths of VA mental health care may together help explain the small absolute number of visits that were associated with shifts away from VA overall after Medicaid expansion.

Finally, it is worth considering extrinsic factors that influence utilization among newly dual-eligible veterans. For example, hospitalizations are less likely to be planned than outpatient services, translating to a greater importance of proximity to a nearby medical facility than a veteran’s preference of where to seek care. In the same vein, major VA medical centers are fewer and more distant on average than VA outpatient clinics, therefore reducing the advantage of a Medicaid-reimbursed outpatient clinic in terms of distance.³⁶ These realities may partially explain the proportionally larger shifts away from the VA for hospitalizations compared to outpatient care for depression.

These shifts in utilization after Medicaid expansion may have important implications for VA policymakers. First, more study is needed to know which types of veterans are more likely to use Medicaid instead of VA services—or use both Medicaid and VA services. Our research indicates unsurprisingly that veterans without service-connected disability ratings and eligible for VA services due to low income are more likely to use at least some Medicaid services. Further understanding of who switches will be useful for the VA both tailoring its services to those who prefer VA and for reaching out to specific types of patients who might be better served by staying within the VA system. Finally, VA clinicians and administrators can prioritize improving care coordination for those who chose to use both Medicaid and VA services.

Limitations and Future Directions

Our results should be interpreted within methodological and data limitations. With only 2 states in our sample, NY demonstrably skewed overall results, contributing 1.7 to 3 times more observations than AZ across subanalyses—a challenge also cited by Sommers and colleagues.¹⁹ Our veteran groupings were also unable to distinguish those veterans classified as service-connected who may also have qualified by income-eligible criteria (which would tend to understate the size of results) and those veterans who gained and then lost Medicaid coverage in a given year. Our study also faces limitations in generalizability and establishing causality. First, we included only 2 historical state Medicaid expansions, compared with the 38 states and Washington, DC, that have now expanded Medicaid to date under the ACA. Just in the 2 states from our study, we noted significant heterogeneity in the shifts associated with Medicaid expansion, which makes extrapolating specific trends difficult. Differences in underlying health care resources, legislation, and other external factors may limit the applicability of Medicaid expansion in the era of the ACA, as well as the Veterans Choice and MISSION acts. Second, while we leveraged a difference-in-difference analysis using demographically matched, neighboring comparison states, our findings are nevertheless drawn from observational data obviating causality. VA data for other sources of coverage such as private insurance are limited and not included in our study, and MAX datasets vary by quality across states, translating to potential gaps in our study cohort.²⁸Finally, as in any study using diagnoses, visits addressing care for depression may have been missed if other diagnoses were noted as primary (eg, VA clinicians carrying forward old diagnoses, like PTSD, on the problem list) or nondepression care visits may have been captured if a depression diagnosis was used by default.

Moving forward, our study demonstrates the potential for applying a natural experimental approach to studying dual-eligible veterans at the interface of Medicaid expansion. We focused on changes in VA reliance for the specific condition of depression and, in doing so, invite further inquiry into the impact of state mental health policy on outcomes more proximate to veterans’ outcomes. Clinical indicators, such as rates of antidepressant filling, utilization and duration of psychotherapy, and PHQ-9 scores, can similarly be investigated by natural experimental design. While current limits of administrative data and the siloing of EHRs may pose barriers to some of these avenues of research, multidisciplinary methodologies and data querying innovations such as natural language processing algorithms for clinical notes hold exciting opportunities to bridge the gap between policy and clinical efficacy.

Conclusions

This study applied a difference-in-difference analysis and found that Medicaid expansion is associated with decreases in VA reliance for both inpatient and outpatient services for depression. As additional data are generated from the Medicaid expansions of the ACA, similarly robust methods should be applied to further explore the impacts associated with such policy shifts and open the door to a better understanding of implications at the clinical level.

Acknowledgments

We acknowledge the efforts of Janine Wong, who proofread and formatted the manuscript.

The US Department of Veterans Affairs (VA) is the largest integrated health care system in the United States, providing care for more than 9 million veterans.¹ With veterans experiencing mental health conditions like posttraumatic stress disorder (PTSD), substance use disorders, and other serious mental illnesses (SMI) at higher rates compared with the general population, the VA plays an important role in the provision of mental health services.^2-5 Since the implementation of its Mental Health Strategic Plan in 2004, the VA has overseen the development of a wide array of mental health programs geared toward the complex needs of veterans. Research has demonstrated VA care outperforming Medicaid-reimbursed services in terms of the percentage of veterans filling antidepressants for at least 12 weeks after initiation of treatment for major depressive disorder (MDD), as well as posthospitalization follow-up.⁶

Eligible veterans enrolled in the VA often also seek non-VA care. Medicaid covers nearly 10% of all nonelderly veterans, and of these veterans, 39% rely solely on Medicaid for health care access.⁷ Today, Medicaid is the largest payer for mental health services in the US, providing coverage for approximately 27% of Americans who have SMI and helping fulfill unmet mental health needs.^8,9 Understanding which of these systems veterans choose to use, and under which circumstances, is essential in guiding the allocation of limited health care resources.¹⁰

Beyond Medicaid, alternatives to VA care may include TRICARE, Medicare, Indian Health Services, and employer-based or self-purchased private insurance. While these options potentially increase convenience, choice, and access to health care practitioners (HCPs) and services not available at local VA systems, cross-system utilization with poor integration may cause care coordination and continuity problems, such as medication mismanagement and opioid overdose, unnecessary duplicate utilization, and possible increased mortality.^11-15 As recent national legislative changes, such as the Patient Protection and Affordable Care Act (ACA), Veterans Access, Choice and Accountability Act, and the VA MISSION Act, continue to shift the health care landscape for veterans, questions surrounding how veterans are changing their health care use become significant.^16,17

Here, we approach the impacts of Medicaid expansion on veterans’ reliance on the VA for mental health services with a unique lens. We leverage a difference-in-difference design to study 2 historical Medicaid expansions in Arizona (AZ) and New York (NY), which extended eligibility to childless adults in 2001. Prior Medicaid dual-eligible mental health research investigated reliance shifts during the immediate postenrollment year in a subset of veterans newly enrolled in Medicaid.¹⁸ However, this study took place in a period of relative policy stability. In contrast, we investigate the potential effects of a broad policy shift by analyzing state-level changes in veterans’ reliance over 6 years after a statewide Medicaid expansion. We match expansion states with demographically similar nonexpansion states to account for unobserved trends and confounding effects. Prior studies have used this method to evaluate post-Medicaid expansion mortality changes and changes in veteran dual enrollment and hospitalizations.^10,19 While a study of ACA Medicaid expansion states would be ideal, Medicaid data from most states were only available through 2014 at the time of this analysis. Our study offers a quasi-experimental framework leveraging longitudinal data that can be applied as more post-ACA data become available.

Given the rising incidence of suicide among veterans, understanding care-seeking behaviors for depression among veterans is important as it is the most common psychiatric condition found in those who died by suicide.^20,21 Furthermore, depression may be useful as a clinical proxy for mental health policy impacts, given that the Patient Health Questionnaire-9 (PHQ-9) screening tool is well validated and increasingly research accessible, and it is a chronic condition responsive to both well-managed pharmacologic treatment and psychotherapeutic interventions.^22,23

In this study, we quantify the change in care-seeking behavior for depression among veterans after Medicaid expansion, using a quasi-experimental design. We hypothesize that new access to Medicaid would be associated with a shift away from using VA services for depression. Given the income-dependent eligibility requirements of Medicaid, we also hypothesize that veterans who qualified for VA coverage due to low income, determined by a regional means test (Priority group 5, “income-eligible”), would be more likely to shift care compared with those whose serviced-connected conditions related to their military service (Priority groups 1-4, “service-connected”) provide VA access.

Methods

To investigate the relative changes in veterans’ reliance on the VA for depression care after the 2001 NY and AZ Medicaid expansions We used a retrospective, difference-in-difference analysis. Our comparison pairings, based on prior demographic analyses were as follows: NY with Pennsylvania(PA); AZ with New Mexico and Nevada (NM/NV).¹⁹ The time frame of our analysis was 1999 to 2006, with pre- and postexpansion periods defined as 1999 to 2000 and 2001 to 2006, respectively.

Data

We included veterans aged 18 to 64 years, seeking care for depression from 1999 to 2006, who were also VA-enrolled and residing in our states of interest. We counted veterans as enrolled in Medicaid if they were enrolled at least 1 month in a given year.

Using similar methods like those used in prior studies, we selected patients with encounters documenting depression as the primary outpatient or inpatient diagnosis using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 296.2x for a single episode of major depressive disorder, 296.3x for a recurrent episode of MDD, 300.4 for dysthymia, and 311.0 for depression not otherwise specified.^18,24 We used data from the Medicaid Analytic eXtract files (MAX) for Medicaid data and the VA Corporate Data Warehouse (CDW) for VA data. We chose 1999 as the first study year because it was the earliest year MAX data were available.

Our final sample included 1833 person-years pre-expansion and 7157 postexpansion in our inpatient analysis, as well as 31,767 person-years pre-expansion and 130,382 postexpansion in our outpatient analysis.

Outcomes and Variables

Our primary outcomes were comparative shifts in VA reliance between expansion and nonexpansion states after Medicaid expansion for both inpatient and outpatient depression care. For each year of study, we calculated a veteran’s VA reliance by aggregating the number of days with depression-related encounters at the VA and dividing by the total number of days with a VA or Medicaid depression-related encounters for the year. To provide context to these shifts in VA reliance, we further analyzed the changes in the proportion of annual VA-Medicaid dual users and annual per capita utilization of depression care across the VA and Medicaid. Changes in the proportion would indicate a relative shift in usage between the VA and Medicaid. Annual per capita changes demonstrate changes in the volume of usage. Understanding how proportion and volume interact is critical to understanding likely ramifications for resource management and cost. For example, a relative shift in the proportion of care toward Medicaid might be explained by a substitution effect of increased Medicaid usage and lower VA per capita usage, or an additive (or complementary) effect, with more Medicaid services coming on top of the current VA services.

We conducted subanalyses by income-eligible and service-connected veterans and adjusted our models for age, non-White race, sex, distances to the nearest inpatient and outpatient VA facilities, and VA Relative Risk Score, which is a measure of disease burden and clinical complexity validated specifically for veterans.²⁵

Statistical Analysis

We used fractional logistic regression to model the adjusted effect of Medicaid expansion on VA reliance for depression care. In parallel, we leveraged ordered logit regression and negative binomial regression models to examine the proportion of VA-Medicaid dual users and the per capita utilization of Medicaid and VA depression care, respectively. To estimate the difference-in-difference effects, we used the interaction term of 2 categorical variables—expansion vs nonexpansion states and pre- vs postexpansion status—as the independent variable. We then calculated the average marginal effects with 95% CIs to estimate the differences in outcomes between expansion and nonexpansion states from pre- to postexpansion periods, as well as year-by-year shifts as a robustness check. We conducted these analyses using Stata MP, version 15.

This project was approved by the Baylor College of Medicine Institutional Review Board (IRB # H-40441) and the Michael E. Debakey Veterans Affairs Medical Center Research and Development Committee.

Results

Baseline and postexpansion characteristics

VA Reliance

Overall, we observed postexpansion decreases in VA reliance for depression care

At the state level, reliance on the VA for inpatient depression care in NY decreased by 13.53 pp (95% CI, -22.58 to -4.49) for income-eligible veterans and 16.67 pp (95% CI, -24.53 to -8.80) for service-connected veterans. No relative differences were observed in the outpatient comparisons for both income-eligible (-0.58 pp; 95% CI, -2.13 to 0.98) and service-connected (0.05 pp; 95% CI, -1.00 to 1.10) veterans. In AZ, Medicaid expansion was associated with decreased VA reliance for outpatient depression care among income-eligible veterans (-8.60 pp; 95% CI, -10.60 to -6.61), greater than that for service-connected veterans (-2.89 pp; 95% CI, -4.02 to -1.77). This decrease in VA reliance was significant in the inpatient context only for service-connected veterans (-4.55 pp; 95% CI, -8.14 to -0.97), not income-eligible veterans (-8.38 pp; 95% CI, -17.91 to 1.16).

By applying the aggregate pp changes toward the postexpansion number of visits across both expansion and nonexpansion states, we found that expansion of Medicaid across all our study states would have resulted in 996 fewer hospitalizations and 10,109 fewer outpatient visits for depression at VA in the postexpansion period vs if no states had chosen to expand Medicaid.

Dual Use/Per Capita Utilization

Overall, Medicaid expansion was associated with greater dual use for inpatient depression care—a 0.97-pp (95% CI, 0.46 to 1.48) increase among service-connected veterans and a 0.64-pp (95% CI, 0.35 to 0.94) increase among income-eligible veterans.
At the state level, NY similarly showed increases in dual use among both service-connected (1.48 pp; 95% CI, 0.80 to 2.16) and income-eligible veterans (0.73 pp; 95% CI, 0.39 to 1.07) after Medicaid expansion. However, dual use in AZ increased significantly only among service-connected veterans (0.70 pp; 95% CI, 0.03 to 1.38), not income-eligible veterans (0.31 pp; 95% CI, -0.17 to 0.78).

Among outpatient visits, Medicaid expansion was associated with increased dual use only for income-eligible veterans (0.16 pp; 95% CI, 0.03-0.29), and not service-connected veterans (0.09 pp; 95% CI, -0.04 to 0.21). State-level analyses showed that Medicaid expansion in NY was not associated with changes in dual use for either service-connected (0.01 pp; 95% CI, -0.16 to 0.17) or income-eligible veterans (0.03 pp; 95% CI, -0.12 to 0.18), while expansion in AZ was associated with increases in dual use among both service-connected (0.42 pp; 95% CI, 0.23 to 0.61) and income-eligible veterans (0.83 pp; 95% CI, 0.59 to 1.07).

Concerning per capita utilization of depression care after Medicaid expansion, analyses showed no detectable changes for either inpatient or outpatient services, among both service-connected and income-eligible veterans. However, while this pattern held at the state level among hospitalizations, outpatient visit results showed divergent trends between AZ and NY. In NY, Medicaid expansion was associated with decreased per capita utilization of outpatient depression care among both service-connected (-0.25 visits annually; 95% CI, -0.48 to -0.01) and income-eligible veterans (-0.64 visits annually; 95% CI, -0.93 to -0.35). In AZ, Medicaid expansion was associated with increased per capita utilization of outpatient depression care among both service-connected (0.62 visits annually; 95% CI, 0.32-0.91) and income-eligible veterans (2.32 visits annually; 95% CI, 1.99-2.65).

Discussion

Our study quantified changes in depression-related health care utilization after Medicaid expansions in NY and AZ in 2001. Overall, the balance of evidence indicated that Medicaid expansion was associated with decreased reliance on the VA for depression-related services. There was an exception: income-eligible veterans in AZ did not shift their hospital care away from the VA in a statistically discernible way, although the point estimate was lower. More broadly, these findings concerning veterans’ reliance varied not only in inpatient vs outpatient services and income- vs service-connected eligibility, but also in the state-level contexts of veteran dual users and per capita utilization.

Given that the overall per capita utilization of depression care was unchanged from pre- to postexpansion periods, one might interpret the decreases in VA reliance and increases in Medicaid-VA dual users as a substitution effect from VA care to non-VA care. This could be plausible for hospitalizations where state-level analyses showed similarly stable levels of per capita utilization. However, state-level trends in our outpatient utilization analysis, especially with a substantial 2.32 pp increase in annual per capita visits among income-eligible veterans in AZ, leave open the possibility that in some cases veterans may be complementing VA care with Medicaid-reimbursed services.

The causes underlying these differences in reliance shifts between NY and AZ are likely also influenced by the policy contexts of their respective Medicaid expansions. For example, in 1999, NY passed Kendra’s Law, which established a procedure for obtaining court orders for assisted outpatient mental health treatment for individuals deemed unlikely to survive safely in the community.²⁶ A reasonable inference is that there was less unfulfilled outpatient mental health need in NY under the existing accessibility provisioned by Kendra’s Law. In addition, while both states extended coverage to childless adults under 100% of the Federal Poverty level (FPL), the AZ Medicaid expansion was via a voters’ initiative and extended family coverage to 200% FPL vs 150% FPL for families in NY. Given that the AZ Medicaid expansion enjoyed both broader public participation and generosity in terms of eligibility, its uptake and therefore effect size may have been larger than in NY for nonacute outpatient care.

Our findings contribute to the growing body of literature surrounding the changes in health care utilization after Medicaid expansion, specifically for a newly dual-eligible population of veterans seeking mental health services for depression. While prior research concerning Medicare dual-enrolled veterans has shown high reliance on the VA for both mental health diagnoses and services, scholars have established the association of Medicaid enrollment with decreased VA reliance.^27-29 Our analysis is the first to investigate state-level effects of Medicaid expansion on VA reliance for a single mental health condition using a natural experimental framework. We focus on a population that includes a large portion of veterans who are newly Medicaid-eligible due to a sweeping policy change and use demographically matched nonexpansion states to draw comparisons in VA reliance for depression care. Our findings of Medicaid expansion–associated decreases in VA reliance for depression care complement prior literature that describe Medicaid enrollment–associated decreases in VA reliance for overall mental health care.

Implications

From a systems-level perspective, the implications of shifting services away from the VA are complex and incompletely understood. The VA lacks interoperability with the electronic health records (EHRs) used by Medicaid clinicians. Consequently, significant issues of service duplication and incomplete clinical data exist for veterans seeking treatment outside of the VA system, posing health care quality and safety concerns.³⁰ On one hand, Medicaid access is associated with increased health care utilization attributed to filling unmet needs for Medicare dual enrollees, as well as increased prescription filling for psychiatric medications.^31,32 Furthermore, the only randomized control trial of Medicaid expansion to date was associated with a 9-pp decrease in positive screening rates for depression among those who received access at around 2 years postexpansion.³³ On the other hand, the VA has developed a mental health system tailored to the particular needs of veterans, and health care practitioners at the VA have significantly greater rates of military cultural competency compared to those in nonmilitary settings (70% vs 24% in the TRICARE network and 8% among those with no military or TRICARE affiliation).³⁴ Compared to individuals seeking mental health services with private insurance plans, veterans were about twice as likely to receive appropriate treatment for schizophrenia and depression at the VA.³⁵ These documented strengths of VA mental health care may together help explain the small absolute number of visits that were associated with shifts away from VA overall after Medicaid expansion.

Finally, it is worth considering extrinsic factors that influence utilization among newly dual-eligible veterans. For example, hospitalizations are less likely to be planned than outpatient services, translating to a greater importance of proximity to a nearby medical facility than a veteran’s preference of where to seek care. In the same vein, major VA medical centers are fewer and more distant on average than VA outpatient clinics, therefore reducing the advantage of a Medicaid-reimbursed outpatient clinic in terms of distance.³⁶ These realities may partially explain the proportionally larger shifts away from the VA for hospitalizations compared to outpatient care for depression.

These shifts in utilization after Medicaid expansion may have important implications for VA policymakers. First, more study is needed to know which types of veterans are more likely to use Medicaid instead of VA services—or use both Medicaid and VA services. Our research indicates unsurprisingly that veterans without service-connected disability ratings and eligible for VA services due to low income are more likely to use at least some Medicaid services. Further understanding of who switches will be useful for the VA both tailoring its services to those who prefer VA and for reaching out to specific types of patients who might be better served by staying within the VA system. Finally, VA clinicians and administrators can prioritize improving care coordination for those who chose to use both Medicaid and VA services.

Limitations and Future Directions

Our results should be interpreted within methodological and data limitations. With only 2 states in our sample, NY demonstrably skewed overall results, contributing 1.7 to 3 times more observations than AZ across subanalyses—a challenge also cited by Sommers and colleagues.¹⁹ Our veteran groupings were also unable to distinguish those veterans classified as service-connected who may also have qualified by income-eligible criteria (which would tend to understate the size of results) and those veterans who gained and then lost Medicaid coverage in a given year. Our study also faces limitations in generalizability and establishing causality. First, we included only 2 historical state Medicaid expansions, compared with the 38 states and Washington, DC, that have now expanded Medicaid to date under the ACA. Just in the 2 states from our study, we noted significant heterogeneity in the shifts associated with Medicaid expansion, which makes extrapolating specific trends difficult. Differences in underlying health care resources, legislation, and other external factors may limit the applicability of Medicaid expansion in the era of the ACA, as well as the Veterans Choice and MISSION acts. Second, while we leveraged a difference-in-difference analysis using demographically matched, neighboring comparison states, our findings are nevertheless drawn from observational data obviating causality. VA data for other sources of coverage such as private insurance are limited and not included in our study, and MAX datasets vary by quality across states, translating to potential gaps in our study cohort.²⁸Finally, as in any study using diagnoses, visits addressing care for depression may have been missed if other diagnoses were noted as primary (eg, VA clinicians carrying forward old diagnoses, like PTSD, on the problem list) or nondepression care visits may have been captured if a depression diagnosis was used by default.

Moving forward, our study demonstrates the potential for applying a natural experimental approach to studying dual-eligible veterans at the interface of Medicaid expansion. We focused on changes in VA reliance for the specific condition of depression and, in doing so, invite further inquiry into the impact of state mental health policy on outcomes more proximate to veterans’ outcomes. Clinical indicators, such as rates of antidepressant filling, utilization and duration of psychotherapy, and PHQ-9 scores, can similarly be investigated by natural experimental design. While current limits of administrative data and the siloing of EHRs may pose barriers to some of these avenues of research, multidisciplinary methodologies and data querying innovations such as natural language processing algorithms for clinical notes hold exciting opportunities to bridge the gap between policy and clinical efficacy.

Conclusions

This study applied a difference-in-difference analysis and found that Medicaid expansion is associated with decreases in VA reliance for both inpatient and outpatient services for depression. As additional data are generated from the Medicaid expansions of the ACA, similarly robust methods should be applied to further explore the impacts associated with such policy shifts and open the door to a better understanding of implications at the clinical level.

Acknowledgments

We acknowledge the efforts of Janine Wong, who proofread and formatted the manuscript.

Schizophrenia spectrum disorders (SSDs) represent some of the most debilitating mental health disorders.¹ While these disorders have myriad presentations, the prototypical patient with SSD is often thought to possess positive symptoms. More recently, clinicians and researchers are raising awareness of another presentation of SSD: predominantly negative and cognitive symptoms. This symptom profile is not a novel phenomenon; for many years this presentation was recognized as a “deficit” presentation, referring to negative symptoms as the prominent feature.^2,3 However, it presents unique diagnostic and treatment considerations that are often underappreciated in clinical settings.

Negative symptoms (blunted/flat affect, avolition, alogia, anhedonia, asociality) have long been identified as key features of SSD and are widely recognized as predictive of poor prognostic outcomes for patients with SSDs.¹ In many patients, negative symptoms may precede the development of positive symptoms and emerge as a more robust predictor of functional outcomes than positive symptoms.¹ Negative symptoms also appear to be inextricably linked to cognitive symptoms. Specifically, patients with primary negative symptoms seem to perform poorly on measures of global cognitive functioning.¹ Similar to negative symptoms, cognitive symptoms of SSDs are a primary source of functional impairment and persistent disability.¹ Despite this, little attention is given in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to the neurocognitive and social cognitive deficits seen in patients with SSDs. Previous research highlights broad deficits in a range of neurocognitive abilities, including attention, working memory, processing speed, executive functioning, learning and memory, and receptive and expressive language.⁴ Similarly, patients also display deficits in domains of social cognition, such as emotion processing, identifying and utilizing social cues, evaluating attributions of others, and perspective-taking.⁵

A predominantly negative and cognitive symptom presentation can present diagnostic and treatment challenges. We present a case of a patient with such a presentation and the unique considerations given to diagnostic clarification and her treatment.

Case Presentation

A 33-year-old female veteran presented to the emergency department (ED) at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, in 2020. She was brought to the ED by local police following an attempted assault of her neighbor. Per collateral information from the police, the veteran stated she “had the urge to hurt someone” but was unable to provide any other information about this event. The veteran demonstrated diminished speech output, providing 2- to 3-word responses before refusing to speak entirely. She also presented with markedly blunted affect and tangential speech. She was not oriented to situation, stating confusion as to how she was brought to the hospital, and appeared to be responding to internal stimuli. She was subsequently admitted to the inpatient mental health unit due to unspecified psychosis.

The veteran presented as an unreliable historian, and much of her medical history was obtained via a review of US Department of Defense (DoD) records and collateral interview with her parents. Before her hospitalization, the veteran had been diagnosed with major depressive disorder (MDD) and adjustment disorder while serving in the Navy. Her psychiatric history before her military career was otherwise unremarkable. At that time, she began a trial of sertraline 50 mg and completed 10 sessions of psychotherapy. After approximately 1 year, she elected to stop taking sertraline due to improved mental health. However, shortly after this she began experiencing significant depressive symptoms and was ultimately released early from the Navy due to her mental health concerns.

The veteran’s parents provided interim history between her discharge and establishing care at MEDVAMC as the veteran was reluctant to discuss this period of her life. According to her parents the veteran had prior diagnoses of borderline personality disorder and MDD and had difficulty adhering to her current medications (bupropion and duloxetine) for about 1 month before her hospitalization. During the previous month, her parents observed her staying in her room around the clock and “[going] mute.”

The veteran remained hospitalized for about 1 month, during which she was diagnosed with schizoaffective disorder and stabilized on injections of long-acting olanzapine 210 mg (administered every 2 weeks). She was referred for outpatient psychotherapy in a specialty clinic for veterans with SSDs. However, she did not attend her initial intake assessment.

About 2 weeks after discharge from the hospital, the veteran presented for her injection appointment. At this time, she was noted to be disorganized in her thinking and behavior, displaying thought blocking and catatonic behavior. Her parents also described concerning behavior since her discharge. They stated she went to a hotel after her discharge and spent all her available money. She then returned to her parents’ home, where she did not sleep or bathe for several days. She was observed wandering around the house aimlessly and in a confused manner and had become verbally aggressive and threatening toward her parents. The veteran was again psychiatrically admitted due to psychosis and concerns for her safety. She was discharged about 2 weeks later and continued olanzapine injections. She was also referred for outpatient psychotherapy; although she did not initially engage in psychotherapy, she was referred again about 5 months after discharge and began psychotherapy at that time.

The veteran began a course of weekly outpatient psychotherapy employing cognitive behavior therapy for psychosis (CBTp).⁶ During this time, she described her primary concerns as anxiety and feeling disconnected from others. She reported a history of depression but not of schizoaffective disorder. When asked about this, the veteran stated that she did not feel this diagnosis was accurate and instead believed she had severe depression. When asked why she was prescribed olanzapine, the veteran stated that this medication was for depression. As with her inpatient stays, the veteran demonstrated several negative symptoms during her course of psychotherapy. She presented with noticeably blunted affect, evidenced by lack of facial expression and monotonic speech. She also routinely displayed alogia (ie, lack of speech), often stating that she “did not feel like talking much.” She described difficulty finding motivation to initiate tasks (avolition) as well as a tendency toward social isolation (asociality).

The veteran also described concerns related to neurocognitive and social cognitive symptoms. She reported difficulties in processing speed, cognitive set-shifting (mentally switching between tasks), and inhibition, describing how these concerns interfered with her occupational functioning. She noted difficulty maintaining the expected pace of work at her previous positions, stating that she felt it took her longer to complete tasks compared with others. In addition, she displayed some difficulties with attention and memory. On more than one occasion, she seemed to have forgotten the previous day’s conversations with clinicians. Regarding social cognitive symptoms, she noted difficulties in emotion processing, indicating that it was difficult for her to identify and manage her emotions. This was especially prominent during times of depressed mood.

She also displayed a hostile attribution bias, or tendency to overattribute hostile intent to others’ ambiguous actions. For example, she described an instance where a family member sat too close to her on the couch, stating that she felt this behavior indicated the family member did not care about her. Relatedly, the veteran demonstrated difficulty with perspective taking, which became evident during cognitive restructuring regarding interpretations of her family’s behavior. Finally, the veteran displayed some deficits in social perception, or the ability to identify social context and rules based on nonverbal communication, verbal cues, and vocal intonation. She stated that she often felt conversing with others was difficult for her and indicated that she was “not good at conversations.” This may have in part been due to deficits in social perception.

During the first 2 months of psychotherapy, the veteran regularly attended sessions (conducted over telephone due to the COVID-19 pandemic) and was adherent to twice-weekly olanzapine injections. Despite this, she began experiencing an increase in depressive symptoms accompanied by a noticeable worsening of her blunted affect, alogia, and avolition. After about 2 months of psychotherapy, she described active suicidal ideation and requested to be voluntarily hospitalized. During this hospitalization, the veteran was consulted about the use of clozapine in treatment-refractory conditions and began a trial of clozapine 400 mg. She demonstrated marked improvement in her depressed mood after taking the medication and was discharged about 2 weeks after admission. The veteran completed 10 sessions of CBTp before electing to terminate due to an upcoming move. She was adherent to weekly blood draws per the requirements of clozapine and described intentions to engage in mental health care after her move. The patient’s mother contacted the clinic to inform the treatment team that the patient and her family had moved to a different city and the patient had started receiving care at the VAMC in that city.

Discussion

As the veteran’s case highlights, a predominantly negative and cognitive symptom presentation may present diagnostic challenges. Since this presentation may not be viewed as representative of SSDs, patients with this presentation may be misdiagnosed. This was evident in the current case, not only in the veteran’s prodromal phase of illness while in the Navy, but also in her reported previous diagnoses of borderline personality disorder and MDD. More than one clinician at the MEDVAMC provisionally considered a diagnosis of MDD before collecting collateral information from the veteran’s family regarding her clear psychotic symptoms. Unfortunately, such misdiagnoses may have prevented early intervention of the veteran’s schizoaffective disorder, which is found to be instrumental in reducing impairment and disability among patients with SSDs.^7,8

These misdiagnoses are understandable given the considerable symptom overlap between SSDs and other mental health disorders. For instance, anhedonia and avolition are 2 key symptoms seen in depressive episodes. Both anhedonia and lack of positive emotion are often seen in posttraumatic stress disorder. Additionally, anxiety disorders may induce a lack of positive emotion, loss of interest in previously enjoyed activities, and lack of motivation secondary to primary symptoms of anxiety. Furthermore, schizoaffective disorder requires the presence of a major mood episode. In the absence of apparent positive symptoms (as is the case for patients with a predominantly negative symptom presentation), schizoaffective disorder may be easily misdiagnosed as a mood disorder.

Patients with predominantly negative or cognitive symptoms may also be less accepting of a diagnosis of SSD. A wealth of research points to the clear stigma of SSDs, with many suggesting that these disorders are among the most stigmatized mental health disorders.⁹ Therefore, patients with predominantly negative and cognitive symptoms may be more likely to attribute their symptoms to another, less stigmatized mental health disorder. This was seen in the current case, as the veteran repeatedly denied a diagnosis of schizoaffective disorder and instead claimed to have severe depression. This reluctance to accept a diagnosis of an SSD, coupled with the diagnostic ambiguity of negative symptoms, is likely to make it challenging for clinicians to accurately identify patients with a predominantly negative and cognitive symptom presentation of SSDs.

Clinicians working within a team-based setting may be less likely to misdiagnose patients as they can consult others. Diagnostic clarity in the current case was undoubtedly facilitated by the multidisciplinary team involved in the veteran’s care; clinicians involved in her care were able to consult with one another to determine that her symptoms were indicative of an SSD rather than a mood disorder. Mental health professionals in private practice are unlikely to have access to such multidisciplinary specialty services and may be particularly vulnerable to misdiagnoses.

Treatment Considerations

This case also highlights several psychotherapy and psychopharmacology treatment considerations for patients with a predominantly negative and cognitive symptom presentation. The veteran was initially difficult to engage in psychotherapy. Although patients with SSDs often have difficulty engaging in treatment, patients with a predominant negative and cognitive symptom profile may experience more difficulty doing so.¹⁰ Previous research suggests that both negative symptoms and cognitive symptoms are inversely related to treatment engagement.^11,12

By their very nature, negative symptoms may make it difficult to fully engage in psychotherapy. First, avolition and amotivation likely make it difficult for patients to attend psychotherapy appointments. Furthermore, negative symptoms may make it difficult to emotionally engage with the content of psychotherapy, thus limiting the potential benefits. Cognitive symptoms may also make it more difficult for patients to fully reap the benefits of psychotherapy. Deficits in attention, memory, and abstract reasoning seen in other mental health and medical conditions are associated with poorer treatment outcomes in psychotherapy.^13,14 Thus, it may be especially difficult to engage patients with primarily negative and cognitive symptoms of SSDs in psychotherapy. However, given the link between these symptoms and functional impairment, it is even more important to evaluate and address such barriers to treatment.

This case highlights the utility of clozapine in the treatment of SSDs. Many commonly prescribed antipsychotic medications have questionable efficacy in treating negative symptoms, and none of the currently available antipsychotics are approved for this indication.¹⁵ In our case, the veteran saw a limited reduction of her negative or cognitive symptoms from her use of olanzapine. However, case reports, naturalistic follow-up, and open-label studies suggest that clozapine may be efficacious in targeting negative symptoms of SSDs.^16-19 Previous research also suggests clozapine is more effective than other antipsychotic medications, including olanzapine, quetiapine, and risperidone, in decreasing overall SSD symptoms.^20,21 Additionally, there is initial evidence of the efficacy of clozapine in treating cognitive symptoms, suggesting that some areas of cognition may improve in response to this medication.^22-24 On the other hand, a recent case study suggests high doses of clozapine may be associated with cognitive impairment, although cognitive impairment was still greater without medication than at this higher dose.²⁵ Thus, further research is needed to refine our understanding of the impact of clozapine on cognitive symptoms in SSDs.

Despite the promising research behind clozapine, it remains widely underprescribed, likely due to concerns regarding the potential adverse effects.^26,27 Clozapine has been associated with many adverse effects, the most concerning being neutropenia, which can lead to serious infection and death. Thus, one concern among clinicians may be the potential lethality of clozapine. However, a wealth of research indicates clozapine can be safely administered under medical supervision.^26,28 In fact, clozapine has been linked to lower all-cause mortality rates and lower mortality rates by suicide compared with other antipsychotic medications.^29-31 It may therefore be argued that clozapine lowers the overall risk of mortality. Prescribers may also be weary of adherence to regular blood tests that patients must undergo to monitor their risk for neutropenia. This is the most frequently cited anticipated barrier to beginning a trial of clozapine.²⁷ These concerns may not be unfounded; indeed, if avolition and amotivation make it difficult to attend psychotherapy sessions, these factors may logically make it difficult to attend blood draw appointments. In response to such barriers, several solutions have been suggested regarding potential blood draw nonadherence, including the use of in-home treatment teams and point-of-care monitoring.^32,33

Conclusions

Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for patients with such presentations. As our case highlights, patients with such presentations may often be misdiagnosed, as negative and cognitive symptoms may be attributed to other disorders. Additionally, patients with this presentation may experience difficulty engaging in psychotherapy and may not see the same benefits from common antipsychotic medications as patients with predominantly positive symptoms. Clozapine emerges as a promising treatment for addressing negative and cognitive symptoms, although it remains widely underutilized. In cases where clinicians encounter patients with predominantly negative and cognitive symptoms, we strongly recommend consultation and referral to psychiatric care for medication management.

The current case highlights the need for individually tailored treatment plans for individuals seeking mental health care. Clinicians of patients with any mental disorder, but especially those with SSDs of predominantly negative and cognitive symptoms, should carefully formulate a treatment plan based on relevant case history, presentation, and current empirical literature. A singular, one-size-fits-all approach should not be universally implemented for such patients. Our case demonstrates how careful multidisciplinary evaluations, review of medical records, collateral information from patients’ family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

Acknowledgments

A.K. is supported by the US Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Central Texas Veterans Affairs Health Care System, and the VISN 17 Center of Excellence for Research on Returning War Veterans.

Schizophrenia spectrum disorders (SSDs) represent some of the most debilitating mental health disorders.¹ While these disorders have myriad presentations, the prototypical patient with SSD is often thought to possess positive symptoms. More recently, clinicians and researchers are raising awareness of another presentation of SSD: predominantly negative and cognitive symptoms. This symptom profile is not a novel phenomenon; for many years this presentation was recognized as a “deficit” presentation, referring to negative symptoms as the prominent feature.^2,3 However, it presents unique diagnostic and treatment considerations that are often underappreciated in clinical settings.

Negative symptoms (blunted/flat affect, avolition, alogia, anhedonia, asociality) have long been identified as key features of SSD and are widely recognized as predictive of poor prognostic outcomes for patients with SSDs.¹ In many patients, negative symptoms may precede the development of positive symptoms and emerge as a more robust predictor of functional outcomes than positive symptoms.¹ Negative symptoms also appear to be inextricably linked to cognitive symptoms. Specifically, patients with primary negative symptoms seem to perform poorly on measures of global cognitive functioning.¹ Similar to negative symptoms, cognitive symptoms of SSDs are a primary source of functional impairment and persistent disability.¹ Despite this, little attention is given in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to the neurocognitive and social cognitive deficits seen in patients with SSDs. Previous research highlights broad deficits in a range of neurocognitive abilities, including attention, working memory, processing speed, executive functioning, learning and memory, and receptive and expressive language.⁴ Similarly, patients also display deficits in domains of social cognition, such as emotion processing, identifying and utilizing social cues, evaluating attributions of others, and perspective-taking.⁵

A predominantly negative and cognitive symptom presentation can present diagnostic and treatment challenges. We present a case of a patient with such a presentation and the unique considerations given to diagnostic clarification and her treatment.

Case Presentation

A 33-year-old female veteran presented to the emergency department (ED) at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, in 2020. She was brought to the ED by local police following an attempted assault of her neighbor. Per collateral information from the police, the veteran stated she “had the urge to hurt someone” but was unable to provide any other information about this event. The veteran demonstrated diminished speech output, providing 2- to 3-word responses before refusing to speak entirely. She also presented with markedly blunted affect and tangential speech. She was not oriented to situation, stating confusion as to how she was brought to the hospital, and appeared to be responding to internal stimuli. She was subsequently admitted to the inpatient mental health unit due to unspecified psychosis.

The veteran presented as an unreliable historian, and much of her medical history was obtained via a review of US Department of Defense (DoD) records and collateral interview with her parents. Before her hospitalization, the veteran had been diagnosed with major depressive disorder (MDD) and adjustment disorder while serving in the Navy. Her psychiatric history before her military career was otherwise unremarkable. At that time, she began a trial of sertraline 50 mg and completed 10 sessions of psychotherapy. After approximately 1 year, she elected to stop taking sertraline due to improved mental health. However, shortly after this she began experiencing significant depressive symptoms and was ultimately released early from the Navy due to her mental health concerns.

The veteran’s parents provided interim history between her discharge and establishing care at MEDVAMC as the veteran was reluctant to discuss this period of her life. According to her parents the veteran had prior diagnoses of borderline personality disorder and MDD and had difficulty adhering to her current medications (bupropion and duloxetine) for about 1 month before her hospitalization. During the previous month, her parents observed her staying in her room around the clock and “[going] mute.”

The veteran remained hospitalized for about 1 month, during which she was diagnosed with schizoaffective disorder and stabilized on injections of long-acting olanzapine 210 mg (administered every 2 weeks). She was referred for outpatient psychotherapy in a specialty clinic for veterans with SSDs. However, she did not attend her initial intake assessment.

About 2 weeks after discharge from the hospital, the veteran presented for her injection appointment. At this time, she was noted to be disorganized in her thinking and behavior, displaying thought blocking and catatonic behavior. Her parents also described concerning behavior since her discharge. They stated she went to a hotel after her discharge and spent all her available money. She then returned to her parents’ home, where she did not sleep or bathe for several days. She was observed wandering around the house aimlessly and in a confused manner and had become verbally aggressive and threatening toward her parents. The veteran was again psychiatrically admitted due to psychosis and concerns for her safety. She was discharged about 2 weeks later and continued olanzapine injections. She was also referred for outpatient psychotherapy; although she did not initially engage in psychotherapy, she was referred again about 5 months after discharge and began psychotherapy at that time.

The veteran began a course of weekly outpatient psychotherapy employing cognitive behavior therapy for psychosis (CBTp).⁶ During this time, she described her primary concerns as anxiety and feeling disconnected from others. She reported a history of depression but not of schizoaffective disorder. When asked about this, the veteran stated that she did not feel this diagnosis was accurate and instead believed she had severe depression. When asked why she was prescribed olanzapine, the veteran stated that this medication was for depression. As with her inpatient stays, the veteran demonstrated several negative symptoms during her course of psychotherapy. She presented with noticeably blunted affect, evidenced by lack of facial expression and monotonic speech. She also routinely displayed alogia (ie, lack of speech), often stating that she “did not feel like talking much.” She described difficulty finding motivation to initiate tasks (avolition) as well as a tendency toward social isolation (asociality).

The veteran also described concerns related to neurocognitive and social cognitive symptoms. She reported difficulties in processing speed, cognitive set-shifting (mentally switching between tasks), and inhibition, describing how these concerns interfered with her occupational functioning. She noted difficulty maintaining the expected pace of work at her previous positions, stating that she felt it took her longer to complete tasks compared with others. In addition, she displayed some difficulties with attention and memory. On more than one occasion, she seemed to have forgotten the previous day’s conversations with clinicians. Regarding social cognitive symptoms, she noted difficulties in emotion processing, indicating that it was difficult for her to identify and manage her emotions. This was especially prominent during times of depressed mood.

She also displayed a hostile attribution bias, or tendency to overattribute hostile intent to others’ ambiguous actions. For example, she described an instance where a family member sat too close to her on the couch, stating that she felt this behavior indicated the family member did not care about her. Relatedly, the veteran demonstrated difficulty with perspective taking, which became evident during cognitive restructuring regarding interpretations of her family’s behavior. Finally, the veteran displayed some deficits in social perception, or the ability to identify social context and rules based on nonverbal communication, verbal cues, and vocal intonation. She stated that she often felt conversing with others was difficult for her and indicated that she was “not good at conversations.” This may have in part been due to deficits in social perception.

During the first 2 months of psychotherapy, the veteran regularly attended sessions (conducted over telephone due to the COVID-19 pandemic) and was adherent to twice-weekly olanzapine injections. Despite this, she began experiencing an increase in depressive symptoms accompanied by a noticeable worsening of her blunted affect, alogia, and avolition. After about 2 months of psychotherapy, she described active suicidal ideation and requested to be voluntarily hospitalized. During this hospitalization, the veteran was consulted about the use of clozapine in treatment-refractory conditions and began a trial of clozapine 400 mg. She demonstrated marked improvement in her depressed mood after taking the medication and was discharged about 2 weeks after admission. The veteran completed 10 sessions of CBTp before electing to terminate due to an upcoming move. She was adherent to weekly blood draws per the requirements of clozapine and described intentions to engage in mental health care after her move. The patient’s mother contacted the clinic to inform the treatment team that the patient and her family had moved to a different city and the patient had started receiving care at the VAMC in that city.

Discussion

As the veteran’s case highlights, a predominantly negative and cognitive symptom presentation may present diagnostic challenges. Since this presentation may not be viewed as representative of SSDs, patients with this presentation may be misdiagnosed. This was evident in the current case, not only in the veteran’s prodromal phase of illness while in the Navy, but also in her reported previous diagnoses of borderline personality disorder and MDD. More than one clinician at the MEDVAMC provisionally considered a diagnosis of MDD before collecting collateral information from the veteran’s family regarding her clear psychotic symptoms. Unfortunately, such misdiagnoses may have prevented early intervention of the veteran’s schizoaffective disorder, which is found to be instrumental in reducing impairment and disability among patients with SSDs.^7,8

These misdiagnoses are understandable given the considerable symptom overlap between SSDs and other mental health disorders. For instance, anhedonia and avolition are 2 key symptoms seen in depressive episodes. Both anhedonia and lack of positive emotion are often seen in posttraumatic stress disorder. Additionally, anxiety disorders may induce a lack of positive emotion, loss of interest in previously enjoyed activities, and lack of motivation secondary to primary symptoms of anxiety. Furthermore, schizoaffective disorder requires the presence of a major mood episode. In the absence of apparent positive symptoms (as is the case for patients with a predominantly negative symptom presentation), schizoaffective disorder may be easily misdiagnosed as a mood disorder.

Patients with predominantly negative or cognitive symptoms may also be less accepting of a diagnosis of SSD. A wealth of research points to the clear stigma of SSDs, with many suggesting that these disorders are among the most stigmatized mental health disorders.⁹ Therefore, patients with predominantly negative and cognitive symptoms may be more likely to attribute their symptoms to another, less stigmatized mental health disorder. This was seen in the current case, as the veteran repeatedly denied a diagnosis of schizoaffective disorder and instead claimed to have severe depression. This reluctance to accept a diagnosis of an SSD, coupled with the diagnostic ambiguity of negative symptoms, is likely to make it challenging for clinicians to accurately identify patients with a predominantly negative and cognitive symptom presentation of SSDs.

Clinicians working within a team-based setting may be less likely to misdiagnose patients as they can consult others. Diagnostic clarity in the current case was undoubtedly facilitated by the multidisciplinary team involved in the veteran’s care; clinicians involved in her care were able to consult with one another to determine that her symptoms were indicative of an SSD rather than a mood disorder. Mental health professionals in private practice are unlikely to have access to such multidisciplinary specialty services and may be particularly vulnerable to misdiagnoses.

Treatment Considerations

This case also highlights several psychotherapy and psychopharmacology treatment considerations for patients with a predominantly negative and cognitive symptom presentation. The veteran was initially difficult to engage in psychotherapy. Although patients with SSDs often have difficulty engaging in treatment, patients with a predominant negative and cognitive symptom profile may experience more difficulty doing so.¹⁰ Previous research suggests that both negative symptoms and cognitive symptoms are inversely related to treatment engagement.^11,12

By their very nature, negative symptoms may make it difficult to fully engage in psychotherapy. First, avolition and amotivation likely make it difficult for patients to attend psychotherapy appointments. Furthermore, negative symptoms may make it difficult to emotionally engage with the content of psychotherapy, thus limiting the potential benefits. Cognitive symptoms may also make it more difficult for patients to fully reap the benefits of psychotherapy. Deficits in attention, memory, and abstract reasoning seen in other mental health and medical conditions are associated with poorer treatment outcomes in psychotherapy.^13,14 Thus, it may be especially difficult to engage patients with primarily negative and cognitive symptoms of SSDs in psychotherapy. However, given the link between these symptoms and functional impairment, it is even more important to evaluate and address such barriers to treatment.

This case highlights the utility of clozapine in the treatment of SSDs. Many commonly prescribed antipsychotic medications have questionable efficacy in treating negative symptoms, and none of the currently available antipsychotics are approved for this indication.¹⁵ In our case, the veteran saw a limited reduction of her negative or cognitive symptoms from her use of olanzapine. However, case reports, naturalistic follow-up, and open-label studies suggest that clozapine may be efficacious in targeting negative symptoms of SSDs.^16-19 Previous research also suggests clozapine is more effective than other antipsychotic medications, including olanzapine, quetiapine, and risperidone, in decreasing overall SSD symptoms.^20,21 Additionally, there is initial evidence of the efficacy of clozapine in treating cognitive symptoms, suggesting that some areas of cognition may improve in response to this medication.^22-24 On the other hand, a recent case study suggests high doses of clozapine may be associated with cognitive impairment, although cognitive impairment was still greater without medication than at this higher dose.²⁵ Thus, further research is needed to refine our understanding of the impact of clozapine on cognitive symptoms in SSDs.

Despite the promising research behind clozapine, it remains widely underprescribed, likely due to concerns regarding the potential adverse effects.^26,27 Clozapine has been associated with many adverse effects, the most concerning being neutropenia, which can lead to serious infection and death. Thus, one concern among clinicians may be the potential lethality of clozapine. However, a wealth of research indicates clozapine can be safely administered under medical supervision.^26,28 In fact, clozapine has been linked to lower all-cause mortality rates and lower mortality rates by suicide compared with other antipsychotic medications.^29-31 It may therefore be argued that clozapine lowers the overall risk of mortality. Prescribers may also be weary of adherence to regular blood tests that patients must undergo to monitor their risk for neutropenia. This is the most frequently cited anticipated barrier to beginning a trial of clozapine.²⁷ These concerns may not be unfounded; indeed, if avolition and amotivation make it difficult to attend psychotherapy sessions, these factors may logically make it difficult to attend blood draw appointments. In response to such barriers, several solutions have been suggested regarding potential blood draw nonadherence, including the use of in-home treatment teams and point-of-care monitoring.^32,33

Conclusions

Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for patients with such presentations. As our case highlights, patients with such presentations may often be misdiagnosed, as negative and cognitive symptoms may be attributed to other disorders. Additionally, patients with this presentation may experience difficulty engaging in psychotherapy and may not see the same benefits from common antipsychotic medications as patients with predominantly positive symptoms. Clozapine emerges as a promising treatment for addressing negative and cognitive symptoms, although it remains widely underutilized. In cases where clinicians encounter patients with predominantly negative and cognitive symptoms, we strongly recommend consultation and referral to psychiatric care for medication management.

The current case highlights the need for individually tailored treatment plans for individuals seeking mental health care. Clinicians of patients with any mental disorder, but especially those with SSDs of predominantly negative and cognitive symptoms, should carefully formulate a treatment plan based on relevant case history, presentation, and current empirical literature. A singular, one-size-fits-all approach should not be universally implemented for such patients. Our case demonstrates how careful multidisciplinary evaluations, review of medical records, collateral information from patients’ family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

Acknowledgments

A.K. is supported by the US Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Central Texas Veterans Affairs Health Care System, and the VISN 17 Center of Excellence for Research on Returning War Veterans.

Schizophrenia spectrum disorders (SSDs) represent some of the most debilitating mental health disorders.¹ While these disorders have myriad presentations, the prototypical patient with SSD is often thought to possess positive symptoms. More recently, clinicians and researchers are raising awareness of another presentation of SSD: predominantly negative and cognitive symptoms. This symptom profile is not a novel phenomenon; for many years this presentation was recognized as a “deficit” presentation, referring to negative symptoms as the prominent feature.^2,3 However, it presents unique diagnostic and treatment considerations that are often underappreciated in clinical settings.

Negative symptoms (blunted/flat affect, avolition, alogia, anhedonia, asociality) have long been identified as key features of SSD and are widely recognized as predictive of poor prognostic outcomes for patients with SSDs.¹ In many patients, negative symptoms may precede the development of positive symptoms and emerge as a more robust predictor of functional outcomes than positive symptoms.¹ Negative symptoms also appear to be inextricably linked to cognitive symptoms. Specifically, patients with primary negative symptoms seem to perform poorly on measures of global cognitive functioning.¹ Similar to negative symptoms, cognitive symptoms of SSDs are a primary source of functional impairment and persistent disability.¹ Despite this, little attention is given in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to the neurocognitive and social cognitive deficits seen in patients with SSDs. Previous research highlights broad deficits in a range of neurocognitive abilities, including attention, working memory, processing speed, executive functioning, learning and memory, and receptive and expressive language.⁴ Similarly, patients also display deficits in domains of social cognition, such as emotion processing, identifying and utilizing social cues, evaluating attributions of others, and perspective-taking.⁵

A predominantly negative and cognitive symptom presentation can present diagnostic and treatment challenges. We present a case of a patient with such a presentation and the unique considerations given to diagnostic clarification and her treatment.

Case Presentation

A 33-year-old female veteran presented to the emergency department (ED) at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) in Houston, Texas, in 2020. She was brought to the ED by local police following an attempted assault of her neighbor. Per collateral information from the police, the veteran stated she “had the urge to hurt someone” but was unable to provide any other information about this event. The veteran demonstrated diminished speech output, providing 2- to 3-word responses before refusing to speak entirely. She also presented with markedly blunted affect and tangential speech. She was not oriented to situation, stating confusion as to how she was brought to the hospital, and appeared to be responding to internal stimuli. She was subsequently admitted to the inpatient mental health unit due to unspecified psychosis.

The veteran presented as an unreliable historian, and much of her medical history was obtained via a review of US Department of Defense (DoD) records and collateral interview with her parents. Before her hospitalization, the veteran had been diagnosed with major depressive disorder (MDD) and adjustment disorder while serving in the Navy. Her psychiatric history before her military career was otherwise unremarkable. At that time, she began a trial of sertraline 50 mg and completed 10 sessions of psychotherapy. After approximately 1 year, she elected to stop taking sertraline due to improved mental health. However, shortly after this she began experiencing significant depressive symptoms and was ultimately released early from the Navy due to her mental health concerns.

The veteran’s parents provided interim history between her discharge and establishing care at MEDVAMC as the veteran was reluctant to discuss this period of her life. According to her parents the veteran had prior diagnoses of borderline personality disorder and MDD and had difficulty adhering to her current medications (bupropion and duloxetine) for about 1 month before her hospitalization. During the previous month, her parents observed her staying in her room around the clock and “[going] mute.”

The veteran remained hospitalized for about 1 month, during which she was diagnosed with schizoaffective disorder and stabilized on injections of long-acting olanzapine 210 mg (administered every 2 weeks). She was referred for outpatient psychotherapy in a specialty clinic for veterans with SSDs. However, she did not attend her initial intake assessment.

About 2 weeks after discharge from the hospital, the veteran presented for her injection appointment. At this time, she was noted to be disorganized in her thinking and behavior, displaying thought blocking and catatonic behavior. Her parents also described concerning behavior since her discharge. They stated she went to a hotel after her discharge and spent all her available money. She then returned to her parents’ home, where she did not sleep or bathe for several days. She was observed wandering around the house aimlessly and in a confused manner and had become verbally aggressive and threatening toward her parents. The veteran was again psychiatrically admitted due to psychosis and concerns for her safety. She was discharged about 2 weeks later and continued olanzapine injections. She was also referred for outpatient psychotherapy; although she did not initially engage in psychotherapy, she was referred again about 5 months after discharge and began psychotherapy at that time.

The veteran began a course of weekly outpatient psychotherapy employing cognitive behavior therapy for psychosis (CBTp).⁶ During this time, she described her primary concerns as anxiety and feeling disconnected from others. She reported a history of depression but not of schizoaffective disorder. When asked about this, the veteran stated that she did not feel this diagnosis was accurate and instead believed she had severe depression. When asked why she was prescribed olanzapine, the veteran stated that this medication was for depression. As with her inpatient stays, the veteran demonstrated several negative symptoms during her course of psychotherapy. She presented with noticeably blunted affect, evidenced by lack of facial expression and monotonic speech. She also routinely displayed alogia (ie, lack of speech), often stating that she “did not feel like talking much.” She described difficulty finding motivation to initiate tasks (avolition) as well as a tendency toward social isolation (asociality).

The veteran also described concerns related to neurocognitive and social cognitive symptoms. She reported difficulties in processing speed, cognitive set-shifting (mentally switching between tasks), and inhibition, describing how these concerns interfered with her occupational functioning. She noted difficulty maintaining the expected pace of work at her previous positions, stating that she felt it took her longer to complete tasks compared with others. In addition, she displayed some difficulties with attention and memory. On more than one occasion, she seemed to have forgotten the previous day’s conversations with clinicians. Regarding social cognitive symptoms, she noted difficulties in emotion processing, indicating that it was difficult for her to identify and manage her emotions. This was especially prominent during times of depressed mood.

She also displayed a hostile attribution bias, or tendency to overattribute hostile intent to others’ ambiguous actions. For example, she described an instance where a family member sat too close to her on the couch, stating that she felt this behavior indicated the family member did not care about her. Relatedly, the veteran demonstrated difficulty with perspective taking, which became evident during cognitive restructuring regarding interpretations of her family’s behavior. Finally, the veteran displayed some deficits in social perception, or the ability to identify social context and rules based on nonverbal communication, verbal cues, and vocal intonation. She stated that she often felt conversing with others was difficult for her and indicated that she was “not good at conversations.” This may have in part been due to deficits in social perception.

During the first 2 months of psychotherapy, the veteran regularly attended sessions (conducted over telephone due to the COVID-19 pandemic) and was adherent to twice-weekly olanzapine injections. Despite this, she began experiencing an increase in depressive symptoms accompanied by a noticeable worsening of her blunted affect, alogia, and avolition. After about 2 months of psychotherapy, she described active suicidal ideation and requested to be voluntarily hospitalized. During this hospitalization, the veteran was consulted about the use of clozapine in treatment-refractory conditions and began a trial of clozapine 400 mg. She demonstrated marked improvement in her depressed mood after taking the medication and was discharged about 2 weeks after admission. The veteran completed 10 sessions of CBTp before electing to terminate due to an upcoming move. She was adherent to weekly blood draws per the requirements of clozapine and described intentions to engage in mental health care after her move. The patient’s mother contacted the clinic to inform the treatment team that the patient and her family had moved to a different city and the patient had started receiving care at the VAMC in that city.

Discussion

As the veteran’s case highlights, a predominantly negative and cognitive symptom presentation may present diagnostic challenges. Since this presentation may not be viewed as representative of SSDs, patients with this presentation may be misdiagnosed. This was evident in the current case, not only in the veteran’s prodromal phase of illness while in the Navy, but also in her reported previous diagnoses of borderline personality disorder and MDD. More than one clinician at the MEDVAMC provisionally considered a diagnosis of MDD before collecting collateral information from the veteran’s family regarding her clear psychotic symptoms. Unfortunately, such misdiagnoses may have prevented early intervention of the veteran’s schizoaffective disorder, which is found to be instrumental in reducing impairment and disability among patients with SSDs.^7,8

These misdiagnoses are understandable given the considerable symptom overlap between SSDs and other mental health disorders. For instance, anhedonia and avolition are 2 key symptoms seen in depressive episodes. Both anhedonia and lack of positive emotion are often seen in posttraumatic stress disorder. Additionally, anxiety disorders may induce a lack of positive emotion, loss of interest in previously enjoyed activities, and lack of motivation secondary to primary symptoms of anxiety. Furthermore, schizoaffective disorder requires the presence of a major mood episode. In the absence of apparent positive symptoms (as is the case for patients with a predominantly negative symptom presentation), schizoaffective disorder may be easily misdiagnosed as a mood disorder.

Patients with predominantly negative or cognitive symptoms may also be less accepting of a diagnosis of SSD. A wealth of research points to the clear stigma of SSDs, with many suggesting that these disorders are among the most stigmatized mental health disorders.⁹ Therefore, patients with predominantly negative and cognitive symptoms may be more likely to attribute their symptoms to another, less stigmatized mental health disorder. This was seen in the current case, as the veteran repeatedly denied a diagnosis of schizoaffective disorder and instead claimed to have severe depression. This reluctance to accept a diagnosis of an SSD, coupled with the diagnostic ambiguity of negative symptoms, is likely to make it challenging for clinicians to accurately identify patients with a predominantly negative and cognitive symptom presentation of SSDs.

Clinicians working within a team-based setting may be less likely to misdiagnose patients as they can consult others. Diagnostic clarity in the current case was undoubtedly facilitated by the multidisciplinary team involved in the veteran’s care; clinicians involved in her care were able to consult with one another to determine that her symptoms were indicative of an SSD rather than a mood disorder. Mental health professionals in private practice are unlikely to have access to such multidisciplinary specialty services and may be particularly vulnerable to misdiagnoses.

Treatment Considerations

This case also highlights several psychotherapy and psychopharmacology treatment considerations for patients with a predominantly negative and cognitive symptom presentation. The veteran was initially difficult to engage in psychotherapy. Although patients with SSDs often have difficulty engaging in treatment, patients with a predominant negative and cognitive symptom profile may experience more difficulty doing so.¹⁰ Previous research suggests that both negative symptoms and cognitive symptoms are inversely related to treatment engagement.^11,12

By their very nature, negative symptoms may make it difficult to fully engage in psychotherapy. First, avolition and amotivation likely make it difficult for patients to attend psychotherapy appointments. Furthermore, negative symptoms may make it difficult to emotionally engage with the content of psychotherapy, thus limiting the potential benefits. Cognitive symptoms may also make it more difficult for patients to fully reap the benefits of psychotherapy. Deficits in attention, memory, and abstract reasoning seen in other mental health and medical conditions are associated with poorer treatment outcomes in psychotherapy.^13,14 Thus, it may be especially difficult to engage patients with primarily negative and cognitive symptoms of SSDs in psychotherapy. However, given the link between these symptoms and functional impairment, it is even more important to evaluate and address such barriers to treatment.

This case highlights the utility of clozapine in the treatment of SSDs. Many commonly prescribed antipsychotic medications have questionable efficacy in treating negative symptoms, and none of the currently available antipsychotics are approved for this indication.¹⁵ In our case, the veteran saw a limited reduction of her negative or cognitive symptoms from her use of olanzapine. However, case reports, naturalistic follow-up, and open-label studies suggest that clozapine may be efficacious in targeting negative symptoms of SSDs.^16-19 Previous research also suggests clozapine is more effective than other antipsychotic medications, including olanzapine, quetiapine, and risperidone, in decreasing overall SSD symptoms.^20,21 Additionally, there is initial evidence of the efficacy of clozapine in treating cognitive symptoms, suggesting that some areas of cognition may improve in response to this medication.^22-24 On the other hand, a recent case study suggests high doses of clozapine may be associated with cognitive impairment, although cognitive impairment was still greater without medication than at this higher dose.²⁵ Thus, further research is needed to refine our understanding of the impact of clozapine on cognitive symptoms in SSDs.

Despite the promising research behind clozapine, it remains widely underprescribed, likely due to concerns regarding the potential adverse effects.^26,27 Clozapine has been associated with many adverse effects, the most concerning being neutropenia, which can lead to serious infection and death. Thus, one concern among clinicians may be the potential lethality of clozapine. However, a wealth of research indicates clozapine can be safely administered under medical supervision.^26,28 In fact, clozapine has been linked to lower all-cause mortality rates and lower mortality rates by suicide compared with other antipsychotic medications.^29-31 It may therefore be argued that clozapine lowers the overall risk of mortality. Prescribers may also be weary of adherence to regular blood tests that patients must undergo to monitor their risk for neutropenia. This is the most frequently cited anticipated barrier to beginning a trial of clozapine.²⁷ These concerns may not be unfounded; indeed, if avolition and amotivation make it difficult to attend psychotherapy sessions, these factors may logically make it difficult to attend blood draw appointments. In response to such barriers, several solutions have been suggested regarding potential blood draw nonadherence, including the use of in-home treatment teams and point-of-care monitoring.^32,33

Conclusions

Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for patients with such presentations. As our case highlights, patients with such presentations may often be misdiagnosed, as negative and cognitive symptoms may be attributed to other disorders. Additionally, patients with this presentation may experience difficulty engaging in psychotherapy and may not see the same benefits from common antipsychotic medications as patients with predominantly positive symptoms. Clozapine emerges as a promising treatment for addressing negative and cognitive symptoms, although it remains widely underutilized. In cases where clinicians encounter patients with predominantly negative and cognitive symptoms, we strongly recommend consultation and referral to psychiatric care for medication management.

The current case highlights the need for individually tailored treatment plans for individuals seeking mental health care. Clinicians of patients with any mental disorder, but especially those with SSDs of predominantly negative and cognitive symptoms, should carefully formulate a treatment plan based on relevant case history, presentation, and current empirical literature. A singular, one-size-fits-all approach should not be universally implemented for such patients. Our case demonstrates how careful multidisciplinary evaluations, review of medical records, collateral information from patients’ family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

Acknowledgments

A.K. is supported by the US Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Central Texas Veterans Affairs Health Care System, and the VISN 17 Center of Excellence for Research on Returning War Veterans.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

Reactions to poison ivy, poison oak, and poison sumac, which affect 10 to 50 million Americans a year,¹ are classified as Toxicodendron dermatitis; 50% to 75% of US adults are clinically sensitive to these plants.² Furthermore, people of all ethnicities, skin types, and ages residing in most US geographical regions are at risk.³ Allergenicity is caused by urushiol, which is found in members of the Anacardiaceae family.⁴ Once absorbed, urushiol causes a type IV hypersensitivity reaction in those who are susceptible.⁵

Cutaneous Manifestations

Toxicodendron dermatitis presents with an acute eczematous eruption characterized by streaks of intensely pruritic and erythematous papules and vesicles (Figure 1). Areas of involvement are characterized by sharp margins that follow the pattern of contact made by the plant’s leaves, berries, stems, and vines.⁶ The fluid content of the vesicles is not antigenic and cannot cause subsequent transmission to oneself or others.³ A person with prior contact to the plant who becomes sensitized develops an eruption 24 to 48 hours after subsequent contact with the plant; peak severity manifests 1 to 14 days later.⁷

When left untreated, the eruption can last 3 weeks. If the plant is burned, urushiol can be aerosolized in smoke, causing respiratory tract inflammation and generalized dermatitis, which has been reported among wildland firefighters.² Long-term complications from an outbreak are limited but can include postinflammatory hyperpigmentation and secondary bacterial infection.⁸ Rare reports of nephrotic syndrome also have appeared in the literature.⁹Toxicodendron dermatitis can present distinctively as so-called black dot dermatitis.⁶

Nomenclature

Poison ivy, poison oak, and poison sumac are members of the family Anacardiaceae and genus Toxicodendron,⁶ derived from the Greek words toxikos (poison) and dendron (tree).¹⁰

Distribution

Toxicodendron plants characteristically are found in various regions of the United States. Poison ivy is the most common and is comprised of 2 species: Toxicodendron rydbergii and Toxicodendron radicans. Toxicodendron rydbergii is a nonclimbing dwarf shrub typically found in the northern and western United States. Toxicodendron radicans is a climbing vine found in the eastern United States. Poison oak also is comprised of 2 species—Toxicodendron toxicarium and Toxicodendron diversilobum—and is more common in the western United States. Poison sumac (also known as Toxicodendron vernix) is a small shrub that grows in moist swampy areas. It has a predilection for marshes of the eastern and southeastern United States.^6,11

Identifying Features

Educating patients on how to identify poison ivy can play a key role in avoidance, which is the most important step in preventing Toxicodendron dermatitis. A challenge in identification of poison ivy is the plant’s variable appearance; it grows as a small shrub, low-lying vine, or vine that climbs other trees.

As the vine matures, it develops tiny, rough, “hairy” rootlets—hence the saying, “Hairy vine, no friend of mine!” Rootlets help the plant attach to trees growing near a water source. Vines can reach a diameter of 3 inches. From mature vines, solitary stems extend 1 to 2 inches with 3 characteristic leaves at the terminus (Figure 2), prompting another classic saying, “Leaves of 3, let it be!”¹²

Poison oak is characterized by 3 to 5 leaflets. Poison sumac has 7 to 13 pointed, smooth-edged leaves.⁶

Dermatitis-Inducing Plant Parts

The primary allergenic component of Toxicodendron plants is urushiol, a resinous sap found in stems, roots, leaves, and skins of the fruits. These components must be damaged or bruised to release the allergen; slight contact with an uninjured plant part might not lead to harm.^2,13 Some common forms of transmission include skin contact, ingestion, inhalation of smoke from burning plants, and contact with skin through contaminated items, such as clothing, animals, and tools.¹⁴

Allergens

The catecholic ring and aliphatic chain of the urushiol molecule are allergenic.¹⁵ The degree of saturation and length of the side chains vary with different catechols. Urushiol displays cross-reactivity with poison ivy, poison oak, and poison sumac. Urushiol from these plants differs only slightly in structure; therefore, sensitization to one causes sensitization to all. There also is cross-reactivity between different members of the Anacardiaceae family, including Anacardium occidentale (tropical cashew nut), Mangifera indica (tropical mango tree), Ginkgo biloba (ginkgo tree), and Semecarpus anacardium (Indian marking nut tree).¹²

Poison ivy, poison oak, and poison sumac cause allergic contact dermatitis as a type IV hypersensitivity reaction. First, urushiol binds and penetrates the skin, where it is oxidized to quinone intermediates and bound to haptens. Then, the intermediates bind surface proteins on antigen-presenting cells, specifically Langerhans cells in the epidermis and dermis.⁵

Presentation of nonpeptide antigens, such as urushiol, to T cells requires expression of langerin (also known as CD207) and CD1a.¹⁶ Langerin is a C-type lectin that causes formation of Birbeck granules; CD1a is a major histocompatibility complex class I molecule found in Birbeck granules.^5,17 After Langerhans cells internalize and process the urushiol self-hapten neoantigen, it is presented to CD4⁺ T cells.⁶ These cells then expand to form circulating activated T-effector and T-memory lymphocytes.¹⁸

The molecular link that occurs between the hapten and carrier protein determines the response. When linked by an amino nucleophile, selective induction of T-effector cells ensues, resulting in allergic contact dermatitis. When linked by a sulfhydryl bond, selective induction of suppressor cells occurs, resulting in a reduced allergic contact dermatitis response.¹⁹ In the case of activation of T-effector cells, a cell-mediated cytotoxic immune response is generated that destroys epidermal cells and dermal vasculature.² The incidence and intensity of poison ivy sensitivity decline proportionally with age and the absence of continued exposure.²⁰

Preventive Action—Patients should be counseled that if contact between plant and skin occurs, it is important to remove contaminated clothing or objects and wash them with soap to prevent additional exposure.^14,21 Areas of the skin that made contact with the plant should be washed with water as soon as possible; after 30 minutes, urushiol has sufficiently penetrated to cause a reaction.² Forceful unidirectional washing with a damp washcloth and liquid dishwashing soap is recommended.²²

Several barrier creams are commercially available to help prevent absorption or to deactivate the urushiol antigen. These products are used widely by forestry workers and wildland firefighters.²³ One such barrier cream is bentoquatam (sold as various trade names), an organoclay compound made of quaternium-18 bentonite that interferes with absorption of the allergen by acting as a physical blocker.²⁴

Treatment

After Toxicodendron dermatitis develops, several treatments are available to help manage symptoms. Calamine lotion can be used to help dry weeping lesions.^25,26 Topical steroids can be used to help control pruritus and alleviate inflammation. High-potency topical corticosteroids such as clobetasol and mid-potency steroids such as triamcinolone can be used. Topical anesthetics (eg, benzocaine, pramoxine, benzyl alcohol) might provide symptomatic relief.^27,28

Oral antihistamines can allow for better sleep by providing sedation but do not target the pruritus of poison ivy dermatitis, which is not histamine mediated.^29,30 Systemic corticosteroids usually are considered in more severe dermatitis—when 20% or more of the body surface area is involved; blistering and itching are severe; or the face, hands, or genitalia are involved.^31,32

Clinical Uses

Therapeutic uses for poison ivy have been explored extensively. In 1892, Dakin³³ reported that ingestion of leaves by Native Americans reduced the incidence and severity of skin lesions after contact with poison ivy. Consumption of poison ivy was further studied by Epstein and colleagues³⁴ in 1974; they concluded that ingestion of a large amount of urushiol over a period of 3 months or longer may help with hyposensitization—but not complete desensitization—to contact with poison ivy. However, the risk for adverse effects is thought to outweigh benefits because ingestion can cause perianal dermatitis, mucocutaneous sequelae, and systemic contact dermatitis.²

Although the use of Toxicodendron plants in modern-day medicine is limited, development of a vaccine (immunotherapy) against Toxicodendron dermatitis offers an exciting opportunity for further research.

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.

In an age of changing climate and emerging global pandemics, the ability of residency programs to prepare for and adapt to potential disasters may be paramount in preserving the training of physicians. The current literature regarding residency program disaster preparedness, which focuses predominantly on hurricanes and COVID-19,^1-8 is lacking in recommendations specific to dermatology residency programs. Likewise, the Accreditation Council for Graduate Medical Education (ACGME) guidelines⁹ do not address dermatology-specific concerns in disaster preparedness or response. Herein, we propose recommendations to mitigate the impact of various types of disasters on dermatology residency programs and their trainees with regard to resident safety and wellness, resident education, and patient care (Table).

Resident Safety and Wellness

Role of the Program Director—The role of the program director is critical, serving as a figure of structure and reassurance.^4,7,10 Once concern of disaster arises, the program director should contact the Designated Institutional Official (DIO) to express concerns about possible disruptions to resident training. The DIO should then contact the ACGME within 10 days to report the disaster and submit a request for emergency (eg, pandemic) or extraordinary circumstances (eg, natural disaster) categorization.^4,9 Program directors should promptly prepare plans for program reconfiguration and resident transfers in alignment with ACGME requirements to maintain evaluation and completion of core competencies of training during disasters.⁹ Program directors should prioritize the safety of trainees during the immediate threat with clear guidelines on sheltering, evacuations, or quarantines; a timeline of program recovery based on communication with residents, faculty, and administration should then be established.^10,11

Communication—Establishing a strong line of communication between program directors and residents is paramount. Collection of emergency noninstitutional contact information, establishment of a centralized website for information dissemination, use of noninstitutional email and proxy servers outside of the location of impact, social media updates, on-site use of 2-way radios, and program-wide conference calls when possible should be strongly considered as part of the disaster response.^2-4,12,13

Resident Accommodations and Mental Health—If training is disrupted, residents should be reassured of continued access to salary, housing, food, or other resources as necessary.^3,4,11 There should be clear contingency plans if residents need to leave the program for extended periods of time due to injury, illness, or personal circumstances. Although relevant in all types of disasters, resident mental health and response to trauma also must be addressed. Access to counseling, morale-building opportunities (eg, resident social events), and screening for depression or posttraumatic stress disorder may help promote well-being among residents following traumatic events.¹⁴

Resident Education

Participation in Disaster Relief—Residents may seek to aid in the disaster response, which may prove challenging in the setting of programs with high patient volume.⁴ In coordination with the ACGME and graduate medical education governing bodies, program directors should consider how residents may fulfill dermatology training requirements in conjunction with disaster relief efforts, such as working in an inpatient setting or providing wound care.¹⁰

Continued Didactic Education—The use of online learning and conference calls for continuing the dermatology curriculum is an efficient means to maintaining resident education when meeting in person poses risks to residents.¹⁵ Projections of microscopy images, clinical photographs, or other instructional materials allow for continued instruction on resident examination, histopathology, and diagnostic skills.

Continued Clinical Training—If the home institution cannot support the operation of dermatology clinics, residents should be guaranteed continued training at other institutions. Agreements with other dermatology programs, community hospitals, or private dermatology practices should be established in advance, with consideration given to the number of residents a program can support, funding transfers, and credentialing requirements.^2,4,5

Prolonged Disruptions—Nonessential departments of medical institutions may cease to function during war or mass casualty disasters, and it may be unsafe to send dermatology residents to other institutions or clinical areas. If the threat is prolonged, programs may need to consider allowing current residents a longer duration of training despite potential overlap with incoming dermatology residents.⁷

Patient Care

Disruptions to Clinic Operations—Regarding threats of violence, dangerous exposures, or natural disasters, there should be clear guidelines on sheltering in the clinical setting or stabilizing patients during a procedure.¹¹ Equipment used by residents such as laptops, microscopes, and treatment devices (eg, lasers) should be stored in weather-safe locations that would not be notably impacted by moisture or structural damage to the clinic building. If electricity or internet access are compromised, paper medical records should be available to residents to continue clinical operations. Electronic health records used by residents should regularly be backed up on remote servers or cloud storage to allow continued access to patient health information if on-site servers are not functional.¹² If disruptions are prolonged, residency program administration should coordinate with the institution to ensure there is adequate supply and storage of medications (eg, lidocaine, botulinum toxin) as well as a continued means of delivering biologic medications to patients and an ability to obtain laboratory or dermatopathology services.

In-Person Appointments vs Telemedicine—There are benefits to both residency training and patient care when physicians are able to perform in-person examinations, biopsies, and in-office treatments.¹⁶ Programs should ensure an adequate supply of personal protective equipment to continue in-office appointments, vaccinations, and medical care if a resident or other members of the team are exposed to an infectious disease.⁷ If in-person appointments are limited or impossible, telemedicine capabilities may still allow residents to meet program requirements.^7,10,15 However, reduced patient volume due to decreased elective visits or procedures may complicate the fulfillment of clinical requirements, which may need to be adjusted in the wake of a disaster.⁷

Use of Immunosuppressive Therapies—Residency programs should address the risks of prescribing immunosuppressive therapies (eg, biologics) during an infectious threat with their residents and encourage trainees to counsel patients on the importance of preventative measures to reduce risks for severe infection.¹⁷

Final Thoughts

Disasters often are unpredictable. Dermatology residency programs will not be immune to the future impacts of climate change, violent threats, or emerging pandemics. Lessons from prior natural disasters and the COVID-19 pandemic have made it clear that program directors need to be adaptable. If they plan proactively, comprehensive disaster preparedness can help to maintain high-quality training of dermatology residents in the face of extraordinary and challenging circumstances, promoting the resiliency and sustainability of graduate medical education.