Eczema pathophysiology: Difference between revisions
Jump to navigation
Jump to search
Jose Loyola (talk | contribs) |
No edit summary |
||
| (16 intermediate revisions by 2 users not shown) | |||
| Line 2: | Line 2: | ||
{{Eczema}} | {{Eczema}} | ||
{{CMG}}; {{AE}} | {{CMG}}; {{AE}} {{EdzelCo}} | ||
==Overview== | ==Overview== | ||
There are two main theories on the existence of [[atopic dermatitis]], also known as [[atopic eczema]] - the ''inside-out hypothesis'', and the ''outside-in hypothesis''. | The mechanism of [[disease]] of [[eczema]] involves a complex interplay of abnormalities of [[skin]] [[microbiomes]], a dysfunction in the [[epidermal]] barrier, and an [[immune dysregulation]]. <ref name="pmid27212086">{{cite journal| author=Feld M, Garcia R, Buddenkotte J, Katayama S, Lewis K, Muirhead G | display-authors=etal| title=The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. | journal=J Allergy Clin Immunol | year= 2016 | volume= 138 | issue= 2 | pages= 500-508.e24 | pmid=27212086 | doi=10.1016/j.jaci.2016.02.020 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27212086 }} </ref> There are two main theories on the existence of [[atopic dermatitis]], also known as [[atopic eczema]] - the ''inside-out hypothesis'', and the ''outside-in hypothesis''. | ||
==Pathophysiology== | ==Pathophysiology== | ||
* There are two main theories on the existence of [[atopic dermatitis]], also known as [[atopic eczema]] - the ''inside-out hypothesis'', and the ''outside-in hypothesis''. | |||
===Immunological Dysregulation=== | |||
*Affected [[skin]] involves the uptake of [[antigens]] and [[allergens]] by the [[epidermal]] [[dendritic cells]], [[dermal]] [[dendritic cells]], and [[Langerhan cells]]. | |||
*[[Sensory nerves]] are activated by the released [[cytokines]] interleukins 4,13 and 31 ([[IL-4]], [[IL-13]], and [[IL-31]]), which are responsible for the [[pruritic]] sensation. | |||
*As the event becomes chronic, an increased expression of [[keratinocyte]] and [[Th-cell]]-derived [[cytokines]] is achieved, with more [[pruritogens]] contributing to [[itch]] sensation. <ref name="pmid27212086">{{cite journal| author=Feld M, Garcia R, Buddenkotte J, Katayama S, Lewis K, Muirhead G | display-authors=etal| title=The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. | journal=J Allergy Clin Immunol | year= 2016 | volume= 138 | issue= 2 | pages= 500-508.e24 | pmid=27212086 | doi=10.1016/j.jaci.2016.02.020 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27212086 }} </ref> | |||
===Genetic Inheritance=== | |||
*There are 34 [[genetic loci]] which are thought to be associated with [[eczema]]. | |||
*These regions contain several [[genes]] which have important [[immunological]] functions, such as [[T-cell]] activation, [[type-2 helper cell]] differentiation, and [[innate immunity]]. <ref name="pmid26482879">{{cite journal| author=Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP | display-authors=etal| title=Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. | journal=Nat Genet | year= 2015 | volume= 47 | issue= 12 | pages= 1449-1456 | pmid=26482879 | doi=10.1038/ng.3424 | pmc=4753676 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26482879 }} </ref> <ref name="pmid23886662">{{cite journal| author=Weidinger S, Willis-Owen SA, Kamatani Y, Baurecht H, Morar N, Liang L | display-authors=etal| title=A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis. | journal=Hum Mol Genet | year= 2013 | volume= 22 | issue= 23 | pages= 4841-56 | pmid=23886662 | doi=10.1093/hmg/ddt317 | pmc=3820131 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23886662 }} </ref><ref name="pmid32325630">{{cite journal| author=Martin MJ, Estravís M, García-Sánchez A, Dávila I, Isidoro-García M, Sanz C| title=Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review. | journal=Genes (Basel) | year= 2020 | volume= 11 | issue= 4 | pages= | pmid=32325630 | doi=10.3390/genes11040442 | pmc=7231115 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32325630 }} </ref> | |||
===Epithelium Barrier Dysfunction=== | |||
*Multiple factors cause the disruption of [[epithelial barrier]]. These include: | |||
**''[[FLG]]'' [[mutations]] | |||
**Constant scratching | |||
**[[Microbial]] [[dysbiosis]] brought about by ''Staphylococcus aureus'' and ''Malassezia''. | |||
*As a result, an interrupted normal [[skin]] barrier with elevated [[pH]], high [[skin permeability]], altered [[lipid]] composition, and decreased [[water]] retention is observed. <ref name="pmid8651017">{{cite journal| author=Seidenari S, Giusti G| title=Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. | journal=Acta Derm Venereol | year= 1995 | volume= 75 | issue= 6 | pages= 429-33 | pmid=8651017 | doi=10.2340/0001555575429433 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8651017 }} </ref> <ref name="pmid20132155">{{cite journal| author=Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK | display-authors=etal| title=Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema. | journal=Allergy | year= 2010 | volume= 65 | issue= 7 | pages= 911-8 | pmid=20132155 | doi=10.1111/j.1398-9995.2010.02326.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20132155 }} </ref> <ref name="pmid29969827">{{cite journal| author=Tsakok T, Woolf R, Smith CH, Weidinger S, Flohr C| title=Atopic dermatitis: the skin barrier and beyond. | journal=Br J Dermatol | year= 2019 | volume= 180 | issue= 3 | pages= 464-474 | pmid=29969827 | doi=10.1111/bjd.16934 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29969827 }} </ref> <ref name="pmid27639188">{{cite journal| author=Halling-Overgaard AS, Kezic S, Jakasa I, Engebretsen KA, Maibach H, Thyssen JP| title=Skin absorption through atopic dermatitis skin: a systematic review. | journal=Br J Dermatol | year= 2017 | volume= 177 | issue= 1 | pages= 84-106 | pmid=27639188 | doi=10.1111/bjd.15065 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27639188 }} </ref> <ref name="pmid17512043">{{cite journal| author=Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A | display-authors=etal| title=Cytokine modulation of atopic dermatitis filaggrin skin expression. | journal=J Allergy Clin Immunol | year= 2007 | volume= 120 | issue= 1 | pages= 150-5 | pmid=17512043 | doi=10.1016/j.jaci.2007.04.031 | pmc=2669594 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17512043 }} </ref> <ref name="pmid29421277">{{cite journal| author=Baurecht H, Rühlemann MC, Rodríguez E, Thielking F, Harder I, Erkens AS | display-authors=etal| title=Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration. | journal=J Allergy Clin Immunol | year= 2018 | volume= 141 | issue= 5 | pages= 1668-1676.e16 | pmid=29421277 | doi=10.1016/j.jaci.2018.01.019 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29421277 }} </ref> | |||
===Hypotheses on Development of Eczema=== | |||
* There are two main theories on the existence of [[atopic dermatitis]], also known as [[atopic eczema]] - the ''inside-out hypothesis'', and the ''outside-in hypothesis''.<ref name="pmid26761930">{{cite journal| author=Silverberg NB, Silverberg JI| title=Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis? | journal=Cutis | year= 2015 | volume= 96 | issue= 6 | pages= 359-61 | pmid=26761930 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26761930 }} </ref> | |||
* ''Inside-out hypothesis'' | * ''Inside-out hypothesis'' | ||
** This hypothesis denotes that some [[allergic triggers]] weaken the [[skin]] barrier that leads to more introduction of [[allergens]] to the area, causing more [[inflammatory reaction]].<ref name="pmid26761930">{{cite journal| author=Silverberg NB, Silverberg JI| title=Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis? | journal=Cutis | year= 2015 | volume= 96 | issue= 6 | pages= 359-61 | pmid=26761930 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26761930 }} </ref> | ** This hypothesis denotes that some [[allergic triggers]] weaken the [[skin]] barrier that leads to more introduction of [[allergens]] to the area, causing more [[inflammatory reaction]].<ref name="pmid26761930">{{cite journal| author=Silverberg NB, Silverberg JI| title=Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis? | journal=Cutis | year= 2015 | volume= 96 | issue= 6 | pages= 359-61 | pmid=26761930 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26761930 }} </ref> | ||
| Line 20: | Line 37: | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[ | [[category:needs english review]] | ||
Latest revision as of 07:43, 13 November 2023
|
Eczema Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Eczema On the Web |
|
American Roentgen Ray Society Images of Eczema |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Edzel Lorraine Co, DMD, MD[2]
Overview
The mechanism of disease of eczema involves a complex interplay of abnormalities of skin microbiomes, a dysfunction in the epidermal barrier, and an immune dysregulation. [1] There are two main theories on the existence of atopic dermatitis, also known as atopic eczema - the inside-out hypothesis, and the outside-in hypothesis.
Pathophysiology
Immunological Dysregulation
- Affected skin involves the uptake of antigens and allergens by the epidermal dendritic cells, dermal dendritic cells, and Langerhan cells.
- Sensory nerves are activated by the released cytokines interleukins 4,13 and 31 (IL-4, IL-13, and IL-31), which are responsible for the pruritic sensation.
- As the event becomes chronic, an increased expression of keratinocyte and Th-cell-derived cytokines is achieved, with more pruritogens contributing to itch sensation. [1]
Genetic Inheritance
- There are 34 genetic loci which are thought to be associated with eczema.
- These regions contain several genes which have important immunological functions, such as T-cell activation, type-2 helper cell differentiation, and innate immunity. [2] [3][4]
Epithelium Barrier Dysfunction
- Multiple factors cause the disruption of epithelial barrier. These include:
- As a result, an interrupted normal skin barrier with elevated pH, high skin permeability, altered lipid composition, and decreased water retention is observed. [5] [6] [7] [8] [9] [10]
Hypotheses on Development of Eczema
- There are two main theories on the existence of atopic dermatitis, also known as atopic eczema - the inside-out hypothesis, and the outside-in hypothesis.[11]
- Inside-out hypothesis
- This hypothesis denotes that some allergic triggers weaken the skin barrier that leads to more introduction of allergens to the area, causing more inflammatory reaction.[11]
- Outside-in hypothesis
- This hypothesis suggests that an impairment of the skin barrier should occur first before the onset of atopic dermatitis.
- This involves the down-regulation of filaggrin genes (FLG) responsible for maintenance of the proper function of skin barrier.[11] [12]
References
- ↑ 1.0 1.1 Feld M, Garcia R, Buddenkotte J, Katayama S, Lewis K, Muirhead G; et al. (2016). "The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves". J Allergy Clin Immunol. 138 (2): 500–508.e24. doi:10.1016/j.jaci.2016.02.020. PMID 27212086.
- ↑ Paternoster L, Standl M, Waage J, Baurecht H, Hotze M, Strachan DP; et al. (2015). "Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis". Nat Genet. 47 (12): 1449–1456. doi:10.1038/ng.3424. PMC 4753676. PMID 26482879.
- ↑ Weidinger S, Willis-Owen SA, Kamatani Y, Baurecht H, Morar N, Liang L; et al. (2013). "A genome-wide association study of atopic dermatitis identifies loci with overlapping effects on asthma and psoriasis". Hum Mol Genet. 22 (23): 4841–56. doi:10.1093/hmg/ddt317. PMC 3820131. PMID 23886662.
- ↑ Martin MJ, Estravís M, García-Sánchez A, Dávila I, Isidoro-García M, Sanz C (2020). "Genetics and Epigenetics of Atopic Dermatitis: An Updated Systematic Review". Genes (Basel). 11 (4). doi:10.3390/genes11040442. PMC 7231115 Check
|pmc=value (help). PMID 32325630 Check|pmid=value (help). - ↑ Seidenari S, Giusti G (1995). "Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin". Acta Derm Venereol. 75 (6): 429–33. doi:10.2340/0001555575429433. PMID 8651017.
- ↑ Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L, Høgh JK; et al. (2010). "Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema". Allergy. 65 (7): 911–8. doi:10.1111/j.1398-9995.2010.02326.x. PMID 20132155.
- ↑ Tsakok T, Woolf R, Smith CH, Weidinger S, Flohr C (2019). "Atopic dermatitis: the skin barrier and beyond". Br J Dermatol. 180 (3): 464–474. doi:10.1111/bjd.16934. PMID 29969827.
- ↑ Halling-Overgaard AS, Kezic S, Jakasa I, Engebretsen KA, Maibach H, Thyssen JP (2017). "Skin absorption through atopic dermatitis skin: a systematic review". Br J Dermatol. 177 (1): 84–106. doi:10.1111/bjd.15065. PMID 27639188.
- ↑ Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, Debenedetto A; et al. (2007). "Cytokine modulation of atopic dermatitis filaggrin skin expression". J Allergy Clin Immunol. 120 (1): 150–5. doi:10.1016/j.jaci.2007.04.031. PMC 2669594. PMID 17512043.
- ↑ Baurecht H, Rühlemann MC, Rodríguez E, Thielking F, Harder I, Erkens AS; et al. (2018). "Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration". J Allergy Clin Immunol. 141 (5): 1668–1676.e16. doi:10.1016/j.jaci.2018.01.019. PMID 29421277.
- ↑ 11.0 11.1 11.2 Silverberg NB, Silverberg JI (2015). "Inside out or outside in: does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis?". Cutis. 96 (6): 359–61. PMID 26761930.
- ↑ Leung DY, Guttman-Yassky E (2014). "Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches". J Allergy Clin Immunol. 134 (4): 769–79. doi:10.1016/j.jaci.2014.08.008. PMC 4186710. PMID 25282559.