Skin Diseases Flashcards
Physiology of the skin
•Functions of skin
•Epidermis: structure and cell types, melanin synthesis
•Dermis: structure and cell types, skin appendages
•Hypodermis
•Skin immune system
•Skin microbiome
What’s is the function of the skin?
Protective barrier-physical and chemical
Involved in mechanical support
Prevent loss of moisture
Reduces harmful effects of UV radiation
Sensory organ m-touch, temperature, pressure
Helps regulate body temperature
Immune organ to detect infections
Involved in production of VitD
Excretion of waste products
Gross anatomy of the skin was
1-Epidermis
2-Dermis
3-Hypodermis
•Epidermis consists of 5 distinct layers
Stratum básale layer next to dermis
Stratum spinosum
Stratum granulosum
Stratum lucidum
Stratum Corneum contains layers of keratinocytes which get replaced every two days this is outer layer of skin
Major epidermis cell types:
Keratinocytes:
Main cell type
Numerous layers
Stem cells
Merkel cells present in stratum básale
Pressure attached to nerves sensory neurons different locations in the skin.
Melanocytes in stratum spinosum produce Melanin, protects from uv near to Basal region
Langerhans cells are Immune-dendritic cells in all layers of epidermis sample population of bacteria that live on cell surface of skin and detect if they are good or bad
T cells CD8 positive
Keratinocytes: structure of epidermis?
In the keratinocytes layer what you can see is that down in these stratum básale we have stem cells and these stem stem cells will sled renew and they rapidly proliferate and they can differentiate into any of the other cell types in this area
In stratum spinosum keratinocytes are more cuboidal cells and you can see that these keratinocytes have nuclei but as they work their way up over three to four days for instance they become more flat and once they get into the granular layer you can see they’re losing their nuclei and then once they get into the stratum lucidum there’s no nuclei left here they’re very much flattened and those dead keratinocytes on the surface will eventually flake
now the epidermal layer is not that deep it’s quite a thin layer 10-15µm and these cells in the stratum corneum are enriched with lipid and also with keratin
Keratinocytes can secrete interleukin 1 beta and this is very important in maintaining homeostasis but also an inflammation when these cells can become damaged
How is melanin synthesised?
Melanocytes produce melanin in the skin and melanin is produced from tyrosine.
Tyrosine is metabolised to Dopa then to Dopaquinone vía tyrosinase but in the presence of cysteine Dopaquinone becomes metabolised to 5,6 & 2,6 Cysteinyl-dopa then ti Benzothiazine derivatives into Pheomelanins (red pigment) ginger people/freckles.
However, Dopaquinone can also be metabolised into Leucodopachrome and into Dopachrome via Dopachrome tautomerase and into 5,6 hydroxyindole carboxylate acid and 5,6 hydroxyindole into Quinones via Tyrosine related protein-1b into Eumelanins are black/brown melanin present in darker skin.
Dermis
Middle skin layer 1-6mm fibrous and elastic tissue. Made of connective tissues.
Supportive and cushioning tissue composed mainly of collagen 70% and elastic and fibrillin.
The second layer in the skin is called the dermis and the dermis has two distinct layers the papillary layer of the dermis which is next to the epidermis and then the reticular layer of the dermis
The papillary layer is about 20% of the dermis is a very vascular rich region so it contains lots of capillaries and what those capillaries do is they release oxygen nutrients near the epidermis so that those bottom layers of the epidermis have sufficient oxygen nutrients and that’s why they retain their nuclei but as you go further away from the oxygen and nutrients and the capillaries of the dermis the cells become flattened in the skin in this region you get a lot of connective tissue particularly collagen and this region is called the papillary layer because of these papillae stick out and increase the surface area allowing for more exchange of oxygen and nutrients into the epidermis
The reticular region is this lower region here and this takes up the majority really of the dermis this consists of dense irregular connective tissue and these areas also have elastin and also fibrillin as well so elastin makes it more elastic and collagen makes it more strong it’s connective tissue and in this region there are several types of immune cells and number of other structures like:
Immune cells-several types
Number of structures found/
Nerve ending
Blood vessels m lymph vessels
Piloerector muscles
Sweat glands
Sebaceous glands
Skin appendages
We have lots of skin appendages and different types of Corpuscles
Meissner’s corpuscles are primarily receptors for discriminative touch and are located in the dermal layer of the skin, specifically in the dermal papillae. They are sensitive to light touch and are responsible for detecting sensations such as texture and gentle pressure. I’m sorry, but that statement is not accurate. Meissner’s corpuscles are primarily receptors for discriminative touch and are located in the dermal layer of the skin, specifically in the dermal papillae. They are sensitive to light touch, not light itself, and are responsible for detecting sensations such as texture and gentle pressure. They are not located in the epidermal layer but in dermal layer of skin.
Meissner corpuscles consist of a cutaneous nerve ending responsible for transmitting the sensations of fine, discriminative touch and vibration. [1] Meissner corpuscles are most sensitive to low-frequency vibrations between 10 to 50 Hertz and can respond to skin indentations of less than 10 micrometers.
Pacinian corpuscles can detect vibrations in the skin, hair shaft root hair plexus can detect fine touch all sensory receptors.
Sebaceous oil glands and these are important because they produce oil to keep the skin and hair moist. Oil flows to surface and protects outer keratin layer of the skin. Sebaceous glands can cause problems if they get clogged can cause acne or spots.
Eccrine and apocrine sweat glands. Apocrine present in armpits and pubic regions produce protein rich sweat that supports growth of surface bacteria. Eccrine sweat glands produce watery sweat and waste products excreted products like urea and CO2. When sweat is released into skin it evaporates and this is important for regulating body temperature.
Dermis is rich in Capillaries near surface and down near básale we have venules and arterioles larger blood vessels.
Diversity of the skin at different locations
Face we have sebaceous glands
High density of sebaceous glands hair and eccrine glands
Environmentally exposed
Palm (dry)
Thick layer of skin
Thick stratum corneum
Hairless
High density of eccrine glands
Axilla (armpits)
Moist due to apocrine glands present
High density of hair
Occluded, humid environment.
Subcutaneous tissue (hypodermis)
Subcutaneous fat layer acts as a:
Mechanical layer protector
Thermal insulator
Energy store
Heat regulations uses subcutaneous fat pad (hypodermis) and skin blood supply
Thickness depends on whole body adiposity but need a minimal amount for skeletal bs organ protection
Skin immune system
There are many defence mechanism and different types of immune cells
In epidermis there are langerhans cells which are dendritic cells.
Other cells are CD8 positive T-cells
Keratinocytes they form a physical barrier they are involved in innate immune system and they produced cytokines like IL-1&6 important in inflammation and maintain homeostasis
Dermal layer of skin:
We have dermal dendritic cells, plasma dendritic cells, different types of CD4 cells like TH-1,2,17 cells
NKT cells, mast cells, macrophages, fibroblast and gamma delta T cells all of these produce cytokines.
If damage occurs eg wound, insect bite, toxins or allergy we get an inflammatory response from the skin immune system and this leads to inflammation
Inflammation in the skin
Signal mediated response to cellular insult by:
Infectious agents eg bacteria, fungi, viruses, parasites
Toxins eg chemical, radiation, UV, biological.
Physical stress eg mechanical, burns, trauma.
Protective response- ultimate goal to remove initial cause of injury and consequences of injury- the necrotic cells and tissues.
Skin microbe
1cm2 human skin contains up to 1b microorganisms—bacteria, fungi, viruses, mites. These microorganisms can also exist in hair shaft, sweat glands and sebaceous glands. Eg bacteria clog sebaceous glands and cause acne
Skin microbiome Beneficial:
Protect against disease
But can be Detrimental:
Exacerbate skin lesions
Promote disease
Delay wound healing
Interact with host immune system—BI-directional
Affected by lifestyle
Actinobacteria live on upper parts of body face neck
Proteibacteria live on shoulder and limbs
Firmicutes live on foot
Lots of other different classes of microorganisms live on human body Ik different regions
Skin resident microbial communities: Important for humans as they inhibit pathogens from growing in the area they take up space so pathogens don’t have space to grow also take nutrients form skin so pathogens have no nutrient to thrive.
They produce anti-microbial peptides AMPs and bactericidal compounds that can kill pathogenic compounds and can inhibit S.aureus biofilm formation.
Educate and prime adaptive immunity:
Turn local cytokine production
Epigenetically prime APCs to educate adaptive immunity
Influence regulatory T cell in epidermis.
Enhance host innate immunity:
Increase AMP production, decrease inflammation after injury and strengthen epidermal barrier.
What happens if things go wrong?
So if some change occurs to that microbial community for instance if you get an infection or for instance if you take long term antibiotics it can change the microbial community living on the skin or if you get overgrowth of these that then can lead to an inflammatory response on the skin and causes skin to produce pro-inflammatory cytokines and then you may get inflammation and the inflammation can damage the barrier to the skin that can allow both the immune system to infiltrate into the area you also get a disrupted physical barrier and that allows microbes to actually enter areas that they would normally not enter and so they penetrate sterile tissues and that can cause major problems for us
on the other hand we can have changes to our skin which can affect the microbes as well so for instance A chronic conditions such as diabetes can cause wounds to occur or injury we get an injury to that that changes the microbial community that’s on the skin because they can get taken over by potential pathogens and again these pathogens then can enter areas that they shouldn’t and cause an inflammatory response and that inflammation then can break down the barrier and can impair wound healing and cause more and more problems for us as well so this is a very important area about how the immune system in the skin communicate with the microbes that live on the surface and our microbiome is very important for that
Wound healing lecture
What is a wound?
A wound is a break in the epithelial integrity of the skin may affect deeper layers even to bone.
•Types of wounds
•Stages of acute wound healing
•Chronic wound and impaired •Diabetic ulcers
•Aging
What are the types of wounds?
•Superficial:
Damage to epithelium
Heals rapidly through regeneration of epithelial cells
•Partial thickness:
Involves dermal layer
Vascular damage
•Full thickness:
Involves subcutaneous fat and deeper
Longest to heal-new connective tissues required
Contraction during healing
What are the 4 main stages of wound healing?
First stage:
Injury to skin causes bleeding to occur this is called hemostasis, this forms a blood clot to stop bleeding.
Second stage:
Inflammation; inflammatory phase to stop any infection from occurring lots of immune cells fight infection and body wants to provide a new frame work for new blood vessel growth.
Third stage:
Proliferation or proliferative stage body makes new connective tissues to replace damaged tissue and to pull the wound closed. A new epithelial or epidermal layer is formed
Fourth stage:
Remodelling to bring skin back to normal decrease amount of immune cells in the area contract area back to normal and a vascular scar on surface is apparent at that stage.
How long does it take for wound healing to occur?
First stage bleeding and homeostasis take less than 1 day
Inflammatory stage takes anything between 1-10days but after 1-day neutrophils increase to initiate inflammation to it is peak amount. During this time granulocytes, phagocytosis, macrophages, neutrophils and cytokines initiating a response after 2-3days after a wound. This helps reduce or prevent infection or bacteria but they also ingest dead tissues so body can replace or form new tissues.
After 3 days we get proliferation phase this is when we began to deposit matrix down, body starts to make collagens, fibronectin, proteiglycans and they are all involved in connective tissue; where fibroblasts are proliferating, angiogenesis new blood vessel formation, re-epithelialization forming delicate cover over wound laying down extracellular matrix.
1 month after the wound has occurred last phase occurs which is Matrix remodelling, strengthening occurs, increase in tensile strength, decrease in cellularity and vascularity of area. Remodelling of connective tissue and cellular matrix. Can take up to a year for skin to get back to normal after a wound depending on depth of wound.
What cells & mediators are involved in acute wound healing?
After tissue injury bleeding occurs then inflammation phase; macrophages and neutrophils will produce cytokines, pro-inflammatory cytokines, growth factors (GF) eg MMP, ROS, hydrogen peroxide, IL, TNF, VEGF, TGFB, FGF, PDGF. These growth factors help connective tissue and blood vessels to start growing.
•Granulation and neoangiogenesis
Fibroblasts, macrophages, endothelial cells, MMPs, prolyl hydroxylase, IL, TNF, TGFbeta, VEGF, PDGF, KGF.
•Re-epithelialization (covering of wound)
Keratinocytes, MMPs, EGF, KGF to strengthen and rebuild the epidermis.
•Tissue remodelling
Fibroblasts crosslinks collagen fibre cross-linking to strengthen the area, MMPs, TGFbeta however this stage is not reached sometimes due to chronic inflammation and that can lead or sustained inflammation then causes a chronic wound.
AI:
After tissue injury, a series of biological processes occur to facilitate wound healing. The passage mentions several key factors and cell types involved in the different stages of wound healing.
- Hemostasis and Inflammation:
Following tissue injury, bleeding occurs, leading to the formation of a blood clot. This process, known as hemostasis, helps to stop the bleeding. Subsequently, the inflammatory phase begins, involving the activation of immune cells such as macrophages and neutrophils. These cells produce various molecules called cytokines, including pro-inflammatory cytokines. Additionally, growth factors such as matrix metalloproteinases (MMPs), reactive oxygen species (ROS), hydrogen peroxide, interleukins (IL), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGFB), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) are secreted. These factors play a crucial role in promoting the growth of connective tissue and blood vessels, aiding in the next stage of wound healing. - Granulation and Neoangiogenesis:
During this stage, various cell types, including fibroblasts, macrophages, and endothelial cells, contribute to the formation of granulation tissue. Granulation tissue is characterized by the formation of new blood vessels (neoangiogenesis) and the deposition of extracellular matrix components. The production of MMPs, prolyl hydroxylase, IL, TNF, TGFbeta, VEGF, PDGF, and keratinocyte growth factor (KGF) is involved in this process. - Re-epithelialization:
Re-epithelialization refers to the covering of the wound with a new layer of epithelial cells. Keratinocytes, a type of skin cell, play a crucial role in this stage. MMPs, epidermal growth factor (EGF), and KGF are involved in the proliferation and migration of keratinocytes, facilitating the strengthening and rebuilding of the epidermis. - Tissue Remodeling:
In the final stage of wound healing, tissue remodeling occurs. Fibroblasts are responsible for crosslinking collagen fibers, which helps to strengthen the wound area. MMPs and TGFbeta are involved in this process. However, it is important to note that chronic inflammation can hinder or delay the progression to this stage, leading to the development of chronic wounds.
References:
1. Guo S, Dipietro LA. Factors Affecting Wound Healing. J Dent Res. 2010;89(3):219-229. doi:10.1177/0022034509359125
2. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6. doi:10.1126/scitranslmed.3009337
What is haemostasis?
Micro vascular injury- blood seeps into wound
Injured vessel contract
Coagulation cascade activated by tissue factor aims for Clot formation and platelet aggregation.
Platelet aggregate into that area as well, platelets trapped in clot release PDGF, IGF,EGF,TGF-beta which attract and activate fibroblasts, macrophages and endothelial cells.
- PDGF - Platelet-Derived Growth Factor
- IGF - Insulin-Like Growth Factor
- EGF - Epidermal Growth Factor
- TGF-beta - Transforming Growth Factor-beta
Also serotonin is released, which increases vascular permeability.
Inflammatory phase?
•Early inflammatory phase:
Activation of complement
Infiltration of neutrophils within 24-38h Diapedesis into wound and phagocytosis of bacteria and foreign particles, with ROS and degrading enzymes-prevent infection
Dying cells cleared by macrophages or extrusion to wound surface.
•Late inflammatory phase:
Blood monocytes arrive and become macrophages 48-72hrs
Key cell type for repair in wound healing
Cytokines and growth factors to recruit fibroblasts, keratinocytes and endothelial cells to repair damage
Collagenases to degrade tissue
Poor wound healing when inadequate monocytes/macrophages.
Lymphocytes enter wound >72hr and are involved in remodelling
Proliferative phase
Proliferative phase 72h-2wks
•Fibroblast migration
Produce fibronectin, hyaluronan, collagen, priteiglycans.
Proliferate and construct new ECM
•Collagen synthesis: strength and integrity
•Angiogenesis
TGF beta and PDGF from platelets, TNF and bFGF from macrophages.
Capillary sprouts invade fibrin/fibronectin-rich wound clot and organise micro-vascular network
•Granulation tissue formation
Mainly proliferating fibroblasts, capillaries, macrophages in matrix of collagen GAGs and fibronectin and Tenascin.
•Epithelialisation
Single layer of epidermal cells migrate from wound edges to form delicate covering, basal cells increases proliferation ñ, new basement membrane
EGF stimulates epithelial mitogenesis and chemotaxis, bFGF and KGF stimulate proliferation.
Remodelling phase- long time
Matrix matures and remodels
Fibronectin and HA broken down
Collagen bundles increase in diameter and strength (80% of strength of original)
Ongoing collagen synthesis and breakdown by TGF-beta and MMPs
Collagen becomes more organised and shrink to bring wound margins closer together.
Fibroblasts and macrophages apoptose
Capillary outgrowth halted and blood flow reduced
Acellular, avascular scar results
Chronic wound and impaired healing
When normal process of healing disrupted at one of the stages, usually inflammatory or proliferative.
Disturbance in growth factors, cytokines, proteases, cells
Local factors affecting wound healing eg post surgical
Pressure
Mechanical injury/trauma
Infection/foreign substances
Oedema
Necrosis
Topical agents
Lack of oxygen delivery ischemia
Desiccation and dehydration
Systemic factors affecting wound healing eg postsurgical
Old age
Obesity
Chronic disease eg diabetes, anemia connective tissue disorders
Immunosuppression
Smoking malnutrition
Vascular insufficiency
Stress
Radiation or chemotherapy
What causes chronic wound?
Neuropathy in diabetes mellitus, spinal injuries
Ischemia in atherosclerosis, PVD, microangiopathy DM
Peripheral oedema
DVT, Varicose veins, renal or cardiac failure
Pressure
Poor stability, spinal cord injuries, Dementia, diabetes mellitus, old age, terminal illness.
Other connective tissue disorders leading to vasculitis, systemic diseases, malignancy, smoking, drugs such as corticosteroids and hydroxyurea.
What are the clinical features of chronic wound?
Presence of necrotic and unhealthy tissue
Excess exudate and slough
Lack of adequate blood supply
Absence of healthy granulation tissue
Failure of re-epithelialisation
Cyclical or persistent pain
Recurrent wound breakdown
Clinical or sub clinical infection.
Diabetic ulcers affect on wound healing
There can be motor/sensory or autonomic neuropathy
If there is motor neuropathy damage to neurons and neuron message signal is terminated this results in muscle atrophy. This causes a change in gait (new pressure distribution) and leads to ulcers.
Motor neuropathy can also cause bone changes which leads to deformed foot and ulcers
Sensory neuropathy you can’t detect pain if injury occurs you get painless trauma. If body is injured no pain is detected so could lead to wound and ulcers and complications of ulcer is infection and gangrene (localized death and decomposition of body tissue, resulting from obstructed circulation or bacterial infection.)
Autonomic neuropathy:
Decreased sweating so excess drying of skin occurs. Cracks in skin can cause chronic ulcers.
Eczema (dermatitis)
Eczema (dermatitis) both terms used interchangeably. Eczema inflammation of the epidermis and dermatitis inflammation of the dermis but both occur simultaneously.
Group of skin conditions that cause dry, irritated, inflamed skin.
Inflammatory reaction of the skin:
_Erythema, oedema, oozing, papeles, crusting, thickening and slacking.
_Itching, burning.
What are the different types of eczema?
Atopic dermatitis
Contact dermatitis
Seborrhoeic dermatitis
Dyshidrotic dermatits
Nummular dermatitis
Neurodermatitis
Stasis dermatitis
Atopic dermatitis
Chronic disorder with flare ups and remissions-May clear up for long periods
Most common form of eczema 1-2% adults, 15-20% school children
30% of skin problems in general practise
Manley’s and femalesbequally affected
Type IV hypersensitivity reaction
Often occurs with asthma or hay fever (atopic triad)
Commonly affects knees, elbows, wrists, neck, face.
Atopic eczema
Genetic predisposition-atopic families
Defects in the skin barrier-repair and maintain
Lack of anti-microbial peptides
Defect in the fliaggrin gene-important for maintaining the skin barrier-in most eczema patients.
Abnormalities in the normal inflammatory and allergy responses
Barrier defects makes the skin in affected patients m uh more susceptible to infection and to irritation and allow allergy inducing substances to enter the skin, causing itch abs inflammation.
Abnormalities in the normal inflammatory and allergy responses
Barrier defects makes the skin in affected patients much more susceptible to infection and to irritation and allows allergy inducing substances if enter the skin, causing itch and inflammation.
Immunology of eczema:
Allergen in the skin gets taken up by the dendritic cells are the langerhans cells in epidermis and dermis.
Dendritic cells present antigens to the T-cells, there is a change in the balance of TH1&2 cells so expansion occurs in TH2 cells and this secretes IL-4 activates B-cells to change antibody class and they start to produce IgE, this travels in the blood to mast cells it gets taken up by high affinity receptors on the surface of mast cells and this allows allergens to be taken up, this causes a release of pro-inflammatory mediators that cause the inflammation.
What are the clinical features of atopic eczema?
Often age specific:
Felxural eczema in children
Hand eczema in adults
Dry skin
Itching, May be severe, especially at night
Red to brownish grey patches in affected areas become lichenified
Raw, sensitive, swollen skin from scratching skin infections and sores can occur when scratching breaks the skin.
How to prevent flare ups?
Moisturisers to prevent drying of the skin
Identify and avoid triggers if possible
Mild soaps and short showers/baths
Treatment of the atopic dermatitis?
Emollients to keep skin moisturised
Topical corticosteroids work locally to inhibit the inflammation
Antibiotics if eczema infected
Phototherapy
Next step in treatment:
Systemic corticosteroids if patient doesn’t respond or experiences s/e next step is to use
Topical calcineurin inhibitors TCIs eg pimecrolimus and tacrolimus. These inhibit T-cell response so prevents T helper cells from releasing IL-4.
Next step in treatment is immunosuppressants- ciclosporine, Azathioprine
Dupilimumab-mAb inhibiting IL4/IL13 signalling, inviting switching of classes from b-cells to T-cells.
Alitretinoin-for chronic hand eczema refractory to steroids (retinoids)
What’s contact dermatitis?
Contact dermatitis cause by many substances in the home or work place responsible
Usually exposed parts of the body
2types of contact dermatitis:
•Irritant contact sue to toxic insult or accumulative exposure to some type of toxin or just long term use of water
•Allergic contact
Can distinguish between irritant and allergic contact via a patch test
More common in adults than children
Common in wet work- healthcare, hairdressers, catering, labs, cleaners, industrial factory workers.
Atopic eczema patients have increased susceptibility to both types
What is irritant contact dermatitis?
75% of cases
Exposure to acute toxic insult or cumulative damage from irritants
Detergents and solvents which strip skin of natural oils
Amount of exposure important
Excessive hand washing, dribble rashes or nappy rashes
Occurs under rings
Diagnosis by knowing which substances irritate
What is allergic contact dermatitis?
•Majority of occupational skin disorders
•Type IV hypersensitivity reaction
•Over time of exposure, immune response builds up
•Nickel, rubber, perfumes, preservatives in cosmetics, dyes
•Diagnosis by patch testing
Pathogenesis of AD, ICD, ACD?
•Atopic dermatitis:
Allergen gets taken up by dendritic cells which then presents allergens to T-cells in the lymph node
T cells cause B-cells to have IgE class switching; triggers mast cells to produce many pro-inflammatory mediators which switches on many cells involved in this adaptive immune response, increases production of lots of different cytokines that will disturb epithelial barrier and causes more water loss.
•Irritant contact dermatitis:
Innate immune twosome occurs in ICD. The irritant will directly affect the keratinocytes and this will switch on and secrete many Pro-inflammatory cytokines such as TNF, IL-1, IL-8, GM-CSF and it will switch on dendritic cells via IL-1 secretion.
This activates the up regulation of endothelial cells this allows vasodilation to occur and this allows cellular recruitment in the skin area eg recruitment of neutrophil followed by monocytes which become macrophages, lymphocytes and mast cells. This causes a local inflammatory response. This is innate immunity
•Allergic contact dermatitis:
Consists of a combination of both adaptive and innate immune response
Allergic contact dermatitis is a type of delayed hypersensitivity reaction that occurs when the skin comes into contact with an allergen. The pathogenesis of allergic contact dermatitis involves both adaptive and innate immune responses.
- Sensitization Phase:
- Allergen Penetration: The allergen, such as nickel or fragrance, penetrates the skin and is taken up by dendritic cells (DCs) present in the epidermis.
- Presentation to T-Cells: The DCs migrate to the nearby lymph nodes, where they present the allergen to T-cells. This interaction leads to activation and differentiation of allergen-specific T-cells.
- B-Cell Activation: Activated T-cells produce cytokines that promote B-cell class switching to IgE production. B-cells then produce allergen-specific IgE antibodies.
- IgE Production: The IgE antibodies bind to high-affinity receptors (FcεRI) on mast cells and basophils, sensitizing them to the specific allergen. - Elicitation Phase:
- Re-Exposure to Allergen: Upon re-exposure to the allergen, it binds to the IgE antibodies on mast cells and basophils.
- Mast Cell Activation: Cross-linking of IgE receptors on mast cells triggers the release of various pro-inflammatory mediators, including histamine, leukotrienes, and cytokines.
- Inflammatory Response: The released mediators cause vasodilation, increased vascular permeability, and recruitment of inflammatory cells, such as neutrophils, monocytes/macrophages, lymphocytes, and additional mast cells.
- Epithelial Barrier Dysfunction: The pro-inflammatory cytokines released by mast cells and other immune cells disrupt the epithelial barrier, leading to increased water loss and further inflammation.
The combination of mast cell activation, release of pro-inflammatory mediators, and recruitment of immune cells results in the characteristic symptoms of allergic contact dermatitis, including redness, swelling, itching, and skin lesions.
It’s important to note that the pathogenesis of allergic contact dermatitis may vary depending on the specific allergen and individual immune response.
Treatment of contact dermatitis?
Avoid irritants and allergens
Use emollients
Topical corticosteroids
Oral corticosteroids
Alitretinoin (vitA form) for chronic hand contact dermatitis refractory to steroids (retinoid)
Seborrhoeic dermatitis in adults
1-3% uk population
More common in males bd over age of 20
Common harmless rash wig skin flakes, itchy and sore inflamed red skim with greasy looking white or yellow scales
Ranges from mild dandruff to severe on the scalp
Sebaceous skin zones- face, scalp, chest, ears, skin folds, acúlale, groin
Sue to overgrowth of malassezia yeasts, which are part of the normal skin flora but trigger inflammatory response
Not contagious, aggravated by stress
Seborrhoeic dermatitis (infantile)
Infants aged 3-8 months
Yellow, waxy, scales ok scalp, thick and difficult to remove
Pink flaky patches on forehead, eyebrows, behind ears, nappy area.
Due to developing sebum glands.
Seborrhoeic dermatitis-treatment
Infants:
Emollients or minerals for scalp
Topical steroids with antifungal for body
Adults
Shampoos with ketoconazole, Zn pyrithione, Se sulfide (anti-yeast)
Steroid scalp lotions/mousses
Topical mild corticosteroids with salicylic acid for scalp
Topical mild corticosteroids with anti-yeast creams-ointments (clotrimazole, miconazole and nystatin)
In severe cases and if above treatment fail use Oral antifungals ( severe cases)
What are the other types of eczema?
•Nummular (discoid) dermatitis:
Round oval blistered dry lesions
Usually lower legs/ trunk arms
Affects males and females equally
Unknown cause
Treat with emollients, steroids, antibiotics and phototherapy.
•Neurodermatitis:
12% of the population, commonly mid to late adulthood esp 30-50yesrs
Localised area caused by repeated rubbing it scratching.
Possibly due to compressed nerve or presence of other dermatitis.
Very persistent and recurring
Treat with emollients and topical steroids.
•Stasis dermatitis:
Adults with varicose veins, DVT, or ulcers or where increased pressure in the veins of the leg.
Other risk factors- overweight, standing up
More common in women
Often associated with signs of venous hypertension
Skin become fragile, thin, shiny, inflamed, itchy abs flaky.
Treat with emollients, steroids, compression stocking, exercise, weight loss, elevation of the legs and surgery for varicose veins.
•Dishydrotic dermatitis
Common in people with atopic eczema under the age of 40
Affects hands and feet
Unknown cause but aggravated by heat and stress
Tiny itchy blisters
Treat with emollient, steroids, antibiotics, systemic immunosuppressants and phototherapy.
