Dermatology Flashcards
Epidermis cell type
Stratified cellular epithelium
comes from ectoderm
Epidermis Layers
Basal layer
Prickle layer
Granular layer
Keratin layer
epidermal cell are …
95% keratinocytes
5%: Melonocytes, langerhands and merkel
Basal layer
Made of laminin and collagen IV
- one cell thick
Prickle cell layer
- Larger polyhedral cells
- Lots of desmosomes (connections)
- Concur cohesive strength to the surrounding cells but also promoting movement
Granular layer
2-3 layers of flatter cells
• Large keratohyalin granules – contain structural filaggrin & involucrin proteins
- Bind intermediate keratin filaments together
• Odland bodies (lamellar bodies)
- Cells secrete these into extracellular space resulting in formation of hydrophobic lipid envelope (cornified envelope) – skin barrier
• Cell nuclei lost – non-viable corneocytes
Keratin layer
- Corneocytes: overlapping non-nucleated cell remnants
- Insoluble cornified envelope
- 80% keratin & filaggrin
Melanocytes
Migrate from the neural crest to the epidermis in first 3 months of foetal development
Pigment producing dendrite cells - organelles called melanosome
Convert tyrosine to melanin pigament
- eumelanin (Brown/black)
- phaeomelanin (red/yellow)
Melanin
Melanin caps protect the nuclear DNA in basal cells (protective cap over nucleus) and absorb light
Langerhans cells
Mesenchymal origin – bone marrow
Prickle cell level in epidermis but also found in dermis and lymph nodes
Antigen presenting cells
Racket organelle (Birbeck granule): A rod or tennis racket-shaped cytoplasmic organelle solely found in Langerhans cells and hence a marker for Langerhans cell histiocytosis
Merkel cells
- basal and found between keratinocytes & nerve fibres
* mechanoreceptors
Hair follicles “Pilosebaceous unit”
- Epidermal component plus dermal papilla
- Specialised keratins
- Adjacent sebaceous gland – natural moistures
- Hair pigmentation via melanocytes above dermal papilla
Phases of hair growth
Anagen = growing (2-6 years)
Catagen = involuting (4 week period)
Telogen = resting (5-10%)
Types of hair growth
lanugo, vellus and terminal
Nails
• Specialised keratins • Nail matrix / root similar to hair bulb • Growth rate 0.1mm per day o Fingers > toes o Summer > winter • Some drugs increase nail / hair growth
Dermis layers
Papillary dermis is thin and lies just beneath epidermis
Reticular dermis thicker bundles type 1 collagen
• Reticular dermis contains appendage structures-sweat glands, pilosebaceous units
Ground substance – hyaluronic acid + chondroitin sulphate
Muscles, blood, lymph and nerves
Mesoderm
Lymphatics
Smaller non-contractile vessels ==> larger contractile lymphatic trunks
Sensory nerves
Free nerve endings
Pacinian (pressure and deep cutis) and Meissner (vibration and basal)
Sebaceous glands
holocrine secretion opening into pilary canal. Largest glands face and chest – clinical implications
• hormone sensitive – quiescent pre-puberty
• Produce sebum: squalene, wax esters, TG and FFA
• Functions: control moisture loss, helps protect against fungal infection
Apocrine sweat glands
- Develop as part of pilosebaceous unit
- Axillae and perineum
- Androgen dependent
- Produce oily fluid odour after bacterial decomposition
Eccrine sweat glands
• Whole skin surface o palms, soles and axillae in particular • Sympathetic cholinergic nerve supply – mental, thermal and gustatory stimulation • Functions: cooling by evaporation o moisten palms/soles to aid grip
Skin function
Barrier (physical, chemical and pathogens)
Vit D and thyroid hormone metabolism
thermoregulation
immune defence
communication
sensory function
Blaschko’s lines
developmental growth pattern of skin – not following vessels, nerves or lymphatics. The disease follows the lines
Cephalic Vein
• arises from dorsal venous network o lateral aspect of limb o in deltopectoral groove o drains into axillary vein o becomes subclavian at lateral border of rib 1
Basilic Vein
• arises from dorsal venous network
o medial aspect of limb
o drains into brachial vein
o level of mid-arm
great saphenous vein:
• arises from dorsal venous arch
o medial aspect of limb
o drains into femoral vein
o femoral triangle
small saphenous vein:
• arises from dorsal venous arch
o posterior midline of leg
o drains into popliteal vein
o posterior to knee
Superficial lymphatics in arms
from plexuses in fingers and hand
- Basilic => cubital lymph nodes => lateral axillary lymph nodes
- Cephalic => mainly to apical axillary lymph nodes
Deep lymphatics of arm
o Follow deep veins of upper limb
o Drain into lateral axillary lymph nodes
Superficial lymphatics in legs
Great saphenous vein => superficial inguinal lymph nodes => external iliac nodes or deep inguinal nodes
Small saphenous vein => popliteal nodes => deep inguinal nodes => external iliac nodes
Deep lymphatics of legs
Drain into popliteal lymph nodes =>deep inguinal nodes => external iliac nodes
TH1?
TH2?
TH17?
Associated diseases
TH1 (psoriasis), TH2 (atopic dermatitis) & TH17 (psoriasis and atopic dermatitis).
Plasmacytoid DC (pDC):
produce IFNα. Found in diseased skin
Atopic eczema
• Impairment of skin barrier function is a key factor:
o Mutations in fillagrin gene associated with severe/early onset disease.
o ↓AMP in skin (antimicrobial proteins)
• T cells (TH2), DC, KC, macrophages and mast cells are involved/found in the lesions (probably attracted by stressed KC)
• The defective skin barrier allows access/sensitisation to allergen and promotes colonisation by micro-organisms.
Type 1 allergy
- Immediate reaction - occurs within minutes & up to 2 hours after exposure to allergen
- Routes of exposure – skin contact, inhalation, ingestion and injection
- History – consistent reaction with every exposure
Type 1 allergy signs/symptoms
Urticaria: Lesions appear within 1 hour and last 2-6 hours, sometimes 24 hours
Angioedema: Localised swelling of subcutaneous tissue or mucous membranes
Type 1 allergy Ix
• History – most important!
• Specific IgE (RAST)
- Skin prick or prick-prick testing
• Challenge test: only do if skin prick test is negative
• Serum mast cell tryptase level (during anaphylaxis
Type 1 allergy Mx
Allergen avoidance
• Prevent effects of mast cell activation (anti-histamines)
• Anti-inflammatory agent (corticosteroids)
• Adrenaline autoinjector (for anaphylaxis): 300ug adults and 150ug children. Prescribed 2 pens
• Block mast cell activation (mast cell stabilisers – sodium cromoglycate)
• Immunotherapy – pollens but most allergies have no immunotherapy
Type IV Allergy
- Delayed hypersensitivity
- Antigen specific and T Cell mediated
- Allergic contact dermatitis/eczema
- Onset of reaction typically after 24-48 hours
Type IV allergy Ix
Patch testing. On finn chambers and Removed after 48 hours and read at 48 and 96 hours due to delayed hypersensitivity
Virulence Factors
- Adhesin: Enables binding of the organism to host tissue
- Invasin: Enables the organism to invade a host cell/tissue
- Impedin: Enables the organism to avoid host defence mechanisms
- Aggressin: Causes damage to the host directly
- Modulin: Induces damage to the host indirectly
TSST
Toxic shock syndrome toxin - super antigen from staph aureus
Massive release of cytokines and inappropriate immune response
Toxins
TSST
SSS
Staphylococcal Food poisoning (enterotoxin SeA SeB & SeC)
Toxic shock syndrome diagnosis
Fever: 39˚C
Diffuse Macular rash & desquamation. diffuse macular erythroderma (“sunburn”)
• Hypotension (≤ 90 mm Hg (adults))
• ≥ 3 Organ systems involved e.g. liver, blood, renal, mucous membranes, GI, muscular, CNS.
o Whole body shock
Menstructual shock – staph colonies the tampon from perineum which passes to the vagina and then into the blood
PVL
Panton-Valentine Leukocidin. specific toxicity for Leukocytes
with CA-MRSA (community associated) responsible for necrotizing pnuemonia & contagious severe skin infections.
Staph Aureus infections
Boils and Carbuncles Other minor skin sepsis (infected cuts etc.) Cellulitis Infected eczema Impetigo Wound infection Staphylococcal scalded skin syndrome
Coagulase negative Staphs (e.g. Staphylococcus epidermidis)
Skin commensals - not usually pathogenic
May cause infection in association with implanted artificial material, such as artificial joints, artificial heart valves, intravenous catheters (produces “slime” that allows it to stick to prosthetic material)
Staph. saprophyticus causes urinary tract infection in women of child-bearing age
Strep categories
alpha (viridans and pneuomaniae), beta (A: strep pyogenes, B: agalactiae, C), gamma
Throat, severe skin infections and scarlett fever
strep pyogenes
strep pyogenes infections
• Infected eczema • Impetigo • Cellulitis Erysipelas Necrotising fasciitis
strep and staph treatment
Flucloxacillin (staph and strep)
penicillin (strep)
Vancomycin (MRSA)
Tinea …
o Tinea capitis - scalp o Tinea barbae - beard o Tinea corporis - body o Tinea manuum – hand o Tinea unguium - nails o Tinea cruris - groin o Tinea pedis – foot (athlete’s foot)
Dermatophyte pathogenesis
- Fungus enters abraded or soggy skin
- Hyphae spread in stratum corneum
- Infects keratinised tissues only (skin, hair, nails)
- Increased epidermal turnover causes scaling
- Inflammatory response provoked (dermis)
- Hair follicles and shafts invaded
- Lesion grows outward and heals in centre, giving a “ring” appearance
Fungal infection organisms
- Trichophyton rubrum** (accounts for >70% of lab isolates): Human- human transmission
- Trichophyton mentagraphytes (next most common isolate (>20%): Human-human transmission
- Microsporum canis (occasional isolate): cats, dogs-humans
Exanthematous drug eruptions
measles like, macuale, popular like
• Most common type of drug eruption (90%)
• Idiosyncratic, T-cell mediated delayed type hypersensitivity (Type IV) reaction
• Usually mild & self-limiting – most go away when the drug is stopped
• Widespread symmetrically distributed rash
• Mild fever is common – can make it confusing to differentiate between viral and drug eruption
Onset is 4-21 days after first taking drug
Drugs associated with exanthematous eruptions
- Penicillins esp if glandular fever
- Sulphonamides
- Erythromycin
- Streptomycin
- Allopurinol
- Anti-epileptics: carbamazepine, phenytoin
- NSAIDs
- Chloramphenicol
Urticarial drug reactions
itchy erythematous wheals that move around appear rapidly after drug exposure+/- angioedema/analphyxis
• Usually an immediate IgE-mediated hypersensitivity reaction (Type I) after rechallenge with drug (β-lactam antibiotics, carbamazepine, many other drugs)
• Some drugs can directly release of inflammatory mediators (histamine) from mast cells on first exposure (aspirin, opiates, NSAIDs, muscle relaxants, vancomycin, quinolones)
Pustular or bullous drug eruptions
• Acneiform
o Glucocorticoids (steroid acne)
o Androgens, lithium, isoniazid, phenytoin
• Acute generalised exanthematous pustulosis (AGEP)
o Antibiotics, calcium channel blockers, antimalarials
• Vesicular/bullous reactions can range from mild to severe
• Drug-induced bullous pemphigoid
o ACE inhibitors, penicillin, furosemide
• Linear IgA disease can be triggered by drugs
o Vancomycin
Fixed drug eruptions
- Well demarcated round/ovoid plaques (Red, painful)
- Hands, genitalia, lips, occasionally oral mucosa
- Resolves with persistent pigmentation when drug stopped
- Tetracycline, doxycycline, paracemtol, NSAIDS, carbamazepine, sulfaminades and aspirin
Stevens-Johnson syndrome (SJS)
rare, serious disorder of your skin and mucous membranes. It’s usually a reaction to a medication or an infection. Often, it begins with flu-like symptoms (vague upper respiratory symptoms), followed by a painful red or purplish rash that spreads and blisters
Painful erythematous macules - target lesions. Severe mucosal ulceration of more than 2 surfaces
Toxic epidermal necrolysis (TEN)
o Systemic and multi-organ failure. Flu like symptoms precede skin involvement
o Widespread dusky painful erythema then necrosis of epidermis. Musose affected
o Sulfonamides, cephalosporins, carbamazepine, phenytoin, NSAIDs, nevirapine, lamotrigine, sertraline, pantoprazole, tramadol
o ICU, relieve pain, protect skin and avoid steroids due to risk of infection
Drug reaction with eosinophilia & systemic symptoms (DRESS)
Sulfonamides, anticonvulsants, allopurinol, minocycline, dapsone, NSAIDs, abacavir, nevirapine, vancomycin
Causes of itch:
Pruritoceptive
Neuropathic
Neurogenic
Psychogenic
Itch Mx
- Sedative: anti-histamines (non-sedative antihistamines useless for most itch except where excess histamine in the skin is part of the mechanism)
- Emollients (with menthol, or cooled in fridge – counter-irritant effects)
- Antidepressants, e.g. doxepin and some of the newer ones including SSRIs
- (For some types of neuropathic itch, anti-epileptics)
- Phototherapy
- Opiate antagonists, ondansetron (a serotonin antagonist), etc
Creams
Semisolid emulsion of oil in water
Contain emulsifier & preservative
Ointments
o Semisolid grease/oil (soft paraffin)
o No preservative – be careful because you don’t want bacterial spread
o Occlusive and emollient
Lotions
Liquid formulation
Suspension or solution of medication in water, alcohol or other liquids
Gels
o Thickened aqueous lotions
o Semi-solids, containing high molecular weight polymers eg methylcellulose
Pastes
Semisolids
o Often used in cooling, drying, soothing bandages
o Could at preventing macerating of the skin surrounding the ulcer
• Foams
o Colloid with two – three phases
o Usually hydrophilic liquid in continuous phase with foaming agent dispersed in gaseous phase
Emollients
- Enhance rehydration of epidermis
- For all dry/scaly conditions esp. eczema
- Need to be effective and cosmetically acceptable
- Prescribe 300-500g weekly -see BNF
Topical corticosteroids mechanism
- Vasoconstrictive
- Anti-inflammatory
- Antiproliferative
Examples of corticosteroids and potency
Hydrocortisone mild
Modrasone clobetsone butyrate - moderate
betamethasone valerate potent
clobetasol proprionate - very potent
HYPERKERATOSIS PARAKERATOSIS ACANTHOSIS PAPILLOMATOSIS SPONGIOSIS
• Increased thickness of keratin layer
Persistence of nuclei in the keratin layer
Increased thickness of epithelium
Irregular epithelial thickening
Oedema fluid between squames appears to increase prominence of intercellular prickles. If severe vesicles filled by oedema fluid develop.
UVB leads to direct DNA damage: what are the photo products?
cyclobutane pyrimidine dimers (CPDs) – more common
pyrimidine–pyrimidone (6–4) photo-products – more mutagenic
o Repaired by nucleotide excision repair
o CC → TT UV signature mutation
UVA causes indirect DNA damage: what are the photo products?
o Oxidation of deoxyguanosine forming 8-oxo-deoxyguanosine
o Repaired by base excision repair
o C → A point mutation
MCR1
- One defective copy of MC1R causes freckling
* Two defective copies-red hair and freckles
Freckles (ephilides)
- Patchy increase in melanin pigmentation
- Occurs after UV exposure
- Reflects clumpy distribution of melanocytes
Actinic lentigines
- Related to UV exposure – chronic exposure
- Epidermis elongated rete ridges
- Increase melanin and basal melanocytes
Congenital melanocytic naevi
- Small <2cm diameter
- Medium >2cm but <20cm diameter
- Giant-garment type lesions
- Large lesions 10-15% risk of melanoma so may need surgical excision
Usual type acquired naevi
Junctional naevus (DEJ) - CHILDHOOD
compound naevus - junctional clusters and groups of cells in dermis - early adulthood
intradermal naevus - all junctional activity had ceased - adult
Dysplastic Naevi (DN)
- Generally >6mm diameter, variegated pigment and border asymmetry
- Architectural atypia AND cellular atypia
- Unlike melanoma epidermis not effaced
- Severe dysplasia may be difficult to distinguish from melanoma in-situ
Halo naevi
Peripheral halo of depigmentation. They show inflammatory regression and are overrun by lymphocytes. Young adults – full of lymphocytes attack it and the melanocytes
Blue naevi
entirely dermal and consist of pigment rich dendritic spindle cells
The Spitz naevus
• Consist of large spindle and/or epithelioid cells – melanocytes becomes spindle
• May closely mimic melanoma
• Most are entirely benign
• Spitz naevus-note pink coloration due to prominent vasculature
o Small and well defined
o Epidermal hyperplasia
Alopecia areata
condition that causes hair to fall out in small patches, which can be unnoticeable. These patches may connect, however, and then become noticeable. The condition develops when the immune system attacks the hair follicles, resulting in hair loss.
Hirsutism
Excess hair growth
Vitiligo
autoimmune disease with loss of melanocytes
X-linked ichthyosis
genetic skin disorder that affects males. It is an inborn error of metabolism characterized by a deficiency of the enzyme steroid sulfatase. … The normal shedding of dead skin cells is inhibited and the skin cells build up and clump into scales.
ALBINISM
genetic partial loss of pigment production
• Does have melanocytes but doesn’t produce melanin
congenital disorder characterized in humans by the complete or partial absence of pigment in the skin, hair and eyes.
Albinism is associated with a number of vision defects, such as photophobia, nystagmus, and amblyopia.
NELSON’S SYNDROME
melanin stimulating hormone is produced in excess by the pituitary
- hyperpigmentation is caused by high levels of circulating ACTH that bind to the melanocortin 1 receptor on the surface of dermal melanocytes
- increase in skin pigmentation, so patients may look as if they have a suntan
Merkel cell cancer
Rare and high mortality
caused by viral infection
Contact allergic dermatitis (type IV reaction)
Response to chemicals, topical therapies, nickel, plants etc. Has to be something in contact with the skin e.g. nickel or latex
Pathology of contact dermatitis (IV)
• Langerhans cell in epidermis processes antigen (immunogenicity).
• Processed antigen is then presented to Th cells in dermis
• Sensitised Th cells migrate into lymphatics and then to regional nodes where antigen presentation is amplified
• On subsequent antigen challenge specifically sensitised T-cells proliferate and migrate to and infiltrate skin
o dermatitis
contact allergic dermatitis signs/symptoms
Erythema, scaling, fissuring, lichenification (thick and leathery), nail dystrophy, crusting
contact allergic dermatitis Ix and Mx
Ix: Patch testing
Mx: • Avoid allergens • Cover exposed areas • Treat eczema with emollients • Topical steroid depending on severity • Treat infection
Irritant (contact) dermatitis
• Non-specific physical irritation rather than a specific allergic reaction
E.g.Soap/detergent/cleaning products, water, oil
Irritant (contact) dermatitis signs/symptoms
fissuring, erythema, scaling, crusting, lichenifcation and nail dystrophy
sparing of flexures
Irritant (contact) dermatitis Mx
- Avoid all irritants, hand care (soap subisitiues, regular emollients, careful drying, cotton or cotton lined gloves for wet and dry work
- Topical steroids for acute flare up
Atopic eczema gene
filaggrin
Atopic eczema signs/symptoms
• Pruritus • Ill-defined erythema & scaling • Generalised dry skin • Flexural distribution (varies with age) – folds in the wrist • Associated with other atopic diseases: • ichthyosis vulgaris from filaggrin mutations (dry, thick and itchy skin) - Lichenification - Excoriation
Atopic eczema Ix
Itching plus 3 or more: • Visible flexural rash* • History of flexural rash* • Personal history of atopy (or first degree relative if under 4 yo) • Generally dry skin • Onset before age 2 years
Atopic eczema Mx
- Education
- Plenty of emollients
- Avoid irritants/allergens including shower gels and soaps – washing hear in the sink so the shampoo does not go on the skin
- Topical steroids – exacerbations
- Treat infection
- Phototherapy – mainly UVB
- Systemic immunosuppressants
- (Biologic agents)
complications of atopic eczema
• Crusting indicates Staph aureus infection
• Eczema herpeticum
o Herpes simplex virus
o Monomorphic punched-out lesions
Discoid Eczema
long-term skin condition that causes skin to become itchy, reddened, swollen and cracked in circular or oval patches.
Photosensitive eczema
- Chronic Actinic Dermatitis
- Look for cut offs e.g. cut-off at collar
- These patients are often atopic too
- Drug induced: clinical history showing that drug use is causing it: Secondary to photosensitising drugs
Stasis eczema
need to treat underlying condition issues e.g. varicose vein
- hydrostatic pressure
- oedema
- red cell extravasation
Pompholyx eczema
usually restricted to the hands and feet.
In most cases, pompholyx eczema involves the development of intensely itchy watery blisters, mostly affecting the sides of the fingers, the palms of the hands and the soles of feet.
rapid onset
Psoriasis
Chronic inflammatory skin condition characterised by scaly erythematous plaques which typically follows relapsing remitting course
Psoriasis pathology
Proliferation and dilation of blood vessels in epidermis – infiltration of inflammatory cells such as T cells and neutrophils
o ?Complement mediated attack on keratin layer
o Complement attracts neutrophils to keratin layer
o Munro micro abscesses – a useful diagnostic clue
Psoriasis triggers
Stress, infections (strep pneumonia), koebner phenomenon (trauma), drugs (lithium, NSAIDS and beta-blockers), alcohol, obesity and smoking
Psoriasis types
Chronic plaque psoriasis: symmetrical well-defined red plaques with silvery scale on extensor aspects of the elbows, knees, scalp, sacrum and feet.
Flexural psoriasis: plaques in moist flexural areas (axillary, groins, sub mammary)
Guttate psoriasis: Large numbers of small plaques over the trunk and limbs (young).
Pustular psoriasis (palmoplantar): yellow-brown pustules with plaques affecting palms and soles
Erythrodermic psoriasis (widespread pustular): systemic upset (fever, increase in WBC, dehydration). Medical emergency Nail changes
Psoriasis Ix
Koebner phenomenon: psoriasis develops in area of skin trauma e.g. scratch mark or scar
Auspitz sign: removal of surface scale reveals tiny bleeding points (dilated capillaries in elongated dermal papillae
Psoriasis Mx (mild)
1) EMOLLIENTS
2) Vitamin D analogues
o Calcipotriol (Dovonex)
o Calcitriol (Silkis)
3) Steroid ointments – usually in combination with Vitamin D/ risk of rebound e.g. Betamethasone valerate 0.1% + calcipotriol
o Don’t use for more than 8 weeks and 4 week break before restarting
4) Coal tar – if Vitamin D has failed or widespread: anywhere no limit
5) Dithranol
Psoriasis Mx (moderate to severe)
Phototherapy e.g. Narrowband UVB and PUVA (guttate or plaque)
Systemic treatments e.g. immunosuppresion such as methotrexate
or Immune modulation such as targeted biological agents
e.g. infliximab & etanercept (TNF antagonist), Apremilast (PDE-4 inhibitor)
Guttate Psoriasis Mx
o 1st line = narrow band UVB therapy
o 2nd line = Methotrexate and/or oral retinoid
Scalp Psoriasis Mx
o Potent topical steroid lotion or Vit D analogue scalp prep. Coal tar shampoos may help
Lichenoid disorders
damage to basal epidermis and infiltration between the epidermis and dermis
Lichenoid disorders signs/symptoms
Itchy flat-topped violaceous papules (raised area less than 1cm)
Lichen planus
lesions (flexor aspects of wrists, forearms, ankles and legs) are purple, pruritic, poly-angular, plantar (flat topped), papules seem at any age and have white lacy markings on surface of papules and buccal mucosa (Wickhams straie)
- T cell-mediated inflammation targeting an unknown protein within the skin and mucosal keratinocytes.
- Other lesions: scalp, nails, tongue, mouth (lacy white areas on inner cheek) and gentials
Lichen planus biopsy
o Irregular sawtooth acanthosis (diffuse epidermal hyperplasia)
o Hypergranulosis and orthohyperkeratosis
o Band-like upper dermal infiltrate of lymphocytes
o Basal damage with formation of cytoid bodies
Lichen planus Mx
• Check for possible drug percipient • Emollients • Treat symptomatically o topical steroids (potent or very potent) o oral steroids if extensive
UVB Phototherapy or PUVA
Oral disease: fluticasone spray
Pemphigus Vulgaris
• Loss of integrity of epidermal cell adhesion
o IgG autoantibodies made against desmoglein 1 and 3
• Desmoglein 3 maintains desmosomal attachments
• Immune complexes form on cell surface
• Complement activation and protease release
• Disruption of desmosomes
• End result is ACANTHOLYSIS
Pemphigus Vulgaris signs/symptoms
Flaccid superficial blisters which rupture easily to leave widespread shallow erosions
• Involves skin esp. scalp, face, axillae, groin, trunk
• May affect mucosa e.g. mouth, resp.tract. Extensive mucosal involvement may be fatal
Pemphigus Vulgaris Ix
- Skin biopsy: +ve immunofluorescence (intercellular IgG giving a crazy paving affect)
- Nikolsky’s sign = positive
- Circulating anti-epidermal antibodies can be detected by a blood test (indirect immunofluorescence test).
Pemphigus Vulgaris Mx
- Prednisolone (40-60mg/day PO) with gradual tapering
- Steroid sparing: azathioprine, methotrexate or cyclophosphamide
- Rituximab (anti-CD-20) and IV immunoglobulin in resistant cases
Bullous Pemphigoid
Fragility at the dermo epidermal junction
elderly >80 years old
• Autoimmune disease
• Circulating antibodies (IgG) react with a major and/or minor antigen of the hemidesmosomes anchoring basal cells to basement membrane. The result is local complement activation and tissue damage
Bullous Pemphigoid signs/symptoms and Ix
• Non-specific rash for several weeks before blisters appear
o Urticated itchy plaques rather bullae in early disease
• Subepidermal blister – tense (1-3 cm in size) on inflamed or normal skin
• They develop on areas of skin that often flex — such as the lower abdomen, upper thighs or armpits.
• localized to one area, or widespread on the trunk and proximal limbs
- Skin biopsy +ve IgG and C3 on BM
- Nikolsy sign negative
Bullous Pemphigoid Mx
- Emollients
- Topical antisepsis/hygiene measures
- Very potent topical steroids e.g. clobetasol
- Prednisolone (0.3-1.0mg/kg/day PO)
- Blisters heal however relapsing course 5-10 years
- Tetracycline antibiotics
Dermatitis Herpetiformis
- Strong association with coeliac disease
- IgA antibodies target gliadin component of gluten but cross react with connective tissue matrix proteins
- Immune complexes form in dermal papillae and activate complement and generate neutrophil chemotaxins.
Dermatitis Herpetiformis Ix
- Hallmark is papillary dermal micro abscesses
* DIF shows deposits of IgA in dermal papillae
Epidermolysis Bullosa types
- EB simplex – cells stop sticking together in the epidermis
- Junctional – cells stop sticking together at epidermal-dermis junction
- Dystrophic – at the dermis – scarring – recurring over lifetime. Gradually the digits become shorter and become a stump (very disabling)
Epidermolysis Bullosa signs/symptoms
• Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal.
Acne
Chronic inflammatory disease of the pilosebaceous unit
Acne pathology
- Basal keratinocyte proliferation in pilosebaceous follicles (androgen drive) – poral occlusion
- Increase in sebum production: increase in androgens and androgen sensitivity
- Propionibacterium acnes colinsation
- Inflammation (dermal) and foreign body granulomas
- Comedones (white and black) blocking secretions, hence papules, nodules, cysts and scars
Acne diagnosis
- Mild- scattered papules and pustules, comedones
- Moderate - numerous papules, pustules & mild atrophic scarring
- Severe - cysts, nodules and significant scarring
Mild acne Mx
Topical treatment (mild/moderate acne)
o Benzoyl peroxide – keratolytic, antibacterial
o Topical vitamin A derivatives (retinoid) - drying effect
o Topical antibiotics – antibacterial and anti-inflammatory – clindamycin 1%
Moderate acne Mx
o 1st line: Tetracycline, doxycycline or erythromycin if preg or under 12
o Topical retinoid
Severe acne Mx
Isotretinoin (oral retinoid) –
• +/- oral prednisolone (not long term)
• Laser therapy and dermabrasion for scarring.
Rosacea
Chronic and relapsing disorder of blood vessels and pilosebaceous units in central facial areas typically in fair skinned people
o Patchy inflammation with plasma cells
o Pustules
o Perifollicular granulomas
o Follicular Demodex mites often noted (Allergic reaction to mites)
• Triggered by stress/blushing, alcohol, sunlight and spices
Rosacea signs/symptoms
- Recurrent facial flushing – central with erythema, telangestia
- Visible blood vessels
- Pustules and papules (without comedones)
- Inflammatory nodules
- Thickening of skin - rhinophyma
Rosacea Mx
Reduce aggravating factors:
Metronidazole gel, Ivermectin (to reduce demodex mite)
Oral tetracycline long term or erythromycin if contradicted
Isotretinoin low dose if severe
Telangiectasia : vascular laser
Rhinophyma: surgery/ laser shaving
Porphyria cutanea tarda (PCT)
reduced enzyme activity of uroporphyrinogen decarboxylase resulting in overproduction of photoactive porphyrins
- Triggers e.g. HIV, Hep C, alcohol, increase iron levels (Fe supplements/hemochromatosis)
- Caused chronic liver disease and excess iron build up
Porphyria cutanea tarda (PCT) signs/symptoms
• Vesicles/bullae in sun exposed sites – visible light not UV light
• Hypertrichosis: abnormal amount of hair growth over the body
• Solar urticaria
Hyperpigmentation
• Morphoea: patch or patches of discoloured or hardened skin on the face neck, hands, torso or feet
• Skin fragility
• Scarring (milia)
Porphyria cutanea tarda (PCT) dx
- Faecal & urinary porphyrins (woods lamp – goes red)
- Spectrophotomterer
- Skin biopsy
Porphyria cutanea tarda (PCT) Mx
• Remove and treat percipients (underlying cause) o Alcohol o Viral hepatitis o Oestrogens o Haemochromatosis • Sun avoidance/protection • Regular venesection • Low dose chloroquine
Erythropoietic protoporphyria
deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells (erythrocytes), plasma, skin, and liver.
Erythropoietic protoporphyria signs/symptoms
- Mild anaemia
- Gallstones by 40 – multiple pigment gallstones
- Pain/unpleasant sensation with physical light exposure but no blistering or erythema
Erythropoietic protoporphyria Mx
6 monthly LFTs and RBC porphyrins
• Visible light photoprotection measures
o Behavioural (e.g. avoid middle of day sunlight)
o Clothing (importance of weave, colour, etc)
o Environmental (e.g. shade trees, window films)
o Topical sunscreen
• May need liver and bone marrow transplant
Acute intermittent porphyria
partial deficiency of the enzyme hydroxymethylbilane synthase (also known as porphobilinogen deaminase). This enzyme deficiency can result in the accumulation of porphyrin precursors in the body.
Acute intermittent porphyria signs/symptoms
- Severe abdominal pain.
- Pain in your chest, legs or back.
- Constipation or diarrhoea.
- Nausea and vomiting.
- Muscle pain, tingling, numbness, weakness or paralysis.
- Red or brown urine.
- Mental changes, such as anxiety, confusion, hallucinations, disorientation or paranoia.
Acute intermittent porphyria Ix and Mx
increased urinary porphobilinogen secretion
- Mild attacks can be managed with increased caloric intake and fluid replacement. Recurrent acute attacks should be managed by a porphyria specialist. Hospitalization is often necessary.
- Panhematin, an intravenous medication used to correct heme deficiency, may also be prescribed.
Necrotising faciitis
Bacterial infection spreading along fascial planes below skin surface → rapid tissue destruction
• 2 types:
o Type I – mixed anaerobes & coliforms, usually post-abdominal surgery
o Type II – Group A Strep infection
Necrotising faciitis Mx
surgical debridement
antibiotics
Fungal infections Diagnosis
• Clinical appearance
• Woods light (fluorescence)
• Skin scrapings, nail clippings, hair – taken from the scaly edge of the lesion
o Send to laboratory in a “Dermapak” for microscopy and culture
o N.B. Culture takes 2 weeks +
Fungal infections Mx
Small areas of infected skin, nails o Clotrimazole (Canestan) cream or similar o Topical nail paint (amorolfine)
• Extensive skin infections, nail infections and scalp infections
o Terbinafine orally
o Itraconazole orally
Candida Mx
oral fluconazole
Scabies signs/symptoms
Intensely itchy rash affecting finger webs, wrists, genital area
Scabies Mx
- Permethrin 5% cream (first choice) should be applied all over and left on for 8 hours
- malathion lotion, applied overnight to whole body and washed off next day (second choice)
- Treat again after 7 days
- benzyl benzoate (avoid in children)
Pubic lice Mx
Malathion
Chicken pox and signs/symptoms
Varicella virus
Macules to papules to vesicles to scabs to recovery
fever and itch
Chicken pox Mx
- Live attenuated vaccine is available for chickenpox
- Calamine lotion to keep lesions cool
- Trim nails – lessen damage from scratching
- Flucloxacillin if bacterial superinfection
- Varicella Zoster Immune Globulin
- Acyclovir if immunocompromised or on steroids
shingles
Zoster or Herpes Zoster (reactivation in later age)
Tingling/pain to erythema (see photo) to vesicles to crusts
Post Herpetic Neuralgia
Zoster associated pain (beyond week 4)
Ramsay-Hunt syndrome
Vesicles and pain in auditory canal and throat
Facial palsy (7th nerve palsy): Poorer prognosis than Bell’s palsy (idiopathic 7th nerve palsy)
Irritation of the 8th cranial nerve
– Deafness
– Vertigo
– Tinnitus
Herpes simplex types
HSV Type 1 o main cause of oral lesions HSV Type 2 o rare cause of oral lesions o causes half of genital cases o encephalitis / disseminated infection (particularly in neonates)
Erythema multiforme
Erythema multiforme (EM) is a skin condition of unknown cause; it is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure.
Many triggers including drug reactions and some infections
o Herpes simplex virus
o Mycoplasma pneumoniae bacterium
Molluscum contagiosum (pox virus) and Mx
Fleshy, firm, umbilicated, pearlescent nodules
Mx: self limiting but can use local application of liquid nitrogen
Warts (Human papilloma virus) or Verracus (feet) Mx
1st line: Keratolytics – topical salicylic acid
2nd line: Cryotherapy
3rd line: Imiquimod
Erythema infectiosum (slapped cheek syndrome)
Erythrovirus (formerly parvovirus) B19.
Note slapped cheek appearance.. As the rash on the face fades a lacy macular rash on the body appears.
In adults rash may be absent and an acute polyarthritis of the small joints eg of the hands may be more prominent.
Complications of parvovirus 19
spontaneous abortion
Aplastic crises:
• sudden drop in haemoglobin
• seen in patients with short red cell life span: Thalassaemia, Hereditary spherocytosis and Sickle cell anaemia
Chronic anaemia
• in immunosuppressed patients
Orf
- Firm, fleshy nodule on hands of farmers
- Constitutional symptoms rare
virus of sheep
Tuberous sclerosis signs/symptoms
• Periungual fibromas – around nails • Facial angiofibromas Cortical tubers and/or calcification of falx cerebri Hamartomas Bone cysts • Shagreen patches • Enamel pitting
Xeroderma Pigmentosum (DNA repair syndrome) and complications
Defect in one of seven Nucleotide Excision Repair (NER) genes (XPA - G)
Photosenstivity
Photodamage
Oculocutaneous albinism
• congenital absence of melanin • autosomal recessive • visual defects including: o photophobia o nystagmus o amblyobia
Seborrhoeic keratosis
Benign proliferation of epidermal keratinocytes
Epidermal acanthosis, hyperkeratosis, horn cysts
Malignant Melanoma risk factors
UV exposure (intermittent), sunburn, fair complexion, many (>50) melanocytic or dysplastic naevi, positive family history, childhood sunburn, previous melanoma, old age (>80 years)
Malignant Melanoma signs/symptoms
Melanoma most common on sun-exposed sites scalp, face, neck, arm, trunk, leg
• A – Asymmetry in the outline of the lesion
• B – Border – irregular
• C – Colour variation (more than 2) with shades of black, brown, blue or pink
• D – Diameter >6mm
• E – Evolution – all changing moles e.g. size, elvation and colour
Malignant Melanoma types
Superficial spreading
Acral/mucosal lentiginous
acral and mucosal: palms, soles and subungual
Lentigo maligna: sun-damaged face/neck/scalp: arises from lentigo melanoma
Nodular
Malignant Melanoma Mx
Depends on the tumour depth (Breslow thickness) and ulceration
- Primary excision to give clear margins (1-2cm)
- Some also receive a sentinel node biopsy
o If SN positive - regional lymphadenectomy
Treatment of advanced disease difficult
o Chemo, immunotherapy, genetic therapies
Some acral melanomas have c-kit mutations and may be treated with imatinib (tyrosine kinase inhibitor)
Melanomas on intermittently sun-exposed skin may have a BRAF mutation
- Vemurafenib and Dabrafenib: target the mutated form of B-RAF
Trametinib targets MEK: Inhibiting the downstream signals, blocks proliferation, survival, cell cycle
However, B-RAF resistance increases, better if you use the two in combination
Basal cell carcinoma
pluripotent stem cells in basal epidermis
Most common of malignant skin tumours
Basal cell carcinoma signs/symptoms
- sun exposed sites (head and neck area)
- slow growing lump or non-healing ulcer
- painless and often ignored
- ‘pearly’ or translucent with visible, arborising blood vessels
- Overlying telangiectasia
- central ulceration - “rodent ulcer”
BCC types
‘superficial’: red scaly plaques with raised smooth edge, often on trunk or shoulder.
nodular or nodulocystic (most common): a pearly nodule with rolled telangiectatic edge on the face or on a sun exposed site with or without central ulceration
infiltrative - ‘morphoeic’. Poorly defined, mid facial sites, infiltrate cutaneous nerves (perineural spread). Waxy, scar-like plaque with indistinct borders. Wide and deep subclinical extension
pigmented
BCC Mx
- most can be treated by skin surgery esp nodular (excision of 4mm margin with histology)
- Mohs micrographic surgery for morphoeic variant
- sBCC – topical imiquimod, Photodynamic treatment, cryotherapy
- Vismodegib binds to Smoothened to block hedgehog signalling and prevent cell cycle activation and angiogenesis
squamous cell carcinoma precursor
actinic keratoses: partial thickness dysplasia: scalp, face and hands: precursor to invasive squamous cell carcinoma
Bowen’s disease (carcinoma-in-situ): full thickness dysplasia: lower leg. Scaly patch/plaque, Irregular border, No dermal invasion
squamous cell carcinoma signs/symptoms
- Sun exposed sites: face, scalp, ears, hands
- hyperkeratotic (crusted) lump or ulcer: warty or crusted lump or ulcer
- grow relatively fast, may be painful &/or bleed
- ear, nose, lip and scalp are high risk sites
SSC Mx
• SCC precursors: cryotherapy, 5-Fluorouracil cream, imiquimod, photodynamic therapy
local complete excision: 6mm margin with histology
Radiotherapy
Venous leg ulcer
- Open lesion between knee and ankle unhealed for at least 4 weeks caused by venous hypertension in superficial veins (incompetent valves, DVT).
- Increased pressure leads to poor oxygenation of surrounding skin
Venous leg ulcer signs/symptoms
- Chronic and recurrent lower leg ulceration
- Shallow, sloping-edge ulcer varying size
- Commonly in gaiter area
- Surface slough (dead skin and bacteria)
Venous leg ulcer Ix
• ABPI (Ankle-Brachial Pressure Index) - 0.8-1.3: compression <0.8 arterial >1.3 calcification • Duplex USS • Swab ONLY if clinical signs of infection
Venous leg ulcer Mx
- Analgesia
- Debridement of dead tissue
- Non-adherent dressings +/- desloughing agent
- High compression (four-layer bandaging)
- Leg elevation
- Supporting stocking worn for life after healing to prevent recurrence.
Arterial Leg Ulcer
• Open lesion between knee and ankle unhealed for at least 4 weeks caused by arterial insufficiency
Arterial Leg Ulcer signs/symptoms
- Punched out deep painful ulcers
- Higher (lower?) on the leg, common on the feet
- Cold
- Pale
- Pulseless
- Hairless
- Absent peripheral pulses
Arterial Leg Ulcer Mx
- DO NOT USE COMPRESSION
- Keep clean and covered
- Adequate analgesia
- Referral to vascular surgery
