Herpesviruses and the microbiome David H. Dreyfus, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 132, Issue 6, Pages 1278-1286 (December 2013) DOI: 10.1016/j.jaci.2013.02.039 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A teenage boy with a history of seasonal allergic rhinitis was referred for evaluation of suspected antibiotic allergy and possible Rocky Mountain spotted fever. The previous week, amoxicillin had been administered for pharyngitis and a flu-like illness. On examination, he was afebrile and well appearing, with a diffuse maculopapular rash on his torso (right panel) and the palms of his hands (left panel). Subsequent laboratory testing showed no evidence of Rocky Mountain spotted fever or related rickettsial pathogens but conclusive evidence of recent EBV infection, increased viral capsid antigen IgG and IgM and early antigen levels, and negative EBNA results. Photographs were provided by the author with the patient's consent. Journal of Allergy and Clinical Immunology 2013 132, 1278-1286DOI: (10.1016/j.jaci.2013.02.039) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A teenage boy with a history of allergy, eczema, and asthma was referred for evaluation of urticaria or drug allergy because his hands and feet were “turning blue and itching.” He was taking amoxicillin for sinusitis and had a low-grade fever and flu-like symptoms over the past several weeks, but seasonal allergy and asthma were stable. Examination showed swollen extremities with purpura (left panel). One week later, desquamation of the palms and soles was evident (right panel). An ultrasound for Kawasaki cardiovascular disease was normal. Subsequent serology showed evidence of recent EBV infection, increased viral capsid antigen IgG and IgM and early antigen levels, and negative EBNA results. After a short course of oral corticosteroids, he resumed his normal state of health. Photographs were provided by the author with the patient's consent. Journal of Allergy and Clinical Immunology 2013 132, 1278-1286DOI: (10.1016/j.jaci.2013.02.039) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A woman with previous allergy and eczema was referred for possible contact allergy to her necklace. She had no previous history of contact allergy and had worn the necklace previously without problems. Examination showed erythematous vesicular lesions confined to a single hemi-dermatome region consistent with shingles rather than contact allergy. The rash resolved with topical acyclovir antiviral therapy, and subsequent testing showed no evidence of contact allergy to metal or other contact allergens. Photographs were provided by the author with the patient's consent. Journal of Allergy and Clinical Immunology 2013 132, 1278-1286DOI: (10.1016/j.jaci.2013.02.039) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Cutaneous HSV1 or HSV2 infection presenting with skin lesions, including oral (left panel) and periocular (right panel) lesions termed “eczema herpeticum” can be mistaken for exacerbations of atopic dermatitis or contact allergy. Ocular disease can require prompt therapy with antiviral drugs to prevent subsequent corneal scarring, vision loss, and blindness. Photographs are from www.CDC.gov. Journal of Allergy and Clinical Immunology 2013 132, 1278-1286DOI: (10.1016/j.jaci.2013.02.039) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Atopy (center) represents complex interactions between herpes and other viral infections and vaccines (top left); hygiene, such as exposure to endotoxin and other probiotic agents (top right); colonization with other infectious agents, such as bacteria, parasites, and fungi (bottom right); and the host genome (bottom left). Because each of these factors interact with each other, it might be difficult or impossible in a particular patient to predict the effects of one factor on other factors and atopy; however, trends might be evident in large populations. Journal of Allergy and Clinical Immunology 2013 132, 1278-1286DOI: (10.1016/j.jaci.2013.02.039) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions