Recent insights into atopic dermatitis and implications for management of infectious complications.

Atopic dermatitis (AD) is a common complex disease that frequently follows a chronic relapsing course and affects the quality of life of patients and families in a significant manner. New insights into the pathophysiology of AD point to an important role of structural abnormalities in the epidermis combined with immune dysregulation. Patients with AD have a unique predisposition to colonization or infection by a number of microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. A multipronged approach directed at healing or protecting the skin barrier and addressing the immune dysregulation is necessary to improve the likelihood of successful outcomes.

[1]  B. Moza,et al.  Neutralization of multiple staphylococcal superantigens by a single-chain protein consisting of affinity-matured, variable domain repeats. , 2008, The Journal of infectious diseases.

[2]  D. Leung Our evolving understanding of the functional role of filaggrin in atopic dermatitis. , 2009, The Journal of allergy and clinical immunology.

[3]  D. Leung,et al.  Smallpox vaccination: Risk considerations for patients with atopic dermatitis. , 2002, The Journal of allergy and clinical immunology.

[4]  H. Sampson,et al.  Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens. , 1993, The Journal of clinical investigation.

[5]  J. Carucci,et al.  Low Expression of the IL-23/Th17 Pathway in Atopic Dermatitis Compared to Psoriasis1 , 2008, The Journal of Immunology.

[6]  C. Saha,et al.  Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. , 2010, The Journal of allergy and clinical immunology.

[7]  T. Bieber,et al.  Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double‐blind, controlled study , 2008, The British journal of dermatology.

[8]  S. Foster,et al.  Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage. , 2006, The Journal of infectious diseases.

[9]  T. Beaty,et al.  Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. , 2009, The Journal of allergy and clinical immunology.

[10]  T. Zuberbier,et al.  Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. , 2006, The Journal of allergy and clinical immunology.

[11]  L. Skov,et al.  Application of Staphylococcal enterotoxin B on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism. , 2000, The Journal of allergy and clinical immunology.

[12]  C. Salgado,et al.  Community-acquired methicillin-resistant Staphylococcus aureus. , 2004, JAMA.

[13]  M. Pembrey,et al.  The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study. , 2008, The Journal of allergy and clinical immunology.

[14]  P. Savage,et al.  Ceragenins: a class of antiviral compounds to treat orthopox infections. , 2009, The Journal of investigative dermatology.

[15]  R. Dolin,et al.  Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus , 2004 .

[16]  H. Williams,et al.  Interventions to reduce Staphylococcus aureus in the management of atopic eczema. , 2008, The Cochrane database of systematic reviews.

[17]  J. Ring,et al.  IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. , 2009, The Journal of allergy and clinical immunology.

[18]  Gina Pugliese,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001, Infection Control & Hospital Epidemiology.

[19]  M. Boguniewicz,et al.  10. Atopic dermatitis. , 2006, The Journal of allergy and clinical immunology.

[20]  S. Holland,et al.  The new england journal of medicine Combined Immunodeficiency Associated with DOCK 8 Mutations , 2009 .

[21]  M. Boguniewicz,et al.  Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. , 2001, The Journal of allergy and clinical immunology.

[22]  A. Irvine,et al.  Filaggrin in atopic dermatitis. , 2009, The Journal of allergy and clinical immunology.

[23]  S. Ständer,et al.  Correlation of IL-31 serum levels with severity of atopic dermatitis. , 2008, The Journal of allergy and clinical immunology.

[24]  H. Williams,et al.  Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. , 2009, The Journal of allergy and clinical immunology.

[25]  K. Barnes,et al.  Cytokine modulation of atopic dermatitis filaggrin skin expression. , 2007, The Journal of allergy and clinical immunology.

[26]  H. Cordell,et al.  Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. , 2009, The Journal of allergy and clinical immunology.

[27]  M. D. de Bruin‐Weller,et al.  Cyclosporin A reduces CD4(+)CD25(+) regulatory T-cell numbers in patients with atopic dermatitis. , 2009, The Journal of allergy and clinical immunology.

[28]  C. Deming,et al.  Topographical and Temporal Diversity of the Human Skin Microbiome , 2009, Science.

[29]  A. Rademaker,et al.  Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity , 2009, Pediatrics.

[30]  C. W. Carspecken,et al.  Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3. , 2008, The Journal of allergy and clinical immunology.

[31]  T. Bieber,et al.  Proactive therapy of atopic dermatitis – an emerging concept , 2009, Allergy.

[32]  M. Weichenthal,et al.  Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. , 2009, The Journal of allergy and clinical immunology.

[33]  L. Ou,et al.  T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. , 2004, The Journal of allergy and clinical immunology.

[34]  Donald Y M Leung,et al.  Amendment history : Erratum ( April 2004 ) New insights into atopic dermatitis , 2018 .

[35]  W. Cookson,et al.  The genetics of atopic dermatitis. , 2006, The Journal of allergy and clinical immunology.

[36]  R. Gallo,et al.  Administration of oral vitamin D induces cathelicidin production in atopic individuals. , 2008, The Journal of allergy and clinical immunology.

[37]  C. Naspitz,et al.  The allergic sensitization in infants with atopic eczema from different countries , 2009, Allergy.

[38]  A. Stolfi,et al.  Efficacy of probiotics in the treatment of pediatric atopic dermatitis: a meta-analysis of randomized controlled trials. , 2008, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[39]  G. Plewig,et al.  Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. , 2003, Journal of the American Academy of Dermatology.

[40]  N. Novak,et al.  Pulsed-Field Gel Electrophoresis of Staphylococcus aureus Isolates from Atopic Patients Revealing Presence of Similar Strains in Isolates from Children and Their Parents , 2007, Journal of Clinical Microbiology.

[41]  P. Elias,et al.  Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. , 2008, The Journal of allergy and clinical immunology.

[42]  L. Bielory,et al.  Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. , 2008, The Journal of allergy and clinical immunology.

[43]  G. Stingl,et al.  Atopic dermatitis: therapeutic concepts evolving from new pathophysiologic insights. , 2008, The Journal of allergy and clinical immunology.

[44]  C. Camargo,et al.  Randomized controlled trial of vitamin D supplementation for winter‐related atopic dermatitis in Boston: a pilot study , 2008, The British journal of dermatology.

[45]  A. Wollenberg,et al.  Viral infections in atopic dermatitis: pathogenic aspects and clinical management. , 2003, The Journal of allergy and clinical immunology.

[46]  P. Beattie,et al.  A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases , 2006, The British journal of dermatology.

[47]  M. Flaig,et al.  Cathelicidin deficiency predisposes to eczema herpeticum. , 2006, The Journal of allergy and clinical immunology.

[48]  K. Barnes,et al.  Phenotype of atopic dermatitis subjects with a history of eczema herpeticum. , 2009, The Journal of allergy and clinical immunology.

[49]  R. Kirsner,et al.  Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. , 2008, Journal of the American Academy of Dermatology.

[50]  H Stammer,et al.  Nasal Carriage as a Source of Staphylococcus aureus Bacteremia , 2001 .

[51]  Q. Hamid,et al.  Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. , 2003, The Journal of allergy and clinical immunology.

[52]  B. Neumeister,et al.  Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections , 2004, Nature Medicine.

[53]  J. Redzic,et al.  Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. , 2008, The Journal of investigative dermatology.

[54]  N. Klopp,et al.  Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. , 2006, The Journal of allergy and clinical immunology.

[55]  R. Geha,et al.  Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge , 2007, Proceedings of the National Academy of Sciences.

[56]  P. Savage,et al.  Antibacterial properties of cationic steroid antibiotics. , 2002, FEMS microbiology letters.

[57]  R. Kirsner,et al.  Three Times Weekly Tacrolimus Ointment Reduces Relapse in Stabilized Atopic Dermatitis: A New Paradigm for Use , 2008, Pediatrics.

[58]  J. Ring,et al.  Efficacy and functionality of silver‐coated textiles in patients with atopic eczema , 2006, Journal of the European Academy of Dermatology and Venereology : JEADV.

[59]  S. Holland,et al.  Combined immunodeficiency associated with DOCK8 mutations. , 2009, The New England journal of medicine.

[60]  E. Oren,et al.  Vitamin D and atopic disorders in an obese population screened for vitamin D deficiency. , 2008, The Journal of allergy and clinical immunology.

[61]  James F. Jones,et al.  Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. , 2006, Immunity.

[62]  C. Palmer,et al.  Filaggrin variants confer susceptibility to asthma. , 2008, The Journal of allergy and clinical immunology.

[63]  S. Jolles A review of high‐dose intravenous immunoglobulin treatment for atopic dermatitis , 2002, Clinical and experimental dermatology.

[64]  H. R. Anderson,et al.  Is eczema really on the increase worldwide? , 2008, The Journal of allergy and clinical immunology.

[65]  S. Weber,et al.  Severe eczema vaccinatum in a household contact of a smallpox vaccinee. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[66]  A. Heinzmann,et al.  Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation , 2008, Pediatrics.

[67]  B. Thiers Serum IgE Autoantibodies Target Keratinocytes in Patients with Atopic Dermatitis , 2009 .

[68]  James F. Jones,et al.  Selective Killing of Vaccinia Virus by LL-37: Implications for Eczema Vaccinatum1 , 2004, The Journal of Immunology.

[69]  U. Wahn,et al.  Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. , 1999, The Journal of allergy and clinical immunology.

[70]  Q. Hamid,et al.  Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. , 1994, The Journal of clinical investigation.

[71]  M. Boguniewicz,et al.  Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis. , 2001, The Journal of allergy and clinical immunology.

[72]  P. Savage,et al.  Synthesis and characterization of peptide-cationic steroid antibiotic conjugates. , 2004, Organic letters.

[73]  T. Bieber,et al.  Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment , 2008, Allergy.

[74]  M. Otto Targeted Immunotherapy for Staphylococcal Infections , 2012, BioDrugs.

[75]  Chien-Chang Lee,et al.  Staphylococcus colonization in atopic dermatitis treated with fluticasone or tacrolimus with or without antibiotics. , 2007, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[76]  Donald Y M Leung,et al.  A multidisciplinary approach to evaluation and treatment of atopic dermatitis. , 2008, Seminars in cutaneous medicine and surgery.

[77]  Zhou-Feng Chen,et al.  Cellular Basis of Itch Sensation , 2009, Science.

[78]  I I Lelis,et al.  [Atopic dermatitis]. , 1980, Vestnik dermatologii i venerologii.

[79]  A. Liu,et al.  Severe atopic dermatitis is associated with a high burden of environmental Staphylococcus aureus , 2008, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[80]  J. Istvan,et al.  The prevalence of atopic dermatitis in Oregon schoolchildren. , 2000, Journal of the American Academy of Dermatology.

[81]  R. Geha,et al.  Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen. , 2009, The Journal of allergy and clinical immunology.

[82]  L. Beck,et al.  Atopic dermatitis: a disease caused by innate immune defects? , 2009, The Journal of investigative dermatology.

[83]  Tomas Ganz,et al.  Endogenous antimicrobial peptides and skin infections in atopic dermatitis. , 2002, The New England journal of medicine.

[84]  T. Bieber,et al.  Risk factors of atopic dermatitis patients for eczema herpeticum. , 2007, The Journal of investigative dermatology.

[85]  Asher,et al.  The International Study of Asthma and Allergies in Childhood (ISAAC) , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[86]  A. Mejias,et al.  Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus , 2004, The Pediatric infectious disease journal.

[87]  D. Margolis,et al.  The prevalence of atopic triad in children with physician-confirmed atopic dermatitis. , 2008, Journal of the American Academy of Dermatology.

[88]  M. Boguniewicz,et al.  Severe refractory atopic dermatitis in adults is highly atopic. , 2007, The Journal of allergy and clinical immunology.

[89]  S. Walker,et al.  Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. , 1993, The Journal of clinical investigation.

[90]  M. Steinhoff,et al.  IL-31: a new link between T cells and pruritus in atopic skin inflammation. , 2006, The Journal of allergy and clinical immunology.

[91]  L. Ou,et al.  Staphylococcal enterotoxin B inhibits regulatory T cells by inducing glucocorticoid-induced TNF receptor-related protein ligand on monocytes. , 2006, The Journal of allergy and clinical immunology.

[92]  M. Boguniewicz,et al.  Loricrin and Involucrin Expression is Down-Regulated by Th2 Cytokines through STAT-6 , 2008 .

[93]  M. Kopp,et al.  Probiotics cannot be generally recommended for primary prevention of atopic dermatitis. , 2009, The Journal of allergy and clinical immunology.

[94]  P. Schlievert,et al.  Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis. , 2010, The Journal of allergy and clinical immunology.

[95]  A. Paller,et al.  A multiple-domain framework of clinical, economic, and patient-reported outcomes for evaluating benefits of intervention in atopic dermatitis. , 2007, Journal of drugs in dermatology : JDD.

[96]  R. Beavis,et al.  Bacterial interference caused by autoinducing peptide variants. , 1997, Science.

[97]  O. Schneewind,et al.  Vaccine assembly from surface proteins of Staphylococcus aureus , 2006, Proceedings of the National Academy of Sciences.

[98]  D. Leung,et al.  Antiviral activity of human beta-defensin 3 against vaccinia virus. , 2007, The Journal of allergy and clinical immunology.

[99]  R. Damstra,et al.  Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study , 2003, BMJ : British Medical Journal.

[100]  Junguk Park,et al.  Infection control by antibody disruption of bacterial quorum sensing signaling. , 2007, Chemistry & biology.

[101]  K. Barnes An update on the genetics of atopic dermatitis: scratching the surface in 2009. , 2010, The Journal of allergy and clinical immunology.

[102]  B. Harder,et al.  IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. , 2006, The Journal of allergy and clinical immunology.

[103]  G. K. Khurana Hershey,et al.  Intrinsically defective skin barrier function in children with atopic dermatitis correlates with disease severity. , 2008, The Journal of allergy and clinical immunology.

[104]  Scott R. Presnell,et al.  Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice , 2004, Nature Immunology.

[105]  J. Ring,et al.  Silver-Coated Textiles Reduce Staphylococcus aureus Colonization in Patients with Atopic Eczema , 2003, Dermatology.

[106]  A. Kennedy,et al.  Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA , 2007, Nature Medicine.

[107]  Jonathan Hadgraft,et al.  Epidermal barrier dysfunction in atopic dermatitis. , 2009, The Journal of investigative dermatology.

[108]  A. Shah,et al.  International Study of Asthma and Allergies in Childhood (ISAAC) , 2000, The Journal of the Association of Physicians of India.

[109]  D. Leung,et al.  Antiviral activity of human β-defensin 3 against vaccinia virus , 2007 .

[110]  B. Moza,et al.  Neutralization of staphylococcal enterotoxin B by soluble, high-affinity receptor antagonists , 2007, Nature Medicine.

[111]  P. Schlievert,et al.  Superantigen profile of Staphylococcus aureus isolates from patients with steroid-resistant atopic dermatitis. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[112]  U. Wahn,et al.  Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. , 2000, The Journal of allergy and clinical immunology.

[113]  R. Geha,et al.  Exaggerated IL-17 response to epicutaneous sensitization mediates airway inflammation in the absence of IL-4 and IL-13. , 2009, The Journal of allergy and clinical immunology.

[114]  S. Hong,et al.  Epidemiological Characteristics of Methicillin-Resistant Staphylococcus aureus Isolates from Children with Eczematous Atopic Dermatitis Lesions , 2008, Journal of Clinical Microbiology.

[115]  R. Novick Autoinduction and signal transduction in the regulation of staphylococcal virulence , 2003, Molecular microbiology.

[116]  H. Stark,et al.  The histamine H4 receptor is functionally expressed on T(H)2 cells. , 2009, The Journal of allergy and clinical immunology.

[117]  C. Akdis,et al.  Absence of T-regulatory cell expression and function in atopic dermatitis skin. , 2006, The Journal of allergy and clinical immunology.

[118]  K. Kaulback,et al.  The Socioeconomic Impact of Atopic Dermatitis in the United States: A Systematic Review , 2008, Pediatric dermatology.

[119]  K. Bork,et al.  Increasing incidence of eczema herpeticum: analysis of seventy-five cases. , 1988, Journal of the American Academy of Dermatology.

[120]  R. Gallo,et al.  Antimicrobial peptides and the skin immune defense system. , 2008, The Journal of allergy and clinical immunology.

[121]  Colin N A Palmer,et al.  Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis , 2006, Nature Genetics.