Sandbox:Shalinder: Difference between revisions
Jump to navigation
Jump to search
| Line 16: | Line 16: | ||
* '''Filaggrin:''' | * '''Filaggrin:''' | ||
* '''Proteins related to tight junctions:''' | * '''Proteins related to tight junctions:''' | ||
* '''Other protiens''' | * '''Other protiens:''' | ||
Revision as of 13:43, 28 September 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shalinder Singh, M.B.B.S.[2]
Overview
It is thought that Atopic dermatitis is caused by either skin barrier dysfunction or immune dysregulation.
Pathophysiology
Physiology
The normal physiology of Atopic Dermatitis can be understood as follows:
- Epidermal barrier:
- Regular desquamation
- Intercellular lipid bilayers
- Natural Moisturising Factors
- Production of antimicrobial peptides
- Filaggrin:
- Proteins related to tight junctions:
- Other protiens:
Pathogenesis=
It is understood that Atopic dermatitis is the result of skin barrier dysfunction or by immune dysregulation.[1]
- Dysfunction of the skin barrier:
- Skin barrier abnormalities lead to the permeability of epidermis, causing entry of antigens or pathogens and leading to the production of inflammatory cytokines.
- The major factors to abnormal skin barrier include loss-of-function mutations in the filaggrin gene (FLG) causing Filaggrin deficiency[2], tight junction abnormalities[3], more alkaline surface pH,[4] microbial colonization, altered protease activity in the stratum corneum.[5][6][7][8]
- It leads to increased trans-epidermal water loss, and decreased levels of ceramides and antimicrobial peptides.[9]
- Severe Atopic Dermatitis have been associated with higher levels of transepidermal water loss.[10]
Immune dysregulation:
- Innate immune response:
- Innate immune system recognizes microbes or pathogens through innate immune receptors known as pattern recognition receptors(PRR) which also includes Toll-like receptors(TLRs).
- Adaptive immune response:
- Thymic stromal lymphopoietin:
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathogenesis=
It is understood that Atopic dermatitis is the result of skin barrier dysfunction or by immune dysregulation.[1]
- Dysfunction of the skin barrier:
- Skin barrier abnormalities lead to the permeability of epidermis, causing entry of antigens or pathogens and leading to the production of inflammatory cytokines.
- The major factors to abnormal skin barrier include loss-of-function mutations in the filaggrin gene (FLG) causing Filaggrin deficiency[2], tight junction abnormalities[3], more alkaline surface pH,[4] microbial colonization, altered protease activity in the stratum corneum.[5][6][7][8]
- It leads to increased trans-epidermal water loss, and decreased levels of ceramides and antimicrobial peptides.[9]
- Severe Atopic Dermatitis have been associated with higher levels of transepidermal water loss.[10]
Immune dysregulation:
- Innate immune response:
- Adaptive immune response:
- Thymic stromal lymphopoietin:
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
[Disease name] is transmitted in [mode of genetic transmission] pattern.
OR
Genes involved in the pathogenesis of [disease name] include:
- [Gene1]
- [Gene2]
- [Gene3]
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Associated Conditions
Conditions associated with [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ 1.0 1.1 Boguniewicz M, Leung DY (July 2011). "Atopic dermatitis: a disease of altered skin barrier and immune dysregulation". Immunol. Rev. 242 (1): 233–46. doi:10.1111/j.1600-065X.2011.01027.x. PMC 3122139. PMID 21682749.
- ↑ 2.0 2.1 Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DeBenedetto A, Schneider L, Beck LA, Barnes KC, Leung DY (September 2009). "Cytokine modulation of atopic dermatitis filaggrin skin expression". J. Allergy Clin. Immunol. 124 (3 Suppl 2): R7–R12. doi:10.1016/j.jaci.2009.07.012. PMID 19720210.
- ↑ 3.0 3.1 De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, Berger AE, Zhang K, Vidyasagar S, Yoshida T, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Novak N, Weidinger S, Beaty TH, Leung DY, Barnes KC, Beck LA (March 2011). "Tight junction defects in patients with atopic dermatitis". J. Allergy Clin. Immunol. 127 (3): 773–86.e1–7. doi:10.1016/j.jaci.2010.10.018. PMC 3049863. PMID 21163515.
- ↑ 4.0 4.1 Elias PM, Hatano Y, Williams ML (June 2008). "Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms". J. Allergy Clin. Immunol. 121 (6): 1337–43. doi:10.1016/j.jaci.2008.01.022. PMC 2706021. PMID 18329087.
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 McAleer MA, Irvine AD (February 2013). "The multifunctional role of filaggrin in allergic skin disease". J. Allergy Clin. Immunol. 131 (2): 280–91. doi:10.1016/j.jaci.2012.12.668. PMID 23374260.
- ↑ 7.0 7.1 Margolis DJ, Apter AJ, Gupta J, Hoffstad O, Papadopoulos M, Campbell LE, Sandilands A, McLean WH, Rebbeck TR, Mitra N (October 2012). "The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort". J. Allergy Clin. Immunol. 130 (4): 912–7. doi:10.1016/j.jaci.2012.07.008. PMC 3462287. PMID 22951058.
- ↑ 8.0 8.1 Morizane S, Yamasaki K, Kajita A, Ikeda K, Zhan M, Aoyama Y, Gallo RL, Iwatsuki K (July 2012). "TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis". J. Allergy Clin. Immunol. 130 (1): 259–61.e1. doi:10.1016/j.jaci.2012.03.006. PMC 3387356. PMID 22521249.
- ↑ 9.0 9.1 Cork MJ, Danby SG, Vasilopoulos Y, Hadgraft J, Lane ME, Moustafa M; et al. (2009). "Epidermal barrier dysfunction in atopic dermatitis". J Invest Dermatol. 129 (8): 1892–908. doi:10.1038/jid.2009.133. PMID 19494826.
- ↑ 10.0 10.1 Flohr C, England K, Radulovic S, McLean WH, Campbel LE, Barker J, Perkin M, Lack G (December 2010). "Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age". Br. J. Dermatol. 163 (6): 1333–6. PMID 21137118.