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| '''For patient information, click [[Atopic dermatitis (patient information)|here]]''' | | '''For patient information, click [[Atopic dermatitis (patient information)|here]]''' |
| {{SI}} | | {{SI}} |
| {{CMG}};{{AE}} {{KS}} | | {{CMG}};{{AE}} {{KS}}{{S.S}} |
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| {{SK}} Atopic eczema, Erythrodermic eczema | | {{SK}} Atopic eczema, Erythrodermic eczema |
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| ==[[Atopic dermatitis overview|Overview]]== | | ==[[Atopic dermatitis overview|Overview]]== |
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| ==[[Atopic dermatitis historical perspective|Historical Perspective]]== | | ==[[Atopic dermatitis historical perspective|Historical Perspective]]== |
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| __NOTOC__
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| {{CMG}}; {{AE}} {{S.S}}
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| ==Overview==
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| Atopic dermatitis is a chronic inflammatory skin disorder with an immunologic background and occurs in patients with a personal or family history of atopy (i.e., asthma or allergic rhinitis).<ref name="MihmSoter1976">{{cite journal|last1=Mihm|first1=Martin C|last2=Soter|first2=Nicholas A|last3=Dvorak|first3=Harold F|last4=Austen|first4=K Frank|title=The Structure Of Normal Skin And The Morphology Of Atopic Eczema|journal=Journal of Investigative Dermatology|volume=67|issue=3|year=1976|pages=305–312|issn=0022202X|doi=10.1111/1523-1747.ep12514346}}</ref> It is caused by either skin barrier dysfunction or immune dysregulation of the adaptive and innate immune response leading to an enhanced IgE-mediated, systemic Th2 response. The skin barrier is invaded by exogenous substances, including allergens, irritants and microbes; and brick wall-like’ structure of the stratum corneum is further compromised. Systemically, a dysfunctional innate and adaptive immune response causes further damage to the epidermis<ref name="pmid20109730">{{cite journal |vauthors=Barnes KC |title=An update on the genetics of atopic dermatitis: scratching the surface in 2009 |journal=J. Allergy Clin. Immunol. |volume=125 |issue=1 |pages=16–29.e1–11; quiz 30–1 |date=January 2010 |pmid=20109730 |pmc=2874322 |doi=10.1016/j.jaci.2009.11.008 |url=}}</ref>.
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| ==[[Atopic dermatitis pathophysiology|Pathophysiology]]== | | ==[[Atopic dermatitis pathophysiology|Pathophysiology]]== |
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| == Genetics ==
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| Recent studies have established a strong genetic association with atopic dermatitis. Twin studies have indicated high heritability of atopic dermatitis with a concordance rate of 72–86 % for monozygotic twins compared with 21–23 % percent for dizygotic twins.<ref name="pmid27004062">{{cite journal |vauthors=Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z |title=Molecular Genetic of Atopic dermatitis: An Update |journal=Int J Health Sci (Qassim) |volume=10 |issue=1 |pages=96–120 |date=January 2016 |pmid=27004062 |pmc=4791162 |doi= |url=}}</ref>
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| Genes involved in the pathogenesis of atopic dermatitis include:<ref name="pmid270040623">{{cite journal |vauthors=Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z |title=Molecular Genetic of Atopic dermatitis: An Update |journal=Int J Health Sci (Qassim) |volume=10 |issue=1 |pages=96–120 |date=January 2016 |pmid=27004062 |pmc=4791162 |doi= |url=}}</ref>
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| # '''Filaggrin Gene mutation''':
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| #* Located on chromosome 1q21 (epidermal differentiation complex) loss-of-function mutations in the filaggrin gene FLG, is strongly associated with a broad range of skin and allergic diseases including atopic dermatitis<ref name="pmid21991953">{{cite journal |vauthors=Irvine AD, McLean WH, Leung DY |title=Filaggrin mutations associated with skin and allergic diseases |journal=N. Engl. J. Med. |volume=365 |issue=14 |pages=1315–27 |date=October 2011 |pmid=21991953 |doi=10.1056/NEJMra1011040 |url=}}</ref>. Mutation in this gene is also responsible for ichthyosis vulgaris and pachyonychia congenita.<ref name="pmid17657246">{{cite journal |vauthors=Liao H, Waters AJ, Goudie DR, Aitken DA, Graham G, Smith FJ, Lewis-Jones S, McLean WH |title=Filaggrin mutations are genetic modifying factors exacerbating X-linked ichthyosis |journal=J. Invest. Dermatol. |volume=127 |issue=12 |pages=2795–8 |date=December 2007 |pmid=17657246 |doi=10.1038/sj.jid.5700971 |url=}}</ref> The common genetic variant R510X and 2282del4 are very strongly associated with atopic dermatitis.<ref name="pmid16550169">{{cite journal |vauthors=Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, O'Regan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH |title=Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis |journal=Nat. Genet. |volume=38 |issue=4 |pages=441–6 |date=April 2006 |pmid=16550169 |doi=10.1038/ng1767 |url=}}</ref>
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| #* FLG Gene mutation is associated with developing atopic dermatitis at an early age(≤8 years) but is not associated with late childhood or adulthood atopic dermatitis.<ref name="pmid25314673">{{cite journal |vauthors=Rupnik H, Rijavec M, Korošec P |title=Filaggrin loss-of-function mutations are not associated with atopic dermatitis that develops in late childhood or adulthood |journal=Br. J. Dermatol. |volume=172 |issue=2 |pages=455–61 |date=February 2015 |pmid=25314673 |doi=10.1111/bjd.13477 |url=}}</ref>
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| # '''SPINK5 and LEKTI gene''':
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| #* Located on chromosome 5q32, Serine Protease Inhibitor Kazal-Type 5 (SPINK5) gene encodes a protease inhibitor Lymphoepithelial Kazal-Type-Related Inhibitor (LEKTI), which is involved in converting profilaggrin into filaggrin and is responsible for marinating the permeability of the normal skin.<ref name="pmid270040622">{{cite journal |vauthors=Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z |title=Molecular Genetic of Atopic dermatitis: An Update |journal=Int J Health Sci (Qassim) |volume=10 |issue=1 |pages=96–120 |date=January 2016 |pmid=27004062 |pmc=4791162 |doi= |url=}}</ref>
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| #* LEKTI deficiency leads to enhanced cleavage of intercellular attachments, decreased corneocyte cohesion and impaired skin barrier function.<ref name="pmid168151332">{{cite journal |vauthors=Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ, Tazi-Ahnini R |title=New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions |journal=J. Allergy Clin. Immunol. |volume=118 |issue=1 |pages=3–21; quiz 22–3 |date=July 2006 |pmid=16815133 |doi=10.1016/j.jaci.2006.04.042 |url=}}</ref>
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| # '''MHC (or HLA) genes'''
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| # '''Innate Immune system genes''':
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| #* CARD4 (or NOD1) gene: Caspase recruitment domain–containing protein (CARD) 4
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| #* CARD15 (or NOD2) gene
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| #* Monocyte differentiation antigen (or CD14) gene
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| #* MBL2 gene: mannose-binding lectin '''('''MBL2) gene
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| #* Toll-like receptor( TLR2, TLR4, TLR6 and TLR 9) genes
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| #* DEFB1 gene: human β-defensin 1
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| # '''Adaptive immune system genes'''
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| #* '''Cytokines and related genes''':
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| #** IL-4 gene
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| #** IL-4Rα gene
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| #** STAT6 gene (Signal transducer and activator of transcription )
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| #** IL-10 gene
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| #** IL-6 gene
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| #** TNF-α gene
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| #** TNF-β gene
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| #** IL-1α gene
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| #** IL-β gene
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| #** IFNγ gene
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| #** IL1RL1
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| #** IL-5 gene
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| #** IL-12 β gene
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| #** IL-12R β
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| #** IL-13 gene
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| #** IL-18 gene
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| #** TGF-β1 gene
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| #** GM-CSF gene
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| #** IL-9 gene
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| #** IL-9R gene
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| #* '''Chemokines and related genes''':
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| #** CCL5 gene: Chemokine (C-Cmotif) ligand 5
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| #** CCL11 gene
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| #** CCL17 gene
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| #** CCR3 gene
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| #** CCR4 gene
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| #** CMA1 gene: Mast cell chymase 1
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| #* '''Drug-metabolizing genes'''
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| #** GST genes: glutathione S-transferase
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| #** NAT-2 gene: N-acetyl transferase
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| #* '''Other genes'''
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| #** CTLA-4
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| #** KLK
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| #** RUNX1 gene
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| #** IRF2 gene
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| #** FCER1B gene
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| #** PHF11 gene
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| *
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| ==Associated Conditions==
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| Conditions associated with atopic dermatitis include:
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| *'''Atopic triad'''<ref name="pmid17692428">{{cite journal |vauthors=Kapoor R, Menon C, Hoffstad O, Bilker W, Leclerc P, Margolis DJ |title=The prevalence of atopic triad in children with physician-confirmed atopic dermatitis |journal=J. Am. Acad. Dermatol. |volume=58 |issue=1 |pages=68–73 |date=January 2008 |pmid=17692428 |doi=10.1016/j.jaad.2007.06.041 |url=}}</ref>
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| **Atopic dermatitis
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| **Allergic rhinitis
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| **Asthma
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| *'''Food-induced urticaria/anaphylaxis''' <ref name="pmid10893011">{{cite journal |vauthors=Eigenmann PA, Calza AM |title=Diagnosis of IgE-mediated food allergy among Swiss children with atopic dermatitis |journal=Pediatr Allergy Immunol |volume=11 |issue=2 |pages=95–100 |date=May 2000 |pmid=10893011 |doi= |url=}}</ref>
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| *'''Ichthyosis vulgaris'''<ref name="pmid18455261">{{cite journal |vauthors=Bremmer SF, Hanifin JM, Simpson EL |title=Clinical detection of ichthyosis vulgaris in an atopic dermatitis clinic: implications for allergic respiratory disease and prognosis |journal=J. Am. Acad. Dermatol. |volume=59 |issue=1 |pages=72–8 |date=July 2008 |pmid=18455261 |doi=10.1016/j.jaad.2008.03.029 |url=}}</ref>
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| *'''Ocular comorbidities:'''
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| **Atopic keratoconjunctivitis<ref name="pmid24342754">{{cite journal |vauthors=Chen JJ, Applebaum DS, Sun GS, Pflugfelder SC |title=Atopic keratoconjunctivitis: A review |journal=J. Am. Acad. Dermatol. |volume=70 |issue=3 |pages=569–75 |date=March 2014 |pmid=24342754 |doi=10.1016/j.jaad.2013.10.036 |url=}}</ref>
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| **Vernal keratoconjunctivitis<ref name="pmid25744396">{{cite journal |vauthors=Pattnaik L, Acharya L |title=A comprehensive review on vernal keratoconjunctivitis with emphasis on proteomics |journal=Life Sci. |volume=128 |issue= |pages=47–54 |date=May 2015 |pmid=25744396 |doi=10.1016/j.lfs.2015.01.040 |url=}}</ref>
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| * '''Wiskott-Aldrich syndrome:'''<ref name="pmid11800140">{{cite journal |vauthors=Bradley M, Söderhäll C, Wahlgren CF, Luthman H, Nordenskjöld M, Kockum I |title=The Wiskott-Aldrich syndrome gene as a candidate gene for atopic dermatitis |journal=Acta Derm. Venereol. |volume=81 |issue=5 |pages=340–2 |date=2001 |pmid=11800140 |doi= |url=}}</ref>
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| ** Thrombocytopenia
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| ** Eczema (atopic dermatitis)
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| ** Recurrent infections
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| *'''Hyper-IgE syndrome''':<ref name="pmid16913276">{{cite journal |vauthors=Ohameje NU, Loveless JW, Saini SS |title=Atopic dermatitis or hyper-IgE syndrome? |journal=Allergy Asthma Proc |volume=27 |issue=3 |pages=289–91 |date=2006 |pmid=16913276 |doi= |url=}}</ref>
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| **Eczema (atopic dermatitis)
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| **High serum IgE
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| **Recurrent cold abscesses
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| * '''Anemia'''<ref name="pmid26619045">{{cite journal |vauthors=Drury KE, Schaeffer M, Silverberg JI |title=Association Between Atopic Disease and Anemia in US Children |journal=JAMA Pediatr |volume=170 |issue=1 |pages=29–34 |date=January 2016 |pmid=26619045 |doi=10.1001/jamapediatrics.2015.3065 |url=}}</ref>
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| * '''Psychiatric disorders''':<ref name="pmid30119868">{{cite journal |vauthors=Rønnstad ATM, Halling-Overgaard AS, Hamann CR, Skov L, Egeberg A, Thyssen JP |title=Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis |journal=J. Am. Acad. Dermatol. |volume=79 |issue=3 |pages=448–456.e30 |date=September 2018 |pmid=30119868 |doi=10.1016/j.jaad.2018.03.017 |url=}}</ref>
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| ** Depression<ref name="pmid29929155">{{cite journal |vauthors=Bao Q, Chen L, Lu Z, Ma Y, Guo L, Zhang S, Huang X, Xu S, Ruan L |title=Association between eczema and risk of depression: A systematic review and meta-analysis of 188,495 participants |journal=J Affect Disord |volume=238 |issue= |pages=458–464 |date=October 2018 |pmid=29929155 |doi=10.1016/j.jad.2018.05.007 |url=}}</ref>
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| ** Anxiety<ref name="pmid25795537">{{cite journal |vauthors=Cheng CM, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, Yang AC, Chang WH, Chen TJ, Tsai SJ, Chen MH |title=Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study |journal=J Affect Disord |volume=178 |issue= |pages=60–5 |date=June 2015 |pmid=25795537 |doi=10.1016/j.jad.2015.02.025 |url=}}</ref>
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| ** Suicidal ideations
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| ** Attention deficit hyperactivity disorder<ref name="pmid27105659">{{cite journal |vauthors=Strom MA, Fishbein AB, Paller AS, Silverberg JI |title=Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults |journal=Br. J. Dermatol. |volume=175 |issue=5 |pages=920–929 |date=November 2016 |pmid=27105659 |pmc=5216180 |doi=10.1111/bjd.14697 |url=}}</ref>
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| * '''Angina pectoris'''<ref name="pmid29210061">{{cite journal |vauthors=Thyssen JP, Halling-Overgaard AS, Andersen YMF, Gislason G, Skov L, Egeberg A |title=The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis |journal=Br. J. Dermatol. |volume=178 |issue=6 |pages=1272–1279 |date=June 2018 |pmid=29210061 |doi=10.1111/bjd.16215 |url=}}</ref>
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| ==Gross Pathology==
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| On gross pathology, erythema, edema, and vesiculation with oozing are characteristic findings of atopic dermatitis while chronic atopic dermatitis is characterized by lichenified plaques with prominent skin markings.<ref name="MihmSoter19762">{{cite journal|last1=Mihm|first1=Martin C|last2=Soter|first2=Nicholas A|last3=Dvorak|first3=Harold F|last4=Austen|first4=K Frank|title=The Structure Of Normal Skin And The Morphology Of Atopic Eczema|journal=Journal of Investigative Dermatology|volume=67|issue=3|year=1976|pages=305–312|issn=0022202X|doi=10.1111/1523-1747.ep12514346}}</ref>
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| ==Microscopic Pathology==
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| On microscopic histopathological analysis, characteristic findings of atopic dermatitis include:<ref name="MihmSoter19763">{{cite journal|last1=Mihm|first1=Martin C|last2=Soter|first2=Nicholas A|last3=Dvorak|first3=Harold F|last4=Austen|first4=K Frank|title=The Structure Of Normal Skin And The Morphology Of Atopic Eczema|journal=Journal of Investigative Dermatology|volume=67|issue=3|year=1976|pages=305–312|issn=0022202X|doi=10.1111/1523-1747.ep12514346}}</ref>
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| * '''Acute vesicular lesions''':
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| ** Epidermal psoriasiform hyperplasia
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| ** Marked intercellular edema with spongiotic vesiculation
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| ** Marked perivenular infiltrate
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| ** Epidermal infiltrate, consisting predominately of a lymphohistiocytic infiltrate in the dermis
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| * '''Chronic lichenified plaque''':
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| ** Hyperkeratosis
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| ** psoriasiform hyperplasia
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| ** dyskeratosis
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| ** Marked thickening of the papillary dermis
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| ** Minimal intercellular edema
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| ==References==
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| {{Reflist|2}}
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| {{WH}}
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| {{WS}}
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| [[Category: (name of the system)]]
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| ==[[Atopic dermatitis causes|Causes]]== | | ==[[Atopic dermatitis causes|Causes]]== |
