Eczema pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(25 intermediate revisions by 2 users not shown)
Line 2: Line 2:
{{Eczema}}
{{Eczema}}


{{CMG}}; {{AE}} [[User:Edzelco|Edzel Lorraine Co, D.M.D., M.D.]]
{{CMG}}; {{AE}} {{EdzelCo}}
 
==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]]. <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==
 
===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''
** 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>
* ''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.<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> <ref name="pmid25282559">{{cite journal| author=Leung DY, Guttman-Yassky E| title=Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. | journal=J Allergy Clin Immunol | year= 2014 | volume= 134 | issue= 4 | pages= 769-79 | pmid=25282559 | doi=10.1016/j.jaci.2014.08.008 | pmc=4186710 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25282559  }} </ref>


==References==
==References==
Line 8: Line 37:
{{Reflist|2}}
{{Reflist|2}}


[[Category:Needs content]]
[[category:needs english review]]

Latest revision as of 07:43, 13 November 2023

Eczema Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Eczema from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Social Impact

Future or Investigational Therapies

Case Studies

Case #1

Eczema On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Eczema

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Eczema

CDC on Eczema

Eczema in the news

Blogs on Eczema

Directions to Hospitals Treating Eczema

Risk calculators and risk factors for 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

Genetic Inheritance

Epithelium Barrier Dysfunction

Hypotheses on Development of Eczema

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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).
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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. ↑ 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.
  12. ↑ 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.
Retrieved from "https://www.wikidoc.org/index.php?title=Eczema_pathophysiology&oldid=1736607"