Therapeutic Effect of Dupilumab on Systemic and Vascular Inflammation in Adults with Severe Atopic Dermatitis: Feasibility Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography

Authors

  • Gi-Wook Lee Department of Dermatology, School of Medicine, Pusan National University Hospital, Busan, Korea
  • Keunyoung Kim Department of Nuclear Medicine, Pusan National University Hospital, Busan, Korea
  • Seong-Jang Kim Department of Nuclear Medicine, Pusan National University Hospital, Busan, Korea
  • Kihyuk Shin Department of Dermatology, School of Medicine, Pusan National University Hospital, Busan, Korea
  • Hoonsoo Kim Department of Dermatology, School of Medicine, Pusan National University Hospital, Busan, Korea
  • Hyun-Chang Ko Department of Dermatology, School of Medicine, Pusan National University Hospital, Busan, Korea
  • Moon-Bum Kim Department of Dermatology, School of Medicine, Pusan National University Hospital, Busan, Korea
  • Byungsoo Kim Department of Dermatology, School of Medicine, Pusan National University, Busan, Korea

DOI:

https://doi.org/10.2340/actadv.v103.5320

Keywords:

Atopic dermatitis, Cardiovascular disease, Comorbidity, Dupilumab, Inflammation, PET/CT: positron emission tomography-computed tomography

Abstract

Atopic dermatitis (AD) is an inflammatory skin disease associated with increased systemic and vascular inflammation. Although dupilumab has been proven to be effective against severe AD, imaging studies analysing its inflammation-reducing effect have rarely been reported. The aim of this study was to evaluate the effect of dupilumab on systemic and vascular inflammation in adult patients with severe AD, using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). A total of 33 adult patients with severe AD and 25 healthy controls underwent 18F-FDG PET/CT at baseline. Patients on dupilumab treatment underwent 18F-FDG PET/CT again after achieving a 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75). Patients with AD exhibited increased 18F-FDG uptake values in the liver, spleen, pancreas, and carotid artery compared with healthy controls. However, compared with baseline, there was no statistically significant difference in 18F-FDG uptake in major organs and arteries after achieving EASI-75 with dupilumab treatment. In conclusion, while dupilumab treatment resulted in a significant clinical improvement and reduced serum inflammatory markers in adult patients with severe AD, no changes in systemic and vascular inflammation were observed on 18F-FDG PET/CT imaging.

Downloads

Download data is not yet available.

References

Silverberg JI. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol 2019; 123: 144-151.

https://doi.org/10.1016/j.anai.2019.04.020 DOI: https://doi.org/10.1016/j.anai.2019.04.020

Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, Amagai M, et al., Councilors of the International Eczema Council. increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol 2017; 137: 18-25.

https://doi.org/10.1016/j.jid.2016.08.022 DOI: https://doi.org/10.1016/j.jid.2016.08.022

Furue M, Kadono T. "Inflammatory skin march" in atopic dermatitis and psoriasis. Inflamm Res 2017; 66: 833-842.

https://doi.org/10.1007/s00011-017-1065-z DOI: https://doi.org/10.1007/s00011-017-1065-z

Kwa MC, Silverberg JI. Association between inflammatory skin disease, cardiovascular and cerebrovascular comorbidities in US adults: analysis of Nationwide Inpatient Sample data. Am J Clin Dermatol 2017; 18: 813-823.

https://doi.org/10.1007/s40257-017-0293-x DOI: https://doi.org/10.1007/s40257-017-0293-x

Vaidyanathan S, Patel CN, Scarsbrook AF, Chowdhury FU. FDG PET/CT in infection and inflammation - current and emerging clinical applications. Clin Radiol 2015; 70: 787-800.

https://doi.org/10.1016/j.crad.2015.03.010 DOI: https://doi.org/10.1016/j.crad.2015.03.010

Kim SJ, Park MY, Pak K, Han J, Kim GW, Kim HS, et al. Improvement of depressive symptoms in patients with moderate-to-severe psoriasis treated with ustekinumab: an open label trial validated using beck depression inventory, Hamilton depression rating scale measures and 18fluorodeoxyglucose (FDG) positron emission tomography (PET). J Dermatolog Treat 2018; 29: 761-768.

https://doi.org/10.1080/09546634.2018.1466021 DOI: https://doi.org/10.1080/09546634.2018.1466021

Lawal I, Sathekge M. F-18 FDG PET/CT imaging of cardiac and vascular inflammation and infection. Br Med Bull 2016; 120: 55-74.

https://doi.org/10.1093/bmb/ldw035 DOI: https://doi.org/10.1093/bmb/ldw035

Youn SW, Kang SY, Kim SA, Park GY, Lee WW. Subclinical systemic and vascular inflammation detected by (18) F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with mild psoriasis. J Dermatol 2015; 42: 559-566.

https://doi.org/10.1111/1346-8138.12859 DOI: https://doi.org/10.1111/1346-8138.12859

Mehta NN, Yu Y, Saboury B, Foroughi N, Krishnamoorthy P, Raper A, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol 2011; 147: 1031-1039.

https://doi.org/10.1001/archdermatol.2011.119 DOI: https://doi.org/10.1001/archdermatol.2011.119

Kim BS, Lee WK, Pak K, Han J, Kim GW, Kim HS, et al. Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: feasibility study using 18F-fluorodeoxyglucose PET/CT. J Am Acad Dermatol 2019; 80: 1322-1331.

https://doi.org/10.1016/j.jaad.2018.03.011 DOI: https://doi.org/10.1016/j.jaad.2018.03.011

Ungar B, Pavel AB, Robson PM, Kaufman A, Pruzan A, Brunner P, et al. A preliminary 18F-FDG-PET/MRI study shows increased vascular inflammation in moderate-to-severe atopic dermatitis. J Allergy Clin Immunol Pract 2020; 8: 3500-3506.

https://doi.org/10.1016/j.jaip.2020.07.018 DOI: https://doi.org/10.1016/j.jaip.2020.07.018

Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980; Suppl 92: 44-47.

https://doi.org/10.2340/00015555924447 DOI: https://doi.org/10.2340/00015555924447

Lee H, Kim BR, Kim KH, Lee DH, Na JI. One-year effectiveness and safety of dupilumab treatment for moderate-to-severe atopic dermatitis in Korean patients: a real-world retrospective analysis. Allergy Asthma Immunol Res 2022; 14: 117-122.

https://doi.org/10.4168/aair.2022.14.1.117 DOI: https://doi.org/10.4168/aair.2022.14.1.117

Guttman-Yassky E, Bissonnette R, Ungar B, Suárez-Fariñas M, Ardeleanu M, Esaki H, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol 2019; 143: 155-172.

https://doi.org/10.1016/j.jaci.2018.08.022 DOI: https://doi.org/10.1016/j.jaci.2018.08.022

Villani AP, Pavel AB, Wu J, Fernandes M, Maari C, Saint-Cyr Proulx E, et al. Vascular inflammation in moderate-to-severe atopic dermatitis is associated with enhanced Th2 response. Allergy 2021; 76: 3107-3121.

https://doi.org/10.1111/all.14859 DOI: https://doi.org/10.1111/all.14859

Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009; 50: 1611-1620.

https://doi.org/10.2967/jnumed.109.065151 DOI: https://doi.org/10.2967/jnumed.109.065151

Elnabawi YA, Dey AK, Goyal A, Groenendyk JW, Chung JH, Belur AD, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res 2019; 115: 721-728.

https://doi.org/10.1093/cvr/cvz009 DOI: https://doi.org/10.1093/cvr/cvz009

Kim JD, Lee SH, Seo EH, Woo SY, Kim SH, Chung SM, et al. Role of Th1 and Th17 cells in the development and complexity of coronary artery disease: comparison analysis by the methods of flow cytometry and SYNTAX score. Coron Artery Dis 2015; 26: 604-611.

https://doi.org/10.1097/MCA.0000000000000289 DOI: https://doi.org/10.1097/MCA.0000000000000289

Taleb S. Inflammation in atherosclerosis. Arch Cardiovasc Dis 2016; 109: 708-715.

https://doi.org/10.1016/j.acvd.2016.04.002 DOI: https://doi.org/10.1016/j.acvd.2016.04.002

Radtke MA, Schäfer I, Glaeske G, Jacobi A, Augustin M. Prevalence and comorbidities in adults with psoriasis compared to atopic eczema. J Eur Acad Dermatol Venereol 2017; 31: 151-157.

https://doi.org/10.1111/jdv.13813 DOI: https://doi.org/10.1111/jdv.13813

Madjid M, Awan I, Willerson JT, Casscells SW. Leukocyte count and coronary heart disease: implications for risk assessment. J Am Coll Cardiol 2004; 44: 1945-1956.

https://doi.org/10.1016/j.jacc.2004.07.056 DOI: https://doi.org/10.1016/j.jacc.2004.07.056

Vekaria AS, Brunner PM, Aleisa AI, Bonomo L, Lebwohl MG, Israel A, et al. Moderate-to-severe atopic dermatitis patients show increases in serum C-reactive protein levels, correlating with skin disease activity. F1000Res 2017; 6: 1712.

https://doi.org/10.12688/f1000research.12422.2 DOI: https://doi.org/10.12688/f1000research.12422.2

Published

2023-05-22

How to Cite

Lee, G.-W., Kim, K., Kim, S.-J., Shin, K., Kim, H., Ko, H.-C., Kim, M.-B., & Kim, B. (2023). Therapeutic Effect of Dupilumab on Systemic and Vascular Inflammation in Adults with Severe Atopic Dermatitis: Feasibility Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography. Acta Dermato-Venereologica, 103, adv5320. https://doi.org/10.2340/actadv.v103.5320

Issue

Section

Articles

Categories