Risk of Herpesvirus, Serious and Opportunistic Infections in Atopic Dermatitis

All values are n (%) unless stated otherwise. AD, atopic dermatitis; PY, person-years; IQR, interquartile range; COPD, chronic obstructive pulmonary disease. ^aHerpesvirus infection includes cytomegalovirus, Epstein–Barr virus, herpes simplex virus and varicella zoster virus infections. ^bOpportunistic infection includes actinomycosis/nocardiosis, aspergillosis, BK virus, cryptococcosis, cytomegalovirus, mucormycosis, other mycoses (blastomycosis, coccidioidomycosis, histoplasmosis and paracoccidioidomycosis), pneumocystis, progressive multifocal leukoencephalopathy, tuberculosis and toxoplasmosis. ^cSerious infection includes infections of respiratory tract, urinary tract, gastrointestinal tract/abdominal cavity, bone or joints, central nervous system or meninges, heart, skin or soft tissue, prostate, breast, and eyes and sepsis requiring hospitalization.

CMV, cytomegalovirus; EBV, Epstein–Barr virus; HSV, herpes simplex virus; EH, eczema herpeticum; VZV, varicella zoster virus. Tests for trend with P < 0·001 for all outcomes except EBV in the paediatric cohort (P = 0·42) and opportunistic infection in the paediatric cohort (P = 0·16). ^aAdjusted for age, sex, Townsend score, allergic rhinitis, asthma, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease, depression, diabetes, inflammatory bowel disease, liver disease, and vaccinations for influenza, meningococcus and pneumococcus. ^bAdjusted for same covariates as paediatric cohort as well as body mass index, smoking and alcohol status. ^cOpportunistic infection includes actinomycosis/nocardiosis, aspergillosis, BK virus, cryptococcosis, cytomegalovirus, mucormycosis, other mycoses (blastomycosis, coccidioidomycosis, histoplasmosis and paracoccidioidomycosis), pneumocystis, progressive multifocal leukoencephalopathy, tuberculosis and toxoplasmosis. ^dSerious infection includes infections of respiratory tract, urinary tract, gastrointestinal tract/abdominal cavity, bone or joints, central nervous system or meninges, heart, skin or soft tissue, prostate, breast, and eyes and sepsis requiring hospitalization. Statistically significant hazard rate ratios with P < 0·05 are in bold.

All values are n (%) unless otherwise stated. AD, atopic dermatitis; IQR, interquartile range; PY, person-years; COPD, chronic obstructive pulmonary disease. ^aHerpesvirus infection includes cytomegalovirus, Epstein–Barr virus, herpes simplex virus, and varicella zoster virus infections. ^bOpportunistic infection includes actinomycosis/nocardiosis, aspergillosis, BK virus, cryptococcosis, cytomegalovirus, mucormycosis, other mycoses (blastomycosis, coccidioidomycosis, histoplasmosis and paracoccidioidomycosis), pneumocystis, progressive multifocal leukoencephalopathy, tuberculosis and toxoplasmosis. ^cSerious infection includes infections of respiratory tract, urinary tract, gastrointestinal tract/abdominal cavity, bone or joints, central nervous system or meninges, heart, skin or soft tissue, prostate, breast, and eyes and sepsis requiring hospitalization.

Authors and Disclosures

J. Wan^1,2, D.B. Shin¹, M.N. Syed¹, K. Abuabara³, A.R. Lemeshow⁴ and J.M. Gelfand<sup>1,5

1</sup>Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
²Section of Pediatric Dermatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
³Department of Dermatology, University of California San Francisco (UCSF), San Francisco, CA, USA
⁴Pfizer, Inc., New York, NY, USA
⁵Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Correspondence
Joy Wan. Email: joywan@pennmedicine.upenn.edu

Conflicts of interest
J.W. has received research and fellowship funding from Pfizer, Inc. (paid to the University of Pennsylvania). M.N.S. has received fellowship funding from Pfizer, Inc. (paid to the University of Pennsylvania). K.A. has received research funding from Pfizer, Inc. and L'Oréal (paid to UCSF), and receives consulting fees for serving on the academic steering committee for TARGET RWE. A.R.L. is an employee of Pfizer, Inc. J.M.G. has served as a consultant for and received honoraria from Abcentra, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, GSK, Eli Lilly and Company (data monitoring committee), Janssen Biotech, Novartis, UCB (data and safety monitoring board), Neuro-Derm (data and safety monitoring board), Trevi Therapeutics Inc., and MiNDERA Dx (Mindera Health); he receives research grants (to the trustees of the University of Pennsylvania) from Boehringer Ingelheim and Pfizer Inc.; he has received payment for continuing medical education work related to psoriasis that was supported indirectly by pharmaceutical sponsors; he is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma; he serves as a deputy editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology; he is Chief Medical Editor for Healio Psoriatic Disease (receiving honoraria); and he is a member of the board of directors for the International Psoriasis Council, receiving no honoraria. D.B.S. declares he has no conflicts of interest.

Sidebar 1

What is Already Known About This Topic?

• Atopic dermatitis (AD) is associated with infectious complications, most commonly staphylococcal and herpes simplex virus infections.

• However, the risk of serious infections, opportunistic infections and other herpesvirus infections in patients with AD has not been fully characterized.

Sidebar 2

What Does This Study Add?

• AD is associated with an increased risk of hospitalized infections, opportunistic infections and several herpesvirus infections in both children and adults, with risk being greatest among those with severe skin disease.

• The elevated risks of these infections appear independent of immunosuppressive medication use for AD.