lecture 22 - skin conditions

Question 1

what are functions of the skin?

Answer 1

BARRIER (water proof in both directions)
TEMPERATURE CONTROL (Blood flow to your dermis)
FLUID BALANCE (sweat glands)
SENSATION (nerve endings in dermis)
IMMUNOLOGICAL DEFENSE (Langerhans/dendritic cells)
PROTECTION FROM U.V. (melanocytes)

Question 2

what is our outer skin made of?

Answer 2

keratinocytes differential and die to become outer skin

Question 3

how do disease conditions stop skin differentiation?

Answer 3

28 days for keratinocytes to become your cornified layer (tough, water tight and smooth- structural proteins and lipids).

Interruption means that the terminal differentiation process is not complete

Thus we have proliferating keratinocytes as your cornified layer – leaky (water loss), dry and not smooth (not expressing the right proteins)

Question 4

describe psoriasis

Answer 4

scaly, dry skin not smooth - skin not properly differentiated and not dead

consists of scales, plaques and inflamed skin

Question 5

describe ho the skin conditions have inflammatory component/ how it arises

Answer 5

Inflammation causes the influx of white blood cells

Release of inflammatory mediators (eg IL-1, TNFa, PGs)

Promotes proliferation and keratinocytes don’t terminally differentiate (die))

Increased blood flow (redness), swelling due to capillary leakiness, itching (not all conditions) Pain.

Question 6

describe how innate and adaptive immunity influence the skin conditions underpinning immunology

Answer 6

Innate and adaptive immunity- applies to skin
Innate- recognises bit of beastie (PAMPs) through different receptors (PRRs) on white blood cells, endothelial cells etc.
Activation of PRRs does two things -initiates the first fight back/inflammatory response and passes the recognition on to adaptive system
Adaptive system generates specific T and B cells which fights the beastie (the system adapts).
Lots of different subsets of T cells (Th1, Th2, Th11, Th17) and lots of cytokines

Question 7

what is general pharmacology which help the skin?

Answer 7

Help the skin - Emollients- Occlusion-provides a layer of oil to slow water loss.
Humectant - increased water holding capacity. Lubrication- glide across skin

Question 8

what is assessment symptoms of seborrheic dermatitis?

Answer 8

more common in older males, itching especially around the chin and hairline, excessive dandruff, thickening of the skin, skin, dry and peeling on face

Question 9

what is the treatment of seborrheic dermatitis?

Answer 9

Mediated partly by Malassezia yeast so use an anti-fungal cream ketoconazole
Topical Corticosteroid to combat inflammation short (but not used chronically).
Medicated Shampoo- (ketoconazole or cold Tar extract- cut down inflammation)
I used to use Lassar’s paste (zinc oxide and salicylic acid)

I use Eucerin-works okay (probably cutting down the inflammation)

Question 10

what s the definition of psoriasis?

Answer 10

A chronic, relapsing and remitting papulo-squamous skin disease which can appear on any part of the skin.

Question 11

explain the pathology behind psoriasis as a skin condition

Answer 11

T-cell mediated - TH1-cells secrete cytokines: TNFa, IL-1b and IL-6. Also a Th-17 condition (a lineage (type) of T cell which secretes IL-17).
Dendritic cells release IL-12 to direct CD4+ T-cell to TH 1

Inflammation- causes keratinocytes to proliferate. Keratinocytes also release inflammatory mediators

Question 12

what are pauramoclogical treatment used for psoriasis?

Answer 12

Emollient (occlusion, humifaction, lubrication)
Cold Tar -reduces inflammation.
Dithranol- inhibits proliferation
Corticosteroids (reduces inflammation- not always used)
Tazorotene (Retanoid-promotes differentiation, reduces proliferation, reduces inflammation)
Vitamin D analogues (calcipotirol)- (same profile as retinoid)

Question 13

what are pharmacological agents that can be used to treat more sever conditions?

Answer 13

NBUVB (narrowband UVB light) – Th-1 to Th-2 (not so bad!)
Systemic Ciclosporin/Cyclosporin (calcineurin inhibitor -stops IL-2 production in CD4+T-cells) stop proliferation/expansion of T-cells
Systemic Methotrexate (low dose) – cancer drug so should kill T-cells, dendritic cells.

Biologics- injected into skin
Infliximab/Adalimumab- anti-TNFa antibodies
Etanercept- TNFa receptor fusion protein (antibody)
Ustekinumab- IL-12/IL-23 antibody

Question 14

what is the definition of dermatitis?

Answer 14

Dermatitis- patches of skin that are itchy, dry, cracked and sore

Question 15

what are different underpinning immunology of dermatitis?

Answer 15

Different types – allergic (ATOPIC), contact, contact allergic, Seborrheic- term dermatitis used interchangeably with eczema
Atopic- TH2 disease- Type2 T helper CD4+ cells in skin- stimulate B-cells to make IgE (ATOPIC triad). Also Th17 involvement in Asians. Later on some other T-cell lineages may be involved (Th1 and Th22)
Allergic contact –adaptive immune response to allergen- TH1 -release of TNFa etc. Slow 24-48hr (Type IV delayed hypersensitivity).
Contact- irritant which damages the skin- also may cause inflammation.
Often the condition which gets worse over time fissured skin – but can get remission

Question 16

hat are pharmacological treatments sued for dermatitis?

Answer 16

Atopic – topical steroids (inflammation), tacrolimus (calcineurin inhibitor -like ciclosporin stopping T cell proliferation).
Systemic –methotrexate, cyclosporin. Tralokinumab– IL-13 antibody (CD4+ cells release IL-13 to stimulate B-cells)

Contact Allergic dermatitis-emollients, topical steroids, UV therapy, Tacrolimus. Also allergen patch test to avoid allergen. Avoid soaps
Contact- remove from irritant. Lotions, topical steroids
Antihistamines?- not much benefit (but causes sedation?)

Question 17

what is rosacea?

Answer 17

Rosacea-usually face redness, pimples swelling and superficial dilated blood vessels-AFFECTS FEMALES USUALLY MORE THAN MALES. PROGRESSIVE OVER YEARS

Question 18

what is the treatment for rosacea?

Answer 18

Topical ivermectin (insecticide and ant-helminthic kills mite?), topical antibiotics.
long term systemic antibiotics (metronidazole)/oxytetracycline
Severe rhinophyma- surgery

Question 19

what the definition of impetigo, incidence, and treatment for it?

Answer 19

DEFINITION- superficial infection by staphylococcus aureus or streptococcus pyogenes.
INCIDENCE- rare, except in poor hygiene- Spreads quickly (children)
Clinical features- honey crust on face and hands.
TREATMENT- remove crust-use saline, olive oil
If superficial- use topical antibiotic - fusidic acid.
IF SYSTEMIC- use penicillin/flucloxacillin, erthyromycin (also to prevent streptococcal nephritis.

Question 20

hat happens too T cells in varicella zoster virus ?

Answer 20

Infected T-cells go to skin (and nerves)

Question 21

describe the pathology underpinning vac - chicken pox and shingles.

Answer 21

Virus infects T-cells which take it to skin and nerve bodies innervating the skin (ganglia-DRG)
The innate and adaptive immune response is involved –INFs to limit the spread (innate) and B-cells to make antibodies and T-cells (CD8) to kill virus directly (again to limit the spread)
Symptoms linked to inflammation- itching, pustules, blisters (which dry) and fever etc (more severe in adult).
Shingles- virus lies dormant from childhood and breakouts in nerve endings from the spine - much more painful (neuralgia) than adult chickenpox

Question 22

hat is used for the treatment of VZV?

Answer 22

Analgesic ie, paracetamol for the high temperature/pain – not NSAIDs
Soothing drying lotions for the rash- calamine lotion (zinc oxide)/cooling gel
No topical steroids.
Perhaps anti-histamines for the itching (sedative again).
For more severe adult chickenpox/shingles anti-viral agents (Aciclovir needs to be given early (24-48hr from rash onset)
Vaccine –only given to susceptible individuals

Question 23

SCRIEB FUNGAL INFECTIOSN

Answer 23

Candida albicans- some interesting feature in skin
Uses hydrolytic enzymes such as aspartic proteases and lipases to bury into skin (toes) or nails
Dendritic cells ingulf both the yeast part and the hyphae
The yeast part mediates a TH1 response and the hyphae part a TH2 with different cytokine profiles
Often neutrophils and macrophage (as part of the innate response) –clear an initial infection and you don’t notice

Question 24

describe healkice clinical definition and treatment

Answer 24

DEFINITION- pediculosis corpus infestation
Capitis (head), pubis (pubic hair *std)
INCIDENCE- children, vagrants (but not poor hygiene)
CLLINICAL features- itch ‘dots’ on hair- eggs
Louse egg ‘nit’ hatches get dermatitis/itching from louse bites
TREATMENT – Wet combing, Hedrin (dimeticone which drowns the louse?)
Permethrin lotion (moderate insecticide-neurotoxin)

Kills Lice but eggs combed out or washed away

Question 25

describe scabies definition and treatment

Answer 25

DEFINITION – sarcoptes scabei mite infestation.
AEITIOLOGY- Female mite buries into top layer of skin- lays eggs- 14 day cycle.
Allergic reaction to mite – TH2- IgE and also longer term T-cell reaction
FEATURES- severe itch, fingers and body folds, feet in babies (often in lines)
TREATMENT- Permethrine lotion -24hrs extended areas (head to toe). Also oral ivermectin (insecticide).

Babies 2.5% Sulphur ointment (very safe)