MDedge Dermatology

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

Practice Gap

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas. As such, the nasal area is a common site of onset, constituting approximately 25% of cases. Surgical excision of these cancers generally has a high cure rate.¹

Although complete excision of the tumor is the primary goal of the dermatologic surgeon, achieving a cosmetically satisfactory scar also is important. As a prominent feature of the face, any irregularities to the nose are easily noticeable.² The subsequent scar may exhibit features that are less than ideal and cause notable stress to the patient.

When a scar presents with several complications, using a single surgical technique may not sufficiently address all defects. As a result, it can be challenging for the surgeon to decide which combination of methods among the myriad of nonsurgical and surgical options for scar revision will produce the best cosmetic outcome.

Case and Technique

A 76-year-old man presented 1 year after he underwent Mohs micrographic surgery for squamous cell carcinoma on the nasal dorsum. The tumor cleared after 1 stage and was repaired using a bilateral V-Y advancement flap. Postoperatively, the patient developed pincushioning of the flap, atrophic scarring inferior to the flap, and webbing of the pivotal restraint point at the nasal root (Figures 1A and 1B). We opted to address the pincushioning and nasal root webbing by defatting the flap and performing Z-plasty, respectively.

Pincushioning—Pincushioning of a flap arises due to contraction and lymphedema at the edge of the repair. It is seen more often in nasal repairs due to the limited availability of surrounding skin and changes in skin texture from rhinion to tip.³ To combat this in our patient, an incision was made around the site of the original flap, surrounding tissue was undermined, and the flap was reflected back. Subcutaneous tissue was removed with scissors. The flap was then laid back into the defect, and the subcutaneous tissue and dermis were closed with interrupted buried vertical mattress sutures. The epidermis was closed in a simple running fashion.

Webbing—Webbing of a scar also may develop from the contractile wound-healing process.⁴ Z-plasty commonly is used to camouflage a linear or contracted scar, increase skin availability in an area, or alter scar direction to better align with skin-tension lines.^5,6 In our patient, we incised the webbing of the nasal root along the vertical scar. Two arms were drawn at each end of the scar at a 60° angle (Figure 2); the side arms were drawn equal in length and incised vertically. Full-thickness skin flaps were then undermined at the level of subcutaneous fat, creating 2 triangular flaps. Adequate undermining of the surrounding subcutaneous tissue was performed to achieve proper mobilization of the flaps, which allowed for flap transposition to occur without tension and therefore for proper redirection of the scar.⁶ The flaps were secured using buried vertical mattress sutures and simple running sutures. Using too many buried interrupted sutures can cause vascular compromise of the fragile tips of the Z and should be avoided.³

At 4-month postoperative follow-up, the cosmetic outcome was judged satisfactory (Figure 1C).

Practice Implications

In our patient, pincushioning of the flap was easily addressed by defatting the area. However, doing just this would not have sufficed and necessitated another surgical technique—the Z-plasty—which needed to be designed carefully. The larger the angle between the side arms and central limb, the greater directional change and scar length that is gained (Figure 3). As a result, longer limbs and a greater angle could advantageously break up the scar line but consequently would lengthen the scar considerably. Therefore, if the scar was longer or the skin was inelastic, multiple Z-plasty procedures may have been preferred.

Additionally, for each central limb, both mirror-image options for peripheral arms were considered, with the optimal choice being the one that allowed for final scar lines to mimic relaxed skin-tension lines. Accuracy of the incisions was critical and was assessed by drawing a line between the free ends of the lateral limbs of the Z; this line should pass perpendicularly through the midpoint of the central limb. Last, as with other transposition flap options, Z-plasty has the potential to create a trapdoor or pincushion effect; we reduced this risk by wide undermining to establish an even contraction plate.⁶

When planning the revision, we considered multiple approaches to achieve the best aesthetic outcome in 1 stage. Had there been notable depression in the scar, we may have used a full-thickness skin graft. If the skin surface was lumpy and uneven, dermabrasion or a laser may have been utilized. Another consideration was to avoid using intralesional steroids, which could have made the already atrophied portions of the scar worse.

Overall, the surgical plan that we chose took into consideration the patient’s nasal anatomic structure, the combination of scar defects, the patient’s desires, and the tools available.

Final Thoughts

The ideal scar is inconspicuous, does not impair the function of surrounding structures, and blends well with adjacent skin.⁵ Consequently, the combination of pincushioning and webbing of a scar, especially in the nasal area, can pose a surgical challenge to the surgeon and can cause severe anxiety in the patient. In those circumstances, a single surgical technique is not likely to produce the revision with the best cosmetic outcome. Therefore, the synergy of 2 or more surgical techniques with proper planning and meticulous selection may be necessary. A broad knowledge of various scar revision techniques increases the surgeon’s capability to create the ideal scar.

Acknowledgment—The authors thank the case patient for granting permission to publish this information.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The impacts of anthropogenic climate change on human health are numerous and growing. The evidence that climate change is occurring due to the burning of fossil fuels is substantial, with a 2019 report elevating the data supporting anthropogenic climate change to a gold standard 5-sigma level of significance.¹ In the peer-reviewed scientific literature, the consensus that humans are causing climate change is greater than 99%.² Both the American Medical Association and the American College of Physicians have acknowledged the health impacts of climate change and importance for action. They encourage physicians to engage in environmentally sustainable practices and to advocate for effective climate change mitigation strategies.^3,4 A survey of dermatologists also found that 99.3% (n=148) recognize climate change is occurring, and similarly high numbers are concerned about its health impacts.⁵

Notably, the health care industry must grapple not only with the health impacts of climate change but with the fact that the health care sector itself is responsible for a large amount of carbon emissions.⁶ The global health care industry as a whole produces enough carbon emissions to be ranked as the fifth largest emitting nation in the world.⁷ A quarter of these emissions are attributed to the US health care system.^8,9 Climate science has shown we must limit CO₂ emissions to avoid catastrophic climate change, with the sixth assessment report of the United Nations’ Intergovernmental Panel on Climate Change and the Paris Agreement targeting large emission reductions within the next decade.¹⁰ In August 2021, the US Department of Health and Human Services created the Office of Climate Change and Health Equity. Assistant Secretary for Health ADM Rachel L. Levine, MD, has committed to reducing the carbon emissions from the health care sector by 25% in the next decade, in line with scientific consensus regarding necessary changes.¹¹

The dermatologic impacts of climate change are myriad. Rising temperatures, increasing air and water pollution, and stratospheric ozone depletion will lead to expanded geographic ranges of vector-borne diseases, worsening of chronic skin conditions such as atopic dermatitis/eczema and pemphigus, and increasing rates of skin cancer.¹² For instance, warmer temperatures have allowed mosquitoes of the Aedes genus to infest new areas, leading to outbreaks of viral illnesses with cutaneous manifestations such as dengue, chikungunya, and Zika virus in previously nonindigenous regions.¹³ Rising temperatures also have been associated with an expanding geographic range of tick- and sandfly-borne illnesses such as Lyme disease, Rocky Mountain spotted fever, and cutaneous leishmaniasis.^13,14 Additionally, short-term exposure to air pollution from wildfire smoke has been associated with an increased use of health care services by patients with atopic dermatitis.¹⁵ Increased levels of air pollutants also have been found to be associated with psoriasis flares as well as hyperpigmentation and wrinkle formation.^16,17 Skin cancer incidence is predicted to rise due to increased UV radiation exposure secondary to stratospheric ozone depletion.¹⁸

Although the effects of climate change are significant and the magnitude of the climate crisis may feel overwhelming, it is essential to avoid doomerism and focus on meaningful impactful actions. Current CO₂ emissions will remain in the atmosphere for hundreds to thousands of years, and the choices we make now commit future generations to live in a world shaped by our decisions. Importantly, there are impactful and low-cost, cost-effective, or cost-saving changes that can be made to mitigate the climate crisis. Herein, we provide 10 practical actionable interventions for dermatologists to help combat climate change.

10 Interventions for Dermatologists to Combat Climate Change

1. Consider switching to renewable sources of energy. Making this switch often is the most impactful decision a dermatologist can make to address climate change. The electricity sector is the largest source of greenhouse gas emissions in the US health care system, and dermatology outpatient practices in particular have been observed to have a higher peak energy consumption than most other specialties studied.^19,20 Many dermatology practices—both privately owned and academic—can switch to renewable energy seamlessly through power purchase agreements (PPAs), which are contracts between power providers and private entities to install renewable energy equipment or source renewable energy from offsite sources at a fixed rate. Using PPAs instead of traditional fossil fuel energy can provide cost savings as well as protect buyers from electrical price volatility. Numerous health care systems utilize PPAs such as Kaiser Permanente, Cleveland Clinic, and Rochester Regional Health. Additionally, dermatologists can directly purchase renewable energy equipment and eventually receive a return on investment from substantially lowered electric bills. It is important to note that the cost of commercial solar energy systems has decreased 69% since 2010 with further cost reductions predicted.^21,22

2. Reduce standby power consumption. This refers to the use of electricity by a device when it appears to be off or is not in use, which can lead to considerable energy consumption and subsequently a larger carbon footprint for your practice. Ensuring electronics such as phone chargers, light fixtures, television screens, and computers are switched off prior to the end of the workday can make a large difference; for instance, a single radiology department at the University of Maryland (College Park, Maryland) found that if clinical workstations were shut down when not in use after an 8-hour workday, it would save 83,866 kWh of energy and $9225.33 per year.²³ Additionally, using power strips with an automatic shutoff feature to shut off power to devices not in use provides a more convenient way to reduce standby power.

3. Optimize thermostat settings. An analysis of energy consumption in 157,000 US health care facilities found that space heating and cooling accounted for 40% of their total energy consumption.²⁴ Thus, ensuring your thermostat and heating/cooling systems are working efficiently can conserve a substantial amount of energy. For maximum efficiency, it is recommended to set air conditioners to 74 °F (24 °C) and heaters to 68 °F (20 °C) or employ smart thermostats to optimally adjust temperatures when the office is not in use.²⁵ In addition, routinely replacing or cleaning air conditioner filters can lower energy consumption by 5% to 15%.²⁶ Similarly, improving insulation and ruggedization of both homes and offices may reduce heating and cooling waste and limit costs and emissions as a result.

4. Offer bicycle racks and charging ports for electric vehicles. In the United States, transportation generates more greenhouse gas emissions than any other source, primarily due to the burning of fossil fuels to power automobiles, trains, and planes. Because bicycles do not consume any fossil fuels and the use of electric vehicles has been found to result in substantial air pollution health benefits, encouraging the use of both can make a considerable positive impact on our climate.²⁷ Providing these resources not only allows those who already travel sustainably to continue to do so but also serves as a reminder to your patients that sustainability is important to you as their health care provider. As electric vehicle sales continue to climb, infrastructure to support their use, including charging stations, will grow in importance. A physician’s office that offers a car-charging station may soon have a competitive advantage over others in the area.

5. Ensure properly regulated medical waste management. Regulated medical waste (also known as infectious medical waste or red bag waste) refers to health care–generated waste unsuitable for disposal in municipal solid waste systems due to concern for the spread of infectious or pathogenic materials. This waste largely is disposed via incineration, which harms the environment in a multitude of ways—both through harmful byproducts and from the CO₂ emissions required to ship the waste to special processing facilities.²⁸ Incineration of regulated medical waste emits potent toxins such as dioxins and furans as well as particulate matter, which contribute to air pollution. Ensuring only materials with infectious potential (as defined by each state’s Environmental Protection Agency) are disposed in regulated medical waste containers can dramatically reduce the harmful effects of incineration. Additionally, limiting regulated medical waste can be very cost-effective, as its disposal is 5- to 10-times more expensive than that of unregulated medical waste.²⁹ Simple nudge measures such as educating staff about what waste goes in which receptacle, placing signage over the red bag waste to prompt staff to pause to consider if use of that bin is required before utilizing, using weights or clasps to make opening red bag waste containers slightly harder, and positioning different trash receptacles in different parts of examination rooms may help reduce inappropriate use of red bag waste.

6. Consider virtual platforms when possible. Due to the COVID-19 pandemic, virtual meeting platforms saw a considerable increase in usage by dermatologists. Teledermatology for patient care became much more widely adopted, and traditionally in-person meetings turned virtual.³⁰ The reduction in emissions from these changes was remarkable. A recent study looking at the environmental impact of 3 months of teledermatology visits early during the COVID-19 pandemic found that 1476 teledermatology appointments saved 55,737 miles of car travel, equivalent to 15.37 metric tons of CO₂.³¹ Whether for patient care when appropriate, academic conferences and continuing medical education credit, or for interviews (eg, medical students, residents, other staff), use of virtual platforms can reduce unnecessary travel and therefore substantially reduce travel-related emissions. When travel is unavoidable, consider exploring validated vetted companies that offer carbon offsets to reduce the harmful environmental impact of high-emission flights.

7. Limit use of single-use disposable items. Although single-use items such as examination gloves or needles are necessary in a dermatology practice, there are many opportunities to incorporate reusable items in your workplace. For instance, you can replace plastic cutlery and single-use plates in kitchen or dining areas with reusable alternatives. Additionally, using reusable isolation gowns instead of their single-use counterparts can help reduce waste; a reusable isolation gown system for providers including laundering services was found to consume 28% less energy and emit 30% fewer greenhouse gases than a single-use isolation gown system.³² Similarly, opting for reusable instruments instead of single-use instruments when possible also can help reduce your practice’s carbon footprint. Carefully evaluating each part of your “dermatology visit supply chain” may offer opportunities to utilize additional cost-saving, environmentally friendly options; for example, an individually plastic-wrapped Dermablade vs a bulk-packaged blade for shave biopsies has a higher cost and worse environmental impact. A single gauze often is sufficient for shave biopsies, but many practices open a plastic container of bulk gauze, much of which results in waste that too often is inappropriately disposed of as regulated medical waste despite not being saturated in blood/body fluids.

8. Educate on the effects of climate change. Dermatologists and other physicians have the unique opportunity to teach members of their community every day through patient care. Physicians are trusted messengers, and appropriately counseling patients regarding the risks of climate change and its effects on their dermatologic health is in line with both American Medical Association and American College of Physicians guidelines.^3,4 For instance, patients with Lyme disease in Canada or Maine were unheard of a few decades ago, but now they are common; flares of atopic dermatitis in regions adjacent to recent wildfires may be attributable to harmful particulate matter resulting from fossil-fueled climate change and record droughts. Educating medical trainees on the impacts of climate change is just as vital, as it is a topic that often is neglected in medical school and residency curricula.³³

9. Install water-efficient toilets and faucets. Anthropogenic climate change has been shown to increase the duration and intensity of droughts throughout the world.³⁴ Much of the western United States also is experiencing record droughts. One way in which dermatology practices can work to combat droughts is through the use of water-conserving toilets, faucets, and urinals. Using water fixtures with the US Environmental Protection Agency’s WaterSense label is a convenient way to do so. The WaterSense label helps identify water fixtures certified to use at least 20% less water as well as save energy and decrease water costs.

10. Advocate through local and national organizations. There are numerous ways in which dermatologists can advocate for action against climate change. Joining professional organizations focused on addressing the climate crisis can help you connect with fellow dermatologists and physicians. The Expert Resource Group on Climate Change and Environmental Issues affiliated with the American Academy of Dermatology (AAD) is one such organization with many opportunities to raise awareness within the field of dermatology. The AAD recently joined the Medical Society Consortium on Climate and Health, an organization providing opportunities for policy and media outreach as well as research on climate change. Advocacy also can mean joining your local chapter of Physicians for Social Responsibility or encouraging divestment from fossil fuel companies within your institution. Voicing support for climate change–focused lectures at events such as grand rounds and society meetings at the local, regional, and state-wide levels can help raise awareness. As the dermatologic effects of climate change grow, being knowledgeable of the views of future leaders in our specialty and country on this issue will become increasingly important.

Final Thoughts

In addition to the climate-friendly decisions one can make as a dermatologist, there are many personal lifestyle choices to consider. Small dietary changes such as limiting consumption of beef and minimizing food waste can have large downstream effects. Opting for transportation via train and limiting air travel are both impactful decisions in reducing CO₂ emissions. Similarly, switching to an electric vehicle or vehicle with minimal emissions can work to reduce greenhouse gas accumulation. For additional resources, note the AAD has partnered with My Green Doctor, a nonprofit service for health care practices that includes practical cost-saving suggestions to support sustainability in physician practices.

A recent joint publication in more than 200 medical journals described climate change as the greatest threat to global public health.³⁵ Climate change is having devastating effects on dermatologic health and will only continue to do so if not addressed now. Dermatologists have the opportunity to join with our colleagues in the house of medicine and to take action to fight climate change and mitigate the health impacts on our patients, the population, and future generations.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

The Diagnosis: Syringoma

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma- or tadpole-shaped tail comprised of dilated cystic eccrine ducts. Clinically, syringomas typically present predominantly in the periorbital region in adolescent girls. They may present as solitary or multiple lesions, and sites such as the genital area, palms, scalp, and chest rarely can be involved.¹ Eruptive syringoma is a clinical subtype of syringoma that is seen on the face, neck, chest, and axillae that predominantly occurs in females with skin of color in countries such as Asia and Africa before or during puberty.^2,3 Lesions appear as small, flesh-colored or slightly pigmented, flat-topped papules.³ The condition can be cosmetically disfiguring and difficult to treat, especially in patients with darker skin.

In our patient, dermoscopic evaluation revealed reticular light brown lines, structureless light brown areas, clustered brown dots, globules, and reticular vessels on a faint background (Figure 1A). Glittering yellow-whitish round structures over a fading pink-brown background also were seen at some sites (Figure 1B). Histologic examination of a neck lesion revealed an epidermis with focal acanthosis; the upper dermis had tumor islands and ducts with cells with round to vesicular nuclei and eosinophilic cytoplasm. A well-circumscribed tumor in the dermis composed of tubules of varying sizes lined by cuboidal cells was seen, consistent with syringoma (Figure 2).

Dermoscopic features of syringomas have not been widely studied. Hayashi et al⁴ reported the dermoscopic features of unilateral linear syringomas as a delicate and faint reticular pigmentation network and multiple hypopigmented areas. Sakiyama et al⁵ also defined an incomplete pigment network with faint erythema in 2 eruptive syringoma cases.

Treatment of this condition is for cosmetic reasons only, and there are no reports of long-term morbidity associated with the disease.^6,7 Multiple therapeutic options are available but are associated with complications such as hyperpigmentation and sclerosis in patients with skin of color due to the dermal location of these syringomas. Management of syringomas includes topical and surgical methods, including topical retinoids such as tretinoin and atropine solution 1%; surgical methods include dermabrasion, excision, cryotherapy, electrocautery, electrofulguration, laser therapy, and chemical cautery. However, there is a substantial risk for recurrence with these treatment options. In a case series of 5 patients with periorbital syringomas, treatment using radiofrequency and a CO₂ laser was performed with favorable outcomes, highlighting the use of combination therapies for treatment.8 Seo et al⁹ reported a retrospective case series of 92 patients with periorbital syringomas in which they treated one group with CO₂ laser and the other with botulinum toxin A injection; CO₂ laser combined with botulinum toxin A showed a greater effect than laser treatment alone. The differential diagnosis includes pigmented plane warts, sebaceous hyperplasia, eruptive xanthomas, and hidrocystomas. Pigmented plane warts characteristically present as flat-topped papules with small hemorrhagic dots or tiny pinpoint vessels on dermoscopy. In sebaceous hyperplasia, yellowish umbilicated papular lesions are seen with crown vessels on dermoscopy. Eruptive xanthomas usually are erythematous to yellow, dome-shaped papules that appear mainly over the extensor aspects of the extremities. Hidrocystoma presents as a solitary translucent larger syringomalike lesion commonly seen in the periorbital region and/or on the cheeks.

We report a case of widespread syringomas with multiple close mimickers such as pigmented plane warts; however, dermoscopy of the lesions helped to arrive at the diagnosis. Dermatologists should be aware of this condition and its benign nature to ensure correct diagnosis and appropriate treatment.

In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.^1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.³ In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.

AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.

That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.^4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.

The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.

Additional References

1.            Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235

2.            Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004

3.            Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013

4.            Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482

5.            Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019

6.            Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526

7.            Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028

8.            Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012

In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.^1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.³ In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.

AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.

That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.^4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.

The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.

Additional References

1.            Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235

2.            Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004

3.            Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013

4.            Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482

5.            Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019

6.            Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526

7.            Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028

8.            Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012

In a cross-sectional observational study of 502 Finnish patients with AD, Salava and colleagues found that severe AD was associated with older age, male sex, early age of disease onset, higher body mass index, history of smoking, concomitant asthma, palmar hyperlinearity, hand dermatitis, history of contact allergy, and history of elevated immunoglobulin E levels. Some of these findings are correlated with each other. For example, palmar hyperlinearity was previously found to be a sign associated with early-onset AD in conjunction with Filaggrin loss-of-function mutations and atopic comorbidities.^1,2 The association of AD with increased body mass index is consistent with previous studies that found associations of AD with overweight and obesity.³ In some instances, more severe AD may precede or lead to the association, eg, asthma and hand dermatitis. These results highlight the heterogeneity and complexity of AD, especially in moderate-to-severe disease.

AD is also associated with heterogeneous triggers. In clinical practice, we commonly see patients who consider food a potential trigger for AD. To better understand the role of food-triggered AD, Li and colleagues performed a retrospective study of 372 pediatric patients with AD. They found that more than half of the children with mild, moderate, and severe AD had an immunoglobulin E–mediated food allergy. Nevertheless, food-triggered AD occurred in only 3% of patients with AD. These results are doubly important because they indicate that clinicians should address food allergies to holistically improve the health of patients with AD. On the other hand, food is rarely a reproducible trigger of AD and appropriate treatment should generally not be withheld in favor of testing for food triggers of AD.

That said, it is important to address cutaneous and extra-cutaneous infections that occur in patients with AD to prevent worsening of AD and serious sequelae of infection. Indeed, Han and colleagues examined data from the Korean National Health Insurance Service, a nationwide population-based registry including 70,205 patients with AD and an unspecified number of control patients without AD. They found that AD was associated with significantly higher odds of molluscum contagiosum, impetigo, chickenpox, otitis media, eczema herpeticum, viral warts, and viral conjunctivitis. These results are consistent with previous studies from my research group showing higher rates of these and other infections.^4-8 Anecdotally, I have seen all of these occur commonly in patients with AD, and in many instances these conditions worsen the underlying AD, eg, impetigo and eczema herpeticum.

The above-mentioned studies highlight the heterogeneity and complexity of AD, especially moderate-to-severe disease. Elsawi and colleagues conducted a survey-based study of 1065 adults with AD and found that moderate-to-severe AD was associated with increased patient burden, increased time spent managing AD symptoms, and comorbid depression. In addition, time spent managing AD symptoms was in and of itself a predictor of increased patient burden. These results underscore the many unmet needs that remain in the management of AD, with substantial patient burden from inadequate treatment as well as the inherent burden from the treatments themselves.

Additional References

1.            Meng L, Wang L, Tang H, et al. Filaggrin gene mutation c.3321delA is associated with various clinical features of atopic dermatitis in the Chinese Han population. PloS One. 2014;9:e98235. Doi: 10.1371/journal.pone.0098235

2.            Weidinger S, Illig T, Baurecht H, et al. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol. 2006;118:214-219. Doi: 10.1016/j.jaci.2006.05.004

3.            Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72:606-616.e4. Doi: 10.1016/j.jaad.2014.12.013

4.            Narla S, Silverberg JI. Association between childhood atopic dermatitis and cutaneous, extracutaneous and systemic infections. Br J Dermatol. 2018;178:1467-1468. Doi: 10.1111/bjd.16482

5.            Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Anb Allergy Asthma Immunol. 2018;120:66-72e11. Doi: 10.1016/j.anai.2017.10.019

6.            Ren Z, Silverberg JI. Association of atopic dermatitis with bacterial, fungal, viral, and sexually transmitted skin infections. Dermatitis. 2020;31:157-164. Doi: 10.1097/DER.0000000000000526

7.            Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: a systematic review and meta-analysis. J Acad Am Acad Dermatol. 2019;80:904-912. Doi: 10.1016/j.jaad.2018.11.028

8.            Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133:1041-1047. Doi: 10.1016/j.jaci.2013.08.012

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

A version of this article first appeared on Medscape.com.

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

A version of this article first appeared on Medscape.com.

A variety of treatments, most already commercially available, are under investigation for treating the constellation of overlapping symptoms associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, speakers presented data for a variety of approaches to ease symptoms common across postviral conditions, such as extreme fatigue, postexertional malaise (“crash”), cognitive dysfunction (“brain fog”), orthostatic intolerance including postural orthostatic tachycardia syndrome (POTS), and chronic pain. Most of the modalities are already commercially available for other indications, although some are costly and not covered by payers for these conditions.

“Both post–acute COVID-19 syndrome and ME/CFS are forms of postinfectious viral syndromes and they have overlapping symptoms. ... In the past, patients were told ‘you have chronic fatigue syndrome but there’s nothing we can do for it.’ That certainly is not the case. There aren’t cures, but there are many management techniques to improve symptoms,” Charles W. Lapp, MD, medical director of the Hunter-Hopkins Center, Charlotte, N.C., said in an interview.

A current mainstay of treatment for ME/CFS – including that triggered by COVID-19 – is activity pacing, in which patients learn to stay within their “energy envelopes” in order to avoid postexertional malaise, a worsening of all symptoms with exertion. The use of “graded exercise” is no longer recommended, per U.K. and U.S. guidelines.

Data for the following approaches were presented at the IACFS/ME conference:
 

Pyridostigmine (mestinon, others)

Pyridostigmine, an acetylcholinesterase inhibitor, is approved for the treatment of muscle weakness resulting from myasthenia gravis and is available in generic form. It has previously been shown to produce significant improvement in both symptom burden and heart rate response in POTS.

At the IACFS/ME conference, David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital and director of the Massachusetts General Hospital Cardiopulmonary laboratory, both in Boston, summarized his group’s study in patients with ME/CFS using pyridostigmine as both a potential treatment for improving exercise capacity and a proof-of-concept that neurovascular dysregulation underlies exertional intolerance in the condition.

A total of 45 patients were randomized to 60 mg oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test, and a second test performed 50 minutes later. Peak VO₂ increased after pyridostigmine but decreased after placebo (+13.3 mL/min vs. –40.2 mL/min, P < .05). Cardiac output and right atrial pressure were also significantly improved with pyridostigmine and worse with placebo.

“We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS. ... Pyridostigmine may be a useful repurposed off-label treatment [for] a subset of patients with exercise intolerance,” Dr. Systrom said.

Asked to comment, Dr. Lapp said: “We’ve used Mestinon for years because it helps with POTS and also with neurally mediated hypotension. Systrom is taking it to a new level because he’s shown that it increases preload to the heart.” However, he noted that it’s unclear whether the drug will help patients who don’t have POTS specifically. On the other hand, patients rarely experience side effects from the drug.

Since the generic tablets come only in 60-mg doses, and the starting dose is 30 mg three times a day, he advised cutting the tablets in half during titration up to 60 mg three times a day.
 

Oxaloacetate (benaGene)

David Lyons Kaufman, MD, of the Center for Complex Diseases, Mountain View, Calif., summarized data from his group’s recently published open-label, nonrandomized, “proof-of-concept” study on use of the commercially available nutritional supplement anhydrous enol-oxaloacetate for treating mental and physical fatigue in 76 patients with longstanding ME/CFS and 43 with long-COVID fatigue.

Oxaloacetate is a major step in the Krebs cycle within the mitochondria that are depleted in patients with ME/CFS. It is also an energy metabolite that has multiple effects in cells and mitochondria, Dr. Kaufman explained.

Doses ranging from 500 mg twice daily up to 1,000 mg three times a day were given for 6 weeks. Up to 33% of the patients with ME/CFS and up to 46.8% of the long-COVID group achieved clinical efficacy as measured by physical and mental fatigue scores, compared with just 5.9% of historical ME/CFS controls. All doses showed highly significant improvements.

The only adverse effects were occasional dyspepsia, which was avoided by taking the supplement with food, and insomnia, resolved by having them dose at breakfast and lunch, Dr. Kaufman said.

Following those preliminary data, there is now an ongoing 90-day, randomized, placebo-controlled clinical trial of 80 patients with ME/CFS using 2,000 mg anhydrous enol-oxaloacetate per day. Endpoints include multiple objective measures.

“We have a health care crisis with long COVID, and we’ve had this smoldering crisis with ME/CFS for decades that’s never been addressed. ME/CFS and long COVID, if not identical, are certainly overlapping. ... We have to pursue these translational medicine pilot studies as rapidly as possible,” Dr. Kaufman remarked.

Dr. Lapp told this news organization that it makes sense to use constituents of the Krebs cycle to improve mitochondrial function, but the problem with oxaloacetate is its cost. Dr. Kaufman mentioned that based on the preliminary trial, the therapeutic “sweet spot” appeared to be 1,000 mg twice daily. The manufacturer’s website lists the price for a single bottle of 30 250-mg capsules at $49, or $42 if purchased via a monthly subscription.

“It’s a benign drug, and it’s over the counter. I would give it to any patient who’s got a big wallet,” Dr. Lapp quipped, adding: “If they’ve got the money, they can order it tonight.”
 

Inspiritol

Inspiritol is an investigational “nebulized, inhaled, multimechanism medication designed to treat the major symptoms of respiratory distress with antioxidant, anti-inflammatory, and broad-spectrum antiviral and antibacterial properties. Inspiritol is composed of both endogenously produced and naturally occurring, well-tolerated biochemicals,” according to the company website.

The hypothesis, Liisa K. Selin, MD, PhD, professor of pathology at the University of Massachusetts, Worcester, said at the meeting, is that “ME/CFS and long COVID-19 result from an aberrant response to an immunological trigger like infection, which results in a permanently dysregulated immune system as a result of overactivation of CD8 T cells and subsequent exhaustion.”

Inspiritol, containing five antioxidants, acts as an immune modulator to reverse the CD8 T cell exhaustion and improve symptoms. Administration by inhaler delivers it directly to the brain from the lung. It was originally designed for use in chronic obstructive pulmonary disease and asthma and has shown efficacy for acute COVID-19, Dr. Selin said.

In a preliminary study, four patients with ME/CFS and five with long COVID have been treated with Inspiritol for 2-15 months, and all have self-reported improved symptoms. Cough has been the only reported side effect.

The company is pursuing an Investigational New Drug Application for the product with the Food and Drug Administration and has several patents pending. Dr. Lapp called Inspiritol “very interesting,” and said that reversal of CD8 “exhaustion” also would appear to be a promising approach. However, he noted, “the problem is that we don’t know what’s in it.”
 

Stellate ganglion block

Injection of local anesthetic near the stellate ganglion to block activity of the entire cervical sympathetic chain has been used for nearly a century to treat a variety of sympathetically mediated conditions, including complex regional pain syndrome (CRPS), shingles, and phantom-limb pain. More recently, it has been used in a variety of other conditions, including PTSD, Raynaud’s disease, menopausal hot flashes, and hyperhidrosis.

Insurance companies typically cover it for CRPS, neuropathic upper-extremity pain, hyperhidrosis, and Raynaud’s, said Luke Liu, MD, an anesthesiologist who is founder and chief executive officer of Alaska-based pain management company Neuroversion.

Deborah Duricka, PhD, also with Neuroversion, presented results from a now-published case series of 11 patients with long COVID who underwent stellate ganglion block by a board-certified anesthesiologist, first on one side at the level of C6, then on the contralateral side the following day.

Clinically meaningful benefits were seen in at least five of the patients in fatigue, memory problems, problems concentrating, rapid heartbeat, orthostatic intolerance, sleep problems, postexertional malaise, anxiety, and depression.

The hypothetical mechanism, she said, is that “sympathetic block prevents sympathetically driven vasoconstriction in carotid and vertebral arteries.”

Dr. Liu presented another case series of five patients with ME/CFS who underwent the procedure with ultrasound guidance, again on one side and the other side the next day. All had upper-limb autonomic issues such as Raynaud’s and/or neuropathic pain that had been refractory to more conventional treatments.

All five patients reported improvements in symptoms of ME/CFS, including energy level, cognition, pain, and postexertional malaise. One patient reported “feeling well for the first time in decades.” However, that patient relapsed after a mild viral illness 3.5 months after treatment. Some of the patients have required further treatments.

Dr. Lapp commented that, although the procedure is generally safe when performed by an experienced clinician, “Any time you do an injection like that, there’s a high risk that you could nick an artery or a vein or hit an essential nerve in the neck. That’s why it has to be done under fluoroscopy or ultrasound.”

He said he’s had a few patients undergo the procedure, mostly for CRPS, and they seem to have benefited from it. “It might increase cerebral blood flow and preload to the heart, so it might decrease ME/CFS symptoms and help with POTS as well.”

Nonetheless, Dr. Lapp said he wouldn’t consider stellate ganglion block as first-line treatment for ME/CFS or long COVID. “I think it would be for the treatment-resistant patient, when you’ve gone through all the treatments that we know and addressed all the comorbidities and they’re still not getting better.”

But, he added, it is a standard procedure. “Any pain clinic can do a stellate block.”
 

Transcutaneous auricular vagus nerve stimulation

Nicola Clague-Baker, PhD, a physiotherapist at the University of Liverpool (England), presented findings from an international survey of people with ME/CFS regarding their experience with transcutaneous auricular vagus nerve stimulation (taVNS) to manage their autonomic symptoms. The technique involves stimulation of the autonomic nervous system via the vagus nerve using electrodes applied to part of the ear. The theory is that the technique stimulates the parasympathetic nervous system and improves autonomic balance.

Two small previous trials showing benefit of vagus nerve stimulation for people with ME/CFS used more invasive and less comfortable methods of applying the stimulation rather than to the ear, Dr. Clague-Baker and colleagues noted in a poster. It has also been used successfully in treating POTS, another conference speaker noted.

A total of 131 people with ME/CFS (called simply “ME” in the United Kingdom) responded to a survey advertised on social media and websites. The majority (60%) were from the United Kingdom while the rest were from Europe, Australia, and North America. Most were female, and slightly more than half had lived with ME for 10 or more years.

The majority (72%) were still using taVNS, while 28% had stopped using it. Only 9% had used the modality for longer than a year. Respondents identified more than 30 benefits in symptoms and activities, with improvements in postexertional malaise (39%) and brain fog (37%) being the most common. One reported significant reduction in constipation.

However, respondents also mentioned more than 20 short- and long-term negatives, including headaches (15%) and long-term irritation at the site (9%). One participant reported a “big improvement in neuropathic pain, but not so much for muscles and joints.”

Overall, 80% reported that they would continue using taVNS and 67% said they would recommend it to others with ME, and 56% said that the system was mildly to very beneficial.

Dr. Lapp noted that several types of transcutaneous electrical nerve stimulation units with ear clips are sold online, and he’s seen them work well for migraine treatment. However, he cautioned that some patients have had side effects from the treatment, such as headaches and dizziness. “It’s putting an electrical current through your brain. In my mind, it’s another last-ditch measure.”

Dr. Lapp reported no financial disclosures.

A version of this article first appeared on Medscape.com.

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

• Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
• At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
• At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
• Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

A version of this article first appeared on WebMD.com.

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

A version of this article first appeared on WebMD.com.

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

A version of this article first appeared on WebMD.com.

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The major classifications of thyroid disease include hyperthyroidism, which is seen in Graves disease, and hypothyroidism due to iodine deficiency and Hashimoto thyroiditis, which have potentially devastating health consequences. The prevalence of hyperthyroidism ranges from 0.2% to 1.3% in iodine-sufficient parts of the world, and the prevalence of hypothyroidism in the general population is 5.3% in Europe and 3.7% in the United States.¹ Thyroid hormones physiologically potentiate α- and β-adrenergic receptors by increasing their sensitivity to catecholamines. Excess thyroid hormones manifest as tachycardia, increased cardiac output, increased body temperature, hyperhidrosis, and warm moist skin. Reduced sensitivity of adrenergic receptors to catecholamines from insufficient thyroid hormones results in a lower metabolic rate and decreases response to the sympathetic nervous system.² Nail changes in thyroid patients have not been well studied.³ Our objectives were to characterize nail findings in patients with thyroid disease. Early diagnosis of thyroid disease and prompt referral for treatment may be instrumental in preventing serious morbidities and permanent sequelae.

Methods

PubMed, Scopus, Web of Science, and Google Scholar were searched for the terms nail + thyroid, nail + hyperthyroid, nail + hypothyroid, nail + Graves, and nail + Hashimoto on June 10, 2020, and then updated on November 18, 2020. All English-language articles were included. Non–English-language articles and those that did not describe clinical trials of nail changes in patients with thyroid disease were excluded. One study that utilized survey-based data for nail changes without corroboration with physical examination findings was excluded. Hypothyroidism/hyperthyroidism was defined by all authors as measurement of serum thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone outside of the normal range. Eight studies were included in the final analysis. Patient demographics, thyroid disease type, physical examination findings, nail clinical findings, age at diagnosis, age at onset of nail changes, treatments/medications, and comorbidities were recorded and analyzed.

Results

Nail changes in patients with thyroid disease were reported in 8 studies (7 cross-sectional, 1 retrospective cohort) and are summarized in the Table.^4-11 The mean age was 41.2 years (range, 5–80 years), with a higher representation of females (range, 70%–94% female). The most common nail changes in thyroid patients were koilonychia, clubbing, and nail brittleness. Other changes included onycholysis, thin nails, dryness, and changes in nail growth rate. Frequent physical findings were xerosis, pruritus, and alopecia.

Both koilonychia and clubbing were reported in patients with hyperthyroidism. In a study of 32 patients with koilonychia, 22 (68.8%) were diagnosed with hyperthyroidism.¹⁰ Nail clubbing affected 7.3% of Graves disease patients (n=150)⁶ and 5.0% of hyperthyroid patients (n=120).⁷ Dermopathy presented more than 1 year after diagnosis of Graves disease in 99 (66%) of 150 patients as a late manifestation of thyrotoxicosis.⁶ Additional physical features in patients with Graves disease (n=150) were pretibial myxedema (100%), ophthalmopathy (99.0%), and proptosis (88.0%). Non–Graves hyperthyroid patients showed physical features of soft hair (83.3%) and soft skin (66.0%).⁷

Nail brittleness was a frequently reported nail change in thyroid patients (4/8 studies, 50%), most often seen in 22% of autoimmune patients, 19.6% of nonautoimmune patients, 13.9% of hypothyroid patients, and 9.2% of hyperthyroid patients.^5,8 For comparison, brittle nails presented in 10.8% of participants in a control group.⁵ Brittle nails in thyroid patients often are accompanied by other nail findings such as thinning, onycholysis, and pitting.

Among hypothyroid patients, nail changes included fragility (70%; n=50), slow growth (48%; n=50), thinning (40%; n=50), onycholysis (38%; n=50),⁷ and brittleness (13.9%; n=173).⁵ Less common nail changes in hypothyroid patients were leukonychia (9.4%; n=32), striped nails (6%; n=50), and pitting (1.2%; n=173).^5,7,11 Among hyperthyroid patients, the most common nail changes were koilonychia (100%; n=22), softening (83%; n=120), onycholysis (29%; n=14), and brittleness (9.2%; n=173).^5,7,9,10 Less common nail changes in hyperthyroid patients were clubbing (5%; n=120), thinning (4.6%; n=173), and leukonychia (3%; n=120).^5,7

Additional cutaneous findings of thyroid disorder included xerosis, alopecia, pruritus, and weight change. Xerosis was most common in hypothyroid disease (57.2%; n=460).⁴ In 2 studies,^8,9 alopecia affected approximately 70% of autoimmune, nonautoimmune, and hyperthyroid patients. Hair loss was reported in 42.6% (n=460)⁴ and 33.0% (n=36)⁹ of hypothyroid patients. Additionally, pruritus affected up to 28% (n=32)¹¹ of hypothyroid and 16.0% (n=120)⁷ of hyperthyroid patients and was more common in autoimmune (41%) vs nonautoimmune (32%) thyroid patients.⁸ Weight gain was seen in 72% of hypothyroid patients (n=32),¹¹ and soft hair and skin were reported in 83.3% and 66% of hyperthyroid patients (n=120), respectively.⁷ Flushing was a less common physical finding in thyroid patients (usually affecting <10%); however, it also was reported in 17.1% of autoimmune and 57.1% of hyperthyroid patients from 2 separate studies.^8,9

 

 

Comment

There are limited data describing nail changes with thyroid disease. Singal and Arora³ reported in their clinical review of nail changes in systemic disease that koilonychia, onycholysis, and melanonychia are associated with thyroid disorders. We similarly found that koilonychia and onycholysis are associated with thyroid disorders without an association with melanonychia.

In his clinical review of thyroid hormone action on the skin, Safer¹² described hypothyroid patients having coarse, dull, thin, and brittle nails, whereas in thyrotoxicosis, patients had shiny, soft, and concave nails with onycholysis; however, the author commented that there were limited data on the clinical findings in thyroid disorders. These nail findings are consistent with our results, but onycholysis was more common in hypothyroid patients than in hyperthyroid patients in our review. Fox¹³ reported on 30 cases of onycholysis, stating that it affected patients with hypothyroidism and improved with thyroid treatment. In a clinical review of 8 commonly seen nail abnormalities, Fowler et al¹⁴ reported that hyperthyroidism was associated with nail findings in 5% of cases and may result in onycholysis of the fourth and fifth nails or all nails. They also reported that onychorrhexis may be seen in patients with hypothyroidism, a finding that differed from our results.¹⁴

The mechanism of nail changes in thyroid disease has not been well studied. A protein/amino acid–deficiency state may contribute to the development of koilonychia. Hyperthyroid patients, who have high metabolic activity, may have hypoalbuminemia, leading to koilonychia.¹⁵ Hypothyroidism causes hypothermia from decreased metabolic rate and secondary compensatory vasoconstriction. Vasoconstriction decreases blood flow of nutrients and oxygen to cutaneous structures and may cause slow-growing, brittle nails. In hyperthyroidism, vasodilation alternatively may contribute to the fast-growing nails. Anti–thyroid-stimulating hormone receptor antibodies in Graves disease may increase the synthesis of hyaluronic acid and glycosaminoglycans from fibroblasts, keratinocytes, adipocytes, or endothelial cells in the dermis and may contribute to development of clubbing.¹⁶

Our review is subject to several limitations. We recorded nail findings as they were described in the original studies; however, we could not confirm the accuracy of these descriptions. In addition, some specific nail changes were not described in sufficient detail. In all but 1 study, dermatologists performed the physical examination. In the study by Al-Dabbagh and Al-Abachi,¹⁰ the physical examinations were performed by general medicine physicians, but they selected only for patients with koilonychia and did not assess for other skin findings. Fragile nails and brittle nails were described in hypothyroid and hyperthyroid patients, but these nail changes were not described in detail. There also were studies describing nail changes in thyroid patients; some studies had small numbers of patients, and many did not have a control group.

Conclusion

Nail changes may be early clinical presenting signs of thyroid disorders and may be the clue to prompt diagnosis of thyroid disease. Dermatologists should be mindful that fragile, slow-growing, thin nails and onycholysis are associated with hypothyroidism and that koilonychia, softening, onycholysis, and brittle nail changes may be seen in hyperthyroidism. Our review aimed to describe nail changes associated with thyroid disease to guide dermatologists on diagnosis and promote future research on dermatologic manifestations of thyroid disease. Future research is necessary to explore the association between koilonychia and hyperthyroidism as well as the association of nail changes with thyroid disease duration and severity.

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!

The Cutis Editorial Board is now accepting applications for the 2023 Resident Corner column. The Editorial Board will select 2 to 3 residents to serve as the Resident Corner columnists for 1 year. Articles are posted online only at www.mdedge.com/dermatology but will be referenced in Index Medicus. All applicants must be current residents and will be in residency throughout 2023.

For consideration, send your curriculum vitae along with a brief (not to exceed 500 words) statement of why you enjoy Cutis and what you can offer your fellow residents in contributing a monthly column.

A signed letter of recommendation from the Director of the dermatology residency program also should be supplied.

All materials should be submitted via email to Melissa Sears ([email protected]) by October 28. The residents who are selected to write the column for the upcoming year will be notified by November 4.

We look forward to continuing to educate dermatology residents on topics that are most important to them!