Dermatology

Key Facts

Atopic dermatitis is the most common inflammatory skin disease. Understanding the filaggrin-barrier defect model and the Th2 immune pathway is essential for rational treatment decisions.

Epidemiology

• UK prevalence: 15–20% of children; 2–5% of adults
• 60% develop symptoms in first year of life; 90% by age 5
• Increasing prevalence worldwide (especially in developed countries)
• Stronger maternal than paternal heritability

Aetiology

• Genetic: FLG mutations (epidermal barrier), IL-4/IL-13 pathway polymorphisms
• Environmental triggers: house dust mite, pet dander, food allergens (egg, milk - especially in young children), irritants (soap, detergents)
• Microbiome: S. aureus dominance; reduced microbial diversity
• Psychosocial: stress worsens disease

Pathophysiology

• Th2 skewing: IL-4, IL-13 → IgE class switching, further barrier disruption

• Chronic: Th1/Th22 involvement → lichenification

Age-Related Distribution

• Infants: face, scalp, extensor surfaces; weeping, crusting
• Children: flexures (antecubital, popliteal fossae), wrists, ankles; dry, lichenified
• Adults: hands, face, flexures; may be lichenified or nummular (discoid)

Severity Assessment

• Mild: areas of dry skin, infrequent itch
• Moderate: areas of dry skin, frequent itch, redness ± excoriations
• Severe: widespread dry skin, incessant itch, extensive redness, lichenification, bleeding, oozing

Complications

• Eczema herpeticum: widespread HSV - punched-out erosions, fever; EMERGENCY
• Secondary bacterial infection: S. aureus - crusting, pustules
• Growth restriction: in children on prolonged systemic steroids

Red Flags

• Eczema herpeticum (punched-out erosions + systemic illness)
• Erythroderma (>90% BSA)
• Failure to thrive in infant with severe eczema

Clinical Diagnosis

• Usually clinical; Hanifin & Rajka criteria

If Indicated

• Skin swab: if infected (MC&S for S. aureus; viral PCR for HSV)
• Specific IgE / skin prick tests: if food allergy suspected (children <2 with moderate-severe AD)
• Total IgE: often elevated (non-specific)
• SCORAD/EASI/POEM scores: validated severity tools for monitoring
• Patch testing: if allergic contact dermatitis component suspected
• Skin biopsy: rarely needed; shows spongiotic dermatitis

Complete Emollient Therapy

• 250–500g/week; apply frequently, especially after bathing
• Ointments (Epaderm, emulsifying ointment) for very dry skin
• Creams (Diprobase, Cetraben) for less dry/daytime use
• Soap substitute for washing

Topical Anti-Inflammatory

• Mild: hydrocortisone 1% OD-BD (face, children)
• Moderate: clobetasone butyrate 0.05%
• Potent: betamethasone valerate 0.1% (body - short courses for flares)
• Topical calcineurin inhibitors: tacrolimus 0.03%/0.1%, pimecrolimus 1% (face, flexures, long-term maintenance)
• Proactive maintenance: TCI or low-potency steroid 2×/week to previously affected areas

Adjunct Therapies

• Wet wraps: emollient ± dilute steroid under wet tubular bandages (acute flares)
• Bandages: ichthammol, zinc
• Antihistamines: sedating (hydroxyzine, chlorphenamine) at night for itch - non-sedating have no proven benefit in AD

Systemic (Specialist)

• Phototherapy: narrowband UVB
• Ciclosporin: 3–5mg/kg/day - rapid onset; monitor renal function and BP
• Methotrexate: 10–25mg weekly (slower onset than ciclosporin)
• Azathioprine: 1–3mg/kg/day (check TPMT first)
• Dupilumab: 600mg loading then 300mg SC every 2 weeks - SOLO 1&2, LIBERTY AD trials
• JAK inhibitors: baricitinib 4mg OD, upadacitinib 15–30mg OD, abrocitinib 100–200mg OD

Referral Criteria

• Dermatology: moderate-severe AD not responding to optimised topical therapy
• Urgent: eczema herpeticum, erythroderma
• Allergy: suspected food allergy (children), contact allergy (patch testing)

• 60% of childhood AD clears by adolescence
• 20% have lifelong disease (more likely with FLG mutations, early onset, severe disease)
• AD in childhood increases asthma risk by 3-fold
• QoL impact: comparable to diabetes and heart disease (DLQI studies)
• Dupilumab: sustained improvement at 52 weeks in >60% of patients

Hanifin & Rajka Diagnostic Criteria

NICE Treatment Stepladder

Key Facts

Contact dermatitis is common and underdiagnosed. Distinguishing ICD from ACD requires patch testing. Identifying and avoiding the causative agent is the single most effective intervention.

Epidemiology

• Lifetime prevalence: ~15–20% of general population
• Accounts for ~5–7% of dermatology referrals
• Occupational dermatitis: most common occupational skin disease
• Healthcare workers, hairdressers, food handlers most affected

Aetiology

ICD triggers: water, detergents, solvents, friction, alkalis, acids, wet work ACD common allergens: nickel (jewellery, belt buckles), chromate (cement), PPD (hair dye), fragrances, preservatives (MI/MCI), rubber chemicals, colophony (adhesives, plasters), epoxy resin

Pathophysiology

Irritant Contact Dermatitis

• Well-demarcated erythema at contact site
• Dryness, fissuring, glazed appearance
• Burning/stinging more than itch
• Hands most commonly affected (wet work)
• Onset: immediate or cumulative with repeated exposure

Allergic Contact Dermatitis

• Eczematous: erythema, vesicles, weeping, crusting
• Pruritus is prominent
• Distribution reflects contactant (e.g. wrist = watch/nickel; periorbital = nail varnish via transfer)
• Onset: 24–72 hours after exposure (delayed type IV)
• May spread beyond contact site (id reaction)

Red Flags

• Occupational pattern (worse at work, improves on holiday)
• Distribution suggesting specific allergen
• Failure to respond to treatment (unidentified allergen/irritant)

Patch Testing (for ACD)

• Gold standard: European baseline series (28+ allergens) + extended series based on occupation/exposure
• Method: allergens applied to back in Finn chambers for 48 hours; read at 48 hours and 96 hours
• Grading: +, ++, +++ (erythema through to vesicles/bullae); IR = irritant reaction
• Stop topical steroids 1 week before, oral steroids 4 weeks before

Additional

• Skin biopsy: rarely needed; shows spongiotic dermatitis (indistinguishable from atopic eczema)
• IgE (total/specific): to exclude atopic component
• RAST/skin prick testing: for type I latex allergy (NOT for type IV ACD)

Allergen/Irritant Avoidance

• Identify and avoid causative agent - most important step
• Substitution: alternative materials, products
• Protective equipment: gloves (but avoid latex if latex-allergic; use nitrile)
• Occupational health: workplace assessment, RIDDOR reporting

Pharmacological

• Emollients: foundation of care (as per eczema)
• Topical corticosteroids: potent (betamethasone valerate 0.1%) for body; mild (hydrocortisone 1%) for face/flexures
• Topical calcineurin inhibitors: for face/sensitive areas
• Severe acute ACD: short course oral prednisolone 0.5mg/kg for 5–7 days (e.g. severe poison ivy/plant dermatitis)

Referral Criteria

• Dermatology: for patch testing if ACD suspected
• Occupational health: suspected occupational dermatitis
• Urgent: severe widespread ACD not responding to topical treatment

• ACD: excellent if allergen identified and avoided - complete resolution expected
• ICD: improves with irritant avoidance; chronic exposure leads to persistent disease
• Occupational dermatitis: ~25% change occupation; ~50% have persistent symptoms at 5 years
• Poor prognostic factors: continued exposure, hand involvement, atopic background

ICD vs ACD Comparison

Common Allergens and Sources

Key Facts

Psoriasis is a systemic inflammatory disease, not just a skin condition. Cardiovascular risk is independently increased and should be actively managed. Biologic therapies have transformed outcomes for severe disease.

Epidemiology

• UK prevalence: 2–3% (~1.8 million people)
• Bimodal onset: type I (16–22 years, HLA-Cw6+, family history) and type II (55–60 years)
• 30% have first-degree relative with psoriasis
• Increased cardiovascular mortality: severe psoriasis shortens life expectancy by ~5 years

Aetiology

• Genetic: HLA-Cw6 (strongest association), multiple susceptibility loci (PSORS1-9)
• Environmental triggers: streptococcal pharyngitis (guttate), stress, drugs (lithium, beta-blockers, antimalarials, NSAIDs, ACEi withdrawal of steroids), alcohol, smoking, trauma (Koebner)

Pathophysiology

• Angiogenesis: dilated tortuous capillaries in dermal papillae
• TNF-alpha also contributes: targeted by anti-TNF biologics

Chronic Plaque Psoriasis (~90%)

• Well-demarcated, erythematous plaques with silvery-white scale
• Symmetrical; extensor surfaces (elbows, knees), scalp, sacrum, umbilicus
• Pruritus in ~70%

Guttate Psoriasis

• Small (<1cm) drop-like papules over trunk and proximal limbs
• Often triggered by streptococcal pharyngitis (2–4 weeks prior)
• Common in children/young adults; may be first presentation

Other Types

• Flexural (inverse): smooth, glazed erythema in flexures; minimal scale
• Pustular: localised (palmoplantar) or generalised (von Zumbusch - emergency)
• Erythrodermic: >90% BSA; risk of hypothermia, cardiac failure - EMERGENCY

Nail Psoriasis (~50%)

• Pitting, onycholysis, oil drop sign, subungual hyperkeratosis

Red Flags

• Generalised pustular psoriasis (systemic illness, fever)
• Erythrodermic psoriasis (hypothermia, high-output cardiac failure)
• Rapid worsening after systemic steroid withdrawal

Clinical Diagnosis

• Usually clinical; no investigations needed for typical plaque psoriasis

Severity Assessment

• BSA, PASI, DLQI: required for biologic eligibility (PASI ≥10 and DLQI ≥10)
• PEST questionnaire: screen for psoriatic arthritis

Pre-Treatment Bloods (if systemic therapy)

• FBC, U&Es, LFTs: baseline before methotrexate/ciclosporin
• Hepatitis B/C, HIV: before biologics
• TB screening (IGRA): before anti-TNF biologics
• Lipid profile, HbA1c, BP: cardiovascular risk assessment

Special Tests

• Skin biopsy: if diagnostic uncertainty - regular acanthosis, Munro microabscesses, parakeratosis, dilated capillaries
• Throat swab/ASO titre: if guttate (streptococcal trigger)
• Joint imaging: if psoriatic arthritis suspected (X-ray: pencil-in-cup, periostitis)

Topical (Mild-Moderate)

• Vitamin D analogues: calcipotriol (Dovonex) OD-BD; combined with betamethasone (Dovobet/Enstilar)
• Topical corticosteroids: potent (betamethasone valerate 0.1%) for body; moderate for face/flexures
• Coal tar preparations: for chronic stable plaques; messy but effective
• Dithranol: short-contact therapy in specialist settings
• Emollients: adjunctive; descale before active treatment

Phototherapy (Moderate)

• Narrowband UVB: first-line for moderate-extensive disease; 2–3× weekly for 6–8 weeks
• PUVA: psoralen + UVA - more effective but higher skin cancer risk; limited courses

Systemic (Moderate-Severe)

• Methotrexate: 7.5–25mg weekly (PO or SC) + folic acid 5mg weekly (not same day); monitor FBC, LFTs
• Ciclosporin: 2.5–5mg/kg/day; rapid onset; limit to 1–2 years (nephrotoxicity, hypertension)
• Acitretin: 25–50mg OD; retinoid; teratogenic - women must avoid pregnancy for 3 years after stopping
• Apremilast: PDE4 inhibitor; 30mg BD; oral; fewer monitoring requirements

Biologics (Severe - NICE TA)

• Anti-TNF: adalimumab 40mg alternate weeks, etanercept 50mg weekly
• Anti-IL-17: secukinumab 300mg monthly, ixekizumab, bimekizumab
• Anti-IL-23: guselkumab 100mg every 8 weeks, risankizumab
• Anti-IL-12/23: ustekinumab 45mg every 12 weeks
• Entry criteria: PASI ≥10 AND DLQI ≥10, failed standard systemic therapy

Referral Criteria

• Dermatology: moderate-severe psoriasis, diagnostic uncertainty, biologic consideration
• Rheumatology: suspected psoriatic arthritis
• Urgent: generalised pustular or erythrodermic psoriasis

• Chronic condition: no cure; management aims for control
• Guttate psoriasis: ~60% resolve spontaneously; ~30% develop chronic plaque psoriasis
• Biologics: PASI 90 achieved in 60–80% with modern anti-IL-17/IL-23 agents
• Cardiovascular risk: severe psoriasis independently increases CV mortality; manage risk factors actively
• Quality of life: DLQI improvement is a key treatment target

Psoriasis Treatment Ladder

PASI Score

Key Facts

Psoriatic arthritis is a seronegative spondyloarthropathy with heterogeneous presentation. Early recognition and treatment are essential to prevent irreversible joint damage.

Epidemiology

• Affects 20–30% of psoriasis patients
• Equal sex distribution (unlike RA which is female-predominant)
• Peak onset: 30–50 years
• Skin disease precedes arthritis in ~75%; arthritis precedes skin in ~15%; simultaneous in ~10%

Aetiology

• Genetic: HLA-B27 (axial disease ~50%), HLA-Cw6 (skin psoriasis)
• Environmental: trauma, infection may trigger
• Shared IL-23/IL-17 pathway with psoriasis

Pathophysiology

• Entheseal inflammation is the primary site of disease (distinguishes from RA)
• Both erosive AND proliferative bone changes (unlike RA which is purely erosive)
• Dactylitis: combined synovitis + tenosynovitis + enthesitis of entire digit

Moll & Wright Classification

1. Asymmetric oligoarthritis (~40%): <5 joints; often large joints + dactylitis
2. Symmetric polyarthritis (~25%): resembles RA; RF negative
3. DIP-predominant (~15%): distal interphalangeal joints - characteristic; often with nail disease
4. Spondylitis/sacroiliitis (~5%): axial involvement; often asymmetric sacroiliitis
5. Arthritis mutilans (<5%): severe destructive; telescoping digits (opera-glass hand)

Key Features

• Dactylitis: sausage-shaped digit swelling
• Enthesitis: Achilles tendon, plantar fascia insertion tenderness
• Nail disease: pitting, onycholysis (strongly associated with DIP arthritis)
• Morning stiffness: typically >30 minutes

Red Flags

• Rapidly progressive joint destruction
• Axial symptoms (inflammatory back pain)
• Severe functional impairment

Bloods

• RF: negative in ~95% (seronegative spondyloarthropathy)
• Anti-CCP: negative (helps distinguish from RA)
• CRP/ESR: may be elevated
• FBC, LFTs, U&Es: baseline before DMARD therapy

Imaging

• X-ray hands/feet: pencil-in-cup deformity, periostitis, juxta-articular new bone, joint space narrowing, ankylosis
• MRI: early synovitis, bone marrow oedema, enthesitis - more sensitive than X-ray
• USS: synovitis, enthesitis, tenosynovitis - used in clinic
• MRI sacroiliac joints: if axial disease suspected

Screening

• PEST questionnaire: 5-question screening tool for PsA in psoriasis patients (≥3 = positive screen)

Non-Pharmacological

• Physiotherapy, occupational therapy
• Exercise: maintain joint mobility and muscle strength
• Patient education, psychological support

Pharmacological

Peripheral arthritis:

• NSAIDs: first-line symptomatic relief (e.g. naproxen 500mg BD)
• csDMARDs: methotrexate 15–25mg weekly (first-line); sulfasalazine; leflunomide
• Biologics: if inadequate response to ≥2 csDMARDs
  • Anti-TNF: adalimumab 40mg every 2 weeks, etanercept
  • Anti-IL-17: secukinumab 150–300mg monthly
  • Anti-IL-12/23: ustekinumab
  • JAK inhibitors: tofacitinib 5mg BD, upadacitinib
  • PDE4 inhibitor: apremilast 30mg BD

Axial disease:

• NSAIDs first-line
• Biologics (anti-TNF or anti-IL-17) if inadequate response - csDMARDs NOT effective for axial disease

Enthesitis:

• NSAIDs; local corticosteroid injection (avoid Achilles tendon injection); biologics if persistent

Referral Criteria

• Rheumatology: all suspected PsA for confirmation and treatment
• Early referral: within 6 weeks of suspected inflammatory arthritis (NICE NG100)

• Progressive joint damage in 40–60% within 10 years without treatment
• Early DMARD therapy improves outcomes
• Biologics: 60–70% achieve ACR50 response
• Arthritis mutilans: severe disability but rare (<5%)
• Mortality: increased cardiovascular risk (as with psoriasis)
• Functional outcomes improved with treat-to-target approach

CASPAR Criteria (Score ≥3 = PsA)

PsA vs RA Comparison

Key Facts

Acne is not just a cosmetic condition - it causes significant psychological distress and can lead to permanent scarring. Early effective treatment prevents both physical and psychological sequelae.

Epidemiology

• Affects ~85% of adolescents (12–24 years)
• Adult female acne increasingly recognised (~12% of women >25 years)
• Male:female ~1:1 in adolescence; female predominance in adults

Aetiology

1. Androgen-driven sebum excess: DHT stimulates sebaceous glands
2. Follicular hyperkeratinisation: abnormal desquamation → microcomedone formation
3. C. acnes colonisation: lipophilic anaerobe; produces lipases and pro-inflammatory mediators

Pathophysiology

• Abnormal keratinocyte desquamation in follicular infundibulum → microcomedone (precursor of all acne lesions)
• C. acnes proliferates in sebum-rich, anaerobic follicle → activates innate immunity via TLR2

Non-Inflammatory

• Open comedones (blackheads): dilated pore with oxidised melanin/sebum
• Closed comedones (whiteheads): small flesh-coloured papules

Inflammatory

• Papules: small raised erythematous lesions
• Pustules: papules with visible pus
• Nodules: deep, painful, >5mm
• Cysts: deep fluctuant lesions - risk of scarring

Distribution

• Face (99%), back (60%), chest (15%)

Scarring

• Ice-pick, rolling, boxcar scars
• Post-inflammatory hyperpigmentation (especially darker skin)

Red Flags

• Sudden severe acne in pre-pubertal child (evaluate for androgen excess)
• Acne with virilisation in females (PCOS, adrenal tumour)
• Severe nodulo-cystic acne with systemic symptoms (acne fulminans)
• Significant psychological distress/suicidal ideation

Clinical Diagnosis

• History and examination sufficient in most cases
• Grade severity: mild (comedones ± few papules/pustules), moderate (papulopustular), severe (nodulo-cystic/scarring)

If Indicated

• Hormonal screen (females): if PCOS suspected - testosterone, SHBG, DHEAS, LH, FSH, prolactin
• Pelvic USS: if PCOS features
• Pre-isotretinoin: FBC, LFTs, fasting lipids, pregnancy test (before, during, 1 month after)
• Psychiatric assessment: if significant mood disturbance before/during isotretinoin

Mild (Comedonal/Few Papulopustules)

• First-line: fixed-combination adapalene 0.1% + benzoyl peroxide 2.5% (Epiduo) OD
• Alternative: topical retinoid alone (adapalene, tretinoin) or benzoyl peroxide 5% alone

Moderate (Papulopustular)

• Fixed-combination topical + consider oral antibiotics
• Oral antibiotics: lymecycline 408mg OD or doxycycline 100mg OD for 3 months maximum
• ALWAYS combine oral antibiotic with topical retinoid/BPO (prevents resistance)
• Do NOT use topical and oral antibiotics together

Severe (Nodulo-Cystic/Scarring) or Treatment-Resistant

• Oral isotretinoin 0.5–1mg/kg/day for 16–24 weeks (cumulative dose 120–150mg/kg)
• Teratogenic: mandatory pregnancy prevention programme (2 forms of contraception or abstinence; monthly pregnancy tests)
• Side effects: dry skin/lips (universal), myalgia, raised lipids, raised LFTs, mood changes (monitor)
• Monitor: LFTs and fasting lipids at baseline, 1 month, then 3-monthly

Females with Hormonal Acne

• COCP: co-cyprindiol (Dianette) - anti-androgenic; increased VTE risk (limit to 3–4 courses)
• Spironolactone 50–200mg OD: off-label; anti-androgen; useful in adult female acne

Referral Criteria

• Dermatology: severe/scarring acne, treatment failure with oral antibiotics, consideration for isotretinoin
• Urgent: acne fulminans, severe psychological distress

• Most adolescent acne resolves by mid-20s
• ~12% of women have persistent adult acne
• Isotretinoin: ~80% achieve long-term remission after one course; ~20% need second course
• Scarring: permanent without treatment; early effective therapy prevents
• Psychological impact: depression, anxiety, reduced self-esteem - comparable to chronic disease

Acne Treatment Ladder

Isotretinoin Key Points

Key Facts

Rosacea is a common facial dermatosis often misdiagnosed as acne. The absence of comedones is the key differentiating feature. Treatment is subtype-directed.

Epidemiology

• UK prevalence: ~5–10% of adults (likely underdiagnosed)
• Peak onset: 30–60 years
• More common in fair-skinned individuals (Fitzpatrick types I–II)
• Female:male ~3:1 for papulopustular; rhinophyma more common in males

Aetiology

• Exact cause unknown; multifactorial
• Demodex folliculorum: increased density in rosacea skin; immune reaction to mite antigens
• Dysregulated innate immunity: cathelicidin (LL-37) overproduction → inflammation, angiogenesis
• Neurovascular dysregulation: TRPV1 receptor activation → flushing, erythema

Pathophysiology

• UV damage → dermal connective tissue disruption and vascular dilation

• Demodex mites harbour Bacillus oleronius → innate immune activation
• Chronic inflammation → telangiectasia, fibrosis (rhinophyma)

Subtypes

1. Erythematotelangiectatic:

• Persistent centrofacial erythema
• Flushing episodes
• Telangiectasia
• Burning/stinging sensation

2. Papulopustular:

• Papules and pustules on erythematous background
• Centrofacial distribution
• NO comedones (unlike acne)

3. Phymatous:

• Thickened, nodular skin
• Rhinophyma: bulbous, enlarged nose - most recognised
• Can affect chin (gnathophyma), ears (otophyma)

4. Ocular (~50%):

• Blepharitis, conjunctivitis, dry eyes
• Foreign body sensation
• Keratitis (sight-threatening if severe)

Red Flags

• Keratitis (eye pain, photophobia, visual disturbance)
• Rapid progression or unilateral disease (consider SLE, CTCL)
• Granulomatous rosacea (persistent papules without erythema)

Clinical Diagnosis

• Usually clinical; no investigations needed for typical presentation

If Indicated

• Demodex count: skin scraping - increased density (>5/cm²) suggests Demodex-related rosacea
• ANA: if SLE malar rash suspected
• Skin biopsy: rarely needed; perifollicular/perivascular inflammation, Demodex mites, granulomas in granulomatous variant
• Ophthalmology assessment: if ocular symptoms - slit-lamp examination for keratitis

General Measures

• Trigger avoidance: sun protection (SPF 30+), avoid alcohol, spicy food, extremes of temperature
• Gentle skincare: non-soap cleansers, fragrance-free moisturisers
• Sun protection: daily broad-spectrum SPF 30+ (physical sunscreens preferred)

Erythematotelangiectatic

• Brimonidine 0.33% gel OD: topical alpha-agonist; temporary vasoconstriction; beware rebound erythema
• Laser/IPL: for persistent telangiectasia and erythema (specialist)

Papulopustular

• Topical (first-line): ivermectin 1% cream OD (Soolantra) or metronidazole 0.75% gel BD
• Topical alternatives: azelaic acid 15% gel BD
• Oral (moderate-severe): doxycycline 40mg MR OD (Efracea) for 8–16 weeks - anti-inflammatory, not antibiotic dose
• Severe/refractory: oral isotretinoin low dose (0.25–0.5mg/kg/day) - specialist

Phymatous

• Rhinophyma: surgical debulking, CO2 laser, electrosurgery (dermatology/plastics)
• Oral isotretinoin may prevent progression

Ocular

• Lid hygiene: warm compresses, lid scrubs
• Oral doxycycline 40–100mg OD: for moderate-severe
• Ophthalmology referral: if keratitis or visual symptoms

Referral Criteria

• Dermatology: moderate-severe/refractory rosacea, consideration for laser or isotretinoin
• Ophthalmology: ocular rosacea with keratitis or visual symptoms
• Plastics/dermatology: rhinophyma surgical management

• Chronic relapsing condition; no cure but manageable with treatment
• Papulopustular: good response to topical/oral treatment in most
• Ocular rosacea: can cause permanent visual impairment if keratitis untreated
• Rhinophyma: progressive without treatment but responds well to surgery
• QoL impact: significant psychosocial effect (visible facial disease)

Rosacea Subtypes Summary

Rosacea vs Acne

Key Facts

Urticaria is extremely common, affecting ~15–20% of the population at some point. The key clinical distinction is acute vs chronic, as this determines investigation and management approach.

Epidemiology

• Lifetime prevalence: ~15–20%
• Acute urticaria: very common, especially in children
• CSU: prevalence ~0.5–1%; female:male 2:1; peak age 20–40 years
• CSU duration: median 2–5 years; ~50% resolve within 5 years

Aetiology

Acute: viral infection (commonest cause in children), drugs (NSAIDs, antibiotics, opioids), food (nuts, shellfish, egg), insect stings, latex Chronic spontaneous: autoimmune (~50%; autoantibodies to FcεRI or IgE), idiopathic (~50%); NOT food allergy Physical: dermatographism (most common physical urticaria), cold, cholinergic, pressure, solar, aquagenic

Pathophysiology

• Autoimmune CSU: IgG autoantibodies to high-affinity IgE receptor (FcεRI) on mast cells → chronic activation
• Physical urticarias: specific physical stimulus triggers mast cell degranulation

Typical Wheals

• Raised, erythematous, pruritic
• Variable size (mm to cm)
• Individual wheals resolve within 24 hours leaving normal skin
• Flare-and-wheal response

Angioedema

• Deep tissue swelling (lips, eyelids, tongue, hands, feet, genitalia)
• May accompany urticaria (~40% of CSU patients)
• Lasts 24–72 hours

Physical Urticarias

• Dermatographism: linear wheals from stroking/scratching skin
• Cold urticaria: wheals after cold exposure; risk of anaphylaxis in cold water
• Cholinergic: small 2–3mm wheals after exercise, heat, emotional stress

Red Flags

• Anaphylaxis (urticaria + hypotension, bronchospasm, airway compromise)
• Wheals lasting >24 hours (urticarial vasculitis)
• Angioedema without urticaria (consider hereditary angioedema - C1-INH deficiency)
• Wheals that leave bruising/purpura

Acute Urticaria

• Usually NO investigations needed - clinical diagnosis
• Consider allergy testing (specific IgE, skin prick test) if clear trigger suspected and future avoidance needed

Chronic Spontaneous Urticaria

• FBC + differential: eosinophilia (parasites), basopenia
• CRP/ESR: raised in urticarial vasculitis, autoinflammatory
• TFTs: thyroid autoimmunity associated with CSU (~10%)
• Total IgE: may help predict omalizumab response
• Autologous serum skin test (ASST): research tool for autoimmune CSU
• Extensive allergy testing NOT recommended in CSU

If Urticarial Vasculitis Suspected

• Skin biopsy: leucocytoclastic vasculitis
• Complement (C3, C4): low in hypocomplementaemic urticarial vasculitis (association with SLE)
• ANA, anti-dsDNA: if SLE suspected

Acute Urticaria

• Identify and avoid trigger if clear
• Non-sedating antihistamine: cetirizine 10mg OD, loratadine 10mg OD, or fexofenadine 180mg OD
• Short course oral prednisolone: 30–40mg for 3–5 days for severe acute urticaria/angioedema
• Adrenaline IM: if anaphylaxis

Chronic Spontaneous Urticaria (Stepwise - EAACI/BAD)

Step 1: Standard-dose non-sedating antihistamine (e.g. cetirizine 10mg OD) Step 2: Up-dose to 4× licensed dose (e.g. cetirizine 10mg QDS) - first escalation Step 3: Add omalizumab 300mg SC every 4 weeks (anti-IgE monoclonal - NICE TA339) Step 4: Add ciclosporin 3–5mg/kg/day (off-label; specialist only)

• Avoid: oral corticosteroids long-term; sedating antihistamines as maintenance
• LTRA (montelukast): weak evidence; can be tried as add-on

Physical Urticarias

• Non-sedating antihistamines (may need higher doses)
• Avoidance of specific trigger where possible
• Cold urticaria: desensitisation protocols (specialist)

Referral Criteria

• Dermatology/allergy: CSU not controlled with standard antihistamines
• Immunology: suspected hereditary angioedema
• Urgent: anaphylaxis, wheals >24h (biopsy for urticarial vasculitis)

• Acute urticaria: self-limiting in most cases (days to weeks)
• CSU: median duration 2–5 years; ~50% resolve within 5 years; ~20% persist >10 years
• Omalizumab: ~65–70% achieve good control (UAS7 ≤6)
• Autoimmune CSU: may have longer duration
• Physical urticarias: often persistent but manageable with antihistamines
• QoL: significant impact; comparable to coronary artery disease in some studies

CSU Treatment Stepladder

Urticaria Activity Score (UAS7)

Key Facts

The critical distinction in angioedema is whether it is histamine-mediated (responds to antihistamines/adrenaline) or bradykinin-mediated (does NOT respond to antihistamines; requires specific treatment). Angioedema without urticaria should prompt investigation for HAE or drug causes.

Epidemiology

• Angioedema with urticaria: very common (affects ~40% of CSU patients)
• HAE: rare (~1 in 50,000); autosomal dominant
• ACEi-induced angioedema: ~0.5% of ACEi users; more common in Afro-Caribbean patients

Aetiology

Histamine-mediated: allergic (food, drug, insect venom), idiopathic (often with CSU), physical Bradykinin-mediated: HAE type I (85% - low C1-INH level), HAE type II (15% - normal level, reduced function), HAE type III (rare, normal C1-INH), ACEi-induced

Pathophysiology

Histamine-Mediated Angioedema

• Usually accompanied by urticaria (wheals)
• Pruritus is common
• Responds to antihistamines/adrenaline
• Lips, eyelids, tongue, hands, feet

Hereditary Angioedema

• Recurrent episodes of non-pruritic swelling (face, limbs, genitalia, abdomen)
• NO associated urticaria
• Abdominal attacks: severe pain, vomiting (can mimic surgical abdomen)
• Laryngeal oedema: life-threatening - ~25% mortality if untreated
• Family history (AD) - but ~25% are de novo mutations
• Onset: usually puberty; worsens with oestrogen (pregnancy, OCP)

ACEi-Induced

• Angioedema without urticaria
• Can occur at any time during ACEi therapy (days to years)
• Usually affects lips, tongue, face
• More common in Afro-Caribbean patients

Red Flags

• Tongue/laryngeal swelling (airway compromise)
• Angioedema without urticaria in young patient (HAE)
• Abdominal pain attacks (HAE abdominal involvement)
• Angioedema on ACEi

Acute

• ABC assessment: airway patency is priority
• Mast cell tryptase: if anaphylaxis suspected (peak at 1–2 hours)

Investigating Cause

• C4 level: screening test for HAE - LOW even between attacks (very sensitive)
• C1-INH level: low in HAE type I
• C1-INH function: low in HAE type II (level may be normal)
• C1q level: normal in HAE; LOW in acquired angioedema (associated with lymphoproliferative disorders)

Drug Review

• ACEi: stop and switch to ARB (lower risk but not zero)
• NSAIDs, aspirin: can cause or worsen angioedema

Additional

• Complement panel (C3, C4): C4 low in HAE
• Family screening: if HAE confirmed - genetic testing available

Acute Allergic/Histamine-Mediated Angioedema

• Airway management: ABC approach; call anaesthetics if airway threatened
• Adrenaline IM 0.5mg (1:1000): if anaphylaxis or severe angioedema
• Chlorphenamine 10mg IV: antihistamine
• Hydrocortisone 200mg IV: prevent biphasic reaction

Acute HAE Attack

• C1-INH concentrate (Berinert) IV: first-line
• Icatibant 30mg SC (bradykinin B2 receptor antagonist): self-administered
• Fresh frozen plasma: if C1-INH concentrate unavailable
• Adrenaline and antihistamines are INEFFECTIVE in HAE
• All HAE patients should carry emergency treatment and have management plan

HAE Prophylaxis

• Long-term: danazol (attenuated androgen - increases C1-INH production); tranexamic acid
• Modern prophylaxis: lanadelumab (anti-kallikrein antibody) SC every 2 weeks; berotralstat (oral kallikrein inhibitor)
• Short-term (pre-procedure): C1-INH concentrate before dental/surgical procedures
• Avoid: oestrogen-containing contraceptives (worsen HAE); ACEi contraindicated

ACEi-Induced Angioedema

• Stop ACEi permanently: switch to ARB (discuss small residual risk)
• Acute: antihistamines ± steroids may help; icatibant in severe cases

Referral Criteria

• Immunology: all suspected HAE for diagnosis and management plan
• A&E: acute airway-threatening angioedema
• Allergy: recurrent angioedema of unclear cause

• Allergic angioedema: excellent with trigger avoidance
• HAE: lifelong condition; modern prophylaxis (lanadelumab) dramatically reduces attack frequency
• HAE laryngeal oedema: ~25% mortality if untreated; near-zero with appropriate emergency treatment
• ACEi-induced: resolves after drug withdrawal (may take weeks)
• Acquired C1-INH deficiency: treat underlying lymphoproliferative disorder

HAE Types

Angioedema: Histamine vs Bradykinin

Key Facts

Melanoma is the 5th most common cancer in the UK. Early detection and excision are curative. Advanced melanoma treatment has been revolutionised by immunotherapy and targeted therapy.

Epidemiology

• UK: ~16,000 new cases/year; ~2,300 deaths/year
• 5th most common cancer in UK; incidence rising steeply
• Median age at diagnosis: ~60 years
• More common in fair-skinned individuals (Fitzpatrick I–II)
• Intermittent intense UV exposure (sunburn) is a stronger risk factor than cumulative exposure

Aetiology

• UV radiation: strongest modifiable risk factor; both UVA and UVB
• Multiple naevi (>100): increased risk
• Dysplastic naevi: atypical mole syndrome increases risk
• Family history: ~10% familial; CDKN2A mutations
• Fair skin: Fitzpatrick types I–II
• Immunosuppression: transplant recipients, HIV
• Previous melanoma: 5–8% lifetime risk of second primary

Pathophysiology

• UV-induced DNA damage (cyclobutane pyrimidine dimers) → oncogenic mutations
• BRAF V600E mutation: ~50% of cutaneous melanoma - constitutive MAPK pathway activation
• NRAS mutations: ~20%

• Immune evasion: PD-L1 upregulation on tumour cells → inhibits T-cell killing

Subtypes

• Superficial spreading (~70%): most common; irregular border, colour variation; radial growth initially
• Nodular (~15%): raised, often uniformly dark or amelanotic; vertical growth from onset (aggressive)
• Lentigo maligna (~10%): face of elderly; slow radial growth; large irregular tan-brown macule
• Acral lentiginous (~5%): palms, soles, nail bed; more common in darker skin types; Hutchinson's sign (nail fold pigmentation)

ABCDE Criteria

• Asymmetry
• Border irregularity
• Colour variation (brown, black, red, white, blue)
• Diameter >6mm
• Evolution (change in any feature)

7-Point Checklist (Glasgow/NICE)

• Major (2 points each): change in size, shape, colour
• Minor (1 point each): diameter ≥7mm, inflammation, oozing/bleeding, change in sensation
• Score ≥3: urgent 2-week wait referral

Red Flags

• Rapidly growing pigmented lesion
• New pigmented lesion in older adult
• Hutchinson's sign (periungual pigmentation)
• Amelanotic (non-pigmented) melanoma - easily missed

Diagnosis

• Dermoscopy: performed by trained clinician; improves diagnostic accuracy by 30%
• Excision biopsy: ALWAYS excise completely with 2mm clinical margin - do NOT incisional biopsy (except large lentigo maligna or acral)
• Histopathology: Breslow thickness, ulceration, mitotic rate, margins, lymphovascular invasion

Staging Investigations (if ≥Stage IIB or node-positive)

• CT thorax/abdomen/pelvis: staging
• MRI brain: if neurological symptoms or stage III–IV
• PET-CT: if advanced disease
• Sentinel lymph node biopsy: if Breslow ≥0.8mm or ulcerated; prognostic staging
• BRAF mutation testing: all stage III–IV melanoma (guides targeted therapy)
• LDH: prognostic marker in advanced disease

Surgical

• Wide local excision with margins based on Breslow thickness:
  • In situ: 5mm
  • ≤1mm: 1cm
  • 1.01–2mm: 1–2cm
  • 2.01–4mm: 2cm

  • 4mm: 2–3cm

• SLNB: if Breslow ≥0.8mm or ulcerated - prognostic; completion lymph node dissection not routinely recommended (DeCOG-SLT, MSLT-II trials)

Adjuvant (Stage III - node-positive)

• Nivolumab (anti-PD-1): 12 months; CheckMate 238 trial - 70% RFS at 4 years
• Pembrolizumab: 12 months; KEYNOTE-054 trial
• Dabrafenib + trametinib: if BRAF V600+ - COMBI-AD trial

Advanced/Metastatic (Stage IV)

• Immunotherapy: nivolumab + ipilimumab (CheckMate 067 - 52% 5-year OS); or single-agent anti-PD-1
• Targeted therapy (BRAF V600+): dabrafenib 150mg BD + trametinib 2mg OD (COMBI-d/v trials - 70% response rate)
• Radiotherapy: brain metastases (stereotactic), symptomatic bony metastases

Follow-Up (NICE NG14)

• Stage IA: discharge with written self-monitoring advice
• Stage IB–IIA: 2–3 monthly for 3 years, then 6-monthly to 5 years
• Stage IIB+: more frequent; include imaging surveillance

Referral Criteria

• 2-week wait: any suspicious pigmented lesion (7-point score ≥3)
• Skin cancer MDT: all confirmed melanoma
• Specialist oncology: stage III–IV for systemic therapy

• Stage I: 5-year survival ~95%
• Stage II: 5-year survival ~65–85%
• Stage III (node-positive): 5-year survival ~40–70%
• Stage IV (metastatic): 5-year survival ~25% (improving with immunotherapy)
• Breslow thickness: strongest prognostic factor (<1mm excellent; >4mm poor)
• Ulceration: independent poor prognostic factor
• Immunotherapy has transformed stage IV prognosis: ipilimumab + nivolumab 5-year OS ~52%

Breslow Thickness and Excision Margins

Melanoma Staging (AJCC 8th Edition)

Landmark Trials in Melanoma

Key Facts

BCC is the most common malignancy in humans globally. It is slow-growing, locally invasive, and has an excellent prognosis with appropriate treatment. The incidence is rising significantly, particularly in older populations with fair skin.

Epidemiology

• ~150,000 new cases/year in UK
• M:F ratio ~1.5:1
• Incidence increases with age; peak >70 years
• Most common on sun-exposed sites: head and neck (80%), particularly nose
• Rare in individuals with Fitzpatrick skin types V–VI
• Increasing incidence: ~3–5% per year

Aetiology

• UV radiation: cumulative exposure is the dominant risk factor
• Fair skin (Fitzpatrick types I–II), red/blonde hair, blue eyes
• Immunosuppression: organ transplant recipients have 10× increased risk
• Gorlin syndrome (basal cell naevus syndrome): PTCH1 gene mutation - multiple BCCs from young age
• Previous BCC: 30–50% risk of further BCC within 5 years
• Ionising radiation: previous radiotherapy to skin
• Arsenic exposure: historical occupational risk

Pathophysiology

• Arises from basal layer keratinocytes or hair follicle stem cells
• Key pathway: Hedgehog signalling pathway - mutations in PTCH1 (tumour suppressor) or SMO (oncogene)

• Slow growth, local tissue invasion, rarely metastasises due to stromal dependence

Nodular BCC (60%)

• Pearly/translucent papule or nodule
• Rolled, raised border with telangiectasia
• Central ulceration ('rodent ulcer') - may bleed and crust
• Most common on face, especially nose

Superficial BCC (25%)

• Flat, erythematous, scaly plaque with a thin pearly border
• Often on trunk (back, shoulders)
• May be multifocal
• Can mimic eczema, psoriasis, or Bowen's disease

Morphoeic (Sclerosing) BCC (5–10%)

• Waxy, scar-like, white/yellow plaque
• Ill-defined margins - often larger than clinically apparent
• May be depressed relative to surrounding skin
• Highest recurrence rate after treatment

Pigmented BCC

• Contains melanin - appears brown/black
• Can mimic melanoma clinically
• More common in darker skin types

Red Flags

• Rapid growth (consider SCC or melanoma)
• Perineural invasion: pain, paraesthesia, cranial nerve palsies
• Orbital invasion: visual changes, proptosis
• Large neglected tumours (>2 cm) on high-risk sites (nose, periorbital, ear)

Bedside

• Dermoscopy: arborising (tree-like) vessels, blue-grey ovoid nests, leaf-like areas, ulceration; absence of pigment network
• Clinical photography: baseline documentation

Biopsy

• Punch biopsy (3–4 mm): confirms diagnosis and subtype - essential before non-surgical treatment
• Excision biopsy: small lesions - diagnostic and therapeutic
• Incisional biopsy: large lesions where subtype determination guides management

Imaging

• CT/MRI: only if deep tissue invasion suspected (periorbital, perineural)
• Not routinely required for standard BCC

Special Tests

• Mohs micrographic surgery mapping: for high-risk sites - complete margin assessment
• Genetic testing: if Gorlin syndrome suspected (young patient, multiple BCCs)

Non-Pharmacological

• Sun protection: SPF 30+, protective clothing, avoidance of peak UV hours
• Patient education: self-examination for new lesions; 30–50% risk of second BCC
• Surveillance: follow-up for high-risk subtypes and immunosuppressed patients

Surgical (Mainstay of Treatment)

• Surgical excision: first-line for most BCCs
  • Low-risk: 4 mm peripheral margin
  • High-risk (morphoeic, recurrent, large): wider margins or Mohs
• Mohs micrographic surgery: gold standard for high-risk sites (periorbital, nasal, periauricular) - complete margin assessment with tissue conservation; cure rate >99%
• Curettage and cautery: suitable for small, well-defined, low-risk nodular/superficial BCCs on trunk/limbs; not for morphoeic or high-risk sites

Pharmacological

• Topical imiquimod 5% cream: for superficial BCC - apply 5 nights/week for 6 weeks; stimulates local immune response via TLR7
• Topical 5-fluorouracil (5-FU) 5% cream: for superficial BCC - apply BD for 3–4 weeks
• Photodynamic therapy (PDT): methylaminolaevulinate (MAL) cream + red light - for superficial and thin nodular BCC; good cosmetic outcome
• Vismodegib 150 mg OD (Hedgehog pathway inhibitor): for locally advanced or metastatic BCC not suitable for surgery/radiotherapy - NICE TA489

Radiotherapy

• Alternative for elderly patients or those unfit for surgery
• Useful for difficult anatomical sites
• Not first-line in young patients (risk of secondary malignancy, poor long-term cosmesis)

Referral Criteria

• NICE NG12: 2-week wait referral for suspected skin cancer
• All suspected BCCs should be referred to dermatology or plastic surgery
• Mohs surgery referral: periorbital, periauricular, nasal, morphoeic, recurrent

• Excellent prognosis overall: 5-year cure rate >95% with appropriate treatment
• Mohs surgery: >99% cure rate for primary BCC
• Recurrence rates: excision 2–5%, curettage 5–10%, morphoeic subtype 10–15% higher
• Metastasis: <0.05% - extremely rare
• 30–50% risk of developing a further BCC within 5 years
• Gorlin syndrome: lifelong risk of multiple BCCs
• Mortality attributable to BCC is very rare - almost exclusively from neglected large tumours with local invasion

BCC Subtype Comparison

Gorlin Syndrome (Basal Cell Naevus Syndrome)

Key Facts

Cutaneous SCC is a malignant tumour of epidermal keratinocytes with genuine metastatic potential. It is the second most common skin cancer and the most common skin cancer to cause death after melanoma. Early detection and complete excision are key.

Epidemiology

• ~50,000 new cases/year in UK
• M:F ratio ~2:1
• Incidence increases with age; peak >70 years
• Most common on sun-exposed sites: head/neck, dorsum of hands, forearms
• Incidence rising ~3–4% per year
• Second commonest cause of skin cancer death (after melanoma)

Aetiology

• UV radiation: cumulative UVB exposure - strongest risk factor
• Immunosuppression: organ transplant recipients (65–250× risk), chronic immunosuppressive therapy
• Pre-malignant lesions: actinic keratoses (5–10% progress to SCC), Bowen's disease
• Chronic inflammation/scarring: Marjolin's ulcer (SCC in chronic wound/burn scar)
• HPV: types 16, 18 - particularly periungual and genital SCC
• Arsenic, tar, industrial carcinogens: occupational exposure
• Xeroderma pigmentosum: defective DNA repair → markedly increased skin cancer risk

Pathophysiology

• UV-induced mutations in p53 tumour suppressor gene → loss of cell cycle control
• Field cancerisation: widespread UV-damaged epidermis predisposes to multiple lesions

• Tumour thickness, depth of invasion, and perineural invasion determine metastatic risk

Well-Differentiated SCC

• Firm, flesh-coloured or erythematous, keratinised nodule or plaque
• Central keratin horn or crust
• On sun-exposed skin - scalp, face, ears, dorsal hands

Poorly Differentiated SCC

• Fleshy, friable, rapidly growing nodule
• May ulcerate with necrosis
• Higher metastatic potential

Bowen's Disease (SCC In Situ)

• Well-demarcated, erythematous, scaly plaque
• Slowly enlarging; usually on lower legs in women
• ~3–5% progress to invasive SCC

Keratoacanthoma

• Rapidly growing dome-shaped nodule with central keratin plug
• May regress spontaneously but treat as SCC
• Crateriform architecture

Special Sites

• Lip SCC: lower lip most common; higher metastatic rate (~10–15%)
• Ear SCC: higher recurrence and metastatic rate
• Marjolin's ulcer: SCC in chronic wound - aggressive, high metastatic potential

Red Flags

• Rapid growth
• Pain, paraesthesia (perineural invasion)
• Regional lymphadenopathy (metastasis)
• Non-healing ulcer in a chronic wound or scar
• Immunosuppressed patient with new or changing lesion

Bedside

• Clinical examination: full skin survey, regional lymph node palpation
• Dermoscopy: white structureless areas, keratin, hairpin vessels, polymorphous vessels

Biopsy

• Excision biopsy: preferred for small lesions - diagnostic and therapeutic
• Incisional/punch biopsy: for larger lesions to determine grade and depth before definitive surgery
• Histology: degree of differentiation, depth of invasion, perineural/lymphovascular invasion, Clark level

Imaging

• USS regional lymph nodes: if lymphadenopathy or high-risk features
• CT/MRI: for deep invasion, perineural spread, or staging of metastatic disease
• Sentinel lymph node biopsy: considered for high-risk SCC (not yet standard in UK)

Special Tests

• Fine needle aspiration: palpable lymph nodes
• PET-CT: if distant metastasis suspected

Non-Pharmacological

• Sun protection: SPF 30+, protective clothing, UV avoidance - lifelong
• Patient education: self-examination, prompt reporting of new/changing lesions
• Surveillance: regular dermatology follow-up for high-risk patients (transplant recipients)

Surgical (Mainstay)

• Wide local excision: first-line treatment
  • Low-risk: ≥4 mm peripheral margin
  • High-risk (poorly differentiated, >2 cm, perineural, ear, lip): ≥6 mm margin
• Mohs micrographic surgery: for high-risk sites (periorbital, nose, lip, ear), recurrent SCC, or where tissue conservation is critical
• Curettage and cautery: only for small, well-differentiated, low-risk SCC on trunk/limbs

Pharmacological

• Topical 5-fluorouracil (5-FU) 5%: for Bowen's disease - apply BD for 3–4 weeks
• Topical imiquimod 5%: for Bowen's disease - 5 nights/week for 6 weeks (unlicensed)
• Cemiplimab (anti-PD-1): NICE TA592 - for locally advanced or metastatic SCC not amenable to surgery/radiotherapy

Radiotherapy

• Adjuvant: positive/close margins, perineural invasion
• Primary: inoperable tumours, elderly/unfit for surgery

Referral Criteria

• NICE NG12: 2-week wait referral for suspected skin cancer
• MDT discussion for high-risk SCC
• Oncology referral for metastatic disease

• Overall 5-year survival: >90% for localised disease
• Metastatic rate: 2–5% overall; up to 10–15% for high-risk sites (lip, ear) and immunosuppressed patients
• Lymph node metastasis: 5-year survival drops to ~25–35%
• Recurrence: 3–8% after adequate excision; higher for morphoeic, perineural, or incompletely excised
• Transplant recipients: poorer outcomes, higher recurrence and metastasis rates
• Key prognostic factors: tumour thickness (>4 mm), differentiation, perineural invasion, immunosuppression

SCC Risk Stratification

Pre-Malignant to Malignant Progression

Key Facts

Actinic keratoses (AKs) are the most common pre-malignant skin lesion. They are a marker of chronic UV damage and indicate increased risk of all skin cancers. Treatment is important to prevent progression and as part of skin cancer prevention.

Epidemiology

• Extremely common: affects ~15–25% of adults >40 in UK
• M > F (reflecting historical occupational UV exposure)
• Prevalence increases with age, fair skin, and geographic UV exposure
• Multiple AKs very common in organ transplant recipients

Aetiology

• Cumulative UV exposure (particularly UVB) - predominant cause
• Fair skin: Fitzpatrick types I–II
• Immunosuppression: transplant recipients - accelerated development and higher progression rate
• Occupational exposure: outdoor workers, farmers
• Field cancerisation: indicates widespread subclinical dysplasia in sun-damaged skin

Pathophysiology

• UV-induced mutations (p53, RAS) in epidermal keratinocytes → dysplasia confined to epidermis

• Histologically: disordered maturation of keratinocytes, parakeratosis, solar elastosis in dermis

Typical Presentation

• Rough, scaly, erythematous papules or patches
• 'Sandpaper' texture - often better felt than seen
• Sun-exposed sites: face, ears, bald scalp, dorsal hands, forearms
• Usually multiple - indicates field damage
• May be skin-coloured, pink, or brown
• Typically <1 cm diameter

Variants

• Hypertrophic AK: thicker, keratotic - harder to distinguish from SCC clinically
• Cutaneous horn: conical keratin projection - AK at base (must biopsy to exclude SCC)
• Actinic cheilitis: AK of the lip - diffuse scaling/cracking of lower lip; higher progression risk

Red Flags

• Induration, rapid growth, or tenderness (suggests progression to SCC)
• Lesion >1 cm or increasing thickness
• Cutaneous horn (SCC at base in ~15–20%)
• Failure to respond to treatment
• Immunosuppressed patient - lower threshold for biopsy

Bedside

• Clinical examination: diagnosis is usually clinical; full skin survey for other lesions
• Dermoscopy: strawberry pattern (red pseudo-network with white/yellow scale)

Biopsy

• Not routinely required for typical AKs
• Biopsy indications: diagnostic uncertainty, hypertrophic lesion, suspected SCC, treatment failure, cutaneous horn
• Punch/shave biopsy: to exclude invasive SCC

Imaging

• Not required for AKs

Special Tests

• Reflectance confocal microscopy: emerging non-invasive technique for monitoring field cancerisation

Non-Pharmacological

• Sun protection: SPF 30+, protective clothing, hat - lifelong; essential alongside treatment
• Patient education: self-monitoring, prompt reporting of changing lesions
• Observation: mild, few AKs in elderly - watchful waiting is acceptable with good sun protection

Pharmacological

• Cryotherapy (liquid nitrogen): first-line for isolated/few lesions - single freeze-thaw cycle; cure rate ~75–85%
• Topical 5-fluorouracil (Efudix) 5% cream: field treatment - apply BD for 2–4 weeks; expect marked inflammation; cure rate ~80%
• Topical imiquimod (Aldara) 5% cream: field treatment - 3 nights/week for 4 weeks; immune-mediated response
• Topical diclofenac 3% gel (Solaraze): apply BD for 60–90 days - better tolerated, lower efficacy (~50%)
• Topical tirbanibulin (Klisyri) 1% ointment: newer agent - apply OD for 5 days; NICE-approved
• Photodynamic therapy (PDT): methyl aminolaevulinate (MAL) or aminolaevulinic acid (ALA) + red/daylight activation - excellent for widespread AKs; good cosmetic result

Surgical

• Curettage: for hypertrophic AKs or where biopsy confirmation needed

Referral Criteria

• Dermatology referral: diagnostic uncertainty, treatment failure, immunosuppressed patients
• 2-week wait referral: if SCC suspected (NICE NG12)

• ~5–10% of individual AKs progress to invasive SCC over 10 years
• Spontaneous regression: ~15–25% of AKs may regress spontaneously
• Recurrence after treatment: common, especially with ongoing UV exposure
• Field cancerisation: ongoing risk of new lesions even after treatment
• Organ transplant recipients: higher progression rate - require more aggressive monitoring and treatment
• Patients with AKs are at increased risk of all skin cancers (BCC, SCC, melanoma)

AK Treatment Comparison

AK to SCC Progression Risk Factors

Key Facts

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease in Western countries. It predominantly affects elderly individuals and carries significant morbidity and mortality due to age-related comorbidities and treatment-related complications.

Epidemiology

• Incidence: ~6–7 per 100,000/year in UK; rising
• Median age at onset: ~80 years
• M:F ~equal or slight male predominance
• Strong association with neurological disease: dementia, stroke, Parkinson's disease, multiple sclerosis

Aetiology

• Autoimmune: IgG autoantibodies against BP180 (type XVII collagen, also called BPAG2) and BP230 (BPAG1) - hemidesmosomes at the dermal-epidermal junction
• Drug-induced: DPP-4 inhibitors (vildagliptin, sitagliptin), PD-1 checkpoint inhibitors, furosemide, spironolactone, NSAIDs
• Neurological association: strong epidemiological link - shared neural isoforms of BP180/BP230
• UV exposure: may trigger or exacerbate

Pathophysiology

• Tense blisters because the full-thickness epidermis forms the blister roof

Pre-Bullous Phase

• Pruritus (may be severe) - often precedes blisters by weeks to months
• Urticarial plaques or eczematous eruption without blisters
• Frequently misdiagnosed as eczema or urticaria

Bullous Phase

• Tense blisters (1–3 cm) on erythematous or urticarial base
• Blisters do not rupture easily - subepidermal with full-thickness epidermal roof
• Often on flexural surfaces: inner thighs, forearms, axillae, abdomen
• May involve limbs and trunk; face/oral mucosa rarely affected (<20%)
• Blisters contain clear or haemorrhagic fluid
• Healing without scarring (unless secondary infection)

Nikolsky Sign

• NEGATIVE - lateral pressure on normal skin does NOT cause epidermal separation (distinguishes from pemphigus)

Red Flags

• Widespread blistering with systemic upset - may need hospitalisation
• Secondary infection of blisters (impetiginisation)
• Drug-induced BP - review medication list (especially DPP-4 inhibitors)
• Oral mucosal involvement - consider mucous membrane pemphigoid

Bedside

• Clinical assessment: distribution of blisters, Nikolsky sign, mucosal examination

Bloods

• FBC: eosinophilia (common in BP)
• BP180 and BP230 ELISA antibodies: serum - useful for diagnosis and monitoring; BP180 titre correlates with disease activity
• U&Es, glucose: baseline before immunosuppressive treatment

Biopsy

• Skin biopsy (perilesional): subepidermal blister with eosinophil-rich infiltrate
• Direct immunofluorescence (DIF): perilesional skin - linear IgG and C3 at the basement membrane zone - gold standard diagnostic test
• Indirect immunofluorescence: serum - circulating IgG binding to epidermal side of salt-split skin

Special Tests

• Salt-split skin test: IgG binds to EPIDERMAL side (roof) - distinguishes from epidermolysis bullosa acquisita (dermal side)
• Drug review: exclude drug-induced BP (DPP-4 inhibitors, checkpoint inhibitors)

Non-Pharmacological

• Wound care: non-adherent dressings for ruptured blisters, aseptic technique
• Blister management: large blisters can be aspirated with sterile needle (leave roof intact)
• Nutritional support: important in elderly with widespread disease

Pharmacological

First-line:

• Potent topical corticosteroid: clobetasol propionate 0.05% cream - apply to entire body surface BD; taper over months
• Superior to systemic prednisolone with fewer adverse effects (Burton et al. NEJM trial)
• Typical regimen: 30–40 g/day initially, taper based on new blister count

Second-line (moderate-severe or unable to apply topical):

• Prednisolone 0.5 mg/kg/day - taper over months as disease controlled
• Plus PPI (omeprazole 20 mg OD) and bone protection (alendronate 70 mg weekly + calcium/vitamin D)

Steroid-sparing agents:

• Doxycycline 200 mg OD: non-inferiority to prednisolone shown in BLISTER trial (NEJM 2017); fewer serious adverse events in elderly
• Azathioprine 1–3 mg/kg/day: check TPMT before starting
• Mycophenolate mofetil 1–1.5 g BD: alternative steroid-sparing agent
• Dapsone 50–150 mg OD: check G6PD before starting
• Rituximab: refractory cases - anti-CD20 monoclonal antibody

Referral Criteria

• All suspected BP: dermatology referral for biopsy and DIF
• Widespread or refractory disease: specialist immunobullous clinic
• Drug-induced BP: withdrawal of causative agent with dermatology input

• 1-year mortality: ~25–30% (largely driven by comorbidities and treatment complications in elderly)
• Disease is usually self-limiting: median duration 3–5 years
• Relapse rate: ~30–50% on treatment withdrawal
• Topical clobetasol: associated with lower mortality than systemic prednisolone (Burton trial)
• BLISTER trial: doxycycline non-inferior to prednisolone with fewer serious adverse events at 6 weeks
• Drug-induced BP: usually resolves after drug withdrawal (may take weeks–months)

Autoimmune Blistering Disease Comparison

Landmark Trials

Key Facts

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering disease. It is less common than bullous pemphigoid but carries greater morbidity and mortality. Oral mucosal involvement is often the presenting feature and the most difficult to control.

Epidemiology

• Incidence: ~0.5–1.6 per 100,000/year
• Typically presents age 40–60 years (younger than BP)
• Increased incidence in Ashkenazi Jewish and South Asian populations
• M:F ~equal

Aetiology

• Autoimmune: IgG autoantibodies targeting desmoglein 3 (desmosome component) - causes loss of keratinocyte adhesion (acantholysis)
• Mucosal-dominant: anti-desmoglein 3 only
• Mucocutaneous: anti-desmoglein 3 AND anti-desmoglein 1
• Genetic: HLA-DRB104:02 and HLA-DRB114:01 associations
• Drug-induced pemphigus: penicillamine, captopril, NSAIDs (rare)

Pathophysiology

• 'Desmoglein compensation theory': explains why mucosal-only disease occurs (mucosa relies primarily on Dsg3, while skin has both Dsg1 and Dsg3)
• Suprabasal acantholysis → 'tombstone' appearance of basal cells on histology

Oral Mucosa (Often First Manifestation)

• Painful erosions on buccal mucosa, palate, gingiva, tongue
• Blisters rupture immediately - rarely see intact blisters in mouth
• Difficulty eating, weight loss, drooling
• May precede skin involvement by weeks to months

Skin

• Flaccid blisters on normal or erythematous skin
• Rupture easily → painful, slow-healing erosions
• Any body site; often scalp, face, trunk, axillae, groin
• No scarring (unless secondary infection)
• Blisters may extend with lateral pressure (Nikolsky +ve)

Nikolsky Sign

• POSITIVE: gentle lateral pressure on perilesional skin → epidermal separation and new blister formation
• Asboe-Hansen sign: pressure on intact blister → lateral extension

Red Flags

• Widespread erosions with fluid loss and secondary infection (sepsis risk)
• Inability to eat/drink due to oral erosions
• Rapid deterioration - may need hospitalisation
• Laryngeal/oesophageal involvement: dysphagia, hoarseness

Bedside

• Nikolsky sign: positive - important clinical clue
• Oral examination: erosions, desquamative gingivitis

Bloods

• Desmoglein 1 and 3 ELISA antibodies: serum - diagnostic and for monitoring disease activity; titres correlate with clinical severity
• FBC, U&Es, LFTs, glucose: baseline before immunosuppression
• TPMT activity: before starting azathioprine

Biopsy

• Perilesional skin biopsy: suprabasal acantholysis, 'tombstone' row of basal keratinocytes
• Direct immunofluorescence (DIF): perilesional skin - intercellular IgG and C3 in a 'fishnet'/'chicken-wire' pattern - diagnostic gold standard
• Indirect immunofluorescence: serum IgG binding to intercellular substance of monkey oesophagus

Special Tests

• Tzanck smear: acantholytic (Tzanck) cells - supportive but not specific
• ELISA titre monitoring: desmoglein 1/3 levels guide treatment decisions

Non-Pharmacological

• Wound care: non-adherent dressings, antiseptic washes for erosions
• Oral care: soft diet, chlorhexidine mouthwash, topical analgesics (benzydamine)
• Nutritional support: dietary supplements, NG feeding if severe oral involvement

Pharmacological

Induction:

• Prednisolone 0.5–1 mg/kg/day: initial disease control; taper once remission achieved
• Rituximab 1 g IV on days 0 and 14: now recommended as first-line alongside low-dose prednisolone per RITUX 3 trial - complete remission in 89% at 24 months

Maintenance/Steroid-Sparing:

• Azathioprine 2–3 mg/kg/day (check TPMT): most commonly used
• Mycophenolate mofetil 1–1.5 g BD: alternative
• Rituximab maintenance: 500 mg at 12 and 18 months

Refractory:

• IVIg 2 g/kg over 2–5 days: for acute flares or pre-operative
• Cyclophosphamide: severe refractory disease
• Plasmapheresis: acute severe disease unresponsive to other treatments

Referral Criteria

• All suspected PV: urgent dermatology referral for biopsy and DIF
• Specialist immunobullous centre for management
• Ophthalmology: if ocular involvement suspected
• Dietetics: if oral involvement impairs nutrition

• Pre-corticosteroid era: >75% mortality
• Current mortality: ~5–10% (due to disease complications and immunosuppressive treatment)
• RITUX 3 trial: rituximab as first-line → complete remission off therapy in 89% at 24 months (vs 34% with prednisolone alone)
• Many patients achieve long-term remission with appropriate treatment
• Relapse: common during steroid tapering; desmoglein titres help predict
• Causes of death: sepsis (most common), treatment complications (GI bleeding, osteoporosis)

Pemphigus vs Pemphigoid Comparison

RITUX 3 Trial (Lancet 2017)

Key Facts

Dermatitis herpetiformis (DH) is the cutaneous manifestation of coeliac disease. Despite the name, it has no association with herpes viruses - the term refers to the grouped ('herpetiform') arrangement of vesicles. It is one of the most pruritic skin conditions.

Epidemiology

• Incidence: ~0.8–1.2 per 100,000/year in UK
• M:F ~2:1
• Peak age: 30–40 years (younger than BP)
• More common in Northern European populations
• ~15–25% of coeliac disease patients develop DH

Aetiology

• Coeliac disease: virtually all DH patients have underlying gluten-sensitive enteropathy (often subclinical)
• IgA autoantibodies: against epidermal transglutaminase (eTG) - deposited in dermal papillae
• Gluten sensitivity: IgA anti-tTG cross-reacts with eTG → skin deposition
• HLA association: DQ2 (95%) or DQ8 (5%) - identical to coeliac disease

Pathophysiology

• Skin disease lags behind GI disease - IgA deposits persist for months after gluten withdrawal

Typical Presentation

• Intensely pruritic grouped papules, vesicles, and excoriations
• Often so itchy that vesicles are scratched away before being noticed
• Symmetrical distribution on extensor surfaces:
  • Elbows (most common)
  • Knees
  • Buttocks
  • Scalp, posterior hairline
  • Upper back
• Vesicles may be very small and grouped
• Excoriations and crusted papules more commonly seen than intact vesicles

Associated Features

• GI symptoms of coeliac disease (may be absent in >50%): diarrhoea, bloating, weight loss
• Iron deficiency anaemia
• Other autoimmune conditions: thyroid disease, type 1 diabetes

Red Flags

• Severe malabsorption symptoms
• Failure to respond to gluten-free diet (consider alternative diagnosis or poor compliance)
• Development of lymphoma symptoms (weight loss, lymphadenopathy) - rare but important

Bedside

• Clinical assessment: distribution, morphology, excoriations

Bloods

• Anti-tissue transglutaminase (tTG) IgA: screening for coeliac disease (sensitivity ~90% in DH)
• Anti-endomysial antibodies (EMA) IgA: highly specific for coeliac disease
• Total IgA: exclude IgA deficiency (false-negative serology)
• FBC: iron deficiency anaemia, macrocytic anaemia (B12/folate malabsorption)
• G6PD level: BEFORE starting dapsone (risk of severe haemolysis if deficient)

Biopsy

• Perilesional skin biopsy for DIF: granular IgA deposits at the dermal papillae - pathognomonic
• Lesional skin biopsy (H&E): neutrophilic microabscesses at dermal papillae, subepidermal vesicle

GI Investigations

• Duodenal biopsy (OGD): villous atrophy, crypt hyperplasia, intraepithelial lymphocytes (Marsh classification) - even in asymptomatic patients
• HLA-DQ2/DQ8 typing: negative result essentially excludes coeliac/DH

Special Tests

• Anti-epidermal transglutaminase (eTG) antibodies: most specific serological marker for DH (research/specialist use)

Non-Pharmacological

• Strict lifelong gluten-free diet (GFD): definitive treatment
  • Controls both skin and GI disease
  • Skin improvement may take 6–24 months
  • Allows dapsone dose reduction and eventual withdrawal
  • Reduces long-term lymphoma risk
• Dietitian referral: essential for GFD education and monitoring
• Coeliac UK membership: support and resources

Pharmacological

• Dapsone 50–150 mg OD: rapid symptomatic relief (within 24–48 hours)
  • Check G6PD before starting (haemolysis risk)
  • Monitor FBC weekly for first 4 weeks, then 3-monthly
  • Side effects: methaemoglobinaemia, haemolytic anaemia, agranulocytosis (rare)
  • Aim to reduce/stop once GFD controls disease
• Sulfapyridine 500 mg–1.5 g BD: alternative if dapsone not tolerated

Monitoring

• FBC: weekly for 4 weeks, then 3-monthly on dapsone
• Methaemoglobin level if symptomatic
• Annual coeliac disease review: serology, dietetic, DEXA scan

Referral Criteria

• Dermatology: all suspected DH for biopsy and DIF
• Gastroenterology: duodenal biopsy, coeliac disease management
• Dietetics: GFD education

• Excellent prognosis with strict GFD and dapsone
• GFD: skin clearance in 6–24 months; allows dapsone withdrawal in most patients
• Lifelong condition: relapse on gluten reintroduction
• Lymphoma risk: small increased risk of small bowel lymphoma (as with coeliac disease); reduced by GFD
• Dapsone: rapid and dramatic symptom relief but does not treat underlying enteropathy
• Spontaneous remission: may occur in ~10–15% over decades

DH vs Other Blistering Diseases

Dapsone Monitoring

Key Facts

Lichen planus is a common inflammatory dermatosis that can affect the skin, oral mucosa, genital mucosa, nails, and scalp. It is important because of its association with hepatitis C and the premalignant potential of erosive oral lichen planus.

Epidemiology

• Prevalence: ~0.5–1% of population
• Peak age: 30–60 years
• M:F ~equal for cutaneous; F > M for oral LP
• Oral LP: 1–2% prevalence in adults

Aetiology

• T-cell mediated autoimmune: CD8+ cytotoxic T-cells attack basal keratinocytes
• Hepatitis C: significant association (particularly oral LP); screen all patients
• Drug-induced lichenoid eruption: beta-blockers, NSAIDs, ACE inhibitors, antimalarials, thiazides, gold
• Dental amalgam: lichenoid contact reaction
• Graft-versus-host disease: lichenoid features common

Pathophysiology

• Cytotoxic T-lymphocytes target basal keratinocyte antigens → apoptosis of basal cells (civatte/colloid bodies)
• Band-like (lichenoid) lymphocytic infiltrate at dermal-epidermal junction
• Disruption of basement membrane → pigment incontinence (post-inflammatory hyperpigmentation)
• 'Saw-tooth' irregular acanthosis of rete ridges on histology

Cutaneous Lichen Planus

• 5 Ps: Pruritic, Polygonal, Purple/violaceous, Planar (flat-topped), Papules
• 2–10 mm diameter; shiny surface
• Wickham's striae: white lacy lines on papule surface
• Distribution: flexor surfaces (wrists, forearms), shins, lower back
• Koebner phenomenon: new lesions at sites of trauma
• Resolves with post-inflammatory hyperpigmentation

Oral Lichen Planus

• Reticular: white lacy pattern (Wickham's striae) on buccal mucosa - most common; usually asymptomatic
• Erosive: painful erythematous erosions/ulcers - may affect eating; premalignant (~1% risk of oral SCC)
• Atrophic: red, glazed areas
• Bilateral buccal mucosa involvement is characteristic

Other Sites

• Genital LP: vulval/penile erosions - painful, may cause scarring
• Nail LP: thinning, longitudinal ridging, pterygium (scarring of nail fold)
• Scalp (lichen planopilaris): scarring alopecia - irreversible hair loss

Red Flags

• Erosive oral LP: premalignant - requires long-term monitoring
• Scarring alopecia (lichen planopilaris) - irreversible
• Oesophageal LP: dysphagia - rare
• Drug-induced: review medication list

Bedside

• Clinical examination: characteristic morphology, Wickham's striae (use dermoscopy), Koebner phenomenon
• Oral examination: reticular/erosive changes on buccal mucosa
• Genital, nail, and scalp examination

Bloods

• Hepatitis C serology: screen ALL lichen planus patients
• LFTs: hepatitis C association
• FBC, U&Es: baseline if considering systemic treatment

Biopsy

• Punch biopsy: band-like lymphocytic infiltrate at DEJ, 'saw-tooth' rete ridges, civatte bodies (apoptotic keratinocytes), hypergranulosis
• DIF: rarely needed; may show fibrinogen deposition at BMZ (shaggy fibrin)

Special Tests

• Dermoscopy: Wickham's striae appear as white crossing lines
• Oral biopsy: for erosive oral LP - exclude dysplasia/SCC

Non-Pharmacological

• Patient education: usually self-limiting (1–2 years for cutaneous LP)
• Avoid triggers: review medications for lichenoid drug eruptions; dental amalgam consideration
• Oral LP monitoring: 6–12 monthly review for erosive disease (malignant potential)

Pharmacological

Cutaneous LP:

• Potent topical corticosteroids: clobetasol propionate 0.05% or betamethasone valerate 0.1% - first-line
• Topical tacrolimus 0.1% ointment: steroid-sparing alternative
• Oral prednisolone 0.5–1 mg/kg: short course for severe/widespread disease
• Acitretin 25–50 mg OD: for widespread, refractory cutaneous LP
• Phototherapy (narrowband UVB): for widespread disease

Oral LP:

• Topical corticosteroid mouthwash/paste: betamethasone 0.5 mg dissolved in 10 mL water as mouthwash; or clobetasol in adhesive paste
• Topical tacrolimus 0.1%: for erosive oral LP
• Oral prednisolone: short course for severe erosive flares

Lichen planopilaris:

• Potent topical steroids to scalp
• Hydroxychloroquine 200 mg BD: first-line systemic
• Aim to halt progression - scarring alopecia is irreversible

Referral Criteria

• Dermatology: severe/widespread disease, erosive oral LP, lichen planopilaris
• Oral medicine/maxillofacial: erosive oral LP - long-term monitoring
• Hepatology: if hepatitis C positive

• Cutaneous LP: usually self-limiting within 1–2 years; ~20% may recur
• Oral LP: may persist for decades; erosive form requires long-term monitoring
• Erosive oral LP: ~1% risk of progression to oral SCC over 5–10 years
• Lichen planopilaris: scarring alopecia is irreversible - early treatment to halt progression
• Nail LP: may cause permanent nail dystrophy
• Post-inflammatory hyperpigmentation: common, especially in darker skin types; may persist for months–years

Lichen Planus Variants

Lichenoid Drug Reactions - Common Culprits

Key Facts

Lichen sclerosus (LS) is a chronic, inflammatory skin disease with a predilection for the anogenital region. It is important because of its significant impact on quality of life and its association with vulval and penile SCC.

Epidemiology

• Estimated prevalence: 1 in 300–1,000 women
• Bimodal age distribution: prepubertal girls and postmenopausal women
• F:M ~10:1
• Males (BXO): any age, including children - may present with phimosis

Aetiology

• Autoimmune: strong association with other autoimmune conditions (thyroid disease ~30%, vitiligo, pernicious anaemia)
• Genetic predisposition: HLA-DQ7 association
• Hormonal: oestrogen deficiency may contribute (postmenopausal predominance)
• Chronic irritation/trauma: Koebner phenomenon reported
• NOT sexually transmitted

Pathophysiology

• Autoimmune T-cell mediated attack on dermal-epidermal junction
• Homogenisation and hyalinisation of upper dermis → sclerosis
• Epidermal atrophy with loss of rete ridges
• Progressive scarring → architectural distortion of vulva (labial fusion, clitoral burying) or phimosis in males
• Chronic inflammation → increased SCC risk

Vulval Lichen Sclerosus

• Porcelain-white, atrophic patches affecting vulva and perianal skin
• Figure-of-eight distribution around vulva and anus
• Intense pruritus - worse at night; may cause sleep disturbance
• Skin fragility: fissuring, erosions, purpura, ecchymoses
• Progressive scarring: labial fusion, clitoral hooding/burying, introital narrowing → dyspareunia
• Secondary infection common

Penile Lichen Sclerosus (BXO)

• White patches on glans and prepuce
• Phimosis (inability to retract foreskin) - most common presentation in males
• Meatal stenosis → urinary difficulties
• Frenular scarring

Extragenital Lichen Sclerosus

• ~15–20% of patients have extragenital lesions
• White, atrophic patches on trunk, proximal limbs
• Usually asymptomatic

Red Flags

• Persistent, thickened, or warty area within LS - biopsy to exclude SCC (4–5% lifetime risk)
• Bleeding or non-healing ulcer
• Failure to respond to appropriate topical steroid treatment
• Severe architectural distortion requiring surgical assessment

Bedside

• Clinical examination: often diagnostic in classic presentation; full anogenital examination

Bloods

• Autoimmune screen: thyroid function (TFTs), anti-thyroid antibodies, B12 (pernicious anaemia)
• FBC: if anaemia suspected

Biopsy

• Punch biopsy: not always needed for classic presentation but recommended if:
  • Diagnostic uncertainty
  • Suspected SCC (thickened, warty, or ulcerated area)
  • Treatment failure
  • Pigmented lesion within LS
• Histology: epidermal atrophy, loss of rete ridges, homogenisation of upper dermis, band-like lymphocytic infiltrate beneath sclerotic zone

Special Tests

• Not routinely required
• Vulvoscopy: detailed examination in specialist clinic

Non-Pharmacological

• Patient education: chronic condition requiring long-term maintenance treatment
• Emollients: regular use as soap substitutes and moisturisers (aqueous cream should NOT be used as leave-on - use alternatives)
• Avoid irritants: soap, bubble bath, tight clothing
• Sexual health support: dyspareunia counselling, lubricants

Pharmacological

• Clobetasol propionate 0.05% ointment: first-line - highly effective

• Maintenance: typically 1–2 times per week long-term
  • ~95% respond to appropriate topical steroid treatment
• Topical tacrolimus 0.1%: second-line if steroids contraindicated or ineffective (off-licence)
• Topical oestrogen: may help in postmenopausal women as adjunct (limited evidence)

Surgical

• Circumcision: curative for penile LS (BXO) in most cases
• Vulval surgery: for adhesions, introital stenosis, clitoral de-hooding - improves function
• Meatotomy/meatoplasty: for meatal stenosis in males
• Excision of suspicious lesions: to exclude SCC

Referral Criteria

• Dermatology/vulval clinic: diagnostic uncertainty, treatment failure, suspected malignancy
• Urology: BXO with phimosis or meatal stenosis
• Paediatric dermatology: suspected LS in children
• Safeguarding: LS in children may be misdiagnosed as abuse and vice versa - expert assessment required

• Chronic relapsing condition - lifelong maintenance treatment usually required
• ~95% respond well to topical clobetasol propionate
• Vulval SCC risk: ~4–5% lifetime in women with LS - requires long-term monitoring
• Penile SCC risk: lower but present; circumcision significantly reduces risk
• Prepubertal LS: may improve or resolve at puberty in some girls
• Scarring is irreversible - early, adequate treatment prevents architectural distortion
• Quality of life: significantly impacted by pruritus, dyspareunia, and psychological effects

Lichen Sclerosus vs Lichen Planus (Vulval)

Clobetasol Step-Down Regimen

Key Facts

Fungal skin infections are among the most common dermatological conditions globally. They range from superficial (dermatophytes, Candida, Malassezia) to deep/invasive (rare in immunocompetent hosts). Accurate diagnosis prevents inappropriate treatment (e.g. steroid misuse).

Epidemiology

• Dermatophyte infections: affect ~20–25% of the global population
• Tinea pedis (athlete's foot): most common dermatophyte infection
• Onychomycosis: ~10% of adults, increasing with age
• Candidal infections: common in diabetes, immunosuppression, obesity
• Pityriasis versicolor: common in young adults, especially in tropical/subtropical climates

Aetiology

• Dermatophytes: Trichophyton rubrum (most common), T. mentagrophytes, Microsporum canis, Epidermophyton floccosum
• Candida: C. albicans most common; C. auris emerging concern
• Malassezia: lipophilic yeast; part of normal flora; causes pityriasis versicolor
• Risk factors: warm/moist environment, occlusion, diabetes, immunosuppression, obesity, corticosteroid use

Pathophysiology

• Dermatophytes: keratinophilic - colonise stratum corneum, hair, and nails via keratinase enzymes

Dermatophyte Infections (Tinea)

• Tinea corporis: annular erythematous plaque with raised, scaly advancing edge and central clearing ('ringworm')
• Tinea pedis: interdigital maceration/scaling, moccasin-type scaling, vesicular
• Tinea cruris: erythematous scaly rash in groin/inner thighs; spares scrotum (unlike Candida)
• Tinea capitis: scaly scalp with hair loss ± kerion (boggy, painful mass); common in children
• Onychomycosis: distal/lateral subungual - yellow/white discolouration, thickening, onycholysis

Candidal Infections

• Intertrigo: erythema, maceration in skin folds; satellite papules/pustules
• Oral thrush: white plaques that can be scraped off; sore mouth
• Vulvovaginal candidiasis: pruritus, thick white discharge
• Balanitis: erythema, white plaques on glans
• Nail (candidal paronychia): painful, swollen nail fold

Pityriasis Versicolor (Malassezia)

• Hypo- or hyperpigmented, finely scaly macules/patches
• Trunk, upper arms, neck
• More visible after sun exposure (affected skin does not tan)

Red Flags

• Extensive or rapidly spreading infection in immunocompromised - consider invasive fungal disease
• Kerion (tinea capitis): painful, boggy mass - needs systemic antifungals + possibly steroids
• Steroid-modified tinea (tinea incognito): atypical appearance due to topical steroid misuse

Bedside

• Skin scraping: from active advancing edge; dissolve in 10–20% KOH → microscopy for hyphae/spores
• Wood's lamp: Microsporum species fluoresce green; erythrasma (Corynebacterium) fluoresces coral-red

Microbiology

• Fungal culture: skin/nail/hair sample on Sabouraud's agar - gold standard for species identification; takes 2–6 weeks
• Nail clippings: for suspected onychomycosis - confirm before systemic treatment

Bloods

• Not routinely required for superficial fungal infections
• LFTs: before systemic antifungals (terbinafine, itraconazole)
• Blood glucose/HbA1c: if recurrent candidiasis - screen for diabetes

Special Tests

• Dermoscopy: may show comma hairs in tinea capitis
• Fungal PCR: rapid identification available in some centres

Non-Pharmacological

• Hygiene advice: keep affected areas dry, avoid sharing towels/clothing
• Cotton clothing: reduce occlusion and moisture
• Weight management: reduce intertrigo risk

Pharmacological - Topical

• Clotrimazole 1% cream BD for 2–4 weeks: first-line for localised tinea, cutaneous candidiasis
• Miconazole 2% cream BD: alternative; available combined with hydrocortisone for inflamed infections (short-term only)
• Terbinafine 1% cream OD for 1–2 weeks: effective for localised dermatophyte infections
• Ketoconazole 2% shampoo: pityriasis versicolor - apply to affected areas, leave for 5 minutes, rinse; daily for 5 days
• Nystatin cream: specifically for Candida (not effective against dermatophytes)

Pharmacological - Systemic

• Terbinafine 250 mg OD: first-line systemic for dermatophyte infections
  • Tinea capitis: 4–6 weeks (Trichophyton), 6–8 weeks (Microsporum - may need higher dose)
  • Onychomycosis: 6 weeks (fingernails), 12 weeks (toenails)
• Itraconazole 200 mg OD or pulse dosing: alternative; better for Microsporum, Candida; check LFTs; many drug interactions (CYP3A4 inhibitor)
• Fluconazole 50 mg OD for 2–4 weeks: systemic Candida infections
• Griseofulvin: historically used for tinea capitis in children; being replaced by terbinafine

Referral Criteria

• Dermatology: diagnostic uncertainty, treatment failure, widespread/atypical infection
• Paediatrics: tinea capitis with kerion
• Infectious diseases: suspected deep/invasive fungal infection in immunocompromised

• Localised superficial infections: excellent response to topical antifungals
• Tinea capitis: good prognosis with systemic treatment; untreated may cause permanent scarring alopecia (kerion)
• Onychomycosis: cure rates ~70–80% with terbinafine; recurrence common (~20%)
• Candidal infections: good response to treatment; recurrence related to ongoing risk factors
• Pityriasis versicolor: responds to treatment but high recurrence rate (~60%); pigmentary change may persist for months
• Immunocompromised patients: may develop chronic, widespread, or invasive disease

Dermatophyte Infection Summary by Site

Antifungal Drug Summary

Key Facts

Tinea infections are superficial dermatophyte infections named by the body site affected. They are extremely common and usually straightforward to diagnose and treat. Tinea capitis and onychomycosis require systemic antifungal treatment.

Epidemiology

• Tinea pedis: most common (~15–25% of population)
• Tinea capitis: increasing in UK; predominantly affects children aged 3–14; T. tonsurans now the most common cause
• Onychomycosis: affects ~10% of adults; increases with age
• Tinea corporis and cruris: common in young adults, athletes

Aetiology

• T. rubrum: most common dermatophyte globally; causes tinea pedis, corporis, cruris, unguium
• T. tonsurans: now the commonest cause of tinea capitis in UK (anthropophilic)
• M. canis: zoophilic - acquired from cats/dogs; causes tinea corporis, capitis
• E. floccosum: tinea cruris
• Risk factors: warm/moist environment, communal facilities (pools, gyms), diabetes, immunosuppression, obesity

Pathophysiology

• Dermatophytes produce keratinases → digest keratin in stratum corneum, hair, nails
• Fungal hyphae spread centrifugally in skin → annular lesion with active advancing edge
• Inflammatory response at the periphery → raised, erythematous, scaly border
• Central clearing as immune response controls infection behind the advancing front

Tinea Corporis (Body)

• Annular ('ring-shaped') erythematous plaque
• Raised, scaly advancing edge with central clearing
• Single or multiple lesions
• Can affect any body site

Tinea Pedis (Feet)

• Interdigital: maceration, peeling between toes (especially 4th/5th web space)
• Moccasin-type: diffuse, dry, scaly erythema on soles and lateral feet
• Vesiculobullous: inflammatory vesicles/bullae on instep

Tinea Cruris (Groin)

• Erythematous, scaly rash extending from groin crease to inner thighs
• Well-defined advancing edge
• Spares the scrotum (distinguishing feature from Candida intertrigo)
• Often coexists with tinea pedis

Tinea Capitis (Scalp)

• Scaly patches with hair loss in children
• Broken hairs, black dot pattern (T. tonsurans)
• Kerion: severe inflammatory response - boggy, tender mass with pustules; may cause permanent scarring alopecia
• Posterior cervical lymphadenopathy

Onychomycosis (Nails)

• Distal lateral subungual: yellow/white discolouration from free edge; most common
• Nail thickening, crumbling, onycholysis
• Toenails more commonly affected than fingernails

Red Flags

• Kerion - needs urgent systemic treatment
• Rapidly spreading in immunocompromised
• Tinea incognito - atypical appearance, ask about steroid use

Bedside

• Skin scraping (from advancing edge): KOH preparation - branching septate hyphae
• Hair pluck (tinea capitis): broken/affected hairs for microscopy and culture
• Nail clipping (onychomycosis): send for microscopy and culture - confirm before systemic treatment
• Wood's lamp: Microsporum spp. fluoresce green; T. tonsurans does NOT fluoresce

Microbiology

• Fungal culture on Sabouraud's agar: species identification; takes 2–6 weeks
• Dermatophyte PCR: available in some centres - rapid results

Bloods

• LFTs: before systemic antifungals (terbinafine, itraconazole)
• Blood glucose/HbA1c: recurrent infection - screen for diabetes

Special Tests

• Dermoscopy of scalp: comma hairs, corkscrew hairs (tinea capitis)
• Nail plate biopsy with PAS stain: if culture negative but clinical suspicion high

Non-Pharmacological

• Hygiene: wash and dry feet thoroughly; dry between toes; change socks daily
• Avoid sharing: towels, combs, shoes
• Athlete's foot: antifungal foot powder, breathable footwear
• Contact tracing: tinea capitis - household contacts may be asymptomatic carriers

Pharmacological - Localised Skin Infection

• Terbinafine 1% cream OD for 1–2 weeks: first-line for limited dermatophyte infection
• Clotrimazole 1% cream BD for 2–4 weeks: alternative
• Miconazole 2% cream BD: alternative

Pharmacological - Systemic (Scalp, Nails, Widespread)

Tinea capitis:

• Terbinafine 250 mg OD (adults; weight-based dosing in children): 4 weeks for Trichophyton, 6–8 weeks for Microsporum
• Griseofulvin 500 mg–1 g OD (adults): alternative, especially for Microsporum; 6–8 weeks
• Adjunctive antifungal shampoo (ketoconazole 2%): reduces spore shedding; does not treat infection alone

Onychomycosis:

• Terbinafine 250 mg OD: 6 weeks (fingernails), 12 weeks (toenails); cure rate ~70–80%
• Itraconazole pulse therapy: 200 mg BD for 1 week/month - 2 pulses (fingers), 3 pulses (toes)
• Amorolfine 5% nail lacquer: adjunct for mild, distal involvement

Kerion:

• Systemic antifungal (terbinafine) PLUS short course oral prednisolone 0.5–1 mg/kg to reduce inflammation and scarring

Referral Criteria

• Dermatology: treatment failure, diagnostic uncertainty, widespread infection
• Paediatrics: tinea capitis with kerion
• Podiatry: recurrent onychomycosis

• Tinea corporis/cruris/pedis: excellent with topical treatment; recurrence related to ongoing risk factors
• Tinea capitis: good with systemic treatment; kerion may cause permanent scarring alopecia
• Onychomycosis: cure rate ~70–80% with terbinafine; relapse/reinfection ~20–25%
• Tinea incognito: resolves once steroids stopped and antifungal commenced
• Immunocompromised: chronic, relapsing course; may need prolonged treatment

Tinea Infection Summary

Topical vs Systemic Antifungal Indications

Key Facts

Scabies is a common, highly contagious ectoparasitic infestation. It is a significant public health concern, particularly in care homes, prisons, and overcrowded settings. Outbreaks require coordinated treatment of all contacts.

Epidemiology

• ~300 million cases/year globally
• Common in UK: increased incidence during/post COVID-19
• All ages affected; outbreaks in care homes, schools, prisons
• Not related to hygiene - anyone can be affected
• Crusted scabies: rare, almost exclusively in immunocompromised/elderly

Aetiology

• Sarcoptes scabiei var. hominis: obligate human parasite
• Transmission: prolonged skin-to-skin contact (>15–20 minutes); sexual transmission common
• Fomite transmission: rare in classical scabies; significant in crusted scabies
• Typical mite burden: 10–15 mites in classical scabies; thousands–millions in crusted scabies

Pathophysiology

• Type IV (delayed) hypersensitivity to mite proteins, faeces, and eggs → intense pruritus
• First infestation: sensitisation takes 4–6 weeks → asymptomatic but contagious during this period
• Re-infestation: symptoms develop within 24–48 hours (pre-sensitised)

Classical Scabies

• Intense generalised pruritus - characteristically worse at night
• Burrows: short (5–15 mm), wavy, grey-white lines - pathognomonic
  • Finger web spaces (most common)
  • Flexor aspect of wrists
  • Male genitalia (penile papules/nodules - almost pathognomonic)
  • Female nipples
  • Axillary folds, belt line, buttocks
• Excoriations, secondary eczematisation
• Papules, vesicles on hands and feet
• Face and scalp typically spared in adults (but NOT in infants)

Crusted (Norwegian) Scabies

• Hyperkeratotic, crusted, psoriasiform plaques
• May involve face, scalp, nails
• Pruritus may be minimal (impaired immune response)
• EXTREMELY contagious - thousands to millions of mites
• Risk groups: immunosuppressed, elderly, Down syndrome, neurological conditions

Scabies in Infants

• Lesions on palms, soles, face, scalp (unlike adults)
• Vesiculopustular lesions

Red Flags

• Crusted scabies - infection control emergency; isolate immediately
• Widespread secondary bacterial infection (impetigo, cellulitis)
• Treatment failure - consider crusted scabies, poor compliance, untreated contacts
• Institutional outbreak

Bedside

• Dermoscopy: 'delta-wing jet' sign (mite at end of burrow) - quick and sensitive; 'wake sign' of burrow

Bloods

• Not routinely required
• Eosinophil count: may be elevated
• HIV test: consider if crusted scabies in young patient

Special Tests

• Not usually needed - diagnosis is predominantly clinical
• Biopsy: rarely indicated; shows spongiotic dermatitis with eosinophils; mite may be seen in stratum corneum

Imaging

• Not applicable

Non-Pharmacological

• Treat ALL household contacts and sexual partners simultaneously - even if asymptomatic
• Launder bedding, towels, clothing at ≥60°C on day of treatment; items that cannot be washed - bag and seal for 72 hours
• Infection control: isolation for crusted scabies; barrier nursing
• Patient education: post-scabies itch may persist 2–4 weeks - not treatment failure

Pharmacological

Classical scabies:

• Permethrin 5% cream: first-line
  • Apply to whole body from chin down (include head/face in infants, elderly, immunosuppressed)
  • Leave on for 8–12 hours (overnight), wash off
  • Reapply if hands washed during treatment period
  • Repeat at day 7 (kills newly hatched mites)
• Oral ivermectin 200 mcg/kg: single dose, repeat at day 7 - alternative; particularly useful for outbreaks, treatment failure, or inability to apply topical treatment

Crusted scabies:

• Combined approach: oral ivermectin 200 mcg/kg on days 1, 2, 8, 9, 15 PLUS permethrin 5% daily for 7 days then twice weekly until cured
• Keratolytics to remove crusts
• Isolation and infection control precautions

Symptomatic relief:

• Crotamiton 10% cream: antipruritic, applied BD
• Emollients: for dry, eczematised skin
• Sedating antihistamine (chlorphenamine 4 mg TDS): for nocturnal itch
• Topical corticosteroid: short course for post-scabies eczema (after successful treatment)

Referral Criteria

• Dermatology: diagnostic uncertainty, treatment failure, suspected crusted scabies
• Public health/infection control: institutional outbreaks
• HIV/immunology: crusted scabies in young patient

• Classical scabies: excellent with appropriate treatment of patient AND contacts
• Treatment failure: usually due to untreated contacts, inadequate application, or missed diagnosis of crusted scabies
• Post-scabies itch: common, lasting 2–4 weeks after successful treatment; responds to emollients and mild topical steroids
• Crusted scabies: high morbidity; risk of secondary sepsis; requires aggressive treatment and infection control
• Scabies outbreaks in care homes: can be prolonged and difficult to eradicate without coordinated treatment

Scabies Treatment Summary

Key Distinguishing Features

Key Facts

Head lice infestation (pediculosis capitis) is extremely common in UK schoolchildren. It is not a sign of poor hygiene. Treatment should only be initiated when live lice are found. The emphasis has shifted from insecticide-based treatments to physical agents (dimeticone) and mechanical removal.

Epidemiology

• Very common: affects ~10–20% of primary school children at any time
• Peak age: 4–11 years
• Girls > boys (~3:1)
• No social class or hygiene association
• Year-round incidence; no seasonal peak in UK

Aetiology

• Pediculus humanus capitis: wingless insect, 2–3 mm long
• Transmission: direct head-to-head contact (NOT via hats, combs, or pillows - lice die within 24–48 hours off the host)

• Nits (empty egg cases) cemented to hair shaft ~1 cm from scalp

Pathophysiology

• Sensitisation to saliva → pruritus (takes weeks to develop after first infestation)
• Excoriations → secondary bacterial infection (impetigo)

Typical Presentation

• Scalp pruritus: most common symptom; may be absent in early infestation
• Worse behind ears and nape of neck: preferred feeding sites
• Excoriations and eczematisation from scratching
• Live lice: 2–3 mm, grey-brown wingless insects (move rapidly, hard to spot)
• Nits: white/brown oval egg cases attached to hair shafts - NOT diagnostic of active infection
• Secondary impetigo: crusted, golden lesions from scratched excoriations

Occipital and Post-Auricular Lymphadenopathy

• Reactive, tender nodes - common with active infestation

Red Flags

• Widespread secondary infection requiring antibiotics
• Severe excoriations causing scarring
• Child safeguarding: persistent, severe, untreated infestation may (rarely) raise concerns

Bedside

• Detection combing (wet combing): gold standard
  • Apply conditioner to wet hair → comb systematically with fine-toothed plastic detection comb (0.2–0.3 mm tooth spacing)
  • Check comb after each stroke for live lice and nymphs
  • More sensitive than dry visual inspection (4× more effective)

Microscopy

• Live louse examination: identifies species (rarely needed)
• Nit examination: viable nit is brown, close to scalp; hatched nit is white, further from scalp

Bloods

• Not required

Special Tests

• Not required for diagnosis

Non-Pharmacological

• Wet combing (Bug Busting method): effective alternative to chemical treatment

• Perform on days 1, 5, 9, 13 (covers full life cycle)
  • Continue until no live lice found on 3 consecutive sessions
• Only treat if LIVE lice found: finding nits alone does not require treatment
• Check household contacts: treat only those with confirmed live lice
• School exclusion: NOT recommended by Public Health England

Pharmacological

• Dimeticone 4% lotion (Hedrin): first-line - apply to dry hair, leave 8 hours (or overnight), wash out; repeat at day 7
  • Physical mode of action: coats and suffocates lice; no resistance issues
• Dimeticone 92% (Hedrin Once): spray gel, apply for 8 hours; single application may suffice
• Isopropyl myristate/cyclomethicone solution (Full Marks): physical action; apply for 10 minutes, comb out dead lice; repeat at day 7
• Malathion 0.5% aqueous liquid: second-line - apply to dry hair, leave 12 hours; repeat at day 7; resistance increasingly common
• Permethrin: no longer recommended as first-line due to widespread resistance in UK

Important Notes

• Always repeat treatment at day 7 to kill newly hatched lice from surviving eggs
• Combination of treatment + combing improves success
• Contact tracing: check and treat household members with confirmed live lice

Referral Criteria

• Rarely needed; manage in primary care
• Dermatology: if diagnostic uncertainty or secondary complications
• School nursing: for recurrent outbreaks - education and support

• Excellent with appropriate treatment - cure rates >90% with dimeticone or thorough wet combing
• Treatment failure: usually due to reinfestation from untreated contacts, poor application technique, or treatment resistance
• Resistance: increasing to malathion and permethrin; dimeticone and physical methods unaffected
• Secondary infection: responds well to appropriate antibiotics
• Psychological impact: significant distress to children and parents; reassurance important

Head Lice Treatment Comparison

Bug Busting Schedule

Key Facts

Impetigo is a superficial skin infection that is extremely common in childhood. It is highly contagious and can spread rapidly in schools and nurseries. It is important to distinguish from more serious skin infections and to be aware of rare post-streptococcal complications.

Epidemiology

• Most common bacterial skin infection in children
• Peak age: 2–6 years
• More common in summer/autumn (warm, humid conditions)
• Affects ~2–3% of children annually in UK
• Can occur at any age; common secondary infection of eczema ('eczema herpeticum' is different - HSV)

Aetiology

• S. aureus: ~80% of cases; sole pathogen in bullous impetigo
• S. pyogenes (Group A Streptococcus): ~10–20%; may cause post-streptococcal glomerulonephritis (NOT rheumatic fever)
• MRSA: increasingly recognised cause in community-acquired impetigo
• Risk factors: pre-existing skin condition (eczema, scabies), minor trauma, warm/humid environment, crowding

Pathophysiology

• Bacteria colonise damaged skin (abrasion, insect bite, eczema) → superficial infection of epidermis

Non-Bullous Impetigo (70%)

• Usually perioral, perinasal, or on exposed skin
• Regional lymphadenopathy may be present
• May spread by autoinoculation (finger-to-face)

Bullous Impetigo (30%)

• Flaccid, clear or cloudy fluid-filled blisters 1–3 cm
• Rupture easily → leave thin, lacquer-like crust with erythematous base
• More common in neonates and infants
• Usually on trunk, axillae, flexures

Secondary Impetiginisation

• Bacterial superinfection of pre-existing skin condition (eczema, scabies, herpes, chickenpox)
• Golden crusting developing on top of chronic skin disease

Red Flags

• Systemic symptoms (fever, malaise) - consider cellulitis, abscess, or bacteraemia
• Widespread bullous impetigo in neonate - exclude staphylococcal scalded skin syndrome (SSSS)
• Post-streptococcal glomerulonephritis: haematuria, oedema, hypertension 1–3 weeks after streptococcal impetigo
• Treatment failure - consider MRSA

Bedside

• Clinical diagnosis: usually straightforward from characteristic appearance
• Swab for MC&S: if treatment failure, recurrent episodes, or suspected MRSA; take swab from beneath crust

Bloods

• Not routinely required for uncomplicated impetigo
• ASOT/anti-DNase B: if post-streptococcal glomerulonephritis suspected
• U&Es, urinalysis: if PSGN suspected (haematuria, proteinuria, renal impairment)

Biopsy

• Not required - clinical diagnosis

Special Tests

• Nasal swab: for S. aureus carriage if recurrent impetigo - treat with mupirocin nasal ointment TDS for 5 days

Non-Pharmacological

• Hygiene measures: regular handwashing, avoid sharing towels/flannels
• Wound care: gently remove crusts with warm water and clean cloth
• School exclusion: until lesions crusted over, or 48 hours after starting antibiotics
• Avoid touching/scratching lesions - prevents autoinoculation and spread

Pharmacological

Localised, non-bullous impetigo:

• Topical hydrogen peroxide 1% cream (Crystacide): first-line (NICE CKS) - apply BD-TDS for 5 days; effective, no resistance concerns
• Topical fusidic acid 2% cream/ointment: second-line - TDS for 5 days; increasing S. aureus resistance (~20%)
• Topical mupirocin 2%: alternative, especially if MRSA suspected

Extensive, bullous, or systemically unwell:

• Flucloxacillin 500 mg QDS (adult) or 12.5–25 mg/kg QDS (child) for 5–7 days: first-line oral
• Clarithromycin 250–500 mg BD for 5 days: if penicillin-allergic
• Co-amoxiclav: if mixed streptococcal/staphylococcal suspected

Recurrent impetigo:

• Mupirocin 2% nasal ointment TDS for 5 days + chlorhexidine body wash for 5 days - S. aureus decolonisation
• Treat whole household if recurrent

Referral Criteria

• Rarely needed - manage in primary care
• Dermatology: if diagnostic uncertainty or treatment-resistant
• Paediatrics: neonatal impetigo, suspected SSSS, systemically unwell child

• Excellent: self-limiting even without treatment in many cases; resolves faster with antibiotics
• Heals without scarring
• Post-streptococcal glomerulonephritis: rare (~1–5% after streptococcal impetigo); usually self-limiting
• Rheumatic fever does NOT follow skin streptococcal infections (only throat)
• Recurrence: common; consider nasal S. aureus decolonisation
• SSSS (in neonates): potentially life-threatening if not recognised

Impetigo Treatment Ladder

Complications of Impetigo

Key Facts

Cellulitis is one of the most common reasons for acute medical admission in the UK. Accurate diagnosis is important as many conditions mimic cellulitis ('pseudocellulitis'), leading to unnecessary antibiotic use.

Epidemiology

• Very common: ~20–50 per 1,000 person-years
• Accounts for ~2% of emergency hospital admissions in UK
• Lower limbs: ~70% of cases
• Face (periorbital): important in children
• Recurrence: ~30% within 3 years

Aetiology

• Beta-haemolytic streptococci (particularly Group A - S. pyogenes): most common cause
• S. aureus: second most common; predominates in abscesses, MRSA
• Portal of entry: tinea pedis (most common modifiable risk factor), leg ulcers, eczema, insect bites, trauma, surgical wounds
• Risk factors: lymphoedema (strongest risk factor for recurrence), obesity, venous insufficiency, diabetes, previous cellulitis, immunosuppression

Pathophysiology

• Bacteria enter through breached skin barrier → infection of dermis and subcutaneous tissue
• Bacterial toxins and enzymes (streptolysins, hyaluronidase) → tissue destruction and spread
• Inflammatory response → erythema, oedema, warmth, pain

Typical Presentation

• Acute onset erythema, warmth, swelling, tenderness
• Poorly demarcated, spreading margins
• Usually unilateral (lower limb)
• May have associated fever, rigors, malaise
• Regional lymphadenopathy and lymphangitis (red streaking)

Erysipelas

• Variant with more superficial involvement (upper dermis)
• Well-demarcated, raised, erythematous border ('step' edge)
• More common on face (butterfly distribution)
• Often higher fever and more systemic upset than cellulitis

Periorbital vs Orbital Cellulitis

• Periorbital (preseptal): swelling of eyelid, no visual compromise, no proptosis
• Orbital (postseptal): proptosis, ophthalmoplegia, pain on eye movement, visual loss - EMERGENCY

Red Flags - Necrotising Fasciitis

• Pain DISPROPORTIONATE to clinical signs - key early feature
• Rapidly spreading erythema/necrosis
• Crepitus on palpation
• Systemic toxicity, shock
• Haemorrhagic blisters, dusky skin
• Failure to respond to antibiotics

Bedside

• Mark the edge of erythema with skin marker and date/time - monitor progression
• Observations: temperature, HR, BP, RR, SpO2 - NEWS2 score
• Assess for portal of entry: examine feet for tinea pedis, interdigital maceration

Bloods

• FBC: leucocytosis
• CRP: elevated; useful for monitoring response
• U&Es: renal function (especially if IV antibiotics)
• Blood cultures: if systemically unwell (Class III–IV) - yield low (~5%)
• Lactate: if sepsis suspected
• HbA1c/glucose: screen for diabetes

Imaging

• Not routinely required for uncomplicated cellulitis
• USS Doppler: if DVT suspected
• CT/MRI: if necrotising fasciitis, abscess, or deep tissue infection suspected
• X-ray: if crepitus (gas gangrene) or foreign body

Special Tests

• Wound swab: from portal of entry or draining discharge - guide antibiotic choice
• LRINEC score: laboratory risk indicator for necrotising fasciitis (CRP, WBC, Hb, Na, creatinine, glucose) - score ≥6 suggests necrotising fasciitis

Non-Pharmacological

• Leg elevation: above heart level - reduces oedema and pain
• Mark erythema borders: re-assess at 48 hours
• Treat portal of entry: tinea pedis (topical antifungal), eczema (emollients)
• Compression: after acute phase in patients with lymphoedema/chronic venous insufficiency

Pharmacological

Eron Class I (mild, no systemic upset):

• Flucloxacillin 500 mg QDS for 5–7 days: first-line oral
• Clarithromycin 500 mg BD: if penicillin-allergic
• Increase to 1 g QDS flucloxacillin if poor response at 48 hours

Eron Class II–III (moderate-severe/systemic upset):

• IV flucloxacillin 1–2 g QDS: plus IV benzylpenicillin 1.2 g QDS (if streptococcal suspected)
• IV co-amoxiclav 1.2 g TDS: alternative
• IV vancomycin: if MRSA suspected (dose per protocol, trough monitoring)
• Step down to oral when improving (typically 48–72 hours)
• Consider OPAT (outpatient parenteral antibiotic therapy) for IV treatment at home

Eron Class IV (necrotising fasciitis/sepsis):

• Urgent surgical exploration and debridement - DO NOT delay for imaging
• Broad-spectrum IV antibiotics: piperacillin-tazobactam 4.5 g TDS + IV clindamycin 600 mg QDS (toxin inhibition)
• ICU admission for septic shock

Prevention of recurrence:

• Phenoxymethylpenicillin 250 mg BD long-term (PATCH trial - BMJ 2017): prophylaxis for patients with ≥2 episodes in 12 months; reduces recurrence by ~45% while taking antibiotic
• Treat chronic oedema/lymphoedema (compression)
• Treat tinea pedis - key modifiable risk factor

Referral Criteria

• Hospital admission: Eron Class III–IV, failure of oral antibiotics, suspected necrotising fasciitis
• Surgical: abscess drainage, necrotising fasciitis
• Dermatology: if diagnostic uncertainty or recurrent cellulitis
• Lymphoedema service: chronic oedema management

• Uncomplicated cellulitis: excellent prognosis; responds to antibiotics within 48–72 hours
• Recurrence: ~30% within 3 years; reduced by prophylactic penicillin (PATCH trial)
• Necrotising fasciitis: mortality ~20–30% even with treatment; delays in diagnosis worsen outcomes
• Complications: abscess formation (5–10%), bacteraemia, sepsis, lymphoedema (from lymphatic damage)
• Orbital cellulitis: risk of visual loss, cavernous sinus thrombosis - requires urgent ENT/ophthalmology input

Eron Classification

PATCH Trial (BMJ 2017)

Cellulitis Mimics ('Pseudocellulitis')

Key Facts

Herpes zoster (shingles) results from reactivation of latent VZV. It is common, affecting approximately 1 in 3 people during their lifetime. The risk increases with age and immunosuppression. Early antiviral treatment and vaccination are the key management strategies.

Epidemiology

• Lifetime risk: ~30%
• Incidence increases with age: ~1% per year in >80s
• UK: ~50,000 cases/year in >70s
• Recurrence: ~5% over a lifetime (higher in immunosuppressed)
• PHN: ~10–15% overall; ~20% in >60 years; ~30% in >80 years

Aetiology

• Reactivation triggers: declining cell-mediated immunity (ageing), immunosuppression (HIV, chemotherapy, transplant, corticosteroids), stress, trauma