Skin Flashcards
What are the symptoms of eczema?
Pruritus
Blisters
Scaling plaques
Infection may result
Describe the pathophysiology of eczema
Dermal oedema and inflammatory cell infiltration
Spongiosis and fluid filled vesicles
Scales
Epidermal hyperplasia and hyperkeratosis
What are the different types of dermatitis?
Primary irritant dermatitis Allergic contact dermatitis Atopic dermatitis Drug-related eczematous dermatitis Photoeczematous dermatitis
Describe the mechanism of the sensitisation phase of contact dermatitis
Antigen gets recognised by Langerhans cells
These are antigen presenting cells which present the antigen to naive T cells
The T cells then differentiate to form memory and effector T cells which elicit an immune response
Describe the mechanism of the re-exposure phase of contact dermatitis
Antigen gets recognised by Langerhans cells and activated T memory cells
Cytokines are released and an immune response elicited
Describe the mechanism of action of tacrolimus and pimecrolimus
Forms a complex with FKBP12 to inhibit calcineurin
Prevents phosphorylation of NFAT
Inhibiting the translocation of NFAT and thus the production of interleukins
What are the indications of tacrolimus and pimecrolimus?
Pimecrolimus - mild-to-moderate eczema
Tacrolimus - moderate-to-severe eczema
What ADRs are associated with tacrolimus and pimecrolimus?
Burning
Pruritus
What cautions surround the use of tacrolimus and pimecrolimus?
Increased risk of skin infection
Increased risk of skin cancer
Avoid exposure to UV light
What are the contraindications for the use of tacrolimus and pimecrolimus?
Hypersensitivity (including other macrolides e.g. erythromycin, sirolimus)
Skin barrier defects
Immunodeficiency
What interactions are associated with tacrolimus and pimecrolimus?
Immunosuppressants
What class of drug is ciclosporin?
A calcineurin inhibitor
Describe the mechanism of action of ciclosporin
Forms a complex with cyclophilin, inhibiting calcineurin which inhibits the phosphorylation of NFAT, inhibiting the translocation of NFAT to the nucleus and inhibiting the production/release of interleukins
What ADRs are associated with ciclosporin?
Nephrotoxicity, HTN, neurotoxicity, hepatotoxicity, hyperlipidaemia, neoplasms, infection
What cautions surround the use of ciclosporin?
Avoid UV light
Monitor renal function
Existing infection
What are the contraindications for the use of ciclosporin?
Hypersensitivity Poor renal function HTN Uncontrolled infection Cancer
What interactions are associated with ciclosporin?
Immunosuppressants
CYP3A4
Describe the mechanism of action of methotrexate
Inhibits dihydrofolate reductase
- decreased nucleotide synthesis
- increased apoptosis of T cells
- increase in adenosine is anti-inflammatory
What ADRs are associated with methotrexate?
Bone marrow suppression and blood dyscrasia Hepatotoxicity Nephrotoxicity GI ulceration Risk of infection
What cautions surround the use of methotrexate?
Impaired liver function
Blood disorder
GI ulceration
Impaired renal function
What are the contraindications for the use of methotrexate?
Severe renal or hepatic impairment
Pregnancy and lactation
What interactions are associated with methotrexate?
NSAIDs - inhibit tubular secretion, both compete for OAT3
Antifolate antibiotics - both inhibit folate synthesis
How is methotrexate secreted?
Tubular secretion by OAT3
Describe the mechanism of action of glucocorticoids
Bind with GR to promote translocation to nucleus, increasing production of anti-inflammatory cytokines and decreasing the production of pro-inflammatory cytokines
- inhibition of inflammatory gene expression
- induction of anti-inflammatory gene expression
- inhibition of leukocyte migration and activity
- inhibition of prostanoid/leukotriene synthesis
- inhibition of T lymphocyte proliferation
What ADRs are associated with glucocorticoids?
Inhibition of hypothalamic/pituitary/adrenal axis Weight gain and DM Redistribution of fat Broad anti-inflammatory effects HTN Euphoria Buffalo hump Moon face Easy bruising Poor wound healing
What cautions surround the use of glucocorticoids?
Short term use only
Avoid potent glucocorticoids in psoriasis
What are the contraindications for the use of glucocorticoids?
Uncontrolled infections
Describe the mechanism of action of retinoids
Form a complex with RAR and RXR to promote translocation to the nucleus and production of the genes regulating differentiation and proliferation, and genes that regulate apoptosis
Give examples of retinoids and their indications
Alitretinoin - eczema
Tazoretene - psoriasis
Acitretin - severe psoriasis
What ADRs are associated with the use of retinoids?
Burning, erythema
Teratogenic
What are the contraindications for the use of retinoids?
Pregnancy
Hyperlipidaemia
Hepatic and renal impairment
Give examples of vitamin D analogues
Calcipotriol, calcitriol, tacalcitol
Describe the mechanism of action of vitamin D analogues
Inhibit epidermal cell proliferation
Induce keratinocyte differentiation
Anti-inflammatory (inhibit T cell proliferation and cytokine production)
What ADRs are associated with vitamin D analogues?
Burning Erythema Pruritus Paraesthesia Hypercalcaemia
What are the contraindications for the use of vitamin D analogues?
Calcium metabolism disorders
Give examples of TNF-alpha inhibitors
Etanercept
Infliximab
Adalimumab
What ADRs are associated with TNF-alpha inhibitors?
Increased risk of infection
What cautions surround the use of TNF-alpha inhibitors?
Predisposition to infection
What are the contraindications for the use of TNF-alpha inhibitors?
Uncontrolled infection
What interactions are associated with TNF-alpha inhibitors?
Live vaccines
What class of drug is ustekinumab?
IL12/IL23 inhibitor
What ADRs are associated with the use of ustekinumab?
Increased risk of infection
What cautions surround the use of ustekinumab?
Predisposition to infection
What are the contraindications for the use of ustekinumab?
Uncontrolled infection
What interactions are associated with ustekinumab?
Live vaccines
What are the functions of the skin?
Regulate body temperature Store blood Protect body from external environment Detect cutaneous sensations Excretion and absorption Synthesis of vitamin D
What is the function of keratinocytes?
Produce keratin and lamellar granules to decrease water loss from skin and protect skin from heat, microbes and chemicals
Name the 5 layers of the epidermis
Stratum basale Stratum spinousum Stratum granulosum Stratum lucidum Stratum corneum
Outline the process of keratinisation
Keratinocytes accumulate keratin, and are pushed up from the stratum basale, and undergo apoptosis at the stratum granulosum and are sloughed off when they reach the stratum corneum.
Describe atopic dermatitis
Most commonly affects flexures
Type IgE mediated
FH of atopy
What type of dermatitis is type IgE mediated?
Atopic dermatitis
What patient groups get gravitational dermatitis?
Those with varicose veins
What type of dermatitis is type IV mediated?
Allergic contact dermatitis
What are the 4 Ps of lichen planus?
Pruritic
Purple
Polygonal
Papules
Describe the process of healing by primary intention
Acute inflammation Platelets Thromboplastin Vasodilation Neutrophils and macrophages Fibroblasts Scab Epithelial cells Healed 2-3w
Outline the process of healing by secondary intention
Necrosis
- debridement
Granulation
- inflammation
- infiltration with erythrocytes, leukocytes and platelets
- endothelial cells
- growth factors
Epithelialisation
Which part of a hydrocolloid dressing is hydrophilic?
Granules
Which part of a hydrocolloid dressing is hydrophobic?
Adhesive matrix
How do hydrocolloid dressings work?
Slowly absorb fluid from wound, forming cohesive or hydrophilic gel
What are the components of foams?
Absorbent polyurethane with other components:
- hydrocellular foams
- hydropolymer foams
- soft silicone foams
- foam and silver
- foam and charcoal
What component of an alginate dressing forms a soft flexible gel?
Mannuronic acid
What component of alginate dressings form a firm gel?
Guluronic acid
What types of dressing can be used in a low granulating wound?
Foams
hydrogels
What types of dressings can be used in a wound with light to medium exudate?
Foams
Alginates
Thin hydrocolloids
Hydrogels
What types of dressings can be used in a wound with medium to heavy exudate?
Alginates
Hydrocolloids
Foams
What types of dressings can be used in a wound with heavy exudate?
Alginates
Hydrocolloids
Foams
