Wk10 - Dermatology Flashcards
3 main functions of the skin
Three main functions: Protection, Regulation and Sensation
Primary function as a barrier (physical and immunological)
- mechanical impacts
- protects and detects pressure
- detects variations in temperature,
- barrier to micro-organisms
- barrier to radiation / chemicals
Physiological regulation - body temperature via sweat, hair and changes in peripheral circulation - fluid balance via sweat and insensible loss - synthesis of Vitamin D
Network of nerve cells that detect and relay changes in the environment (heat, cold, touch, and pain)
Layers of epidermis
Stratum corneum Stratum lucidum Stratum granulosum Stratu spinosum Stratum basale
Embryology of the skin
Epidermis is derived from the ectoderm
5th week, the skin of the embryo is covered by simple cuboidal epithelium
7th week single squamous layer (periderm), and a basal layer
4th month, an intermediate layer, containing several cell layers, is interposed between the basal cells and the periderm
Early fetal period the epidermis invaded by melanoblasts, cells of the neural crest origin
Hair- 3rd month as an epidermal proliferation into dermis.
Cells of the epithelial root sheath proliferate to form a sebaceous gland bud. Sweat glands develop as downgrowths of epithelial cords into dermis.
Recognise interactions between immune system and skin and how this can manifest as skin disease
Langerhans cells are members of the dendritic family, residing in basal layers.
They specialise in antigen presentation:
- Acquire antigens in peripheral tissue and transports to lymph nodes
- Presents them to naive T cells which initiate cytokine cascade
- This initiates an adaptive immune response
Langerhans cells are also involved in microbial immunity, induction of hypersensitivites and pathogenesis of chronic inflammatory diseases of the skin
Skin allergy
- Skin irritation by nonallergenic and allergenic compounds induces - Langerhans cell migration and maturation
Langerhans cells migrate from epidermis to draining lymph nodes - Initial sensitization takes 10-14 days from initial exposure to allergen (nickel, dye, rubber etc)
- Once an individual is sensitized to a chemical, allergic contact dermatitis can then develop within hours of repeat exposure exposure
Ultraviolet effects on skin
Damaging effects of ultraviolet on skin - direct cellular damage and alterations in immunologic function. Direct effects include photoaging, DNA damage and carcinogenesis
- P53 tumour suppressor genes are mutated by DNA damage, developing melanoma and non melanoma skin cancers (UV light switches off p53)
Keratinocytes and melanocytes work together to protect cells from UV DNA damage - keratinocytes flood between cells to provide protective cover
Chronic UV exposure in humans leads eventually to loss of skin elasticity, fragility, abnormal pigmentation and hemorrhage of blood vessels. Wrinkles and premature ageing
Vitamin D and the skin
During exposure to sunlight, solar UVB photons
(290-315 nm) are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D(3)
Pre-vitamin D(3) undergoes transformation within the plasma membrane to active vitamin D(3)
During our winter there is minimal pre-vitamin D(3) production in the skin. Few foods naturally contain Vit D
Associations of vitamin D deficiency - increased risk of common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease
Skin sensation - Merkel cells
Merkel cells at the base of the epidermis, respond to sustained gentle and localised pressure, assess shape /edge
Skin sensations - Meissner corpuscels
Meissner corpuscles situated immediately below epidermis and are particularly well represented on the palmar surfaces of the fingers and lips They are especially sensitive to light touch
e.g. cotton wools
Skin sensation - Ruffinis corpuscles
Ruffini’s corpuscles , situated in the dermis are receptors sensitive to deep pressure and stretching
Skin sensation - Pacinian corpuscles
Pacinian corpuscles are mechanoreceptors present in the deep dermis, sensitive to deep touch, rapid deformation of skin surface and around joints for position/proprioception
Other free nerve endings – Pain, temperature
Dermatology descriptions: Macule Papule Pustule Plaque Vesicle Bulla Ulceration
Macule - flat area of skin (different colour) Papule - raised from skin Pustule - raised and full of pus Plaque - raised, big Vesicle - small blister Bulla - large blister Erythematous - red Ulceration - epidermis has been removed, could be traumatic ulceration
Aetiology of acne
Acne is caused by:
- Keratin and thick sebum blockage of sebaceous gland
- Androgenic increased –> sebum production and viscosity
- Proprioni bacterium inflammation
- -> marked inflammation and scarring
Clinical features of acne
Papules Pustules Erythema Comedones (black heads - oxidised sebum; White heads - not oxidised (closed) Nodules Cysts Scarring
Distribution of acne vulgaris
Face
Chest
Back / Shoulders
Occassionally legs, scalp
Subtypes of acne & grading scale
Acne vulgaris:
Papulopustular (most common subtype), Nodulocystic, Comedonal
Steroid induced
Acne fulminans
Acne rosacea - mainly on face
Acne Inversus - mainly in armpits or groin (Hidradenitis suppuritiva)
Grading scale - Graded using Leeds acne grading system - Grades 1-12
Treatment options for acne
Reduce plugging through a topical retinoid or topical benzoyl peroxide
Reduce bacteria Topical antibiotics (erythromycin, clindamycin) or oral antbiotics (tetracyclines, erythromycin) - Benzoyl peroxide reduced bacterial resistance
Reduce sebum production using hormones – anti androgen ie Dianette / OCP (Change viscoity and quantity of oil produced)
Side effects
Topical agents – irritant, burning, peeling, bleaching
Oral antibiotics – gastro upset
OCP- possible DVT risk
Oral Isotretinoin is an oral retinoid for severe acne.
Dietary modification controversial
Reduced dietary/ glycaemic load eg milk, choc
Oral isotretinoin for Tx of acne
Is the only oral retinoid licensed for severe acne vulgaris
Concentrated form of vitamin A
Reduces sebum, plugging and bacteria
Remission of acne in around 80% teenagers
Standard course for 16 weeks 1mg/kg
Multiple side effects – most are trivial - Dry lips, nose bleeds, dry skin, myalgia
Serious side effects - Deranged liver function, raised lipids,
mood disturbance , teratogenicity
Pregnancy Prevention Program - Women have to be contraceptive
Pregnancy test done every 4 weeks
Expensive , consumes lots of clinical time
Eczema - Definitions & aetiology
Terms eczema and dermatitis interchangeable
Dermatitis - inflammation of the skin
Aetiology - combination of genetic, immune and reactivity to a variety of stimuli
Inflammation in eczema primarily due to inherited abnormalities in skin so called “barrier defect”.
Leads to increased permeability and reduces its antimicrobial function
An inherited abnormality in filaggrin expression considered a primary cause of disordered barrier function. Filaggrins are proteins which bind to keratin fibres in the epidermal cells (form the barrier defect).
The gene for filaggrin is on Chromosome 1 (if have genetic defect - more likely to get eczema)
Name the subtypes of eczema
Endogeneous - Atopic, Seborrhoeic, Discoid, Varicose (Venous), Pompholyx
Exogeneous - contact (allergy, irritant), Photoreaction (allergic, drug)
Atopic eczema
Itchy inflammatory skin condition
Associated with asthma, allergic rhinitis, conjunctivitis, hayfever (atopy)
High Ig-E immunoglobulin antibody levels
Genetic and immune aetiology
10-15% of infants affected
Remission occurs in 75% by 15 years
2/3 have a family history of atopy
Infant atopic eczema
Itchy Occasionally vesicular (small blisters) Often facial component Secondary infection < 50% still have eczema by 18 months occasionally aggravated by food (ie milk)
Complications of atpic eczema
Break in barrier defect - risk of infection
Bacterial infection - Staph. aureus
Viral infection - Molluscum - Viral warts - Eczema herpeticum
Tiredness
Growth reduction
Psychological impact
Management of atopic eczema
Emollients
Topical steroids (to reduce the inflammation)
Bandages (to prevent them from scratching)
Antihistamines (to try suppress itch response)
Antibiotics / anti-virals
Education for parents /child National Eczema Society
Avoidance of exacerbating factors
rarely dietary avoidance / house dust mite etc
Systemic drugs eg ciclosporin (immunosuppressive),methotrexate
Newest biologic agent IL4/13 blocker Dupilumab
Contact dermatitis
Precipitated by an exogenous agent
Irritant - direct noxious effect on skin barrier
Contact dermitis - common allergensAllergic - Type IV hypersensitivity reaction
Contact dermatitis - common allergens
Nickel - Jewellery, zips, scissors, coins
Chromate - Cement, tanned leather
Cobalt - Pigment /dyes
Colophony - Glue, adhesive tape, plasters
Fragrance- Cosmetics, creams, soaps
Features of Seborrhoeic dermatitis
Chronic, scaly inflammatory condition
Often thought to be “dandruff”
Face, scalp, and eyebrows, occ upper chest
Reaction due to overgrowth of Pityrosporum Ovale yeast
Can be worse in teenagers
Occasionally confused with facial psoriasis
Can be severe in HIV - should do HIV test
Management of Seborrhoeic Dermatitis
Scalp - medicated anti yeast shampoo
(ie Antifungal ketoconazole -Nizoral, Selsun)
Face - anti-microbial, mild steroid
(ie Daktacort cream)
Simple moisturiser
Rarely systemic antifungals
Often improves with UV / sunlight
(can give medical sunbed treatment)
Features of Venous Dermatitis
Underlying venous disease
Affects lower legs
Incompetence of deep perforating veins
Increased hydrostatic pressure
More severe - Deposits iron and haemosiderin - brown appearance
Management of venous dermatitis
Emollients
Mild / moderate topical steroid
Compression bandaging / stockings
Consider early venous surgical intervention
Definition of Psoriasis
Definition -
a chronic relapsing and remitting scaling skin disease which may appear at any age and affect any part of the skin
Prevalence 1.5 - 3%
Age onset often two peaks age 20-30y or 50-60y
What causes psoriasis?
Caused by T-cell mediated autoimmune disease- Abnormal infiltration of T Cells causes release of inflammatory cytokines (interferon, interleukins and TNF)
which cause increased keratinocyte proliferation.
Environmental and genetic factors (PSORS1 on chromosome 6)
Genes associated with psoriasis
PSORS genes (e.g. PSORS1, Chromosome 6) and HLA-Cw0602 associated in certain subtypes
Types of psoriasis
Plaque Guttate Pustular Erythrodermic Flexural / Inverse Palmar/plantar pustulosis
Psoriasis at sites of trauma / scars – Koebner phenomenon
(not Auspitz) - this has came up in exam previously
Nail findings with psoriasis
Oncholysis (painless separation of the nail from the nail bed)
Nail pitting
3 features seen with psoraisis
Salmon-pink colour
Well de-markated
Scaling on top
Relationship between psoriasis and arthritis
Up to 20% of patients with psoriasis develop psoriatic arthritis
Treatments for psoriasis
In order of increasing effectiveness (and toxicity)
Topical creams and ointments (moisturises will reduce dryness and flakiness; steroids will reduce inflammation and redness; Vit D analogues and topical retinoid treatment will slow keratinocyte proliferation)
Phototherapy light treatment (this reduces T cell proliferation, encourages Vit D production (reducing skin turnover); UV-B light most commonly used
UV-A with psoralen photosensitiser) - risks include burning and inc. risk of cancer)
Oral retinoids such as Acitretin (slows down turnover of keratinocytes)
Immunosuppressant - Methotrexate or Ciclosporin (often targets TNF)
Biologic therapies Adalumimab or Infliximab (anti TNF) Ustekinumab (anti IL12/23)
Secukinumab
Brodilumab
Fumaric acid esters
Most drugs have potent side effects i.e. liver dysfunction, hypertension, risk of infection - so need to be tailored to patient
Are screened for TB
UV Phototherapy is different to Photodynamic therapy PDT used in skin cancer
At least 2 dinstinct pathways interact or converge to cause skin cancer
- Direct action of UV on target cells (keratinocytes) for neoplastic transformation via DNA damage (This can cause immune suppression –> leads directly to skin cancer; Can also cause p53 mutation –> cancer)
- Effects of UV on the host’s immune system
(UV causes trans-UCA transformation into cis-UCA –> causes immunosuppression
What are the 3 main skin cancer types?
Basal cell carcinoma
Squamous cell carcinoma
Malignant melanoma
Features of Basal-cell carcinoma
The most common type of skin cancer
The process of creating new skin cells is controlled by a basal cell’s DNA.
A mutation in the DNA causes a basal cell to multiply rapidly and continue growing when it would normally die. Eventually the accumulating abnormal cells may form a tumour.
PTCH gene mutation may predispose to tumour development
Clinical presentation:
80 percent of basal-cell cancers are found on the head and neck / UV exposed sites
Rarely metastasis or kills
Basal cell carcinoma subtypes
1) Nodular - Circular, nodule (i.e. >0.5cm raisde lesion), shiny (‘pearly’), broken blood vessels (Telangiectasia), central ulceration often
2) Superficial - No raised nodule Roled margin Broken blood vessels No ulceration Presence of sun-damaged skin --> freckles, redness etc.
3) Pigmented - slightly raised edge, tend to be in darker skin, pigmented sections
4) Morphoeic/sclerotic - more invasive, harder to diagnose, harder for patient to pick up, the biopsy needs to be bigger as often infiltrates beneath skin –> makes it difficult to excise
Treatment of basal cell carcinoma
Gold standard – Surgical excision 3-4mm margin
Curettage and cautery
Cryotherapy - liquid nitrogen
Photodynamic therapy (painful, long and needs repeating)
Topical imiquimod / 5-fluorouracil cream (SBCC responds better, causes an immune response)
Mohs micrographic surgery (time consuming and expensive)
Features of squamous cell carcinoma
May occur in normal skin or in skin that has been injured (burns) or chronically inflamed
Originates from keratinocytes
2nd commonest skin cancer
Pre malignant variants - actinic keratoses, Bowens disease
Most SCC occur on skin that is regularly exposed to sunlight or other ultraviolet radiation
Risk of metastasis from a high risk SCC from
10 to 30% (high risk sites- ears, lips)
