Describe the process of embryological development 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
- In the early foetal 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 down-growths of epithelial cords into dermis.
What are the functions of skin?
Three main functions: protection, regulation and sensation
Protection 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 balances via sweat and insensible loss synthesis of vitamin D
Network of nerve cells that detect and relay changes in the environment (heat, cold, touch, pain)
How does the skin interact with the immune system and how does this lead to inflammatory disease?
- Langerhans cells (LC) reside in the basal layers, specialising in antigen presentation
- Acquire antigens in peripheral tissues, transport them to regional lymph nodes, present to naive T cells and initiate adaptive immune response
- Skin irritation by non-allergenic and allergenic compounds induces LC migration and maturation
- LC migrate from epidermis to draining lymph nodes
- Initial sensitisation takes 10-14 days from initial exposure to allergen (nickel, dye, rubber etc)
- Once an individual is sensitised to a chemical, allergic contact dermatitis can then develop within hours of repeat exposure
Describe what external factors (UV) can influence the 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 mutated by DNA damage
- Implicated in development of melanoma and non melanoma skin cancers
- Keratinocytes and melanocytes work together to protect cells from UV DNA damage
- Chronic UV exposure in humans leads eventually to loss of skin elasticity, fragility, abnormal pigmentation and haemorrhage of blood vessels. Wrinkles and premature ageing
Know some descriptive terms used in dermatology:
see dermatology descriptors in summary sheets
What causes acne vulgaris?
- Initial keratin and thick sebum blockage of sebaceous gland
- Androgenic increased sebum production and viscosity
- Proprionibacterium proliferation causing mild inflammation initially, progressing to marked inflammation and scarring
Characterised by papule, pustules, erythema, comedones (blocked hair follicles), nodules, cysts, scarring
What are the treatment options for acne?
Reduce plugging:
- topical retinoid
- topical benzoyl peroxide
Reduce bacteria:
- topical antibiotics (erythromycin, clindamycin)
- oral abx (tetracyclines, erythromycin)
- benzoyl peroxide reduces bacterial resistance
Reduce sebum production:
- hormones; anti androgen
Oral isotretinoin:
- concentrated form of vitamin A
- reduces sebum, plugging and bacteria
- SEs: dry skin, nose bleeds, myalgia, deranged liver function, raised lipids, mood disturbance, teratogenicity
SEs:
- topical agents: irritation, burning, peeling, bleaching
- Oral abx- gastro upset
- OPC- possible DVT risk
What is psoriasis?
Definition: a chronic replacing and remitting scaling skin disease which may appear at any age and affect any part of the skin
Genetics:
- one sibling, risk is 24%
- one parent, risk is 28%
- one sibling and one parent, risk is 41%
- two parents, risk is 65%
- if both parents and sibling, risk is 83%
PSORS genes (chromosome 6) and HLA-Cw0602 associated in certain subtypes
What are the immune mechanisms associated with development of psoriasis?
T cell mediated autoimmune disease
Abnormal infiltration of T Cells
Release of inflammatory cytokines incl interferon, interleukins and TNF (Tumour necrosis factor)
increased keratinocyte proliferation
Enviromental and genetic factors
Linked to: Psoriatic arthritis
Metabolic syndrome
Liver disease / alcohol misuse
Depression
What are the main treatment options for psoriasis?
Management: depends on severity what patient wants what patient can cope with if have arthropathy - Scoring systems: DLQI PASI PEST
Treatment in order of increasing effectiveness (and toxicity)
- Topical creams and ointments
- moisturisers, steroids, agents to slow down keratinocyte proliferation
- Phototherapy light treatment
- non-specific immunosuppressant therapy can reduce T cell proliferations, as well as reducing skin turnover
- Acitretin
- oral retinoid
- Methotrexate
- Ciclosporin
Biologic therapies
What are the conditions associated with psoriasis?
Psoriatic joint disease, metabolic syndrome
What are the subtypes of eczema?
Endogenous:
- atopic
- sebhorrhoeic
- discoid
- varicose
- pomphyolyx
Exogenous:
- contact (allergic/irritant)
- photo-reaction (allergic/drug)
What are the main treatment options for eczema?
Atopic:
- emollients
- topical steroids
- bandages
- antihistamines
- antibiotics / anti-virals
- education for parents /child
- avoidance of exacerbating factors
- systemic drugs eg ciclosporin ,methotrexate
- newest biologic agent IL4/13 blocker Dupilumab
Contact: avoidance of causative agent
Sebhorroeic:
Scalp - medicated anti yeast shampoo Face - anti-microbial, mild steroid Simple moisturiser Rarely systemic antifungals Often improves with UV / sunlight
Venous:
Emollients
Mild / moderate topical steroid
Compression bandaging / stockings
Consider early venous surgical intervention
What diseases are associated with eczema?
Hay fever, asthma, allergy
What are the effects of ultraviolet light in the skin?
At least two distinct pathways interact or converge to cause skin cancer
- Direct action of UV on target cells (keratinocytes) for neoplastic transformation via DNA damage
- Effects of UV on the host’s immune system
What are the clinical features, prognosis and management of basal cell carcinoma?
CFs:
- proliferation of basal cell
- 80% found on head and neck/ UV exposed sites
- 3/10 caucasians may develop BCC
- PTCH gene mutation may predispose
- Subtypes:
- nodular
- superficial
- pigmented
- morphoeic/sclerotic
Prognosis:
- Metastasis rare
Management:
Gold standard – Surgical excision 3-4mm margin Curettage and cautery Cryotherapy Photodynamic therapy Topical imiquimod / 5-fluorouracil cream Mohs micrographic surgery
What are the clinical features, prognosis and management of squamous cell carcinoma?
CFs:
- originates from keratinocytes
- may occur in normal skin or skin that has been injured (burns/chronic inflammation)
- pre-malignant variants:
- actinic keratoses
- bowens disease
- most SCC occur on skin that is regularly exposed to sunlight or other UV radiation
Prognosis:
- risk of metastasis from a high risk SCC from 10-30%
- high risk sites are ears and lips
Treatment:
Gold standard – Surgical excision 4mm margin
Curettage and cautery
Pre-malignant /squamous cell in-situ
Topical imiquimod / 5-fluorouracil cream
Cryotherapy
Photodynamic therapy
Sun protection
What are the clinical features, prognosis and management of malignant melanoma?
CFs:
- malignant tumour of melanocytes
- most common in skin but can be present in bowl/eye
- DNA damage, mainly UV, rarely genetic
- Radial growth, then vertical growth
Prognosis:
- accounts for 75% of deaths from skin cancer
- spread via lymphatics
- has premalignant form
- depth of presentation determines prognosis
- Assessed with Clark’s levels and Breslow depth
- measures (breslow) depth of tumour (mm)
- Clark’s levels: 1-5, affecting areas from epidermis (1) to subcutaneous tissue (5)
Treatment:
Surgical excision (Breslow < 1mm) – 1cm margin (Breslow > 1mm) – 2cm margin Immunotherapy ipilimumab Immune check point / MEK inhibitors Biologic antibodies eg BRAF genetic defects (debrafanib)
Imaging /scanning CT / MRI / PET
Long term follow up up to 5 years
Assessment for Lymph node / organ spread
Genetic testing in families, multiple primary melanomas
Describe some tumour syndromes with cutaneous presentations:
Gorlin’s syndrome
(multiple BCCs, jaw cysts, risk of breast ca)
Brook Spiegler syndrome
(multiple BCCs, trichoepitheliomas)
Gardner Syndrome – soft tissue tumours, polyps, bowel ca
Cowden’s Syndrome – multiple hamartomas thyroid, breast ca
Describe the normal skin anatomy:
Split into epidermis and dermis
Epidermis: Stratum basale Stratum spinosum Stratum granulosum Stratum lucidum Stratum corneum
Subcutaneous fat underneath dermis
Also contains hair follicles, sebaceous and eccrine glands, LC, Merkel cells, other nerve fibres
Describe the different types of psoriasis subtype:
Plaque Guttate Pustular Erythrodermic Flexural / Inverse ?palmar/plantar pustulosis
Psoriasis at sites of trauma / scars – Koebner phenomenon (not Auspitz)
How does eczema present in the skin?
Eczema and dermatitis are interchangeable terms, hence eczema is 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. The gene for filaggrin is on Chromosome 1
What 3 clinical features are required to make a diagnosis of acne?
Papules, pustules and comedones
Describe impetigo CFs, lab samples, severity, treatment and management:
CFs:
- Golden encrusted skin lesions with inflammation -localised to the dermis
- Most common in children
- Contagious and may occur in small outbreaks
Caused by S. aureus and usually mild and self-limiting
Treatment;
Treat with topical fusidic acid or systemic antibiotics if required
