Sandbox:Shalinder

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 skin barrier function and immune regulation can be understood as follows:

• Skin Barrier: In the epidermis, stratum corneum consisting of stacks of anucleate corneocytes filled with keratin filaments serves as the first line of defense between the body and the environment. Interactions between terminally differentiated keratinocytes and structural proteins such as lipids, regulatory enzymes, and filaggrin, determine the permeability of epidermis.
  • Filaggrin is one of the major determinants of barrier function.. Encoded by the FLG gene, filaggrin monomers constitute keratin-filament-aggregating properties.
  • Following its synthesis primarily as profilaggrin, it undergoes extensive phosphorylation, resulting in the formation of filaggrin monomers, which on further breakdown are major components of the natural moisturizer factor (NMF).
  • The main function of natural moisturizer factor is to maintains skin hydration and water retention within the stratum corneum.
  • Other proteins involved in production of natural moisturizer factor are desmoglein-1, desmocollin-1, filaggrin-2, corneodesmosin, transglutaminase-3 and enzymes such as caspase-14 and arginase-1.

• immune regulation:
  • Innate immune: It is a rapid and first line immune response to the invading pathogen before host initiates the adaptive immune response. It consists of 4 types of barrier functions of the epidermis.
    • physical: stratum corneum and tight junctions
    • chemical: antimicrobial peptides, keratinocytes, cytokines, and chemokines
    • microbiome: skin resident microflora promote the preservation of the normal skin flora while inhibiting the skin pathogens.
    • immunologic: T cells, neutrophils, eosinophils, NK cells and antigen presenting cells promote the immunologic recognition of antigens or pathogens.

Pathogenesis=

• The exact pathogenesis of [disease name] is not completely understood.

OR

• It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
• [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].