Letters
Figure. Trends in Indoor Tanning Among US High School Students, National Youth Risk Behavior Survey, 2009-2013 Females 40
Use of Indoor Tanning, %
35
NH white (β=–0.24, P=.03)
30 25
All (β=–0.22, P=.03)
20 15
NH other (β=–0.07, P=.76) Hispanic (β=–0.25, P=.12)
10 5
NH black (β=–0.05, P=.82) 0 2009
2011
2013
Year Males 10
Use of Indoor Tanning, %
8
NH white (β=–0.14, P=.21) All (β=–0.18, P=.06) NH other (β=–0.06, P=.76) Hispanic (β=–0.22, P=.23)
6
4
NH black (β=–0.50, P=.02) 2
0 2009
2011
2013
Year
Author Affiliations: Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia (Guy, Berkowitz, Holman, Watson); Division of Adolescent and School Health, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia (Everett Jones); Advanced Technology Logistics, Inc, Atlanta, Georgia (Garnett). Accepted for Publication: October 23, 2014. Corresponding Author: Gery P. Guy Jr, PhD, MPH, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, MS F-76, Atlanta, GA 30341 ([email protected]). Published Online: December 23, 2014. doi:10.1001/jamadermatol.2014.4677. Author Contributions: Dr Guy and Ms Berkowitz had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Guy, Berkowitz, Holman, Garnett, Watson. Acquisition, analysis, or interpretation of data: Guy, Berkowitz, Everett Jones, Holman, Garnett. Drafting of the manuscript: Guy, Berkowitz, Everett Jones, Garnett, Watson. Critical revision of the manuscript for important intellectual content: Guy, Berkowitz, Holman. Statistical analysis: Guy, Berkowitz, Everett Jones. Administrative, technical, or material support: Guy, Garnett, Watson. Study supervision: Guy. Conflict of Interest Disclosures: None reported. Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 450
Indoor tanning is defined as using an indoor tanning device (eg, sunlamp, sunbed, tanning booth) at least once during the 12 months before the survey and does not include getting a spray-on tan. Changes in indoor tanning were examined using logistic regression analyses controlling for age (ⱕ14, 15, 16, 17, and ⱖ18 years) and race/ethnicity (non-Hispanic [NH] white, NH black, NH other, and Hispanic) among all races/ethnicities and ages in the race/ethnicity– specific analyses.
1. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol. 2014;70(5):847-857.e1-18. 2. Wehner MR, Shive ML, Chren MM, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. BMJ. 2012;345:e5909. 3. Wehner MR, Chren MM, Nameth D, et al. International prevalence of indoor tanning: a systematic review and meta-analysis. JAMA Dermatol. 2014;150(4): 390-400. 4. US Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent Skin Cancer. Washington, DC: US Dept of Health and Human Services, Office of the Surgeon General; 2014. 5. AIM at Melanoma. Ongoing legislation. http://www.aimatmelanoma.org/en /aim-for-a-cure/legislative-accomplishments-in-melanoma.html. Accessed August 4, 2014. 6. Guy GP Jr, Berkowitz Z, Jones SE, et al. State indoor tanning laws and adolescent indoor tanning. Am J Public Health. 2014;104(4):e69-e74.
The Risk of Melanoma in Pilots and Cabin Crew: UV Measurements in Flying Airplanes Recently, a meta-analysis reported an increased incidence of melanoma in pilots and cabin crew, which was possibly due to occupational exposures.1 Cabin crews’ exposure to cosmic radiation was assessed in different studies and always found below the allowed dose limit. 2 However, the cumulative
JAMA Dermatology April 2015 Volume 151, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
jamadermatology.com
Letters
Table 1. UV Measurements Performed at Pilot Seat Inside a Socata TBM850 at Different Altitudes San Jose, CA (49 ft)a UV-A and UV-B, μW/cm2
Altitude, ft
Las Vegas, NV (2030 ft)a UV-B only, μW/cm2
UV-A and UV-B, μW/cm2
UV-B only, μW/cm2
Ground level
137
0
127
0
2500
135
0
128
0
6000
138
0
132
0
10 000
189
0
182
0
15 000
228
0
NA
0
20 000
234
0
212
0
25 000
250
0
210
0
30 000
NA
0
242
0
Table 2. UV-A Carcinogenic Effective Doses in Airplanes and in Tanning Beds
Location
Carcinogenic Effective Irradiance, mW/m2
Time to Receive the UV-A Dose of a Tanning Bed Session, 2940 J/m2, min
Inside tanning bed
2.45
20.00
In pilot seat at 30 000 ft
0.87
56.60
exposure of pilots and cabin crew to UV radiation, a known risk factor for melanoma, has not been assessed to our knowledge. Airplane windshields are commonly made of polycarbonate plastic or multilayer composite glass. UV-B (280-320 nm) transmission through both plastic and glass windshields was reported to be less than 1%. However, UV-A (320-380 nm) transmission ranged from 0.41% to 53.5%, with plastic attenuating more UV radiation than glass.3 Intrigued by our findings and the clinical observation of pilots developing melanomas on sun-exposed skin, we measured the amount of UV radiation in airplane cockpits during flight and compared them with measurements performed in tanning beds. Methods | UV radiation measurements were performed using a Solartech UV index meter designed to measure UV radiation from 280 to 400 nm (UV-B and UV-A) and a Solartech UV index meter designed to measure UV-B only (280-322 nm) (Solartech Inc). We first measured UV radiation in the pilot seat inside a general aviation turboprop airplane (Socata TBM850) through the acrylic plastic windshield (1.6-cm thick) at ground level and at 2500, 6000, 10 000, 15 000, 20 000, 25 000, and 30 000 feet above sea level. The measurements were taken in 2 locations with different solar exposures: San Jose, California, and Las Vegas, Nevada, around midday in April. Later, the same meters were used to measure UV radiation levels in an Omega UV-A tanning bed. The study design has been reviewed and approved by the Committee on Human Research, University of California, San Francisco. Results | Our measurements inside the airplane revealed that the windshields blocked UV-B but allowed UV-A transmission. The amount of UV-A at 30 000 feet measured in Las Vegas, Nevada, was approximately 242 μW/cm2 (Table 1). The jamadermatology.com
Abbreviation: NA, not available. a
Measurements in parentheses indicate height above sea level.
UV-A dose in a UV-A–only tanning bed was 706 μW/cm2. The carcinogenic effective dose was calculated using the Skin Cancer Utrecht–Philadelphia human action spectrum,4 and the dose for a 20-minute tanning session was 2940 mJ/m2. The carcinogenic effective doses of UV-A radiation in tanning beds and airplanes are compared in Table 2. Discussion | The pathogenic role of UV-A in melanoma is well established. UV-A is capable of causing DNA damage in cell culture5 and in animal models.6 Pilots flying for 56.6 minutes at 30 000 feet receive the same amount of UV-A carcinogenic effective radiation as that from a 20-minute tanning bed session. These levels could be significantly higher when flying over thick cloud layers and snow fields, which could reflect up to 85% of UV radiation. Airplane windshields do not completely block UV-A radiation and therefore are not enough to protect pilots. UV-A transmission inside airplanes can play a role in pilots’ increased risk of melanoma. We recommend further studies to establish recommendations for occupation-related UV radiation dose limits. These studies should include more precise measurement in several airplanes. We believe that better UV protection on aircraft windshields is necessary to offer cabin crew a hazard-free work environment. We strongly recommend the use of sunscreens and periodical skin checks for pilots and cabin crew. Martina Sanlorenzo, MD Igor Vujic, MD Christian Posch, MD James E. Cleaver, PhD Pietro Quaglino, MD Susana Ortiz-Urda, MD, PhD Author Affiliations: Department of Dermatology, Mount Zion Cancer Research Center, University of California, San Francisco (Sanlorenzo, Vujic, Posch, Cleaver, Ortiz-Urda); Department of Medical Sciences, University of Turin, Turin, Italy (Quaglino). Accepted for Publication: October 23, 2014. Corresponding Author: Martina Sanlorenzo, MD, Department of Dermatology, Mount Zion Cancer Research Center, University of California, San Francisco, San Francisco, CA 94115 ([email protected]). Published Online: December 17, 2014. doi:10.1001/jamadermatol.2014.4643. Author Contributions: Drs Sanlorenzo and Ortiz-Urda had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Sanlorenzo, Ortiz-Urda. (Reprinted) JAMA Dermatology April 2015 Volume 151, Number 4
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
451
Letters
Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Sanlorenzo, Vujic, Cleaver, Ortiz-Urda. Critical revision of the manuscript for important intellectual content: Sanlorenzo, Vujic, Posch, Quaglino, Ortiz-Urda. Statistical analysis: Sanlorenzo. Obtained funding: Ortiz-Urda. Administrative, technical, or material support: Vujic, Cleaver, Ortiz-Urda. Study supervision: Posch, Quaglino, Ortiz-Urda. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported in part by the National Cancer Institute of the National Institutes of Health under award number K08CA155035. Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
tion score of 10, we considered the diagnosis definite.3 Discontinuation of amoxicillin therapy and initiation of treatment with topical and systemic corticosteroids led to rapid resolution of this episode. A patch test with amoxicillin performed 6 weeks later showed a pustular skin reaction, further implicating amoxicillin as the trigger of this AGEP. Nine months later, the patient again developed a generalized pustular reaction with systemic inflammatory response syndrome 3 days after a throat infection with β-hemoFigure 1. Clinical Photograph of the Head After the First-Described Acute Generalized Pustular Eruption
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional Contributions: Timothy Dattels, MDA, and the Melanoma Research Alliance provided funding. We are indebted to James T. McGrath, EE, and Radhika Gulhar, University of California, San Francisco, for their technical help in the UV measurements. They were not compensated for their contributions. 1. Sanlorenzo M, Wehner MR, Linos E, et al. The risk of melanoma in airline pilots and cabin crew: a meta-analysis [published online September 3, 2014]. JAMA Dermatol. doi:10.1001/jamadermatol.2014.1077. 2. Zeeb H, Hammer GP, Blettner M. Epidemiological investigations of aircrew: an occupational group with low-level cosmic radiation exposure. J Radiol Prot. 2012;32(1):N15-N19. 3. Nakagawara VB, Montgomery RW, Marshall JW. Optical Radiation Transmittance of Aircraft Windscreens and Pilot Vision. Washington, DC: Federal Aviation Administration; 2007. 4. de Gruijl FR, Van der Leun JC. Estimate of the wavelength dependency of ultraviolet carcinogenesis in humans and its relevance to the risk assessment of a stratospheric ozone depletion. Health Phys. 1994;67(4):319-325. 5. Ananthaswamy HN, Pierceall WE. Molecular mechanisms of ultraviolet radiation carcinogenesis. Photochem Photobiol. 1990;52(6):1119-1136. 6. Ley RD. Ultraviolet radiation A–induced precursors of cutaneous melanoma in Monodelphis domestica. Cancer Res. 1997;57(17):3682-3684. Compatible with acute generalized exanthematous pustulosis, nonfollicular pustules on confluent erythematous and edematous plaques are seen on the head.
OBSERVATION
Homozygous Missense Mutation in IL36RN in Generalized Pustular Dermatosis With Intraoral Involvement Compatible With Both AGEP and Generalized Pustular Psoriasis
Figure 2. Right Thoracic Histologic Specimen Taken After the First-Described Generalized Pustular Eruption
Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) show multiple overlapping clinical features. Recently, mutations in the IL36RN gene encoding the interleukin (IL)-36 receptor antagonist (IL-36Ra) have been found to cause increased secretion of inflammatory cytokines in GPP and in a subset of AGEP.1,2 In both conditions, half of the patients with IL36RN variants had oral involvement.1,2 Report of a Case | Herein we report a man in his 40s who initially presented with fever, systemic inflammatory response syndrome, and generalized, sterile, nonfollicular pustules (Figure 1) accentuated in the major flexures and on the palatal mucosa 5 days after intake of amoxicillin, which he took as postoperative prophylaxis after surgery of the thumb. His family history was negative for psoriasis. Medical history and clinicopathologic findings (Figure 2) were consistent with AGEP due to amoxicillin. After obtaining a EuroSCAR AGEP valida452
Numerous subcorneal pustules, necrotic keratinocytes, edema of the papillary dermis, and perivascular lymphocytic infiltrate consisting mainly of neutrophils and eosinophils (hematoxylin-eosin, original magnification ×100).
JAMA Dermatology April 2015 Volume 151, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
jamadermatology.com
Figure. Trends in Indoor Tanning Among US High School Students, National Youth Risk Behavior Survey, 2009-2013 Females 40
Use of Indoor Tanning, %
35
NH white (β=–0.24, P=.03)
30 25
All (β=–0.22, P=.03)
20 15
NH other (β=–0.07, P=.76) Hispanic (β=–0.25, P=.12)
10 5
NH black (β=–0.05, P=.82) 0 2009
2011
2013
Year Males 10
Use of Indoor Tanning, %
8
NH white (β=–0.14, P=.21) All (β=–0.18, P=.06) NH other (β=–0.06, P=.76) Hispanic (β=–0.22, P=.23)
6
4
NH black (β=–0.50, P=.02) 2
0 2009
2011
2013
Year
Author Affiliations: Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia (Guy, Berkowitz, Holman, Watson); Division of Adolescent and School Health, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia (Everett Jones); Advanced Technology Logistics, Inc, Atlanta, Georgia (Garnett). Accepted for Publication: October 23, 2014. Corresponding Author: Gery P. Guy Jr, PhD, MPH, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, MS F-76, Atlanta, GA 30341 ([email protected]). Published Online: December 23, 2014. doi:10.1001/jamadermatol.2014.4677. Author Contributions: Dr Guy and Ms Berkowitz had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Guy, Berkowitz, Holman, Garnett, Watson. Acquisition, analysis, or interpretation of data: Guy, Berkowitz, Everett Jones, Holman, Garnett. Drafting of the manuscript: Guy, Berkowitz, Everett Jones, Garnett, Watson. Critical revision of the manuscript for important intellectual content: Guy, Berkowitz, Holman. Statistical analysis: Guy, Berkowitz, Everett Jones. Administrative, technical, or material support: Guy, Garnett, Watson. Study supervision: Guy. Conflict of Interest Disclosures: None reported. Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 450
Indoor tanning is defined as using an indoor tanning device (eg, sunlamp, sunbed, tanning booth) at least once during the 12 months before the survey and does not include getting a spray-on tan. Changes in indoor tanning were examined using logistic regression analyses controlling for age (ⱕ14, 15, 16, 17, and ⱖ18 years) and race/ethnicity (non-Hispanic [NH] white, NH black, NH other, and Hispanic) among all races/ethnicities and ages in the race/ethnicity– specific analyses.
1. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol. 2014;70(5):847-857.e1-18. 2. Wehner MR, Shive ML, Chren MM, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. BMJ. 2012;345:e5909. 3. Wehner MR, Chren MM, Nameth D, et al. International prevalence of indoor tanning: a systematic review and meta-analysis. JAMA Dermatol. 2014;150(4): 390-400. 4. US Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent Skin Cancer. Washington, DC: US Dept of Health and Human Services, Office of the Surgeon General; 2014. 5. AIM at Melanoma. Ongoing legislation. http://www.aimatmelanoma.org/en /aim-for-a-cure/legislative-accomplishments-in-melanoma.html. Accessed August 4, 2014. 6. Guy GP Jr, Berkowitz Z, Jones SE, et al. State indoor tanning laws and adolescent indoor tanning. Am J Public Health. 2014;104(4):e69-e74.
The Risk of Melanoma in Pilots and Cabin Crew: UV Measurements in Flying Airplanes Recently, a meta-analysis reported an increased incidence of melanoma in pilots and cabin crew, which was possibly due to occupational exposures.1 Cabin crews’ exposure to cosmic radiation was assessed in different studies and always found below the allowed dose limit. 2 However, the cumulative
JAMA Dermatology April 2015 Volume 151, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
jamadermatology.com
Letters
Table 1. UV Measurements Performed at Pilot Seat Inside a Socata TBM850 at Different Altitudes San Jose, CA (49 ft)a UV-A and UV-B, μW/cm2
Altitude, ft
Las Vegas, NV (2030 ft)a UV-B only, μW/cm2
UV-A and UV-B, μW/cm2
UV-B only, μW/cm2
Ground level
137
0
127
0
2500
135
0
128
0
6000
138
0
132
0
10 000
189
0
182
0
15 000
228
0
NA
0
20 000
234
0
212
0
25 000
250
0
210
0
30 000
NA
0
242
0
Table 2. UV-A Carcinogenic Effective Doses in Airplanes and in Tanning Beds
Location
Carcinogenic Effective Irradiance, mW/m2
Time to Receive the UV-A Dose of a Tanning Bed Session, 2940 J/m2, min
Inside tanning bed
2.45
20.00
In pilot seat at 30 000 ft
0.87
56.60
exposure of pilots and cabin crew to UV radiation, a known risk factor for melanoma, has not been assessed to our knowledge. Airplane windshields are commonly made of polycarbonate plastic or multilayer composite glass. UV-B (280-320 nm) transmission through both plastic and glass windshields was reported to be less than 1%. However, UV-A (320-380 nm) transmission ranged from 0.41% to 53.5%, with plastic attenuating more UV radiation than glass.3 Intrigued by our findings and the clinical observation of pilots developing melanomas on sun-exposed skin, we measured the amount of UV radiation in airplane cockpits during flight and compared them with measurements performed in tanning beds. Methods | UV radiation measurements were performed using a Solartech UV index meter designed to measure UV radiation from 280 to 400 nm (UV-B and UV-A) and a Solartech UV index meter designed to measure UV-B only (280-322 nm) (Solartech Inc). We first measured UV radiation in the pilot seat inside a general aviation turboprop airplane (Socata TBM850) through the acrylic plastic windshield (1.6-cm thick) at ground level and at 2500, 6000, 10 000, 15 000, 20 000, 25 000, and 30 000 feet above sea level. The measurements were taken in 2 locations with different solar exposures: San Jose, California, and Las Vegas, Nevada, around midday in April. Later, the same meters were used to measure UV radiation levels in an Omega UV-A tanning bed. The study design has been reviewed and approved by the Committee on Human Research, University of California, San Francisco. Results | Our measurements inside the airplane revealed that the windshields blocked UV-B but allowed UV-A transmission. The amount of UV-A at 30 000 feet measured in Las Vegas, Nevada, was approximately 242 μW/cm2 (Table 1). The jamadermatology.com
Abbreviation: NA, not available. a
Measurements in parentheses indicate height above sea level.
UV-A dose in a UV-A–only tanning bed was 706 μW/cm2. The carcinogenic effective dose was calculated using the Skin Cancer Utrecht–Philadelphia human action spectrum,4 and the dose for a 20-minute tanning session was 2940 mJ/m2. The carcinogenic effective doses of UV-A radiation in tanning beds and airplanes are compared in Table 2. Discussion | The pathogenic role of UV-A in melanoma is well established. UV-A is capable of causing DNA damage in cell culture5 and in animal models.6 Pilots flying for 56.6 minutes at 30 000 feet receive the same amount of UV-A carcinogenic effective radiation as that from a 20-minute tanning bed session. These levels could be significantly higher when flying over thick cloud layers and snow fields, which could reflect up to 85% of UV radiation. Airplane windshields do not completely block UV-A radiation and therefore are not enough to protect pilots. UV-A transmission inside airplanes can play a role in pilots’ increased risk of melanoma. We recommend further studies to establish recommendations for occupation-related UV radiation dose limits. These studies should include more precise measurement in several airplanes. We believe that better UV protection on aircraft windshields is necessary to offer cabin crew a hazard-free work environment. We strongly recommend the use of sunscreens and periodical skin checks for pilots and cabin crew. Martina Sanlorenzo, MD Igor Vujic, MD Christian Posch, MD James E. Cleaver, PhD Pietro Quaglino, MD Susana Ortiz-Urda, MD, PhD Author Affiliations: Department of Dermatology, Mount Zion Cancer Research Center, University of California, San Francisco (Sanlorenzo, Vujic, Posch, Cleaver, Ortiz-Urda); Department of Medical Sciences, University of Turin, Turin, Italy (Quaglino). Accepted for Publication: October 23, 2014. Corresponding Author: Martina Sanlorenzo, MD, Department of Dermatology, Mount Zion Cancer Research Center, University of California, San Francisco, San Francisco, CA 94115 ([email protected]). Published Online: December 17, 2014. doi:10.1001/jamadermatol.2014.4643. Author Contributions: Drs Sanlorenzo and Ortiz-Urda had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Sanlorenzo, Ortiz-Urda. (Reprinted) JAMA Dermatology April 2015 Volume 151, Number 4
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
451
Letters
Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Sanlorenzo, Vujic, Cleaver, Ortiz-Urda. Critical revision of the manuscript for important intellectual content: Sanlorenzo, Vujic, Posch, Quaglino, Ortiz-Urda. Statistical analysis: Sanlorenzo. Obtained funding: Ortiz-Urda. Administrative, technical, or material support: Vujic, Cleaver, Ortiz-Urda. Study supervision: Posch, Quaglino, Ortiz-Urda. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported in part by the National Cancer Institute of the National Institutes of Health under award number K08CA155035. Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
tion score of 10, we considered the diagnosis definite.3 Discontinuation of amoxicillin therapy and initiation of treatment with topical and systemic corticosteroids led to rapid resolution of this episode. A patch test with amoxicillin performed 6 weeks later showed a pustular skin reaction, further implicating amoxicillin as the trigger of this AGEP. Nine months later, the patient again developed a generalized pustular reaction with systemic inflammatory response syndrome 3 days after a throat infection with β-hemoFigure 1. Clinical Photograph of the Head After the First-Described Acute Generalized Pustular Eruption
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional Contributions: Timothy Dattels, MDA, and the Melanoma Research Alliance provided funding. We are indebted to James T. McGrath, EE, and Radhika Gulhar, University of California, San Francisco, for their technical help in the UV measurements. They were not compensated for their contributions. 1. Sanlorenzo M, Wehner MR, Linos E, et al. The risk of melanoma in airline pilots and cabin crew: a meta-analysis [published online September 3, 2014]. JAMA Dermatol. doi:10.1001/jamadermatol.2014.1077. 2. Zeeb H, Hammer GP, Blettner M. Epidemiological investigations of aircrew: an occupational group with low-level cosmic radiation exposure. J Radiol Prot. 2012;32(1):N15-N19. 3. Nakagawara VB, Montgomery RW, Marshall JW. Optical Radiation Transmittance of Aircraft Windscreens and Pilot Vision. Washington, DC: Federal Aviation Administration; 2007. 4. de Gruijl FR, Van der Leun JC. Estimate of the wavelength dependency of ultraviolet carcinogenesis in humans and its relevance to the risk assessment of a stratospheric ozone depletion. Health Phys. 1994;67(4):319-325. 5. Ananthaswamy HN, Pierceall WE. Molecular mechanisms of ultraviolet radiation carcinogenesis. Photochem Photobiol. 1990;52(6):1119-1136. 6. Ley RD. Ultraviolet radiation A–induced precursors of cutaneous melanoma in Monodelphis domestica. Cancer Res. 1997;57(17):3682-3684. Compatible with acute generalized exanthematous pustulosis, nonfollicular pustules on confluent erythematous and edematous plaques are seen on the head.
OBSERVATION
Homozygous Missense Mutation in IL36RN in Generalized Pustular Dermatosis With Intraoral Involvement Compatible With Both AGEP and Generalized Pustular Psoriasis
Figure 2. Right Thoracic Histologic Specimen Taken After the First-Described Generalized Pustular Eruption
Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) show multiple overlapping clinical features. Recently, mutations in the IL36RN gene encoding the interleukin (IL)-36 receptor antagonist (IL-36Ra) have been found to cause increased secretion of inflammatory cytokines in GPP and in a subset of AGEP.1,2 In both conditions, half of the patients with IL36RN variants had oral involvement.1,2 Report of a Case | Herein we report a man in his 40s who initially presented with fever, systemic inflammatory response syndrome, and generalized, sterile, nonfollicular pustules (Figure 1) accentuated in the major flexures and on the palatal mucosa 5 days after intake of amoxicillin, which he took as postoperative prophylaxis after surgery of the thumb. His family history was negative for psoriasis. Medical history and clinicopathologic findings (Figure 2) were consistent with AGEP due to amoxicillin. After obtaining a EuroSCAR AGEP valida452
Numerous subcorneal pustules, necrotic keratinocytes, edema of the papillary dermis, and perivascular lymphocytic infiltrate consisting mainly of neutrophils and eosinophils (hematoxylin-eosin, original magnification ×100).
JAMA Dermatology April 2015 Volume 151, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/28/2015
jamadermatology.com
