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Photoprotection Prevents Skin Cancer: Let’s Make It Fashionable to Wear Sun-Protective Clothing

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Photoprotection Prevents Skin Cancer: Let’s Make It Fashionable to Wear Sun-Protective Clothing
In partnership with the Association of Military Dermatologists

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.4 Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.5 This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.6

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).3 Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.7 Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.1 Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.8

 

 

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.5 The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.11 Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.12 Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.13

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.14 Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.14 Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.15 Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.6

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.16 Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.17 Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.16

 

 

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

References
  1. Prevent skin cancer. American Academy of Dermatology website. https://www.aad.org/public/spot-skin-cancer/learn-about-skin-cancer/prevent. Accessed January 4, 2017.
  2. What can I do to reduce my risk of skin cancer? Centers for Disease Control and Prevention website. http://www.cdc.gov/cancer/skin/basic_info/prevention.htm. Accessed January 4, 2017.
  3. Cancer facts & figures 2016. American Cancer Society website. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed January 4, 2017.
  4. Diffey BL, Cheeseman J. Sun protection with hats. Br J Dermatol. 1992;127:10-12.
  5. Bray FN. Florida school boards restrict access to outdoor sun protection: an observational study. J Am Acad Dermatol. 2016;75:642-644.
  6. Yeung H, Luk KM, Chen SC. Focal photodamage on the occipital scalp. JAMA Dermatol. 2016;152:1060-1062.
  7. Lee T, Williams VF, Clark LL. Incident diagnoses of cancers in the active component and cancer-related deaths in the active and reserve components, U.S. Armed Forces, 2005-2014. MSMR. 2016;23:23-31.
  8. Parkin DM, Mesher D, Sasieni P. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in 2010. Br J Cancer. 2011;105(suppl 2):S66-S69.
  9. Casper K. Elementary schools consider “no hat no play policy.” Coolibar website. http://blog.coolibar.com/elementary-schools-consider-no-hat-no-play-policy/. Published March 27, 2012. Accessed January 4, 2017.
  10. Slip, slop, slap, seek & slide: Sid Seagull. SunSmart Victoria website. http://www.sunsmart.com.au/tools/videos/current-tv-campaigns/slip-slop-slap-seek-slide-sid-seagull.html. Accessed January 4, 2017.
  11. McGrath JM, Fisher V, Krejci-Manwaring J. Skin cancer warnings and the need for new preventive campaigns - a pilot study. Am J Prev Med. 2016;50:E62-E63.
  12. Parker G, Williams B, Driggers P. Sun exposure knowledge and practices survey of maintenance squadrons at Travis AFB. Mil Med. 2015;180:26-31.
  13. Holman DM, Berkowitz Z, Guy GP Jr, et al. Patterns of sunscreen use on the face and other exposed skin among US adults [published online May 19, 2015]. J Am Acad Dermatol. 2015;73:83-92.e1.
  14. Stanton SL. Headgear. In: Stanton SL. U.S. Army Uniforms of the Vietnam War. Harrisburg, PA: Stackpole Books; 1992:26-61.
  15. Richmond-Sinclair NM, Pandeya N, Ware RS, et al. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population [published online July 31, 2008]. J Invest Dermatol. 2009;129:323-328.
  16. Gies P, Javorniczky J, Roy C, et al. Measurements of the UVR protection provided by hats used at school. Photochem Photobiol. 2006;82:750-754.
  17. Winterhalter C, DiLuna K, Bide M. Characterization of the Ultraviolet Protection of Combat Uniform Fabrics. Natick, MA: US Army Solider and Biological Chemical Command; 2002. Technical report 02/006.
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Author and Disclosure Information

Dr. Milch is from Fox Army Health Center, Hunstville, Alabama. Dr. Logemann is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Jeffrey M. Milch, DO, Fox Army Health Center, 4100 Goss Rd, Redstone Arsenal, Huntsville, AL 35805 ([email protected]).

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Author and Disclosure Information

Dr. Milch is from Fox Army Health Center, Hunstville, Alabama. Dr. Logemann is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Jeffrey M. Milch, DO, Fox Army Health Center, 4100 Goss Rd, Redstone Arsenal, Huntsville, AL 35805 ([email protected]).

Author and Disclosure Information

Dr. Milch is from Fox Army Health Center, Hunstville, Alabama. Dr. Logemann is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Jeffrey M. Milch, DO, Fox Army Health Center, 4100 Goss Rd, Redstone Arsenal, Huntsville, AL 35805 ([email protected]).

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In partnership with the Association of Military Dermatologists
In partnership with the Association of Military Dermatologists

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.4 Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.5 This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.6

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).3 Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.7 Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.1 Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.8

 

 

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.5 The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.11 Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.12 Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.13

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.14 Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.14 Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.15 Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.6

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.16 Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.17 Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.16

 

 

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

Photoprotection is the foundation of all skin cancer prevention, as UV radiation (UVR) exposure is the only known modifiable risk factor for skin cancer. With the majority of UVR exposure–induced skin cancers found on the scalp, ears, face, and neck, public health initiatives call for wise choices in personal fashion that emphasize the importance of covering these areas.1-3 From a science of fashion perspective, research has shown that wide-brimmed hats provide better means of ensuring the largest area of coverage compared to standard baseball-style hats.4 Thus, for maximum protection, wide-brimmed hats should be favored. However, in academic and military settings, individual style is not optional and is instead influenced or directed by policy, which may not be aligned with the goal of providing photoprotection and raises additional concern for individuals working in environments with longer periods of peak daylight UVR exposure.

In all military branches, service members don uniforms that include head coverage when operating outdoors; however, the choice of headgear is not always aimed at reducing UVR exposure. Similarly, in our counterpart civilian populations, wearing hats that provide the best photoprotection may be influenced by school policies, which frequently mandate clothing choices for children, or by the press or fashion industry in the general public, which might portray sun-protective garments as unfashionable or in some cases threatening if perceived as demonstrating gang affiliation.5 This article serves to encourage health care providers to not only discuss the use of sunscreen when educating patients on sun protection but also to emphasize the benefits of wearing photoprotective garments, particularly wide-brimmed hats given their simplicity, reusability, and affordability. Hat use is particularly important for men with comorbid androgenetic alopecia.6

Skin Cancer Risk

Unfortunately, the incidence of most common types of skin cancer, specifically nonmelanoma skin cancers such basal cell carcinomas and squamous cell carcinomas (ie, keratinocyte carcinomas [KCs]), is difficult to estimate properly, as these cases are not required to be reported to worldwide cancer registries. However, more than 5.4 million cases of skin cancers were diagnosed among 3.3 million Americans in 2016, with an estimated 13,650 deaths associated with skin cancers (not including KCs).3 Tracking and data analyses of cases diagnosed in the active and reserve component populations of the US Armed Forces reflect parallel findings.7 Keratinocyte carcinomas could be considered largely preventable, as most are the result of UVR exposure.1 Additionally, it has been suggested that the vast majority of mutations in melanoma skin cancers (up to 86%) are caused by UVR exposure.8

 

 

Prevention

United States–based national public health services such as the American Cancer Society, the Centers for Disease Control and Prevention, and the American Academy of Dermatology embrace photoprotection as the central practice in reducing risk factors for skin cancers. Guidelines put forth by these and other national preventive medical institutions specifically recommend the use of wide-brimmed hats as the best option for protection of the face, head, ears, and neck, in addition to more common recommendations such as seeking shade, avoiding sunlight during peak hours of the day, and using sunscreen.1-3 At state and local levels, policies should be adapted from these recommendations to support protective practices and skin cancer education that begins early for school-aged children. Unfortunately, in some school districts, wearing hats of any kind may be perceived as disruptive or in some cases baseball hats may be a sign of gang affiliation and are therefore banned in the schoolyard.5 The opposite is true in certain parts of the world where sun protection is embraced by the population as a whole, such as Australia where the widely accepted “slip, slop and slap, seek and slide” campaign has extended to some school policymakers who have considered adopting a “no hat, no play” policy.9,10

Sunscreen use as a primary component of photoprotection has its disadvantages in comparison to wearing protective clothing, as sunscreen cannot be reused and proper usage requires reapplication after swimming, when sweating, and following 2 hours of application.1-3 The need for reapplication of sunscreen can lead to considerable expense as well as time spent in application and reapplication. Additionally, for individuals who are physically active (eg, operationally engaged service members, outdoor athletes), sunscreen applied to the face may become a hindrance to function, as it may drip or enter the eyes with excessive sweating, possibly impairing vision. Some individuals may be averse to applying lotions or creams to the skin in general, as they do not prefer the textural changes or appearance of the skin after application. The application of sunscreen also could impair use of lifesaving military gear (eg, gas masks, helmets) from fitting or securing appropriately.

Patient Education

From a military perspective, a review of a recent targeted pilot study in which skin cancer patients at a US Veterans Administration hospital were surveyed on personal knowledge of UVR protection showed that respondents who had a history of skin cancer diagnosis did not feel that they had ever been at an increased risk for skin cancers and did not receive skin cancer prevention education during their tours of service. The overwhelming majority of all participants in this study agreed that the military should issue sun-protective clothing and sunscreen to active-duty personnel.11 Another 2015 survey of 356 current US Air Force flight line personnel noted that active-duty service members tend not to use sunscreen when at work or while at home, and 43% of participants reported using no sun-protective methods while working outdoors.12 Although these studies focused on military personal, the data mirror findings within the general public, as it was shown in a survey by the Centers for Disease Control and Prevention that Americans do not fully take advantage of the benefits of UVR protection, specifically with regard to sunscreen use. Little to no usage was correlated with low socioeconomic status, suggesting that a reusable form of protection could be preferred.13

Public health initiatives typically promote education on the use of sunscreen in populations that spend a considerable amount of time working outdoors (eg, construction workers, farmers, military personnel); however, we feel emphasis should be placed on the benefits of wearing hats, as the UVR exposure protection they provide does not wear off, is cost effective, does not require reapplication, and has the advantage of being a recyclable and affordable form of photoprotection.

History of the Military-Grade Wide-Brimmed Hat

One military-specific example of a sun-protective hat is the boonie hat, known at the time of its inception as the tropical or hot-weather hat, which first became popular during the Vietnam War. This hat option was initially proposed on April 7, 1966, when it was realized that a full-brimmed field hat was needed to protect soldiers’ faces and necks from rain and sun in harsh tropical climates.14 Unfortunately, despite the protective advantages of this style of head covering and favorable support from service members themselves, the boonie hat was not widely accepted, as commanders disliked its “unmilitary appearance.” Fervent protests by units throughout Vietnam eventually led to a compromise in policy that allowed unit-level commanders to authorize the use of boonie hats for units in combat or combat support field operations.14 Today, the boonie hat continues to garnish mixed emotions from unit commanders, as wearing this garment often is interpreted as not being in line with an appropriate military appearance, which is similar to the public fashion zeitgeist that also does not openly endorse the use of sun-protective garments. A change in fashion culture and policy (both military and civilian) that promotes sun-protective measures is needed.

Wide-Brimmed Hats Are Superior to Baseball Hats

The distribution of skin cancers across anatomic sites is consistent and proportional with the level and frequency of chronic UVR exposure, with the occurrence of most skin cancers being greatest on the nose, forehead/temples, cheeks/perioral areas, and ears.15 Additionally, higher incidences of skin cancers have been noted in chronically sun-exposed areas of the head and neck in men versus women. It is thought that hair distribution in these areas may be the causal factor.6

Baseball-style hats are worn by all branches of the US military as part of standard training and work duty uniform requirements, primarily for the sake of tradition by maintaining a standard appearance and uniform dress code but also to provide photoprotection to these vulnerable areas of the body. Standard, nonmilitary, baseball-style hats have been shown to provide UV protection factor (UPF) equivalents ranging from 2 to 10 on sites known for the highest levels of exposure.16 Military “patrol caps,” fashioned similar to the baseball-style hat but constructed from military-grade textiles, provide greater levels of photoprotection with UPF ratings from 35 to 50 and higher depending on the fabric color.17 Although patrol caps have a favorable UPF rating and are advantageous compared to former military headgear styles (eg, berets), wide-brimmed hats would provide greater overall coverage.4,6 Studies in school environments also revealed that wide-brimmed hats come out ahead in side-by-side testing against baseball hats and are shown to provide greater photoprotection for the cheeks, chin, ears, and neck.16

 

 

Final Thoughts

The battle to educate the public about adequate photoprotection to prevent skin cancers caused by UVR exposure applies to all providers, both military and civilian. Our ongoing initiatives should not only sustain current practices but should further stress the importance of wearing wide-brimmed hats as a vital part of coverage of the skin and protection from UVR. We must combat the public perception that wearing wide-brimmed hats is a detractor of personal fashion and that instead it is desirable to reduce the risk for skin cancer. The wide-brimmed hat is a simple, reusable, and easily executed recommendation that should be made to all patients, both military and civilian, young and old. In conclusion, by improving patients’ perceptions and acknowledgment of the importance of photoprotection as well as making a concerted effort to integrate our knowledge in the fashion industry, in policies at schools, in the military, and in popular culture, we will undoubtedly come to agree that it is not unfashionable to wear a wide-brimmed hat, but it is unfashionable to risk developing skin cancer.

References
  1. Prevent skin cancer. American Academy of Dermatology website. https://www.aad.org/public/spot-skin-cancer/learn-about-skin-cancer/prevent. Accessed January 4, 2017.
  2. What can I do to reduce my risk of skin cancer? Centers for Disease Control and Prevention website. http://www.cdc.gov/cancer/skin/basic_info/prevention.htm. Accessed January 4, 2017.
  3. Cancer facts & figures 2016. American Cancer Society website. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed January 4, 2017.
  4. Diffey BL, Cheeseman J. Sun protection with hats. Br J Dermatol. 1992;127:10-12.
  5. Bray FN. Florida school boards restrict access to outdoor sun protection: an observational study. J Am Acad Dermatol. 2016;75:642-644.
  6. Yeung H, Luk KM, Chen SC. Focal photodamage on the occipital scalp. JAMA Dermatol. 2016;152:1060-1062.
  7. Lee T, Williams VF, Clark LL. Incident diagnoses of cancers in the active component and cancer-related deaths in the active and reserve components, U.S. Armed Forces, 2005-2014. MSMR. 2016;23:23-31.
  8. Parkin DM, Mesher D, Sasieni P. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in 2010. Br J Cancer. 2011;105(suppl 2):S66-S69.
  9. Casper K. Elementary schools consider “no hat no play policy.” Coolibar website. http://blog.coolibar.com/elementary-schools-consider-no-hat-no-play-policy/. Published March 27, 2012. Accessed January 4, 2017.
  10. Slip, slop, slap, seek & slide: Sid Seagull. SunSmart Victoria website. http://www.sunsmart.com.au/tools/videos/current-tv-campaigns/slip-slop-slap-seek-slide-sid-seagull.html. Accessed January 4, 2017.
  11. McGrath JM, Fisher V, Krejci-Manwaring J. Skin cancer warnings and the need for new preventive campaigns - a pilot study. Am J Prev Med. 2016;50:E62-E63.
  12. Parker G, Williams B, Driggers P. Sun exposure knowledge and practices survey of maintenance squadrons at Travis AFB. Mil Med. 2015;180:26-31.
  13. Holman DM, Berkowitz Z, Guy GP Jr, et al. Patterns of sunscreen use on the face and other exposed skin among US adults [published online May 19, 2015]. J Am Acad Dermatol. 2015;73:83-92.e1.
  14. Stanton SL. Headgear. In: Stanton SL. U.S. Army Uniforms of the Vietnam War. Harrisburg, PA: Stackpole Books; 1992:26-61.
  15. Richmond-Sinclair NM, Pandeya N, Ware RS, et al. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population [published online July 31, 2008]. J Invest Dermatol. 2009;129:323-328.
  16. Gies P, Javorniczky J, Roy C, et al. Measurements of the UVR protection provided by hats used at school. Photochem Photobiol. 2006;82:750-754.
  17. Winterhalter C, DiLuna K, Bide M. Characterization of the Ultraviolet Protection of Combat Uniform Fabrics. Natick, MA: US Army Solider and Biological Chemical Command; 2002. Technical report 02/006.
References
  1. Prevent skin cancer. American Academy of Dermatology website. https://www.aad.org/public/spot-skin-cancer/learn-about-skin-cancer/prevent. Accessed January 4, 2017.
  2. What can I do to reduce my risk of skin cancer? Centers for Disease Control and Prevention website. http://www.cdc.gov/cancer/skin/basic_info/prevention.htm. Accessed January 4, 2017.
  3. Cancer facts & figures 2016. American Cancer Society website. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed January 4, 2017.
  4. Diffey BL, Cheeseman J. Sun protection with hats. Br J Dermatol. 1992;127:10-12.
  5. Bray FN. Florida school boards restrict access to outdoor sun protection: an observational study. J Am Acad Dermatol. 2016;75:642-644.
  6. Yeung H, Luk KM, Chen SC. Focal photodamage on the occipital scalp. JAMA Dermatol. 2016;152:1060-1062.
  7. Lee T, Williams VF, Clark LL. Incident diagnoses of cancers in the active component and cancer-related deaths in the active and reserve components, U.S. Armed Forces, 2005-2014. MSMR. 2016;23:23-31.
  8. Parkin DM, Mesher D, Sasieni P. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in 2010. Br J Cancer. 2011;105(suppl 2):S66-S69.
  9. Casper K. Elementary schools consider “no hat no play policy.” Coolibar website. http://blog.coolibar.com/elementary-schools-consider-no-hat-no-play-policy/. Published March 27, 2012. Accessed January 4, 2017.
  10. Slip, slop, slap, seek & slide: Sid Seagull. SunSmart Victoria website. http://www.sunsmart.com.au/tools/videos/current-tv-campaigns/slip-slop-slap-seek-slide-sid-seagull.html. Accessed January 4, 2017.
  11. McGrath JM, Fisher V, Krejci-Manwaring J. Skin cancer warnings and the need for new preventive campaigns - a pilot study. Am J Prev Med. 2016;50:E62-E63.
  12. Parker G, Williams B, Driggers P. Sun exposure knowledge and practices survey of maintenance squadrons at Travis AFB. Mil Med. 2015;180:26-31.
  13. Holman DM, Berkowitz Z, Guy GP Jr, et al. Patterns of sunscreen use on the face and other exposed skin among US adults [published online May 19, 2015]. J Am Acad Dermatol. 2015;73:83-92.e1.
  14. Stanton SL. Headgear. In: Stanton SL. U.S. Army Uniforms of the Vietnam War. Harrisburg, PA: Stackpole Books; 1992:26-61.
  15. Richmond-Sinclair NM, Pandeya N, Ware RS, et al. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population [published online July 31, 2008]. J Invest Dermatol. 2009;129:323-328.
  16. Gies P, Javorniczky J, Roy C, et al. Measurements of the UVR protection provided by hats used at school. Photochem Photobiol. 2006;82:750-754.
  17. Winterhalter C, DiLuna K, Bide M. Characterization of the Ultraviolet Protection of Combat Uniform Fabrics. Natick, MA: US Army Solider and Biological Chemical Command; 2002. Technical report 02/006.
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Photoprotection Prevents Skin Cancer: Let’s Make It Fashionable to Wear Sun-Protective Clothing
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Practice Points

  • Routine wear of wide-brimmed hats is the simplest, most inexpensive, and only reusable form of photoprotection for the head and neck and should be an everyday practice for reducing the risk for preventable skin cancers.
  • The regular wear of clothing and head cover with adequate UV protection factor is equally as important to utilize in the prevention of UV-induced skin cancers as the application of topical sunscreens and sunblocks.
  • The medical community should make a concerted effort to dispel any public policy or fashion trend that does not promote personal protection from sun-induced skin cancers. Policies that restrict wearing photoprotective garments, such as in schools and in the military, need to be changed.
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Psoriasis Treatment Considerations in Military Patients: Unique Patients, Unique Drugs

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Psoriasis Treatment Considerations in Military Patients: Unique Patients, Unique Drugs
In partnership with the Association of Military Dermatologists

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.1 Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.12 Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.13 In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.13 Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.2 Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.2,3 Ustekinumab, however, has the major drawback of high cost.12 Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.14

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.16 As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.16 After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

 

 

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

References
  1. Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
  2. Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2015;151:961-969.
  3. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2009.
  4. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2007.
  5. Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
  6. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.
  7. Enbrel [package insert]. Thousand Oaks, CA: Amgen; 2015.
  8. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.
  9. Methotrexate [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc; 2016.
  10. Gengraf [package insert]. North Chicago, IL: Abbvie Inc; 2015.
  11. Acitretin [package insert]. Mason, OH: Prasco Laboratories; 2015.
  12. Beyer V, Wolverton SE. Recent trends in systemic psoriasis treatment costs. Arch Dermatol. 2010;146:46-54.
  13. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2013.
  14. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326-338.
  15. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis [published online June 8, 2016]. N Engl J Med. 2016;375:345-356.
  16. Papp K, Reich K, Leonardi CL, et al. Apremilast, anoral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
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Drs. Evans and Logemann are from Walter Reed National Military Medical Center, Bethesda, Maryland. Dr. Davidson is from Uniformed Services University of the Health Sciences, Bethesda.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Thomas Evans, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3031, 4954 N Palmer Rd, Bethesda, MD 20889 ([email protected]).

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Drs. Evans and Logemann are from Walter Reed National Military Medical Center, Bethesda, Maryland. Dr. Davidson is from Uniformed Services University of the Health Sciences, Bethesda.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Thomas Evans, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3031, 4954 N Palmer Rd, Bethesda, MD 20889 ([email protected]).

Author and Disclosure Information

Drs. Evans and Logemann are from Walter Reed National Military Medical Center, Bethesda, Maryland. Dr. Davidson is from Uniformed Services University of the Health Sciences, Bethesda.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Navy, US Army, or the Department of Defense.

Correspondence: Thomas Evans, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3031, 4954 N Palmer Rd, Bethesda, MD 20889 ([email protected]).

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Related Articles
In partnership with the Association of Military Dermatologists
In partnership with the Association of Military Dermatologists

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.1 Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.12 Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.13 In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.13 Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.2 Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.2,3 Ustekinumab, however, has the major drawback of high cost.12 Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.14

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.16 As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.16 After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

 

 

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

Psoriasis is a common dermatologic problem with nearly 5% prevalence in the United States. There is a bimodal distribution with peak onset between 20 and 30 years of age and 50 and 60 years, which means that this condition can arise before, during, or after military service.1 Unfortunately, for many prospective recruits psoriasis is a medically disqualifying condition that can prevent entry into active duty unless a medical waiver is granted. For active-duty military, new-onset psoriasis and its treatment can impair affected service members’ ability to perform mission-critical work and can prevent them from deploying to remote or austere locations. In this way, psoriasis presents a unique challenge for active-duty service members.

Many therapies are available that can effectively treat psoriasis, but these treatments often carry a side-effect profile that limits their use during travel or in austere settings. Herein, we discuss the unique challenges of treating psoriasis patients who are in the military at a time when global mobility is critical to mission success. Although in some ways these challenges truly are unique to the military population, we strongly believe that similar but perhaps underappreciated challenges exist in the civilian sector. Close examination of these challenges may reveal that alternative treatment choices are sometimes indicated for reasons beyond just efficacy, side-effect profile, and cost.

Treatment Considerations

The medical treatment of psoriasis has undergone substantial change in recent decades. Before the turn of the century, the mainstays of medical treatment were steroids, methotrexate, and phototherapy. Today, a wide array of biologics and other systemic drugs are altering the impact of psoriasis in our society. With so many treatment options currently available, the question becomes, “Which one is best for my patient?” Immediate considerations are efficacy versus side effects as well as cost; however, in military dermatology, the ability to store, transport, and administer the treatment can be just as important.

Although these problems may at first seem unique to active-duty military members, they also affect a substantial segment of the civilian sector. Take for instance the government contractor who deploys in support of military contingency actions, or the foreign aid workers, international businessmen, and diplomats around the world. In fact, any person who travels extensively might have difficulty carrying and storing their medications (Table) or encounter barriers that prevent routine access to care. Travel also may increase the risk of exposure to virulent pathogens such as Mycobacterium tuberculosis, which may further limit treatment options. This group of world travelers together comprises a minority of psoriasis patients who may be better treated with novel agents rather than with what might be considered the standard of care in a domestic setting.

Options for Care

Methotrexate

In many ways, methotrexate is the gold standard of psoriasis treatment. It is a first-line medication for many patients because it is typically well tolerated, has well-established efficacy, is easy to administer, and is relatively inexpensive.12 Although it is easy to store, transport, and administer, it requires regular laboratory monitoring at 3-month intervals or more frequently with dosage changes. It also is contraindicated in women of childbearing age who plan to become pregnant, which can be a considerable hindrance in the young active-duty population.

Cyclosporine

Cyclosporine is another inexpensive medication that can produce excellent results in the treatment of psoriasis.1,12 Although long-term use of cyclosporine in transplant patients has been well studied, its use for the treatment of dermatologic conditions is usually limited to 1 year. The need for monthly blood pressure checks and at least quarterly laboratory monitoring means it is not an optimal choice for a deployed service member.

Acitretin

Acitretin is another systemic medication with an established track record in psoriasis treatment. Although close follow-up and laboratory monitoring is required for both males and females, use of this medication can have a greater effect on women of childbearing age, as it is absolutely contraindicated in any female trying to conceive.13 In addition, acitretin is stored in fat cells, and traces of the drug can be found in the blood for up to 3 years. During this period, patients are advised to strictly avoid pregnancy and are even restricted from donating blood.13 Given these concerns, acitretin is not always a reasonable treatment option for the military service member.

Biologics

Biologics are the newest agents in the treatment of psoriasis. They require less laboratory monitoring and can provide excellent results. Adalimumab is a reasonable first-line biologic treatment for some patients. We find the laboratory monitoring is minimally obtrusive, side effects usually are limited, and the efficacy is great enough that most patients elect to continue treatment. Unfortunately, adalimumab has some major drawbacks in our specific use scenario in that it requires nearly continuous refrigeration and is never to exceed 25°C (77°F), it has a relatively close-interval dosing schedule, and it can cause immunosuppression. However, for short trips to nonaustere locations with an acceptable risk for pathogenic exposure, adalimumab may remain a viable option for many travelers, as it can be stored at room temperature for up to 14 days.2 Ustekinumab also is a reasonable choice for many travelers because dosing is every 12 weeks and it carries a lower risk of immunosuppression.2,3 Ustekinumab, however, has the major drawback of high cost.12 Newer IL-17A inhibitors such as secukinumab or ixekizumab also can offer excellent results, but long-term infection rates have not been reported. Overall, the infection rates are comparable to ustekinumab.14,15 After the loading phase, secukinumab is dosed monthly and logistically could still pose a problem due to the need for continued refrigeration.14

Apremilast

Although it is not the best first-line treatment for every patient, apremilast carries 3 distinct advantages in treating the military patient population: (1) laboratory monitoring is required only once per year, (2) it is easy to store, and (3) it is easy to administer. However, the major downside is that apremilast is less effective than other systemic agents in the treatment of psoriasis.16 As with other systemic drugs, adjunctive topical treatment can provide additional therapeutic effects, and for many patients, this combined approach is sufficient to reach their therapeutic goals.

For these reasons, in the special case of deployable, active-duty military members we often consider starting treatment with apremilast versus other systemic agents. As with all systemic psoriasis treatments, we generally advise patients to return 16 weeks after initiating treatment to assess efficacy and evaluate their deployment status. Although apremilast may take longer to reach full efficacy than many other systemic agents, one clinical trial suggested this time frame is sufficient to evaluate response to treatment.16 After this initial assessment, we revert to yearly monitoring, and the patient is usually cleared to deploy with minimal restrictions.

 

 

Final Considerations

The manifestation of psoriasis is different in every patient, and military service poses additional treatment challenges. For all of our military patients, we recommend an initial period of close follow-up after starting any new systemic agent, which is necessary to ensure the treatment is effective and well tolerated and also that we are good stewards of our resources. Once efficacy is established and side effects remain tolerable, we generally endorse continued treatment without specific travel or work restrictions.

We are cognizant of the unique nature of military service, and all too often we find ourselves trying to practice good medicine in bad places. As military physicians, we serve a population that is eager to do their job and willing to make incredible sacrifices to do so. After considering the wide range of circumstances unique to the military, our responsibility as providers is to do our best to improve service members’ quality of life as they carry out their missions.

References
  1. Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
  2. Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2015;151:961-969.
  3. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2009.
  4. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2007.
  5. Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
  6. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.
  7. Enbrel [package insert]. Thousand Oaks, CA: Amgen; 2015.
  8. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.
  9. Methotrexate [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc; 2016.
  10. Gengraf [package insert]. North Chicago, IL: Abbvie Inc; 2015.
  11. Acitretin [package insert]. Mason, OH: Prasco Laboratories; 2015.
  12. Beyer V, Wolverton SE. Recent trends in systemic psoriasis treatment costs. Arch Dermatol. 2010;146:46-54.
  13. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2013.
  14. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326-338.
  15. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis [published online June 8, 2016]. N Engl J Med. 2016;375:345-356.
  16. Papp K, Reich K, Leonardi CL, et al. Apremilast, anoral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
References
  1. Bolognia J, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.
  2. Kalb RE, Fiorentino DF, Lebwohl MG, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2015;151:961-969.
  3. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2009.
  4. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2007.
  5. Cosentyx [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016.
  6. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.
  7. Enbrel [package insert]. Thousand Oaks, CA: Amgen; 2015.
  8. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.
  9. Methotrexate [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc; 2016.
  10. Gengraf [package insert]. North Chicago, IL: Abbvie Inc; 2015.
  11. Acitretin [package insert]. Mason, OH: Prasco Laboratories; 2015.
  12. Beyer V, Wolverton SE. Recent trends in systemic psoriasis treatment costs. Arch Dermatol. 2010;146:46-54.
  13. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2013.
  14. Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326-338.
  15. Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis [published online June 8, 2016]. N Engl J Med. 2016;375:345-356.
  16. Papp K, Reich K, Leonardi CL, et al. Apremilast, anoral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37-49.
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Practice Points

  • Establishing goals of treatment with each patient is a critical step in treating the patient rather than the diagnosis.
  • A good social history can reveal job-related impact of disease and potential logistical roadblocks to treatment.
  • Efficacy must be weighed against the burden of logistical constraints for each patient; potential issues include difficulty complying with follow-up visits, access to laboratory monitoring, exposure to pathogens, and adequacy of medication transport and storage.
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Exploration of Modern Military Research Resources

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Exploration of Modern Military Research Resources
In partnership with the Association of Military Dermatologists

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.1 It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.2 Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).5

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in 30°C freezers, making it one of the largest repositories in the world.3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.7

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.4 The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.6 Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.8 Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.5

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

 

 

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.8 With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.8 However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.10 The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

References
  1. Liao SJ. Immunity status of military recruits in 1951 in the United States. I. results of Schick tests. Am J Hyg. 1954;59:262-272.
  2. Rubertone MV, Brundage JF. The defense medical surveillance system and the department of defense serum repository: glimpses of the future of public health surveillance. Am J Public Health. 2002;92:1900-1904.
  3. Department of Defense Serum Repository. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Department-of-Defense-Serum-Repository. Accessed August 2, 2016.
  4. Perdue CL, Eick-Cost AA, Rubertone MV. A brief description of the operation of the DoD serum repository. Mil Med. 2015;180(10 suppl):10-12.
  5. DeFraites RF. The Armed Forces Health Surveillance Center: enhancing the Military Health System’s public health capabilities. BMC Public Health. 2011;11(suppl 2):S1.
  6. Pavlin JA, Welch RA. Ethics, human use, and the department of defense serum repository. Mil Med. 2015;180:49-56.
  7. Defense Medical Surveillance System. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Defense-Medical-Surveillance-System. Accessed August 2, 2016.
  8. Perdue CL, Eick-Cost AA, Rubertone MV, et al. Description and utilization of the United States Department of Defense Serum Repository: a review of published studies, 1985-2012. Plos One. 2015;10:1-16.
  9. Mancuso JD, Mallon TM, Gaydos JC. Maximizing the capabilities of the DoD serum repository to meet current and future needs: report of the needs panel. Mil Med. 2015;180:14-24.
  10. Department of Defense. Department of Defense Instruction. http://www.dtic.mil/whs/directives/corres/pdf/600014p.pdf. Posted September 26, 2001. Updated October 3, 2013. Accessed August 2, 2016.
  11. Lindler LE. Building a DoD biorepository for the future: potential benefits and way forward. Mil Med. 2015;180:90-94.
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From the Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

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The opinions expressed in this article are solely those of the authors and should not be interpreted as representative of or endorsed by the Uniformed Services University of the Health Sciences, the US Army, the US Navy, the Department of Defense, or any other federal government agency.

Correspondence: Jon H. Meyerle, MD, Uniformed Services University of the Health Sciences, Department of Dermatology, 4301 Jones Bridge Rd, Bethesda, MD 20814 ([email protected]).

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The opinions expressed in this article are solely those of the authors and should not be interpreted as representative of or endorsed by the Uniformed Services University of the Health Sciences, the US Army, the US Navy, the Department of Defense, or any other federal government agency.

Correspondence: Jon H. Meyerle, MD, Uniformed Services University of the Health Sciences, Department of Dermatology, 4301 Jones Bridge Rd, Bethesda, MD 20814 ([email protected]).

Author and Disclosure Information

From the Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions expressed in this article are solely those of the authors and should not be interpreted as representative of or endorsed by the Uniformed Services University of the Health Sciences, the US Army, the US Navy, the Department of Defense, or any other federal government agency.

Correspondence: Jon H. Meyerle, MD, Uniformed Services University of the Health Sciences, Department of Dermatology, 4301 Jones Bridge Rd, Bethesda, MD 20814 ([email protected]).

Article PDF
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In partnership with the Association of Military Dermatologists
In partnership with the Association of Military Dermatologists

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.1 It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.2 Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).5

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in 30°C freezers, making it one of the largest repositories in the world.3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.7

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.4 The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.6 Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.8 Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.5

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

 

 

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.8 With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.8 However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.10 The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

Advances in medical biotechnologies, data-gathering techniques, and -omics technologies have resulted in the broader understanding of disease pathology and treatment and have facilitated the individualization of health care plans to meet the unique needs of each patient. Military medicine often has been on the forefront of medical technology, disease understanding, and clinical care both on and off the battlefield, in large part due to the unique resources available in the military health care system. These resources allow investigators the ability to integrate vast amounts of epidemiologic data with an extensive biological sample database of its service members, which in the modern age has translated into advances in the understanding of melanoma and the treatment of scars.

History of Research in the Military

Starting in the 1950s, the US Department of Defense (DoD) started to collect serum samples of its service members for the purpose of research.1 It was not until 1985 that the DoD implemented a long-term frozen storage system for serum samples obtained through mandatory screening for human immunodeficiency virus (HIV) in service members.2 Subsequently, the Department of Defense Serum Repository (DoDSR) was officially established in 1989 as a central archive for the long-term storage of serum obtained from active-duty and reserve service members in the US Navy, Army, and Marines.2,3 In the mid-1990s, the DoDSR expanded its capabilities to include the storage of serum samples from all military members, including the US Air Force, obtained predeployment and postdeployment.3,4 At that time, a records-keeping system was established, now known as the Defense Medical Surveillance System (DMSS). The creation of the DMSS provided an extensive epidemiologic database that provided valuable information such as demographic data, service records, deployment data, reportable medical events, exposure history, and vaccination records, which could be linked to the serum samples of each service member.2-4 Since 2008, the responsibilities of maintaining the DoDSR and the DMSS were transferred to the Armed Forces Health Surveillance Center (AFHSC).5

There have been several other databases created over the years that provide additional support and resources to military investigators. The Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services both help investigators to track the incidence of specific cancers in the military population and provide them with pathologic specimens. Additionally, electronic medical records including the composite health care system and the Armed Forces Health Longitudinal Technology Application supplemented with insurance claims data accessible from the Military Health System Management and Reporting Tool (M2) database have made it possible to track patient data.

Utilization of Military Research Resources

Today, the DoDSR is a secure facility that maintains more than 56 million serum specimens from more than 11 million individuals in 30°C freezers, making it one of the largest repositories in the world.3,6 Each serum sample is linked with an individual’s DMSS record, providing a way for investigators to study how external factors such as deployment history, occupation, and exposure history relate to an individual’s unique genetic and physiological makeup. Furthermore, these data can be used for seroepidemiologic investigations that contribute to all facets of clinical care. The AFHSC routinely publishes findings related to notifiable diseases, disease outbreaks, and disease trends in a monthly report.7

There are strict guidelines in place that limit access to the DoDSR and service members’ data. Use of the repository for information directly related to a patient’s health care is one reason for access, such as analyzing serum for antibodies and seroconversion to assist in the diagnosis of a disease such as HIV. Another reason would be to obtain information needed for criminal investigations and prosecution. Typically, these types of requests require a judge-issued court order and approval by the Assistant Secretary of Defense for Health Affairs.4 The DoDSR also is used to study force health protection issues, such as infectious disease incidence and disease prevalence in the military population.

Obtaining access to the DoDSR and service members’ data for research purposes requires that the principal investigator be a DoD employee. Each research proposal is reviewed by members of the AFHSC to determine if the DoDSR is able to meet the demands of the project, including having the appropriate number of serum samples and supporting epidemiologic data available. The AFHSC provides a letter of support if it deems the project to be in line with its current resources and capabilities. Each research proposal is then sent to an institutional review board (IRB) to determine if the study is exempt or needs to go through a full IRB review process. A study might be exempt if the investigators are not obtaining data through interaction with living individuals or not having access to any identifiable protected health information associated with the samples.6 Regardless of whether the study is exempt or not exempt, the AFHSC will de-identify each sample before releasing the samples to the investigators by using a coding system to shield the patient’s identity from the investigator.

Resources within the military medical research system provide investigators with access to an extensive biorepository of serum and linked epidemiological data. Samples from the DoDSR have been used in no less than 75 peer-reviewed publications since 1985.8,9 Several of these studies have been influential in expanding knowledge about conditions seen more commonly in the military population such as stress fractures, traumatic brain injuries, posttraumatic stress disorder, and suicide.8 Additionally, DoDSR samples have been used to form military vaccination policies and track both infectious and noninfectious conditions in the military; for example, during the H1N1 influenza virus outbreak of 2009, AFHSC was essential in helping to limit the spread of the virus within the military community by using its data and collaborating with groups such as the Centers for Disease Control and Prevention to develop a plan for disease surveillance and control.5

Several military research resources are currently being used for a melanoma study that aims to assess if specific phenotypic features, melanoma risk alleles, and environmental factors (eg, duty station location, occupation, amount of UV exposure) can be used to develop better screening models to identify individuals who are at risk for developing melanoma. Secondarily, the study aims to determine if recently developed multimarker diagnostic and prognostic assays for melanoma will prove useful in the diagnostic and prognostic assessment of melanocytic neoplasms in the military population. For this study, one of the authors (J.H.M) is utilizing DoDSR serum from 1700 retrospective cases of invasive melanoma and 1700 matched controls. Additionally, the Automated Central Tumor Registry and Department of Pathology and Area Laboratory Services databases are being used to obtain tissue from more than 300 melanoma cases and nevi controls.

 

 

Limitations of the Current System

Despite the impressive capabilities of the current system, there are some issues that limit its potential. One such limitation is associated with the way that the serum samples at the DoDSR are utilized. Through 2012, the DoDSR had 54,542,658 serum specimens available, of which only 228,610 (0.42%) had ever been accessed for study.8 With such a wealth of information and relative availability, why are the serum samples not being accessed more frequently for studies? The inherent nature of the DoDSR being a restricted facility and only accessible to DoD-affiliated investigators may contribute, which allows the DoDSR to fulfill its primary purpose of contributing to military-relevant investigations but at the same time limits the number and type of investigations that can be performed. One idea that has been proposed is allowing civilian investigator access to the DoDSR if it can be proven that the research is targeted toward military-relevant issues.8 However, the current AFHSC access guidelines would need revision and would require additional safeguards to ensure that military-protected health information is not compromised. Nonetheless, such a change may result in more extensive use of DoDSR resources in the future.

An ethical issue that needs to be addressed pertains to how the DoDSR permits use of human serum samples for research purposes without getting consent from the individuals being studied. The serum samples are collected as part of mandatory predeployment and postdeployment examinations for HIV screening of all military members. These individuals are not informed of potential use of their serum specimens for research purposes and no consent forms or opt-out options are provided. Although it is true that military members must comply with specific requirements pertaining to military readiness (eg, receiving appropriate vaccinations, drug testing, regular medical screening), it is debated whether they still retain the right as patients to refuse participating in research and clinical trials.10 The AFHSC does have several regulatory steps in place to ensure that military members’ samples are used in an appropriate manner, including requiring a DoD primary investigator, IRB review of every research proposal, and de-identification of samples. At a minimum, giving military members the ability to provide informed consent would ensure that the military system is adhering to evolving human research standards.

The current lack of biological specimens other than serum in the DoDSR is another limitation of the current system. Recent advances in molecular analyses are impacted by expanding -omics techniques, such as epigenomics, transcriptomics, and proteomics. The field of epigenomics is the study of reversible changes to DNA (eg, methylation) associated with specific disease states or following specific environmental exposures.9,11 Transcriptomics, which analyzes messenger RNA transcript levels of expressed genes, and proteomics, which uses expression of proteins, are 2 techniques being used to develop biomarkers associated with specific diseases and environmental exposures.9,11 Serum alone does not provide the high-quality nucleic acids needed for many of these studies to take place. Adding whole-blood specimens or blood spot samples of military service members to the DoDSR would allow researchers to use these techniques to investigate many new biomarkers associated with military-relevant diseases and exposures. These techniques also can be used in the expanding field of personalized medicine so that health care providers are able to tailor all phases of care, including diagnosis and treatment, to an individual’s genetic profile.

Conclusion

The history of research in military medicine has been built on achieving the primary goal of serving those men and women who put their lives in danger to protect this country. In an evolving environment of new technologies that have led to changes in service members’ injuries, exposures, and diseases, military medicine also must adapt. Resources such as the DoDSR and DMSS, which provide investigators with the unique ability to link epidemiological data with serum samples, have been invaluable contributors to this overall mission. As with any large system, there are always improvements that can be made. Improving access to the DoDSR serum samples, educating and obtaining consent from military service members to use their samples in research, and adding specimens to the DoDSR that can be used for -omics techniques are 3 changes that should be considered to maximize the potential of the military medical research system.

References
  1. Liao SJ. Immunity status of military recruits in 1951 in the United States. I. results of Schick tests. Am J Hyg. 1954;59:262-272.
  2. Rubertone MV, Brundage JF. The defense medical surveillance system and the department of defense serum repository: glimpses of the future of public health surveillance. Am J Public Health. 2002;92:1900-1904.
  3. Department of Defense Serum Repository. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Department-of-Defense-Serum-Repository. Accessed August 2, 2016.
  4. Perdue CL, Eick-Cost AA, Rubertone MV. A brief description of the operation of the DoD serum repository. Mil Med. 2015;180(10 suppl):10-12.
  5. DeFraites RF. The Armed Forces Health Surveillance Center: enhancing the Military Health System’s public health capabilities. BMC Public Health. 2011;11(suppl 2):S1.
  6. Pavlin JA, Welch RA. Ethics, human use, and the department of defense serum repository. Mil Med. 2015;180:49-56.
  7. Defense Medical Surveillance System. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Defense-Medical-Surveillance-System. Accessed August 2, 2016.
  8. Perdue CL, Eick-Cost AA, Rubertone MV, et al. Description and utilization of the United States Department of Defense Serum Repository: a review of published studies, 1985-2012. Plos One. 2015;10:1-16.
  9. Mancuso JD, Mallon TM, Gaydos JC. Maximizing the capabilities of the DoD serum repository to meet current and future needs: report of the needs panel. Mil Med. 2015;180:14-24.
  10. Department of Defense. Department of Defense Instruction. http://www.dtic.mil/whs/directives/corres/pdf/600014p.pdf. Posted September 26, 2001. Updated October 3, 2013. Accessed August 2, 2016.
  11. Lindler LE. Building a DoD biorepository for the future: potential benefits and way forward. Mil Med. 2015;180:90-94.
References
  1. Liao SJ. Immunity status of military recruits in 1951 in the United States. I. results of Schick tests. Am J Hyg. 1954;59:262-272.
  2. Rubertone MV, Brundage JF. The defense medical surveillance system and the department of defense serum repository: glimpses of the future of public health surveillance. Am J Public Health. 2002;92:1900-1904.
  3. Department of Defense Serum Repository. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Department-of-Defense-Serum-Repository. Accessed August 2, 2016.
  4. Perdue CL, Eick-Cost AA, Rubertone MV. A brief description of the operation of the DoD serum repository. Mil Med. 2015;180(10 suppl):10-12.
  5. DeFraites RF. The Armed Forces Health Surveillance Center: enhancing the Military Health System’s public health capabilities. BMC Public Health. 2011;11(suppl 2):S1.
  6. Pavlin JA, Welch RA. Ethics, human use, and the department of defense serum repository. Mil Med. 2015;180:49-56.
  7. Defense Medical Surveillance System. Military Health System and the Defense Health Agency website. http://www.health.mil/Military-Health-Topics/Health-Readiness/Armed-Forces-Health-Surveillance-Branch/Data-Management-and-Technical-Support/Defense-Medical-Surveillance-System. Accessed August 2, 2016.
  8. Perdue CL, Eick-Cost AA, Rubertone MV, et al. Description and utilization of the United States Department of Defense Serum Repository: a review of published studies, 1985-2012. Plos One. 2015;10:1-16.
  9. Mancuso JD, Mallon TM, Gaydos JC. Maximizing the capabilities of the DoD serum repository to meet current and future needs: report of the needs panel. Mil Med. 2015;180:14-24.
  10. Department of Defense. Department of Defense Instruction. http://www.dtic.mil/whs/directives/corres/pdf/600014p.pdf. Posted September 26, 2001. Updated October 3, 2013. Accessed August 2, 2016.
  11. Lindler LE. Building a DoD biorepository for the future: potential benefits and way forward. Mil Med. 2015;180:90-94.
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  • Large patient databases and tissue repositories are increasingly being used to improve patient care through the use of clinical data, genomics, proteinomics, and metabolomics.
  • The US Military has an established electronic medical record as well as tissue and serum repositories that can be leveraged to study melanoma and other dermatologic diseases.
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Managing Residual Limb Hyperhidrosis in Wounded Warriors

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Managing Residual Limb Hyperhidrosis in Wounded Warriors
In partnership with the Association of Military Dermatologists

We live in a time when young, otherwise healthy, active-duty individuals are undergoing traumatic amputations at an exceedingly high rate due to ongoing military engagements. According to US military casualty statistics through September 1, 2014, Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans have undergone a total of 1573 amputations.1 Walter Reed National Military Medical Center (WRNMMC) is one of several military facilities that has managed the care of these unique patients returning from the many ongoing conflicts around the globe. Multidisciplinary teams composed of surgeons, anesthesiologists, physical therapists, prosthetists, and others have joined forces to provide extraordinary emergency and recovery care for these patients. Even in the best hands, however, these traumatic amputee patients often experience long-term and lifelong sequelae of their injuries. As dermatologists at this facility (S.P. was at WRNMMC for 3 years before transferring to Madigan Army Medical Center), we are often asked to assist in the management of a subset of these sequelae: residual limb dermatoses. Residual limb dermatoses such as recurrent bacterial and fungal infections, cysts, abrasions, blistering, irritant and allergic dermatitis, pressure ulcers, acroangiodermatitis, stump edema, and many others have a high prevalence in our wounded warrior population and impact both amputee quality of life and utilization of medical resources. As many as 73% of amputees will experience a variety of residual limb dermatoses at some point in their life, with the highest prevalence in younger, more active patients.2,3 We have observed that many, if not most, of these cutaneous problems can be attributed to or are exacerbated by hyperhidrosis of the residual limb. Hyperhidrosis in this population of patients can be related to excessive sweat production, but more commonly, it is attributed to the lack of evaporation of normal perspiration.

Excess Sweat and the Prosthesis

To understand hyperhidrosis in amputee patients, it is important to understand the anatomy of the prosthesis. There are a variety of materials that are used to create prosthetic limbs. The most commonly used materials are a combination of plastic and carbon graphite/carbon fiber. The modern prosthetic limb uses a suspension system that attaches the prosthetic limb to the residual limb by creating a vacuum. There are several mechanisms to create this vacuum; however, they all depend on a liner that fits snugly over the residual limb. This liner-limb interface is responsible for protection, mitigation of sheering forces, and comfort, and it is the anchor for a good fit in the prosthesis. Unfortunately, this liner is the primary factor contributing to residual limb dermatologic problems. The liner usually is made of silicone or polyurethane and is designed to be water and sweat resistant; any excess water that finds its way into the liner-prosthetic interface will affect the seal of the device and cause slippage of the prosthesis.4 This water-resistant barrier is what induces the hyperhidrotic environment over the residual limb that is covered. These patients sweat with exertion, and because of the water-resistant liner, there is no mechanism for sweat evaporation. This leads to a localized environment of hyperhidrosis, increasing patients’ susceptibility to chronic skin conditions. In addition to the dermatologic pathology of the residual limb, there are notable functional concerns caused by excessive sweating. Increased moisture due to sweating not only leads to pathologic dermatoses but also to impaired fit and loss of suction by leaking into the prosthetic-limb interface, which in turn can lead to decreased stamina in the prosthesis, falls, and in severe cases even prosthetic abandonment.5

 

 

Treating Hyperhidrosis

While working with wounded warriors in the dermatology, prosthetics, and wound care clinics at WRNMMC, it repeatedly became clear that our current treatment options for hyperhidrosis in this population were not routinely tolerated or efficacious. Although hyperhidrosis of the axillary or palmoplantar region is a commonly encountered problem with clear treatment algorithms and management strategies, hyperhidrosis in the setting of a residual limb following amputation is somewhat unique and without definitive permanent cure. In approaching this problem, our institution has implemented a variety of therapies to the residual limb that have been well described and effective in the treatment in the axillary region.

Topical antiperspirants (ie, aluminum chloride) are well-documented treatments of hyperhidrosis and work by the formation of a metal iron precipitate when binding with mucopolysaccharides. These complexes cause damage to epithelial cells lining the ostia of eccrine glands, forming a plug in the lumen of the eccrine duct.6 Unfortunately, irritant contact dermatitis has affected the majority of our residual limb patients who have used topical antiperspirants and has led to poor compliance. Glycopyrrolate, an antimuscarinic agent, often is used with varying degrees of success. It works as a competitive antagonist blocking the acetylcholine muscarinic receptors that are responsible for the innervation of eccrine sweat glands. Several of our residual limb patients have a history of global hyperhidrosis and have responded favorably to 1- to 2-mg doses of glycopyrrolate administered twice daily. The side-effect profile headlined by xerostomia, urinary retention, and constipation has, as it often does, limited the dosing. We have observed that with the use of glycopyrrolate, these patients admit to less overall sweating but experience only a mild decrease in the cutaneous problems they experience over the residual limbs, which is likely attributed to the prosthetic liner that induces hyperhidrosis by preventing sweat evaporation from the residual limb. Patients may not be sweating as much, but they are still sweating and that sweat is unable to evaporate from under the liner.

Botulinum toxin is a common treatment of axillary hyperhidrosis and its effects on residual limbs are the same.5,7 Botulinum toxin types A, B, and E specifically cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which prevents neurosecretory vesicles from fusing with the interior surface of the plasma membrane of the nerve synapse, thereby blocking release of acetylcholine.8 In inhibiting acetylcholine release, the signal for eccrine secretion is blocked. This therapy has been effective in our residual limb patients who tolerate the treatment. It typically involves the injection of 300 to 500 U of botulinum toxin type A diluted with 0.9% saline at 2 to 5 U per 0.1 mL into the residual limb.5 As with the other treatments, there are side effects that complicate compliance. Most residual limb treatments require 150 injections, which can be uncomfortable for this patient cohort. The majority of these wounded warriors have abnormal anatomy because of the traumatic nature of their injuries (ie, improvised explosive device attacks, artillery injury), and they often experience hyperesthesia, phantom limb pain, and notable scarring. These injections can be extremely painful, which often limits their utility. In addition, the therapy only provides 3 to 6 months of symptom relief. Our compliance rate for returning patients has not been good and we suspect that it is likely due to the discomfort associated with the injections.

Other therapies such as laser hair removal and iontophoresis have been attempted but have not yielded great results or compliance. In addition to the limitations of these treatment methods, the residual limbs have presented their own unique set of challenges; complications have included varied anatomy of the residual limbs, scarring, sensitivities, and heterotopic ossification. Temporary remedies such as botulinum toxin injections also present logistical complications because they require repetitive procedural appointments that can be quite burdensome to attend when these patients move back home, often far away from our large military treatment facilities.

A New Therapy With Exciting Potential

With the recent advent of microwave thermal ablation technology, the potential for a different, possibly permanent treatment was discovered. Microwave thermal ablation of the eccrine coils has been proven safe and effective in the prolonged reduction of hyperhidrosis of the axillae and has presented as a potential therapy for our residual limb hyperhidrosis patient population. This technology produces heat that is targeted to a specific depth in the treated tissue while cooling the epidermis. There are various treatment levels that can be used to deliver graded intensities of heat. When the deep dermis is targeted, adnexal structures are denatured and destroyed, causing diminished or eliminated function. Eccrine sweat glands, apocrine glands, and even hair follicles are affected by the therapy. The manufacturer of the only microwave thermal ablation device on the market that is approved by the US Food and Drug Administration to treat axillary hyperhidrosis has suggested that these effects are long-term and possibly permanent.9 After several iterations with this technology, we have been able to successfully apply microwave thermal ablation of eccrine coils to 5 residual limbs and are excited about the promise that this technique possesses. A report of our index case will be published soon,10 and we are looking forward to launching our protocol treating traumatic lower extremity amputee patients that have hyperhidrosis with microwave therapy ablation technology here at WRNMMC.

 

 

Final Thoughts

Amputation residual limb dermatoses have a high prevalence and impact on amputee quality of life, particularly among young military members who strive to maintain a highly active lifestyle. Many of these dermatoses are directly related to hyperhidrosis of the residual limb that is covered by the prosthetic device and the liner that interfaces with the skin. Although many treatments for residual limb hyperhidrosis have been used with varying efficacy, none have offered a cost-effective or sustained response. Many of our wounded warriors in this amputee population have or will be transitioning out of the military in the coming years. It is imperative to our government, our institution, and most importantly our patients that efforts are made to develop a more permanent and efficacious treatment application to provide relief to these wounded heroes. This amputee population is unique in that they are younger, healthier, and highly motivated to live as “normal” of a life as possible. The ability to ambulate in a prosthetic device can have a huge social and psychological impact, and providing a therapy that minimizes complications associated with prosthetic use is invaluable. We are excited about the results we have seen with the microwave thermal ablation device and feel that there is potential benefit for other amputee populations if the procedure is perfected.

It is an exciting age in medicine where technology and biology have remarkably honed our diagnostic and treatment capabilities. We hope that everyone in the dermatology community shares our enthusiasm and will continue to explore and test these new technologies to improve and better the lives of the patients we treat.

References
  1. Fischer H. A guide to U.S. military casualty statistics: Operation Inherent Resolve, Operation New Dawn, Operation Iraqi Freedom, and Operation Enduring Freedom. http://ibiblio.org/hyperwar/NHC/CasualtyStats2014Nov/CasualtyStats2014Nov.htm. Congressional Research Service 7-5700; RS22452. Published November 20, 2014. Accessed May 13, 2016.
  2. Yang NB, Garza LA, Foote CE, et al. High prevalence of stump dermatoses 38 years or more after amputation. Arch Dermatol. 2012;148:1283-1286.
  3. Koc E, Tunca M, Akar A, et al. Skin problems in amputees: a descriptive study. Int J Dermatol. 2008;47:463-466.
  4. Ghoseiri K, Safari MR. Prevalence of heat and perspiration discomfort inside prostheses: literature review. J Rehabil Res Dev. 2014;51:855-868.
  5. Gratrix M, Hivnor C. Botulinum A toxin treatment for hyperhidrosis in patients with prosthetic limbs. Arch Dermatol. 2010;146:1314-1315.
  6. Hölzle E. Topical pharmacological treatment. Curr Probl Dermatol. 2002;30:30-43. 
  7. Lee KYC, Levell NJ. Turning the tide: a history and review of hyperhidrosis treatment. JRSM Open. 2014;5. doi:10.1177/2042533313505511.
  8. Dressler D, Adib Saberi F. Botulinum toxin: mechanisms of action. Eur Neurol. 2005;53:3-9.
  9. Lupin M, Hong HC, O’Shaughnessy KF. Long-term efficacy and quality of life assessment for treatment of axillary hyperhidrosis with a microwave device. Dermatol Surg. 2014;40:805-807.
  10. Mula K, Winston J, Pace S, et al. Use of microwave device for treatment of amputation residual limb hyperhidrosis. Dermatol Surg. In press.
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Dr. Pace is from Madigan Army Medical Center, Tacoma, Washington. Dr. Kentosh is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army, US Navy, or the Department of Defense.

Correspondence: Joshua Kentosh, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3025, 4954 N Palmer Rd, Bethesda, MD 20889.

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Dr. Pace is from Madigan Army Medical Center, Tacoma, Washington. Dr. Kentosh is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army, US Navy, or the Department of Defense.

Correspondence: Joshua Kentosh, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3025, 4954 N Palmer Rd, Bethesda, MD 20889.

Author and Disclosure Information

Dr. Pace is from Madigan Army Medical Center, Tacoma, Washington. Dr. Kentosh is from Walter Reed National Military Medical Center, Bethesda, Maryland.

The authors report no conflict of interest.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army, US Navy, or the Department of Defense.

Correspondence: Joshua Kentosh, DO, Department of Dermatology, Walter Reed NMMC Bethesda, Room 3025, 4954 N Palmer Rd, Bethesda, MD 20889.

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Article PDF
In partnership with the Association of Military Dermatologists
In partnership with the Association of Military Dermatologists

We live in a time when young, otherwise healthy, active-duty individuals are undergoing traumatic amputations at an exceedingly high rate due to ongoing military engagements. According to US military casualty statistics through September 1, 2014, Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans have undergone a total of 1573 amputations.1 Walter Reed National Military Medical Center (WRNMMC) is one of several military facilities that has managed the care of these unique patients returning from the many ongoing conflicts around the globe. Multidisciplinary teams composed of surgeons, anesthesiologists, physical therapists, prosthetists, and others have joined forces to provide extraordinary emergency and recovery care for these patients. Even in the best hands, however, these traumatic amputee patients often experience long-term and lifelong sequelae of their injuries. As dermatologists at this facility (S.P. was at WRNMMC for 3 years before transferring to Madigan Army Medical Center), we are often asked to assist in the management of a subset of these sequelae: residual limb dermatoses. Residual limb dermatoses such as recurrent bacterial and fungal infections, cysts, abrasions, blistering, irritant and allergic dermatitis, pressure ulcers, acroangiodermatitis, stump edema, and many others have a high prevalence in our wounded warrior population and impact both amputee quality of life and utilization of medical resources. As many as 73% of amputees will experience a variety of residual limb dermatoses at some point in their life, with the highest prevalence in younger, more active patients.2,3 We have observed that many, if not most, of these cutaneous problems can be attributed to or are exacerbated by hyperhidrosis of the residual limb. Hyperhidrosis in this population of patients can be related to excessive sweat production, but more commonly, it is attributed to the lack of evaporation of normal perspiration.

Excess Sweat and the Prosthesis

To understand hyperhidrosis in amputee patients, it is important to understand the anatomy of the prosthesis. There are a variety of materials that are used to create prosthetic limbs. The most commonly used materials are a combination of plastic and carbon graphite/carbon fiber. The modern prosthetic limb uses a suspension system that attaches the prosthetic limb to the residual limb by creating a vacuum. There are several mechanisms to create this vacuum; however, they all depend on a liner that fits snugly over the residual limb. This liner-limb interface is responsible for protection, mitigation of sheering forces, and comfort, and it is the anchor for a good fit in the prosthesis. Unfortunately, this liner is the primary factor contributing to residual limb dermatologic problems. The liner usually is made of silicone or polyurethane and is designed to be water and sweat resistant; any excess water that finds its way into the liner-prosthetic interface will affect the seal of the device and cause slippage of the prosthesis.4 This water-resistant barrier is what induces the hyperhidrotic environment over the residual limb that is covered. These patients sweat with exertion, and because of the water-resistant liner, there is no mechanism for sweat evaporation. This leads to a localized environment of hyperhidrosis, increasing patients’ susceptibility to chronic skin conditions. In addition to the dermatologic pathology of the residual limb, there are notable functional concerns caused by excessive sweating. Increased moisture due to sweating not only leads to pathologic dermatoses but also to impaired fit and loss of suction by leaking into the prosthetic-limb interface, which in turn can lead to decreased stamina in the prosthesis, falls, and in severe cases even prosthetic abandonment.5

 

 

Treating Hyperhidrosis

While working with wounded warriors in the dermatology, prosthetics, and wound care clinics at WRNMMC, it repeatedly became clear that our current treatment options for hyperhidrosis in this population were not routinely tolerated or efficacious. Although hyperhidrosis of the axillary or palmoplantar region is a commonly encountered problem with clear treatment algorithms and management strategies, hyperhidrosis in the setting of a residual limb following amputation is somewhat unique and without definitive permanent cure. In approaching this problem, our institution has implemented a variety of therapies to the residual limb that have been well described and effective in the treatment in the axillary region.

Topical antiperspirants (ie, aluminum chloride) are well-documented treatments of hyperhidrosis and work by the formation of a metal iron precipitate when binding with mucopolysaccharides. These complexes cause damage to epithelial cells lining the ostia of eccrine glands, forming a plug in the lumen of the eccrine duct.6 Unfortunately, irritant contact dermatitis has affected the majority of our residual limb patients who have used topical antiperspirants and has led to poor compliance. Glycopyrrolate, an antimuscarinic agent, often is used with varying degrees of success. It works as a competitive antagonist blocking the acetylcholine muscarinic receptors that are responsible for the innervation of eccrine sweat glands. Several of our residual limb patients have a history of global hyperhidrosis and have responded favorably to 1- to 2-mg doses of glycopyrrolate administered twice daily. The side-effect profile headlined by xerostomia, urinary retention, and constipation has, as it often does, limited the dosing. We have observed that with the use of glycopyrrolate, these patients admit to less overall sweating but experience only a mild decrease in the cutaneous problems they experience over the residual limbs, which is likely attributed to the prosthetic liner that induces hyperhidrosis by preventing sweat evaporation from the residual limb. Patients may not be sweating as much, but they are still sweating and that sweat is unable to evaporate from under the liner.

Botulinum toxin is a common treatment of axillary hyperhidrosis and its effects on residual limbs are the same.5,7 Botulinum toxin types A, B, and E specifically cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which prevents neurosecretory vesicles from fusing with the interior surface of the plasma membrane of the nerve synapse, thereby blocking release of acetylcholine.8 In inhibiting acetylcholine release, the signal for eccrine secretion is blocked. This therapy has been effective in our residual limb patients who tolerate the treatment. It typically involves the injection of 300 to 500 U of botulinum toxin type A diluted with 0.9% saline at 2 to 5 U per 0.1 mL into the residual limb.5 As with the other treatments, there are side effects that complicate compliance. Most residual limb treatments require 150 injections, which can be uncomfortable for this patient cohort. The majority of these wounded warriors have abnormal anatomy because of the traumatic nature of their injuries (ie, improvised explosive device attacks, artillery injury), and they often experience hyperesthesia, phantom limb pain, and notable scarring. These injections can be extremely painful, which often limits their utility. In addition, the therapy only provides 3 to 6 months of symptom relief. Our compliance rate for returning patients has not been good and we suspect that it is likely due to the discomfort associated with the injections.

Other therapies such as laser hair removal and iontophoresis have been attempted but have not yielded great results or compliance. In addition to the limitations of these treatment methods, the residual limbs have presented their own unique set of challenges; complications have included varied anatomy of the residual limbs, scarring, sensitivities, and heterotopic ossification. Temporary remedies such as botulinum toxin injections also present logistical complications because they require repetitive procedural appointments that can be quite burdensome to attend when these patients move back home, often far away from our large military treatment facilities.

A New Therapy With Exciting Potential

With the recent advent of microwave thermal ablation technology, the potential for a different, possibly permanent treatment was discovered. Microwave thermal ablation of the eccrine coils has been proven safe and effective in the prolonged reduction of hyperhidrosis of the axillae and has presented as a potential therapy for our residual limb hyperhidrosis patient population. This technology produces heat that is targeted to a specific depth in the treated tissue while cooling the epidermis. There are various treatment levels that can be used to deliver graded intensities of heat. When the deep dermis is targeted, adnexal structures are denatured and destroyed, causing diminished or eliminated function. Eccrine sweat glands, apocrine glands, and even hair follicles are affected by the therapy. The manufacturer of the only microwave thermal ablation device on the market that is approved by the US Food and Drug Administration to treat axillary hyperhidrosis has suggested that these effects are long-term and possibly permanent.9 After several iterations with this technology, we have been able to successfully apply microwave thermal ablation of eccrine coils to 5 residual limbs and are excited about the promise that this technique possesses. A report of our index case will be published soon,10 and we are looking forward to launching our protocol treating traumatic lower extremity amputee patients that have hyperhidrosis with microwave therapy ablation technology here at WRNMMC.

 

 

Final Thoughts

Amputation residual limb dermatoses have a high prevalence and impact on amputee quality of life, particularly among young military members who strive to maintain a highly active lifestyle. Many of these dermatoses are directly related to hyperhidrosis of the residual limb that is covered by the prosthetic device and the liner that interfaces with the skin. Although many treatments for residual limb hyperhidrosis have been used with varying efficacy, none have offered a cost-effective or sustained response. Many of our wounded warriors in this amputee population have or will be transitioning out of the military in the coming years. It is imperative to our government, our institution, and most importantly our patients that efforts are made to develop a more permanent and efficacious treatment application to provide relief to these wounded heroes. This amputee population is unique in that they are younger, healthier, and highly motivated to live as “normal” of a life as possible. The ability to ambulate in a prosthetic device can have a huge social and psychological impact, and providing a therapy that minimizes complications associated with prosthetic use is invaluable. We are excited about the results we have seen with the microwave thermal ablation device and feel that there is potential benefit for other amputee populations if the procedure is perfected.

It is an exciting age in medicine where technology and biology have remarkably honed our diagnostic and treatment capabilities. We hope that everyone in the dermatology community shares our enthusiasm and will continue to explore and test these new technologies to improve and better the lives of the patients we treat.

We live in a time when young, otherwise healthy, active-duty individuals are undergoing traumatic amputations at an exceedingly high rate due to ongoing military engagements. According to US military casualty statistics through September 1, 2014, Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn veterans have undergone a total of 1573 amputations.1 Walter Reed National Military Medical Center (WRNMMC) is one of several military facilities that has managed the care of these unique patients returning from the many ongoing conflicts around the globe. Multidisciplinary teams composed of surgeons, anesthesiologists, physical therapists, prosthetists, and others have joined forces to provide extraordinary emergency and recovery care for these patients. Even in the best hands, however, these traumatic amputee patients often experience long-term and lifelong sequelae of their injuries. As dermatologists at this facility (S.P. was at WRNMMC for 3 years before transferring to Madigan Army Medical Center), we are often asked to assist in the management of a subset of these sequelae: residual limb dermatoses. Residual limb dermatoses such as recurrent bacterial and fungal infections, cysts, abrasions, blistering, irritant and allergic dermatitis, pressure ulcers, acroangiodermatitis, stump edema, and many others have a high prevalence in our wounded warrior population and impact both amputee quality of life and utilization of medical resources. As many as 73% of amputees will experience a variety of residual limb dermatoses at some point in their life, with the highest prevalence in younger, more active patients.2,3 We have observed that many, if not most, of these cutaneous problems can be attributed to or are exacerbated by hyperhidrosis of the residual limb. Hyperhidrosis in this population of patients can be related to excessive sweat production, but more commonly, it is attributed to the lack of evaporation of normal perspiration.

Excess Sweat and the Prosthesis

To understand hyperhidrosis in amputee patients, it is important to understand the anatomy of the prosthesis. There are a variety of materials that are used to create prosthetic limbs. The most commonly used materials are a combination of plastic and carbon graphite/carbon fiber. The modern prosthetic limb uses a suspension system that attaches the prosthetic limb to the residual limb by creating a vacuum. There are several mechanisms to create this vacuum; however, they all depend on a liner that fits snugly over the residual limb. This liner-limb interface is responsible for protection, mitigation of sheering forces, and comfort, and it is the anchor for a good fit in the prosthesis. Unfortunately, this liner is the primary factor contributing to residual limb dermatologic problems. The liner usually is made of silicone or polyurethane and is designed to be water and sweat resistant; any excess water that finds its way into the liner-prosthetic interface will affect the seal of the device and cause slippage of the prosthesis.4 This water-resistant barrier is what induces the hyperhidrotic environment over the residual limb that is covered. These patients sweat with exertion, and because of the water-resistant liner, there is no mechanism for sweat evaporation. This leads to a localized environment of hyperhidrosis, increasing patients’ susceptibility to chronic skin conditions. In addition to the dermatologic pathology of the residual limb, there are notable functional concerns caused by excessive sweating. Increased moisture due to sweating not only leads to pathologic dermatoses but also to impaired fit and loss of suction by leaking into the prosthetic-limb interface, which in turn can lead to decreased stamina in the prosthesis, falls, and in severe cases even prosthetic abandonment.5

 

 

Treating Hyperhidrosis

While working with wounded warriors in the dermatology, prosthetics, and wound care clinics at WRNMMC, it repeatedly became clear that our current treatment options for hyperhidrosis in this population were not routinely tolerated or efficacious. Although hyperhidrosis of the axillary or palmoplantar region is a commonly encountered problem with clear treatment algorithms and management strategies, hyperhidrosis in the setting of a residual limb following amputation is somewhat unique and without definitive permanent cure. In approaching this problem, our institution has implemented a variety of therapies to the residual limb that have been well described and effective in the treatment in the axillary region.

Topical antiperspirants (ie, aluminum chloride) are well-documented treatments of hyperhidrosis and work by the formation of a metal iron precipitate when binding with mucopolysaccharides. These complexes cause damage to epithelial cells lining the ostia of eccrine glands, forming a plug in the lumen of the eccrine duct.6 Unfortunately, irritant contact dermatitis has affected the majority of our residual limb patients who have used topical antiperspirants and has led to poor compliance. Glycopyrrolate, an antimuscarinic agent, often is used with varying degrees of success. It works as a competitive antagonist blocking the acetylcholine muscarinic receptors that are responsible for the innervation of eccrine sweat glands. Several of our residual limb patients have a history of global hyperhidrosis and have responded favorably to 1- to 2-mg doses of glycopyrrolate administered twice daily. The side-effect profile headlined by xerostomia, urinary retention, and constipation has, as it often does, limited the dosing. We have observed that with the use of glycopyrrolate, these patients admit to less overall sweating but experience only a mild decrease in the cutaneous problems they experience over the residual limbs, which is likely attributed to the prosthetic liner that induces hyperhidrosis by preventing sweat evaporation from the residual limb. Patients may not be sweating as much, but they are still sweating and that sweat is unable to evaporate from under the liner.

Botulinum toxin is a common treatment of axillary hyperhidrosis and its effects on residual limbs are the same.5,7 Botulinum toxin types A, B, and E specifically cleave soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which prevents neurosecretory vesicles from fusing with the interior surface of the plasma membrane of the nerve synapse, thereby blocking release of acetylcholine.8 In inhibiting acetylcholine release, the signal for eccrine secretion is blocked. This therapy has been effective in our residual limb patients who tolerate the treatment. It typically involves the injection of 300 to 500 U of botulinum toxin type A diluted with 0.9% saline at 2 to 5 U per 0.1 mL into the residual limb.5 As with the other treatments, there are side effects that complicate compliance. Most residual limb treatments require 150 injections, which can be uncomfortable for this patient cohort. The majority of these wounded warriors have abnormal anatomy because of the traumatic nature of their injuries (ie, improvised explosive device attacks, artillery injury), and they often experience hyperesthesia, phantom limb pain, and notable scarring. These injections can be extremely painful, which often limits their utility. In addition, the therapy only provides 3 to 6 months of symptom relief. Our compliance rate for returning patients has not been good and we suspect that it is likely due to the discomfort associated with the injections.

Other therapies such as laser hair removal and iontophoresis have been attempted but have not yielded great results or compliance. In addition to the limitations of these treatment methods, the residual limbs have presented their own unique set of challenges; complications have included varied anatomy of the residual limbs, scarring, sensitivities, and heterotopic ossification. Temporary remedies such as botulinum toxin injections also present logistical complications because they require repetitive procedural appointments that can be quite burdensome to attend when these patients move back home, often far away from our large military treatment facilities.

A New Therapy With Exciting Potential

With the recent advent of microwave thermal ablation technology, the potential for a different, possibly permanent treatment was discovered. Microwave thermal ablation of the eccrine coils has been proven safe and effective in the prolonged reduction of hyperhidrosis of the axillae and has presented as a potential therapy for our residual limb hyperhidrosis patient population. This technology produces heat that is targeted to a specific depth in the treated tissue while cooling the epidermis. There are various treatment levels that can be used to deliver graded intensities of heat. When the deep dermis is targeted, adnexal structures are denatured and destroyed, causing diminished or eliminated function. Eccrine sweat glands, apocrine glands, and even hair follicles are affected by the therapy. The manufacturer of the only microwave thermal ablation device on the market that is approved by the US Food and Drug Administration to treat axillary hyperhidrosis has suggested that these effects are long-term and possibly permanent.9 After several iterations with this technology, we have been able to successfully apply microwave thermal ablation of eccrine coils to 5 residual limbs and are excited about the promise that this technique possesses. A report of our index case will be published soon,10 and we are looking forward to launching our protocol treating traumatic lower extremity amputee patients that have hyperhidrosis with microwave therapy ablation technology here at WRNMMC.

 

 

Final Thoughts

Amputation residual limb dermatoses have a high prevalence and impact on amputee quality of life, particularly among young military members who strive to maintain a highly active lifestyle. Many of these dermatoses are directly related to hyperhidrosis of the residual limb that is covered by the prosthetic device and the liner that interfaces with the skin. Although many treatments for residual limb hyperhidrosis have been used with varying efficacy, none have offered a cost-effective or sustained response. Many of our wounded warriors in this amputee population have or will be transitioning out of the military in the coming years. It is imperative to our government, our institution, and most importantly our patients that efforts are made to develop a more permanent and efficacious treatment application to provide relief to these wounded heroes. This amputee population is unique in that they are younger, healthier, and highly motivated to live as “normal” of a life as possible. The ability to ambulate in a prosthetic device can have a huge social and psychological impact, and providing a therapy that minimizes complications associated with prosthetic use is invaluable. We are excited about the results we have seen with the microwave thermal ablation device and feel that there is potential benefit for other amputee populations if the procedure is perfected.

It is an exciting age in medicine where technology and biology have remarkably honed our diagnostic and treatment capabilities. We hope that everyone in the dermatology community shares our enthusiasm and will continue to explore and test these new technologies to improve and better the lives of the patients we treat.

References
  1. Fischer H. A guide to U.S. military casualty statistics: Operation Inherent Resolve, Operation New Dawn, Operation Iraqi Freedom, and Operation Enduring Freedom. http://ibiblio.org/hyperwar/NHC/CasualtyStats2014Nov/CasualtyStats2014Nov.htm. Congressional Research Service 7-5700; RS22452. Published November 20, 2014. Accessed May 13, 2016.
  2. Yang NB, Garza LA, Foote CE, et al. High prevalence of stump dermatoses 38 years or more after amputation. Arch Dermatol. 2012;148:1283-1286.
  3. Koc E, Tunca M, Akar A, et al. Skin problems in amputees: a descriptive study. Int J Dermatol. 2008;47:463-466.
  4. Ghoseiri K, Safari MR. Prevalence of heat and perspiration discomfort inside prostheses: literature review. J Rehabil Res Dev. 2014;51:855-868.
  5. Gratrix M, Hivnor C. Botulinum A toxin treatment for hyperhidrosis in patients with prosthetic limbs. Arch Dermatol. 2010;146:1314-1315.
  6. Hölzle E. Topical pharmacological treatment. Curr Probl Dermatol. 2002;30:30-43. 
  7. Lee KYC, Levell NJ. Turning the tide: a history and review of hyperhidrosis treatment. JRSM Open. 2014;5. doi:10.1177/2042533313505511.
  8. Dressler D, Adib Saberi F. Botulinum toxin: mechanisms of action. Eur Neurol. 2005;53:3-9.
  9. Lupin M, Hong HC, O’Shaughnessy KF. Long-term efficacy and quality of life assessment for treatment of axillary hyperhidrosis with a microwave device. Dermatol Surg. 2014;40:805-807.
  10. Mula K, Winston J, Pace S, et al. Use of microwave device for treatment of amputation residual limb hyperhidrosis. Dermatol Surg. In press.
References
  1. Fischer H. A guide to U.S. military casualty statistics: Operation Inherent Resolve, Operation New Dawn, Operation Iraqi Freedom, and Operation Enduring Freedom. http://ibiblio.org/hyperwar/NHC/CasualtyStats2014Nov/CasualtyStats2014Nov.htm. Congressional Research Service 7-5700; RS22452. Published November 20, 2014. Accessed May 13, 2016.
  2. Yang NB, Garza LA, Foote CE, et al. High prevalence of stump dermatoses 38 years or more after amputation. Arch Dermatol. 2012;148:1283-1286.
  3. Koc E, Tunca M, Akar A, et al. Skin problems in amputees: a descriptive study. Int J Dermatol. 2008;47:463-466.
  4. Ghoseiri K, Safari MR. Prevalence of heat and perspiration discomfort inside prostheses: literature review. J Rehabil Res Dev. 2014;51:855-868.
  5. Gratrix M, Hivnor C. Botulinum A toxin treatment for hyperhidrosis in patients with prosthetic limbs. Arch Dermatol. 2010;146:1314-1315.
  6. Hölzle E. Topical pharmacological treatment. Curr Probl Dermatol. 2002;30:30-43. 
  7. Lee KYC, Levell NJ. Turning the tide: a history and review of hyperhidrosis treatment. JRSM Open. 2014;5. doi:10.1177/2042533313505511.
  8. Dressler D, Adib Saberi F. Botulinum toxin: mechanisms of action. Eur Neurol. 2005;53:3-9.
  9. Lupin M, Hong HC, O’Shaughnessy KF. Long-term efficacy and quality of life assessment for treatment of axillary hyperhidrosis with a microwave device. Dermatol Surg. 2014;40:805-807.
  10. Mula K, Winston J, Pace S, et al. Use of microwave device for treatment of amputation residual limb hyperhidrosis. Dermatol Surg. In press.
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Cutis - 97(6)
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Managing Residual Limb Hyperhidrosis in Wounded Warriors
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  • Hyperhidrosis of residual limbs often is induced by the occlusive effects of the water-resistant prosthetic liner that fits snugly over the limb.
  • Commonly accepted treatments of hyperhidrosis often are less effective or poorly tolerated by these patients. The microwave thermal ablation device is a promising tool that may provide long-term relief of symptoms.
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