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

🚑 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?

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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.

Feature	Bullous pemphigoid	Pemphigus vulgaris
Age	Over 70	40–60
Blisters	Tense, deep, intact	Flaccid, superficial, rupture easily
Itch	Very itchy	Painful rather than itchy
Mouth	Rare	Common -often first
Nikolsky sign	Negative	Positive
Antigen	BP180, BP230 (hemidesmosomes)	Desmoglein 3 (desmosomes)
Immunofluorescence	Linear IgG/C3 at the basement membrane	Intercellular IgG ("chicken wire")
Treatment	Very potent topical steroids, doxycycline, oral prednisolone	Oral steroids plus rituximab

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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

Emergency	Key features and first action
Anaphylaxis	Urticaria with airway, breathing or circulation problems -IM adrenaline.
Angioedema (airway)	Lip, tongue or throat swelling -airway; stop ACE inhibitor; C1-inhibitor or icatibant for HAE.
SJS / TEN	Painful dusky rash, blisters, mucositis after a new drug -stop drug, burns unit or ICU, eye care.
DRESS	Fever, rash, facial swelling, eosinophilia, hepatitis 2–8 weeks after a drug -stop drug, steroids.
Erythroderma	Over 90% red skin -admit, warmth, fluids, emollients, find the cause.
Generalised pustular psoriasis	Widespread pustules with fever -admit; specialist systemic treatment.
Eczema herpeticum	Punched-out erosions in eczema, fever -aciclovir now.
Staphylococcal scalded skin syndrome	Child, tender skin, superficial peeling, mucosa spared -IV flucloxacillin.
Necrotising fasciitis	Pain out of proportion, rapid spread -urgent surgery.
Meningococcal sepsis	Non-blanching purpuric rash with fever -IV ceftriaxone or benzylpenicillin immediately.
Pemphigus vulgaris	Widespread erosions and mouth ulcers -admit; steroids and rituximab.
Purpura fulminans	Rapidly spreading purpura and necrosis (sepsis, DIC, protein C deficiency) -ICU.

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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.

Type	Features and management
Venous (about 70%)	Gaiter area (above the medial malleolus); shallow, large, irregular edge, sloughy or granulating base, exudate; surrounding venous eczema, haemosiderin staining, lipodermatosclerosis, atrophie blanche, oedema, varicose veins; aching, better with elevation. Treatment -compression therapy (bandages or hosiery) once ABPI shows adequate arterial supply, leg elevation, exercise, emollients and steroids for eczema, refer for venous assessment (endovenous treatment speeds healing and reduces recurrence); lifelong compression hosiery afterwards.
Arterial	Feet, toes, pressure points, shin; "punched-out", deep, well-defined, pale base; painful (worse lying flat or at night -hangs leg out of bed); cold, pale, hairless, shiny skin; weak or absent pulses; low ABPI. No compression; urgent vascular referral (revascularisation); stop smoking, statin, antiplatelet.
Neuropathic (diabetic)	Pressure points -sole, metatarsal heads, heel; painless, surrounded by callus; reduced sensation; often with ischaemia (neuroischaemic). Same-day or next-day referral to the multidisciplinary diabetic foot service if active ulceration, infection or ischaemia (see the Diabetes chapter); offloading, debridement, glucose control.
Mixed	Venous and arterial features -reduced compression under specialist guidance.
Other	Pyoderma gangrenosum, vasculitis (rheumatoid arthritis, SLE), malignancy (SCC, BCC, melanoma -biopsy atypical or non-healing ulcers), infection (TB, fungal, Buruli), sickle cell disease, calciphylaxis (CKD -painful necrotic ulcers), drugs (hydroxycarbamide, nicorandil), trauma, factitious.

• 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

Condition	Skin signs
Diabetes	Necrobiosis lipoidica (shiny, yellow-brown, atrophic plaques on the shins with telangiectasia), acanthosis nigricans, diabetic dermopathy (brown shin spots), granuloma annulare, recurrent infections (candida, boils), neuropathic ulcers, diabetic bullae.
Thyroid	Graves' -pretibial myxoedema (raised, orange-peel plaques on the shins), thyroid acropachy (clubbing), warm moist skin. Hypothyroid -dry, cold skin, hair loss, loss of outer eyebrows, puffy face.
Liver disease	Jaundice, spider naevi, palmar erythema, leukonychia, gynaecomastia, bruising, caput medusae, pruritus (cholestasis), xanthelasma (PBC).
Kidney disease	Pruritus, pallor, half-and-half nails, uraemic frost (rare), calciphylaxis (painful necrotic plaques), nephrogenic systemic fibrosis (gadolinium).
SLE	Malar ("butterfly") rash sparing the nasolabial folds, photosensitivity, discoid lupus (scarring), mouth ulcers, diffuse hair loss, Raynaud's, livedo reticularis, vasculitis.
Dermatomyositis	Heliotrope rash (purple eyelids), Gottron's papules (over knuckles), "shawl sign", nail fold changes, "mechanic's hands"; screen for cancer in adults (ovary, lung, GI, breast).
Systemic sclerosis	Raynaud's, sclerodactyly, digital ulcers, calcinosis, telangiectasia (face, hands), beaked nose, small mouth (see the Rheumatology chapters).
Sarcoidosis	Erythema nodosum, lupus pernio (purple swelling of the nose and cheeks), papules and plaques in scars and tattoos.
IBD	Erythema nodosum, pyoderma gangrenosum, aphthous mouth ulcers, perianal disease (Crohn's).
Coeliac disease	Dermatitis herpetiformis.
Internal malignancy	Acanthosis nigricans (sudden, extensive -gastric cancer), dermatomyositis, Sweet's syndrome, erythema gyratum repens (wood-grain pattern -lung cancer), acquired ichthyosis and pruritus (lymphoma), migratory necrolytic erythema (glucagonoma), Leser–Trélat sign, thrombophlebitis migrans (pancreatic cancer), skin metastases.
Hyperlipidaemia	Xanthelasma (eyelids), tendon xanthomas (familial hypercholesterolaemia), eruptive xanthomas (very high triglycerides -pancreatitis risk).
Endocarditis	Splinter haemorrhages, Janeway lesions (painless palm and sole macules), Osler's nodes (painful finger pulp nodules), petechiae, clubbing.
Vasculitis	Palpable purpura (IgA vasculitis -buttocks and legs), livedo, ulcers, nodules.
Addison's disease	Generalised hyperpigmentation (palmar creases, buccal mucosa, scars), vitiligo.
HIV	Severe seborrhoeic dermatitis, oral hairy leukoplakia, Kaposi sarcoma, extensive molluscum, recurrent shingles, severe psoriasis.
Neurofibromatosis / tuberous sclerosis	Café-au-lait macules, axillary freckles, neurofibromas / ash leaf macules, facial angiofibromas, shagreen patch.

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Generalised Itch

• Itch without a rash (pruritus) -scratch marks only; ask about timing (night, after bathing), drugs, weight loss, night sweats, fatigue, others affected (scabies).
• Causes:
  • Dry skin (xerosis) -the commonest, especially in older people and winter.
  • Skin disease -scabies, eczema, urticaria, early bullous pemphigoid (older people), dermatitis herpetiformis.
  • Iron deficiency.
  • Chronic kidney disease (uraemic pruritus).
  • Cholestasis -primary biliary cholangitis, primary sclerosing cholangitis, obstruction, intrahepatic cholestasis of pregnancy (palms and soles).
  • Thyroid disease (hyper- or hypothyroidism), diabetes.
  • Haematological -polycythaemia vera (itch after a warm bath -"aquagenic pruritus"), Hodgkin lymphoma, other lymphomas, myeloma.
  • Drugs -opioids, ACE inhibitors, chloroquine, statins, hydroxyethyl starch.
  • HIV, hepatitis C; psychological (diagnosis of exclusion); neuropathic (brachioradial, notalgia paraesthetica).
• Tests -FBC, ferritin, U&E, LFTs, TFTs, glucose or HbA1c, ESR; consider HIV, hepatitis serology, chest X-ray (lymphoma), protein electrophoresis, coeliac serology; skin scraping for scabies.
• Management -emollients and soap substitutes; cool baths; avoid overheating; menthol in aqueous cream; treat the cause; sedating antihistamines may help sleep (not the itch itself, except in urticaria).
  • Cholestatic itch -colestyramine, rifampicin, naltrexone, sertraline.
  • Uraemic itch -optimise dialysis, emollients, gabapentin or pregabalin, difelikefalin (NICE TA890 for haemodialysis patients).
  • Phototherapy for some causes.

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Photosensitivity

• Polymorphic light eruption -the commonest photodermatosis: itchy red papules, vesicles or plaques on sun-exposed skin hours to days after the first strong sun of spring or a holiday; improves over the summer ("hardening"); sunscreen with high UVA protection, gradual exposure, prophylactic phototherapy.
• Drug-induced photosensitivity -exaggerated sunburn or eczema on exposed areas (face, V of neck, backs of hands -sparing under the chin and behind the ears): doxycycline, thiazides, amiodarone, NSAIDs, quinine, retinoids, voriconazole, St John's wort.
• Cutaneous lupus -photosensitive rash (subacute cutaneous lupus -annular or psoriasis-like; drugs such as PPIs, terbinafine, thiazides can trigger it).
• Porphyrias -porphyria cutanea tarda (blisters); erythropoietic protoporphyria (children -burning pain within minutes of sun).
• Solar urticaria -wheals within minutes of sun exposure.
• Phytophotodermatitis -blistering streaks after skin contact with plants (giant hogweed, lime juice) and sunlight; leaves pigmentation (can mimic abuse in children).
• Genetic -xeroderma pigmentosum (DNA repair defect -skin cancers in childhood).

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Drug Reference Table

Drug	Key points
Cetirizine / loratadine / fexofenadine	Urticaria -daily; up to four times standard dose for chronic urticaria (specialist advice).
Omalizumab	Chronic spontaneous urticaria not controlled by antihistamines (NICE TA339).
Adrenaline IM	Anaphylaxis and histaminergic angioedema with airway compromise -not effective for bradykinin angioedema.
C1-inhibitor concentrate / icatibant	Acute attacks of hereditary angioedema; icatibant also used in ACE inhibitor angioedema (specialist).
Lanadelumab / berotralstat	Long-term prophylaxis in hereditary angioedema.
50:50 white soft and liquid paraffin	Emollient in SJS/TEN and erythroderma.
Ciclosporin / IVIG	Sometimes used in SJS/TEN (specialist; evidence limited); ciclosporin for pyoderma gangrenosum.
Prednisolone (oral)	DRESS (slow taper), severe bullous pemphigoid, pemphigus (with rituximab), pyoderma gangrenosum, Sweet's syndrome.
Clobetasol propionate	Very potent topical steroid -bullous pemphigoid (whole body), pyoderma gangrenosum (small).
Doxycycline	Milder bullous pemphigoid.
Rituximab	First-line with steroids in pemphigus vulgaris.
Dapsone	Dermatitis herpetiformis, linear IgA disease -check G6PD; haemolysis, methaemoglobinaemia.
Infliximab / adalimumab	Pyoderma gangrenosum (especially with IBD).
Compression bandaging / hosiery	Venous leg ulcers once ABPI 0.8–1.3; lifelong hosiery to prevent recurrence.
Colestyramine / rifampicin / naltrexone / sertraline	Cholestatic itch.
Difelikefalin	Uraemic pruritus in haemodialysis (NICE TA890).

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Spot the Diagnosis

Clue	Diagnosis
Itchy wheals that come and go within hours for 3 months	Chronic spontaneous urticaria
Wheals lasting 3 days and leaving bruises	Urticarial vasculitis
Tongue swelling without hives in a man on ramipril for 5 years	ACE inhibitor angioedema
Recurrent swellings and abdominal attacks since adolescence, low C4	Hereditary angioedema
Widespread itchy maculopapular rash after amoxicillin for glandular fever	Amoxicillin rash in EBV
Dusky patch on the lip recurring each time ibuprofen is taken	Fixed drug eruption
Painful dusky rash, mouth ulcers and sore eyes 2 weeks after starting carbamazepine	Stevens–Johnson syndrome
Over 30% of skin peeling, Nikolsky positive, after allopurinol	Toxic epidermal necrolysis
Fever, facial swelling, rash, eosinophilia and hepatitis 5 weeks after starting lamotrigine	DRESS
Hundreds of tiny pustules on red skin 2 days after amoxicillin	AGEP
Target lesions on the hands 10 days after a cold sore	Erythema multiforme
Tender red shin nodules with bilateral hilar lymphadenopathy and ankle pain	Löfgren syndrome (sarcoidosis)
80-year-old with itch then tense blisters on the thighs; on sitagliptin	Bullous pemphigoid (gliptin-associated)
Months of mouth ulcers then fragile blisters and erosions, Nikolsky positive	Pemphigus vulgaris
Intensely itchy vesicles on the elbows and buttocks with granular IgA	Dermatitis herpetiformis
Blisters and fragile skin on the backs of the hands in a heavy drinker with hepatitis C	Porphyria cutanea tarda
Red, scaly skin over the whole body with shivering	Erythroderma
Shallow ulcer above the medial malleolus with brown staining and oedema	Venous leg ulcer
Painful punched-out ulcer on the toe, worse at night, absent pulses	Arterial ulcer
Painless ulcer under the first metatarsal head with callus in a diabetic	Neuropathic ulcer
Non-blanching redness over the sacrum in a bedbound patient	Category 1 pressure ulcer
Rapidly enlarging painful ulcer with a purple undermined edge in Crohn's disease	Pyoderma gangrenosum
Shiny yellow-brown atrophic plaques on the shins in diabetes	Necrobiosis lipoidica
Purple eyelids and papules over the knuckles with proximal weakness	Dermatomyositis -screen for cancer
Itch after hot baths with a high haemoglobin	Polycythaemia vera
Itchy papules on the face and arms after the first sunny spring weekend	Polymorphic light eruption

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Exam-style Scenarios

1. A 45-year-old woman started allopurinol 3 weeks ago. She now has fever, painful dusky red patches on her trunk that are blistering, crusted lips and red, sore eyes. About 15% of her skin is affected.
Answer: SJS/TEN overlap.

• Stop allopurinol immediately; admit to a burns unit or ICU with dermatology input.
• Warm environment, fluids, analgesia, nutrition, emollients, non-adherent dressings; monitor for infection.
• Daily ophthalmology; oral and genital care; record the allergy -never re-expose.

2. A 68-year-old man on lisinopril for 6 years attends with marked swelling of his tongue and lips. There's no rash or itch. He has a hoarse voice.
Answer: ACE inhibitor (bradykinin) angioedema with airway risk.

• Airway assessment -senior anaesthetic and ENT help; prepare for a difficult airway.
• Stop lisinopril permanently; antihistamines and adrenaline are unlikely to help (give adrenaline if anaphylaxis can't be excluded).
• Consider icatibant or C1-inhibitor (specialist advice); choose a different antihypertensive.

3. An 82-year-old woman in a care home has had intense itch for 2 months, and now has large tense blisters on her thighs and abdomen. Her mouth is normal. She takes sitagliptin.
Answer: Bullous pemphigoid (possibly gliptin-related).

• Skin biopsy and direct immunofluorescence (linear IgG and C3).
• Stop sitagliptin; very potent topical steroid to the whole body, or doxycycline, or oral prednisolone if severe (with bone and gastric protection).
• Blister care, infection monitoring, nursing support.

4. A 76-year-old woman has a shallow, exuding ulcer above her right medial malleolus for 3 months, with brown pigmentation, eczema and ankle swelling. Pedal pulses are present.
Answer: Venous leg ulcer.

• ABPI first; if 0.8–1.3 -compression bandaging, leg elevation, simple dressings.
• Treat venous eczema (emollients, topical steroid); refer for venous assessment (endovenous treatment).
• Biopsy if atypical or not healing by 12 weeks; lifelong compression hosiery after healing.

5. A 55-year-old man has a 3-month history of generalised itch without a rash, night sweats and weight loss. He has no new medications.
Answer: Generalised itch with systemic symptoms -exclude lymphoma and other systemic causes.

• FBC and film, ferritin, U&E, LFTs, TFTs, glucose, ESR, LDH; HIV and hepatitis serology.
• Chest X-ray and examination for lymphadenopathy and hepatosplenomegaly; urgent referral if lymphoma suspected.
• Emollients and symptom relief while investigating.

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Key Points

• Urticarial wheals last under 24 hours; longer, painful or bruising wheals suggest urticarial vasculitis.
• Chronic urticaria: non-sedating antihistamine up to four times the dose; then omalizumab.
• Angioedema without urticaria -think ACE inhibitors or hereditary angioedema (low C4); doesn't respond to adrenaline.
• Ask about all drugs started in the past 2 months for any new rash.
• SCAR warning signs: skin pain, blisters, mucosal involvement, fever, facial swelling.
• SJS (under 10%), TEN (over 30%): allopurinol, anticonvulsants, sulfonamides, NSAIDs -stop drug, burns unit or ICU, daily eye review.
• HLA-B*1502 (carbamazepine) and HLA-B*5801 (allopurinol) increase SJS/TEN risk in some Asian populations.
• DRESS: 2–8 weeks after drug; fever, facial swelling, eosinophilia, hepatitis -steroids.
• Erythema multiforme: typical targets, acral, HSV-triggered.
• Erythema nodosum: strep, sarcoidosis, IBD, TB, pregnancy, drugs -CXR and ASOT.
• Bullous pemphigoid: elderly, tense blisters, itch, linear IgG; gliptins; very potent topical steroids.
• Pemphigus: mouth ulcers first, flaccid blisters, Nikolsky positive, intercellular IgG; steroids plus rituximab.
• Dermatitis herpetiformis = coeliac; gluten-free diet; dapsone after G6PD check.
• Erythroderma: over 90% red skin -hypothermia, fluid loss, heart failure, infection -admit.
• Check ABPI before compressing a leg ulcer; 0.8–1.3 is safe; under 0.5 -urgent vascular referral.
• Pressure ulcers: SSKIN prevention bundle; category 3–4 are safety incidents.
• Pyoderma gangrenosum: painful ulcer with purple undermined edge; don't debride; steroids, ciclosporin, anti-TNF.
• Dermatomyositis in adults -screen for cancer; necrobiosis lipoidica -diabetes.
• Generalised itch: check ferritin, U&E, LFTs, TFTs, FBC; consider lymphoma and polycythaemia.

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Guidelines and Further Reading

• British Association of Dermatologists: Guidelines for SJS/TEN, bullous pemphigoid, pemphigus vulgaris and urticaria
• BSACI: Guideline for the management of chronic urticaria and angioedema
• NICE TA339: Omalizumab for previously treated chronic spontaneous urticaria
• NICE CKS: Urticaria; Angioedema; Erythema nodosum; Leg ulcer -venous; Pressure ulcers; Itch -widespread
• NICE CG179: Pressure ulcers -prevention and management
• National Wound Care Strategy Programme: Lower limb recommendations
• NICE NG19: Diabetic foot problems
• NICE TA890: Difelikefalin for treating pruritus in people having haemodialysis
• MHRA Yellow Card scheme
• BNF -for current doses

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