Dermatology: Urticaria, drug reactions, blistering, ulcers and emergencies

• Urticaria and drug reactions: Urticaria | Angioedema | Drug Eruptions — Overview | Stevens–Johnson Syndrome and TEN | DRESS and AGEP | Erythema Multiforme | Erythema Nodosum
• Blistering and widespread skin disease: Bullous Pemphigoid | Pemphigus Vulgaris | Dermatitis Herpetiformis | Other Causes of Blisters | Erythroderma | Dermatological Emergencies — Summary
• Ulcers and wounds: Leg Ulcers | Pressure Ulcers | Pyoderma Gangrenosum
• Skin and the whole body: Skin Signs of Systemic Disease | Generalised Itch | Photosensitivity
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🚑 Urticaria, drug reactions, blistering, ulcers and emergencies — the skin can signal life-threatening illness. Stevens–Johnson syndrome and toxic epidermal necrolysis, DRESS, erythroderma and pemphigus cause skin failure. Most leg ulcers are venous and heal with compression — but only after checking the arterial supply. Many systemic diseases have characteristic skin signs worth learning.
Your four questions for every patient: Is this an emergency (mucosal involvement, skin pain, blistering, fever, over 10% skin loss)? Has a new drug been started in the past 8 weeks? Is the skin a clue to a systemic disease? Is the patient able to keep warm, hydrated and infection-free?

Urticaria

• What it is: Itchy, raised wheals (hives) — pale or pink swellings surrounded by redness — from mast cell release of histamine; each wheal lasts under 24 hours and leaves no mark.
• Acute urticaria (under 6 weeks) — common; often no cause found; triggers include viral infections (especially in children), drugs (NSAIDs, aspirin, opioids, antibiotics), foods (nuts, shellfish — with other allergic symptoms within minutes), insect stings, latex.
• Chronic urticaria (6 weeks or more):
  • Chronic spontaneous urticaria — no external trigger; often autoimmune; associated with thyroid autoimmunity; worsened by NSAIDs, stress, heat, alcohol; may last months to years.
  • Inducible urticaria — triggered by physical stimuli: dermographism (stroking or scratching), cold, heat, pressure (delayed deep swelling), cholinergic (small wheals with sweating, exercise, hot showers), solar, aquagenic.
• Tests — usually none needed; FBC, CRP, TFTs for chronic spontaneous urticaria; allergy testing only if a specific trigger is suspected from the history (not routinely); challenge tests for inducible types.
• Treatment:
  • Avoid triggers (NSAIDs, aspirin in many).
  • Non-sedating antihistamine (cetirizine, loratadine, fexofenadine) daily; if not controlled, increase up to four times the standard dose (off-label, specialist advice).
  • Short oral steroid course (3–5 days) for severe acute urticaria only.
  • Chronic spontaneous urticaria not responding — refer: omalizumab (anti-IgE, NICE TA339), then ciclosporin; montelukast in some.
• Urticarial vasculitis — wheals lasting over 24 hours, painful or burning rather than itchy, leaving bruising — biopsy; check complement (low in some — SLE).
• Anaphylaxis — urticaria with breathing or circulation problems — IM adrenaline (see the Allergy and Paediatric Emergencies chapters).

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Angioedema

• What it is: Deeper swelling of the dermis and submucosa — lips, eyelids, tongue, face, genitals, hands, feet, bowel wall (abdominal pain) and larynx (airway obstruction). Often painful or tingling rather than itchy; lasts up to 72 hours.
• Two main types:
  • Histamine (mast cell)-mediated — usually with urticaria; allergic triggers; responds to antihistamines, steroids and adrenaline.
  • Bradykinin-mediated — without urticaria; doesn't respond to antihistamines, steroids or adrenaline:
    • ACE inhibitor-induced — the commonest cause of angioedema in emergency departments; can start any time, even after years of use; more common in people of African heritage; also gliptins, sacubitril–valsartan, alteplase.
    • Hereditary angioedema — autosomal dominant C1-esterase inhibitor deficiency: recurrent swellings from childhood or adolescence, abdominal attacks, triggered by trauma, dental work, oestrogens; low C4 (check C4, then C1-inhibitor level and function).
    • Acquired C1-inhibitor deficiency — older people with lymphoma or autoimmune disease (low C1q).
• Emergency management — airway first (stridor, voice change, drooling, tongue swelling) — senior anaesthetic and ENT help; IM adrenaline if allergic features; for bradykinin types — stop the ACE inhibitor (never restart; ARBs with caution), and for HAE give C1-inhibitor concentrate or icatibant (bradykinin receptor blocker).
• HAE prevention — prophylaxis before surgery or dental work (C1-inhibitor), long-term prophylaxis (lanadelumab, berotralstat); patient-held treatment for attacks.

⚠️ Safety Pearl: Tongue swelling without hives in someone on an ACE inhibitor is bradykinin angioedema — it won't respond to adrenaline or antihistamines. Protect the airway early, stop the ACE inhibitor permanently, and get senior help.

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Drug Eruptions — Overview

• Ask about every drug — prescribed, over-the-counter, herbal, recreational — started in the past 2 months.
• Common, mild reactions:
  • Morbilliform (maculopapular) exanthem — the commonest: widespread red macules and papules starting on the trunk, usually 4–14 days after starting the drug (antibiotics — especially penicillins, sulfonamides; anticonvulsants; allopurinol); itchy; fades in 1–2 weeks after stopping. Amoxicillin in EBV infection causes a rash in most people (not a true allergy).
  • Urticaria and angioedema — see above.
  • Fixed drug eruption — one or a few round, dusky red-purple patches (sometimes blistering) that recur at exactly the same site each time the drug is taken (lips, genitals, hands); leaves brown pigmentation; NSAIDs, paracetamol, tetracyclines, sulfonamides.
  • Photosensitive eruptions — sunburn-like in sun-exposed areas (doxycycline, thiazides, amiodarone, NSAIDs, quinine).
  • Lichenoid, acneiform (steroids, lithium, EGFR inhibitors), pigmentary (amiodarone, minocycline), drug-induced lupus (hydralazine, procainamide, isoniazid, minocycline, anti-TNF), psoriasis flare (lithium, beta-blockers).
• Severe cutaneous adverse reactions (SCARs) — emergencies: SJS/TEN, DRESS, AGEP, generalised fixed drug eruption.
• Warning signs of a severe reaction — skin pain, blisters or skin peeling, mucosal involvement (mouth, eyes, genitals), fever, facial swelling, lymphadenopathy, abnormal bloods (eosinophilia, raised LFTs, AKI).
• Management — stop the suspected drug (and any non-essential drugs); document the allergy clearly; report to the MHRA via the Yellow Card scheme; consider penicillin allergy de-labelling for doubtful histories.

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Stevens–Johnson Syndrome and TEN

• What they are: Rare, life-threatening reactions with widespread death of the epidermis and mucosa — on a spectrum by the area of skin detached: SJS (under 10% of body surface area), SJS/TEN overlap (10–30%), TEN (over 30%).
• Causes — usually drugs, typically 4–28 days after starting:
  • Allopurinol, carbamazepine, lamotrigine (fast titration, with valproate), phenytoin, phenobarbital.
  • Sulfonamides (co-trimoxazole, sulfasalazine), other antibiotics (penicillins, cephalosporins, quinolones).
  • NSAIDs (oxicams), nevirapine.
  • Mycoplasma pneumoniae (especially in children — mucositis with little skin involvement).
  • Genetic risk — HLA-B*1502 (carbamazepine, phenytoin — Han Chinese, Thai, Malaysian people; test before starting), HLA-B*5801 (allopurinol — Han Chinese, Korean, Thai).
• Features:
  • Prodrome — fever, malaise, sore throat, sore eyes (1–3 days).
  • Painful skin; dusky red or purple macules and atypical target lesions (flat, two zones) on the trunk and face, merging; blisters and sheets of skin detachment (positive Nikolsky sign).
  • Mucosal involvement (two or more sites in most) — painful mouth ulcers and haemorrhagic crusted lips, conjunctivitis (can scar — blindness), genital erosions; respiratory and GI involvement.
• Severity — SCORTEN (age over 40, malignancy, heart rate over 120, detached area over 10%, urea over 10 mmol/L, bicarbonate under 20, glucose over 14) predicts mortality (TEN mortality about 25–35%).
• Management (BAD guidelines):
  • Stop the culprit drug immediately (and others not essential).
  • Admit to a burns unit or ICU with specialist dermatology input.
  • Supportive care — warm environment (25–28 °C), barrier nursing, fluids (losses as in burns), nutrition (nasogastric if needed), analgesia, pressure-relieving mattress.
  • Skin care — leave detached skin in place as a dressing; emollients (e.g. 50:50 white soft paraffin and liquid paraffin); non-adherent dressings; watch for infection (swabs — no routine antibiotics).
  • Eye care — daily ophthalmology review; lubricants, topical steroids and antibiotics; prevent scarring.
  • Mouth, genital and urinary care — mouthwashes, catheter if needed.
  • Immunomodulatory treatment — ciclosporin, IVIG, corticosteroids or anti-TNF — used in some units (evidence limited).
• Long-term — eye scarring, dry eyes, nail and hair loss, pigment changes, strictures, psychological effects; never re-expose to the drug (record clearly, alert bracelet).

⚠️ Safety Pearl: A new rash with skin pain, mouth ulcers, sore eyes and fever a few weeks after starting allopurinol, carbamazepine, lamotrigine or co-trimoxazole is SJS/TEN until proven otherwise. Stop the drug and admit urgently — check the Nikolsky sign and the eyes.

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DRESS and AGEP

• DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms):
  • Onset — 2–8 weeks after starting the drug (later than other reactions).
  • Drugs — anticonvulsants (carbamazepine, phenytoin, lamotrigine), allopurinol, sulfonamides (sulfasalazine, dapsone), minocycline, vancomycin, antiretrovirals.
  • Features — fever, widespread morbilliform rash (can become erythrodermic), facial swelling, lymphadenopathy; eosinophilia, atypical lymphocytes; organ involvement — hepatitis (most common), nephritis (AKI), pneumonitis, myocarditis, thyroiditis (later); reactivation of HHV-6.
  • Management — stop the drug; supportive care; systemic corticosteroids (slow taper over weeks to months — relapses common); monitor organ function; mortality about 10%; later autoimmune disease (thyroid, diabetes).
• AGEP (Acute Generalised Exanthematous Pustulosis):
  • Onset — rapid, within hours to a few days.
  • Drugs — beta-lactam antibiotics, macrolides, hydroxychloroquine, diltiazem, terbinafine.
  • Features — sudden widespread red skin (often starting in skin folds) covered with many small sterile pustules; fever; neutrophilia.
  • Management — stop the drug; supportive care, topical steroids; resolves within about 2 weeks with peeling.

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Erythema Multiforme

• What it is: An acute, self-limiting immune reaction, usually to an infection — most often herpes simplex (cold sores 1–3 weeks before), also Mycoplasma; drugs are a less common cause.
• Features:
  • Typical target lesions — round, with three zones (dark or blistered centre, pale ring, red outer ring) — on the hands, feet, forearms and legs (acral, symmetrical), spreading towards the trunk.
  • EM minor — skin only (or mild involvement of one mucosa).
  • EM major — with significant mucosal involvement (mouth, eyes, genitals) — but skin detachment is under 10% and lesions are typical targets (unlike SJS).
• Management — treat the cause; symptomatic (antihistamines, topical steroids, mouthwashes); oral steroids for severe mucosal disease; resolves in 2–4 weeks; recurrent HSV-associated EM — suppressive aciclovir.
• EM versus SJS — EM: typical raised targets, acral, infection-triggered, little skin detachment; SJS: atypical flat targets and dusky macules on the trunk, drug-triggered, skin detachment and systemic illness.

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Erythema Nodosum

• What it is: Inflammation of subcutaneous fat (panniculitis) — tender, red, warm nodules on the shins (both legs), sometimes thighs and forearms; often with fever, malaise and joint pains; lesions turn bruise-like and resolve over about 6 weeks without scarring or ulceration.
• Causes:
  • Infection — streptococcal sore throat (the commonest in children), TB, Mycoplasma, Yersinia, Campylobacter, hepatitis B, EBV, fungal infections.
  • Sarcoidosis — Löfgren syndrome (erythema nodosum, bilateral hilar lymphadenopathy, fever, ankle arthritis — good prognosis).
  • Inflammatory bowel disease (Crohn's more than UC).
  • Pregnancy, oral contraceptives.
  • Drugs — sulfonamides, penicillins.
  • Behçet's disease, lymphoma; idiopathic in many.
• Tests — FBC, CRP or ESR, throat swab and ASOT, chest X-ray (sarcoidosis, TB), stool culture if diarrhoea; pregnancy test; TB testing if risk.
• Management — treat the cause; rest and leg elevation, NSAIDs, cool compresses; potassium iodide or steroids for persistent cases (exclude infection first).

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Bullous Pemphigoid

• What it is: The commonest autoimmune blistering disease — IgG autoantibodies against hemidesmosome proteins (BP180, BP230) at the dermo-epidermal junction, so blisters are deep and tense.
• Who — older people (usually over 70); associated with neurological disease (dementia, Parkinson's, stroke).
• Triggers — drugs, especially DPP-4 inhibitors (gliptins), also diuretics, checkpoint inhibitors.
• Features:
  • Often a prodrome of intense itch with eczema-like or urticarial plaques (weeks to months).
  • Large, tense, fluid-filled blisters (clear or blood-stained) on red or normal skin — flexures, inner thighs, abdomen, limbs.
  • Blisters don't break easily; Nikolsky sign negative; mucosa rarely involved.
• Diagnosis — skin biopsy (subepidermal blister with eosinophils) and direct immunofluorescence (linear IgG and C3 along the basement membrane); serum BP180/BP230 antibodies.
• Treatment:
  • Very potent topical steroid (clobetasol propionate) to the whole body — effective and safer than oral steroids for widespread disease (practicalities in frail people).
  • Doxycycline (with or without nicotinamide) for milder disease.
  • Oral prednisolone (e.g. 0.5 mg/kg) for severe disease — bone protection, PPI, glucose monitoring.
  • Steroid-sparing — azathioprine, methotrexate, mycophenolate; dupilumab or omalizumab in resistant cases.
  • Stop a gliptin if taking one.
  • Blister care — puncture large blisters with a sterile needle, leaving the roof as a dressing.
• Prognosis — chronic but often remits in 1–5 years; significant mortality in the first year (frailty, treatment side effects).

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Pemphigus Vulgaris

• What it is: A rare, serious autoimmune blistering disease — IgG autoantibodies against desmoglein 3 (and 1), which hold epidermal cells together, so blisters are superficial and fragile.
• Who — middle age (40–60); more common in people of Ashkenazi Jewish, Mediterranean and South Asian heritage; rarely drug-induced (penicillamine, ACE inhibitors) or paraneoplastic (lymphoma).
• Features:
  • Painful mouth ulcers (erosions) — often the first sign, for weeks or months.
  • Flaccid, fragile blisters that burst easily, leaving painful raw erosions and crusts (scalp, face, chest, back, groin).
  • Nikolsky sign positive.
  • Eyes, nose, throat and genitals may be involved.
• Diagnosis — biopsy (intraepidermal blister with acantholysis); direct immunofluorescence — intercellular IgG ("chicken-wire" or "fishnet" pattern); serum desmoglein antibodies.
• Treatment — systemic corticosteroids plus rituximab (first-line); azathioprine or mycophenolate as steroid-sparing agents; IVIG for refractory disease; mouth care, analgesia, wound care, infection prevention.
• Prognosis — fatal if untreated (fluid loss, infection); now mortality is mostly from treatment complications.

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Dermatitis Herpetiformis

• What it is: The skin manifestation of coeliac disease (gluten sensitivity) — many have few or no gut symptoms.
• Features — intensely itchy small vesicles and papules (often scratched away, leaving excoriations) symmetrically on the elbows, knees, buttocks, shoulders and scalp.
• Diagnosis — biopsy of nearby normal skin for direct immunofluorescence (granular IgA in the dermal papillae); coeliac serology (tissue transglutaminase IgA, with total IgA); duodenal biopsy in some.
• Treatment — lifelong gluten-free diet (controls skin and gut disease and reduces lymphoma risk; takes months to work); dapsone for rapid itch control — check G6PD first (haemolysis), monitor FBC and LFTs (methaemoglobinaemia, agranulocytosis).

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Other Causes of Blisters

• Infections — bullous impetigo, staphylococcal scalded skin syndrome, herpes simplex, chickenpox, shingles, hand foot and mouth disease.
• Physical — friction, burns, insect bites (bullous bite reactions on the legs), cold injury, oedema blisters (severe leg swelling), diabetic bullae (feet and shins).
• Contact dermatitis (plants, chemicals), pompholyx.
• Drug reactions — SJS/TEN, fixed drug eruption, pseudoporphyria (NSAIDs).
• Porphyria cutanea tarda — the commonest porphyria: blisters, erosions and fragile skin on the backs of the hands and other sun-exposed areas, milia, scarring, hypertrichosis (face); triggers — alcohol, hepatitis C, haemochromatosis, oestrogens, HIV; raised urine porphyrins (pink fluorescence); treat with venesection or low-dose hydroxychloroquine, avoid triggers, sun protection.
• Pemphigoid gestationis — itchy urticarial plaques around the umbilicus spreading with blisters in late pregnancy or after birth; risk of preterm or small baby; topical or oral steroids (see the Pregnancy Medical Problems chapter).
• Epidermolysis bullosa — inherited fragile skin with blisters from minor friction from birth; specialist care (DEBRA).
• Linear IgA disease — "cluster of jewels" blisters; vancomycin is a trigger; dapsone.

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Erythroderma

• What it is: Redness and inflammation of over 90% of the skin — a dermatological emergency ("acute skin failure").
• Causes — worsening of existing skin disease: eczema (the commonest), psoriasis (often after stopping oral steroids or ciclosporin); drug reactions (DRESS, others); cutaneous T-cell lymphoma (Sézary syndrome); pityriasis rubra pilaris; crusted scabies; idiopathic (often older men).
• Features — red, hot, scaly or peeling skin over almost the whole body; itch; shivering; lymphadenopathy; hair and nail loss with time.
• Complications — hypothermia (heat loss), fluid and electrolyte loss, low albumin (protein loss), high-output heart failure, infection and sepsis (Staph aureus), AKI, VTE.
• Management:
  • Admit (often to a dermatology ward or HDU); monitor observations, fluid balance, weight, U&E, albumin.
  • Keep warm; IV fluids; nutrition; treat infection.
  • Stop non-essential drugs.
  • Emollients liberally and frequently (e.g. 50:50 white soft and liquid paraffin); wet wraps; mild to moderate topical steroids.
  • Sedating antihistamine for itch and sleep.
  • Find and treat the cause — biopsy, blood film (Sézary cells); specific treatment (e.g. ciclosporin or methotrexate for psoriasis).

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Dermatological Emergencies — Summary

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Leg Ulcers

• Definition — a break in the skin below the knee that hasn't healed within 2 weeks. Common in older people; often recurrent.
• Assess every leg ulcer — history (diabetes, vascular disease, DVT, smoking, rheumatoid arthritis), site, size, edge, base, depth, surrounding skin, pain, pulses, sensation, oedema; ankle–brachial pressure index (ABPI) by Doppler; measure and photograph.

• ABPI interpretation:
  • 0.8–1.3 — normal; full compression is safe.
  • 0.5–0.8 — arterial disease; reduced compression only under specialist advice; vascular referral.
  • Under 0.5 — severe arterial disease (critical ischaemia if very low) — no compression; urgent vascular referral.
  • Over 1.3 — calcified, incompressible arteries (diabetes, CKD) — unreliable; use toe pressures or arterial duplex.
• General ulcer care — clean with water or saline; simple non-adherent dressings (no need for expensive dressings for most); treat infection only if clinically infected (spreading redness, warmth, pain, pus, fever) — not on the basis of a swab alone; analgesia; nutrition; refer if not healing within 12 weeks or atypical.

⚠️ Safety Pearl: Never apply compression to a leg ulcer until the ABPI (or other arterial assessment) is known. Compression on an ischaemic leg can cause necrosis and amputation.

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Pressure Ulcers

• What they are: Localised damage to skin and underlying tissue from pressure, or pressure with shear, usually over bony prominences — sacrum, heels, hips, ischial tuberosities, elbows, back of the head; also under medical devices (oxygen masks, catheters, splints).
• Risk factors — immobility, frailty, older age, acute illness, poor nutrition, incontinence (moisture damage), reduced sensation (stroke, spinal injury, diabetes), reduced consciousness, previous pressure ulcers.
• Categories (NPUAP/EPUAP):
  • Category 1 — intact skin with non-blanching redness (darker skin may look purple or blue, or feel warm or firm).
  • Category 2 — partial-thickness skin loss (shallow open ulcer or blister).
  • Category 3 — full-thickness skin loss; fat visible; no bone or tendon.
  • Category 4 — full-thickness tissue loss with exposed bone, tendon or muscle.
  • Unstageable — base covered by slough or eschar; deep tissue injury — purple or maroon intact skin or blood blister.
• Prevention (NICE CG179) — risk assessment on admission (e.g. Waterlow, Braden, PURPOSE-T) and regularly; skin inspection; the "SSKIN" bundle — Surface (pressure-relieving mattresses and cushions), Skin inspection, Keep moving (repositioning — e.g. every 2–4 hours in bed), Incontinence and moisture management, Nutrition and hydration.
• Treatment — relieve pressure (heels off the bed), appropriate dressings, debridement of necrotic tissue (not dry stable heel eschar in ischaemic limbs), nutrition, treat infection (cellulitis, osteomyelitis — MRI), pain relief; plastic surgery for some category 4 ulcers.
• Governance — category 3, 4 and unstageable ulcers acquired in care should be reported as patient safety incidents; consider safeguarding (neglect).

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Pyoderma Gangrenosum

• What it is: A rare, neutrophilic inflammatory skin disease causing rapidly enlarging, very painful ulcers — not an infection and not gangrene.
• Features — starts as a pustule or nodule (often after minor trauma — pathergy), rapidly breaks down into a painful ulcer with a purple (violaceous), undermined edge; usually on the legs; also around stomas and surgical wounds.
• Associations (in about half) — inflammatory bowel disease, rheumatoid arthritis, haematological disease (myeloma, MGUS, leukaemia, myelodysplasia), hepatitis.
• Diagnosis — clinical, after excluding infection, vasculitis and cancer (biopsy of the edge); often misdiagnosed as infection.
• Management — avoid surgical debridement (pathergy makes it worse); potent topical steroids or tacrolimus for small ulcers; systemic corticosteroids and/or ciclosporin; infliximab or adalimumab (especially with IBD); treat the underlying disease; good analgesia and wound care.
• Sweet's syndrome (acute febrile neutrophilic dermatosis) — a related condition: fever, raised neutrophils and painful red plaques on the face, neck and arms; linked to infection, AML and drugs (G-CSF); rapid response to oral steroids.

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Skin Signs of Systemic Disease