Atopic dermatitis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
Synonyms and keywords: Atopic eczema, Erythrodermic eczema
Overview
Historical Perspective
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Shalinder Singh, M.B.B.S.[4]
Overview
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).[1] 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[2].
Pathophysiology
Genetics
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.[3]
Genes involved in the pathogenesis of atopic dermatitis include:[4]
- Filaggrin Gene mutation:
- 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[5]. Mutation in this gene is also responsible for ichthyosis vulgaris and pachyonychia congenita.[6] The common genetic variant R510X and 2282del4 are very strongly associated with atopic dermatitis.[7]
- 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.[8]
- SPINK5 and LEKTI gene:
- 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.[9]
- LEKTI deficiency leads to enhanced cleavage of intercellular attachments, decreased corneocyte cohesion and impaired skin barrier function.[10]
- MHC (or HLA) genes
- Innate Immune system genes:
- CARD4 (or NOD1) gene: Caspase recruitment domain–containing protein (CARD) 4
- CARD15 (or NOD2) gene
- Monocyte differentiation antigen (or CD14) gene
- MBL2 gene: mannose-binding lectin (MBL2) gene
- Toll-like receptor( TLR2, TLR4, TLR6 and TLR 9) genes
- DEFB1 gene: human β-defensin 1
- Adaptive immune system genes
- Cytokines and related genes:
- IL-4 gene
- IL-4Rα gene
- STAT6 gene (Signal transducer and activator of transcription )
- IL-10 gene
- IL-6 gene
- TNF-α gene
- TNF-β gene
- IL-1α gene
- IL-β gene
- IFNγ gene
- IL1RL1
- IL-5 gene
- IL-12 β gene
- IL-12R β
- IL-13 gene
- IL-18 gene
- TGF-β1 gene
- GM-CSF gene
- IL-9 gene
- IL-9R gene
- Chemokines and related genes:
- CCL5 gene: Chemokine (C-Cmotif) ligand 5
- CCL11 gene
- CCL17 gene
- CCR3 gene
- CCR4 gene
- CMA1 gene: Mast cell chymase 1
- Drug-metabolizing genes
- GST genes: glutathione S-transferase
- NAT-2 gene: N-acetyl transferase
- Other genes
- CTLA-4
- KLK
- RUNX1 gene
- IRF2 gene
- FCER1B gene
- PHF11 gene
- Cytokines and related genes:
Associated Conditions
Conditions associated with atopic dermatitis include:
- Atopic triad[11]
- Atopic dermatitis
- Allergic rhinitis
- Asthma
- Food-induced urticaria/anaphylaxis [12]
- Ichthyosis vulgaris[13]
- Ocular comorbidities:
- Wiskott-Aldrich syndrome:[16]
- Thrombocytopenia
- Eczema (atopic dermatitis)
- Recurrent infections
- Hyper-IgE syndrome:[17]
- Eczema (atopic dermatitis)
- High serum IgE
- Recurrent cold abscesses
- Anemia[18]
- Psychiatric disorders:[19]
- Angina pectoris[23]
Gross Pathology
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.[24]
Microscopic Pathology
On microscopic histopathological analysis, characteristic findings of atopic dermatitis include:[25]
- Acute vesicular lesions:
- Epidermal psoriasiform hyperplasia
- Marked intercellular edema with spongiotic vesiculation
- Marked perivenular infiltrate
- Epidermal infiltrate, consisting predominately of a lymphohistiocytic infiltrate in the dermis
- Chronic lichenified plaque:
- Hyperkeratosis
- psoriasiform hyperplasia
- dyskeratosis
- Marked thickening of the papillary dermis
- Minimal intercellular edema
References
- ↑ Mihm, Martin C; Soter, Nicholas A; Dvorak, Harold F; Austen, K Frank (1976). "The Structure Of Normal Skin And The Morphology Of Atopic Eczema". Journal of Investigative Dermatology. 67 (3): 305–312. doi:10.1111/1523-1747.ep12514346. ISSN 0022-202X.
- ↑ Barnes KC (January 2010). "An update on the genetics of atopic dermatitis: scratching the surface in 2009". J. Allergy Clin. Immunol. 125 (1): 16–29.e1–11, quiz 30–1. doi:10.1016/j.jaci.2009.11.008. PMC 2874322. PMID 20109730.
- ↑ Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z (January 2016). "Molecular Genetic of Atopic dermatitis: An Update". Int J Health Sci (Qassim). 10 (1): 96–120. PMC 4791162. PMID 27004062.
- ↑ Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z (January 2016). "Molecular Genetic of Atopic dermatitis: An Update". Int J Health Sci (Qassim). 10 (1): 96–120. PMC 4791162. PMID 27004062.
- ↑ Irvine AD, McLean WH, Leung DY (October 2011). "Filaggrin mutations associated with skin and allergic diseases". N. Engl. J. Med. 365 (14): 1315–27. doi:10.1056/NEJMra1011040. PMID 21991953.
- ↑ Liao H, Waters AJ, Goudie DR, Aitken DA, Graham G, Smith FJ, Lewis-Jones S, McLean WH (December 2007). "Filaggrin mutations are genetic modifying factors exacerbating X-linked ichthyosis". J. Invest. Dermatol. 127 (12): 2795–8. doi:10.1038/sj.jid.5700971. PMID 17657246.
- ↑ 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 (April 2006). "Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis". Nat. Genet. 38 (4): 441–6. doi:10.1038/ng1767. PMID 16550169.
- ↑ Rupnik H, Rijavec M, Korošec P (February 2015). "Filaggrin loss-of-function mutations are not associated with atopic dermatitis that develops in late childhood or adulthood". Br. J. Dermatol. 172 (2): 455–61. doi:10.1111/bjd.13477. PMID 25314673.
- ↑ Al-Shobaili HA, Ahmed AA, Alnomair N, Alobead ZA, Rasheed Z (January 2016). "Molecular Genetic of Atopic dermatitis: An Update". Int J Health Sci (Qassim). 10 (1): 96–120. PMC 4791162. PMID 27004062.
- ↑ Cork MJ, Robinson DA, Vasilopoulos Y, Ferguson A, Moustafa M, MacGowan A, Duff GW, Ward SJ, Tazi-Ahnini R (July 2006). "New perspectives on epidermal barrier dysfunction in atopic dermatitis: gene-environment interactions". J. Allergy Clin. Immunol. 118 (1): 3–21, quiz 22–3. doi:10.1016/j.jaci.2006.04.042. PMID 16815133.
- ↑ Kapoor R, Menon C, Hoffstad O, Bilker W, Leclerc P, Margolis DJ (January 2008). "The prevalence of atopic triad in children with physician-confirmed atopic dermatitis". J. Am. Acad. Dermatol. 58 (1): 68–73. doi:10.1016/j.jaad.2007.06.041. PMID 17692428.
- ↑ Eigenmann PA, Calza AM (May 2000). "Diagnosis of IgE-mediated food allergy among Swiss children with atopic dermatitis". Pediatr Allergy Immunol. 11 (2): 95–100. PMID 10893011.
- ↑ Bremmer SF, Hanifin JM, Simpson EL (July 2008). "Clinical detection of ichthyosis vulgaris in an atopic dermatitis clinic: implications for allergic respiratory disease and prognosis". J. Am. Acad. Dermatol. 59 (1): 72–8. doi:10.1016/j.jaad.2008.03.029. PMID 18455261.
- ↑ Chen JJ, Applebaum DS, Sun GS, Pflugfelder SC (March 2014). "Atopic keratoconjunctivitis: A review". J. Am. Acad. Dermatol. 70 (3): 569–75. doi:10.1016/j.jaad.2013.10.036. PMID 24342754.
- ↑ Pattnaik L, Acharya L (May 2015). "A comprehensive review on vernal keratoconjunctivitis with emphasis on proteomics". Life Sci. 128: 47–54. doi:10.1016/j.lfs.2015.01.040. PMID 25744396.
- ↑ Bradley M, Söderhäll C, Wahlgren CF, Luthman H, Nordenskjöld M, Kockum I (2001). "The Wiskott-Aldrich syndrome gene as a candidate gene for atopic dermatitis". Acta Derm. Venereol. 81 (5): 340–2. PMID 11800140.
- ↑ Ohameje NU, Loveless JW, Saini SS (2006). "Atopic dermatitis or hyper-IgE syndrome?". Allergy Asthma Proc. 27 (3): 289–91. PMID 16913276.
- ↑ Drury KE, Schaeffer M, Silverberg JI (January 2016). "Association Between Atopic Disease and Anemia in US Children". JAMA Pediatr. 170 (1): 29–34. doi:10.1001/jamapediatrics.2015.3065. PMID 26619045.
- ↑ Rønnstad A, Halling-Overgaard AS, Hamann CR, Skov L, Egeberg A, Thyssen JP (September 2018). "Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: A systematic review and meta-analysis". J. Am. Acad. Dermatol. 79 (3): 448–456.e30. doi:10.1016/j.jaad.2018.03.017. PMID 30119868. Vancouver style error: initials (help)
- ↑ Bao Q, Chen L, Lu Z, Ma Y, Guo L, Zhang S, Huang X, Xu S, Ruan L (October 2018). "Association between eczema and risk of depression: A systematic review and meta-analysis of 188,495 participants". J Affect Disord. 238: 458–464. doi:10.1016/j.jad.2018.05.007. PMID 29929155.
- ↑ Cheng CM, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, Yang AC, Chang WH, Chen TJ, Tsai SJ, Chen MH (June 2015). "Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study". J Affect Disord. 178: 60–5. doi:10.1016/j.jad.2015.02.025. PMID 25795537.
- ↑ Strom MA, Fishbein AB, Paller AS, Silverberg JI (November 2016). "Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults". Br. J. Dermatol. 175 (5): 920–929. doi:10.1111/bjd.14697. PMC 5216180. PMID 27105659.
- ↑ Thyssen JP, Halling-Overgaard AS, Andersen Y, Gislason G, Skov L, Egeberg A (June 2018). "The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis". Br. J. Dermatol. 178 (6): 1272–1279. doi:10.1111/bjd.16215. PMID 29210061. Vancouver style error: initials (help)
- ↑ Mihm, Martin C; Soter, Nicholas A; Dvorak, Harold F; Austen, K Frank (1976). "The Structure Of Normal Skin And The Morphology Of Atopic Eczema". Journal of Investigative Dermatology. 67 (3): 305–312. doi:10.1111/1523-1747.ep12514346. ISSN 0022-202X.
- ↑ Mihm, Martin C; Soter, Nicholas A; Dvorak, Harold F; Austen, K Frank (1976). "The Structure Of Normal Skin And The Morphology Of Atopic Eczema". Journal of Investigative Dermatology. 67 (3): 305–312. doi:10.1111/1523-1747.ep12514346. ISSN 0022-202X.
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