This lecture is about recognizing and managing life-threatening skin conditions — the scenarios where dermatology stops being a "benign" specialty and becomes acute medicine. Most dermatologic emergencies are rare, but when they hit, they escalate fast with significant morbidity and mortality if not promptly diagnosed and treated. The unifying theme: most result from allergic/drug reactions or infection, but some arise from autoimmune disease or flares of primary skin conditions. ^[1]

1. Recognize different types of important dermatologic emergencies ^[1]
2. Investigate for dermatologic emergencies ^[1]
3. Understand the basic management approach to different types of dermatologic emergencies ^[1]

Pemphigus is an autoimmune blistering disease where IgG autoantibodies target desmogleins — the "glue" proteins (cadherin family) that hold keratinocytes together via desmosomes. When these are disrupted, keratinocytes lose intercellular adhesion → acantholysis → intraepidermal blistering. Because the split is within the epidermis (suprabasal), the blisters are flaccid and rupture easily, leaving erosions and crusts rather than intact bullae.

Why does mucosal involvement occur in PV but not PF? The "desmoglein compensation theory": mucous membranes express mainly Dsg 3, so anti-Dsg 3 antibodies → loss of adhesion in mucosa. Skin expresses both Dsg 1 and Dsg 3, so loss of one can be partially compensated. In PF (anti-Dsg 1 only), mucous membranes are spared because they have abundant Dsg 3 to compensate. ^[2]

Pemphigus investigations: ^[1]

• Blood: Anti-skin titre (intercellular pattern), specific autoantibodies: Desmoglein 1 and Desmoglein 3
• Skin biopsy: Histology shows loss of intercellular adhesion, suprabasal splitting, acantholysis of keratinocytes
• IMF (Immunofluorescence): Intercellular pattern IgG/C3 — the classic "chicken-wire" or "fish-net" pattern
• Rule out primary/secondary skin infection: Swab for HSV, bacterial culture
• Work up for underlying malignancy (especially in PnP) as symptoms/age directed

Pemphigus management: ^[1]

• Systemic corticosteroid — mainstay of initial treatment
• Immunosuppressive agents: azathioprine, mycophenolate; Rituximab (anti-CD20 B cell depleting agent)
• Antibiotics if concomitant infection
• IVIg for severe/refractory type
• Maintain good oral and wound care

Why rituximab? B cells produce the pathogenic anti-desmoglein IgG. Depleting B cells with anti-CD20 reduces autoantibody production. Rituximab is now increasingly used as first-line alongside steroids for moderate-severe PV.

BP is the most common form of autoimmune blistering disease ^[1]. IgG autoantibodies target BP180 (collagen XVII) and BP230 — hemidesmosomal proteins at the dermal-epidermal junction (DEJ). This causes complement activation → inflammatory cell recruitment (especially eosinophils) → destruction of the DEJ → subepidermal blister. Because the split is below the entire epidermis, the roof of the blister is thick → blisters are tense and do not rupture easily.

Key points from lecture: ^[1]

• Most cases > 50 years old, more prevalent in elderly with neurological disease (stroke, dementia, Parkinson's disease)
• Triggers: malignancy, drug, infection
• Drug-associated BP: PD1 inhibitor immunotherapies (e.g. pembrolizumab), DPP-4 inhibitors ("gliptins")
• May present with variable features weeks before blisters appear — e.g. urticarial-like red skin (prodromal phase)

Why neurological disease? BP180 antigen (a neural isoform) is also expressed in the CNS. One hypothesis is that neurodegeneration exposes BP180 → immune sensitization → cross-reactive antibodies attack skin BP180. This is a tested association in exams.

BP investigations: ^[1]

• Blood: Anti-skin titre (DEJ — dermo-epidermal junction pattern)
• Specific autoantibodies: BP180 / BP230
• Skin biopsy:
  • Histology: Sub-epidermal blister, dermal neutrophil ± eosinophil infiltrates
  • IMF: Linear IgG/C3 along BMZ
• Important to rule out other autoimmune / drug-induced BP

BP management: ^[1]

• Mild cases: Topical potent corticosteroid, antiseptic solution for wound cleansing
• Mild-moderate: Doxycycline, systemic corticosteroid (usually start 0.5 mg/kg/day)
• Immunosuppressive agents: azathioprine, mycophenolate
• Antibiotics if secondary bacterial infection
• IVIg for severe/refractory type
• Good oral and wound care
• Tense bullae: Aspirate with sterile needle to prevent traumatic de-roofing

EM is a hypersensitivity reaction ^[1], now recognized as a distinct entity from SJS/TEN (previously thought to be on a spectrum, but pathologically and aetiologically different). The immune response is directed against keratinocytes expressing foreign antigens (usually viral), mediated by CD8+ T cells and NK cells, leading to epidermal cell death in a localized pattern.

Causes (from lecture): ^[1]

• HSV 1 & 2 (~50% of cases) — most common cause
• Other infections: CMV, EBV, SARS-CoV-2, Mycoplasma pneumoniae
• Medications: vaccinations (especially infant), antibiotics, anti-epileptics, NSAIDs
• Unknown cause

Key clinical features: ^[1]

• Prodromal symptoms: fatigue, malaise, myalgia, fever
• Skin lesions develop at peripherals before spreading centrally (trunk)
• Distribution: usually symmetrical, preference for extensor surfaces
• Early lesions: round erythematous papules → develop into target lesions
• Target lesions: consist of 3 concentric rings — central dusky area, surrounded by pallor, and peripheral erythematous margin
• Severe reaction → blisters or bullae
• EM Major (EMM) = significant mucosal involvement vs EM Minor = no mucosal involvement
• Episodes can be isolated, recurrent, or persistent
• Most symptoms self-limiting, resolve within 4–6 weeks

EM investigation: ^[1]

• CBC, LFT, ESR, serology for infectious cause, CXR
• Drug history!
• Skin biopsy if diagnosis uncertain — to exclude other autoimmune blistering disease
• For recurrent EM: test for HSV over skin/mucosal lesions
• For persistent EM without clear precipitating cause: consider work-up for solid organ/haematological malignancy (lymphoma, leukaemia), IBD, HCV infection

EM treatment: ^[1]

• Often self-limiting
• Ocular involvement: prompt ophthalmology referral essential (keratitis, conjunctival scarring, uveitis, permanent visual impairment)
• Symptomatic relief: oral antihistamine, topical steroid for itchy lesions, oral antiseptic mouthwashes (e.g. thymol gargles)
• Treat precipitating infections, stop culprit drugs and avoid future use
• Severe mucosal involvement: consider admission for oral intake/IVF support; short course prednisolone (limited evidence)
• Recurrent/refractory: refer specialist, consider ≥ 6 months continuous acyclovir

DHS/DRESS is a specific, severe, unexpected reaction to a medicine affecting several organ systems simultaneously ^[1]. It is classified as a SCAR (Severe Cutaneous Adverse Reaction) alongside SJS/TEN and AGEP. The mechanism involves:

1. Drug or its metabolite acts as a hapten → T cell activation
2. Viral reactivation (HHV-6, EBV, CMV) → amplifies immune response
3. Genetic susceptibility via specific HLA alleles
4. Massive inflammatory cascade → multi-organ involvement

Common drugs causing DHS: ^[1]

• Anticonvulsants: carbamazepine (HLA-B*1502), phenobarbital, phenytoin
• Allopurinol (HLA-B*5801)
• Antibiotics: sulfonamide group

Temporal relationship: ^[1]

• Onset within 2 weeks: beta-lactam antibiotics, iodinated contrast media
• Onset delayed > 2 weeks: anticonvulsants, allopurinol
• Usual onset: 2–8 weeks after starting the responsible drug

DHS/DRESS clinical features: ^[1]

• High fever 38–40°C — usually noticed first
• Skin rash: 80% morbilliform eruption; also targetoid, blisters, pustules
• 10% become erythrodermic (BSA > 90%) or exfoliative dermatitis
• 30% facial swelling; 25% mucosal involvement
• Rash can last many weeks
• Systemic involvement may worsen after stopping the drug
• May continue for weeks or months despite drug withdrawal
• Severity of rash does NOT correlate with extent of internal organ involvement

RegiSCAR inclusion criteria — at least 3 of the following: ^[1]

1. Hospitalisation
2. Reaction suspected to be drug-related
3. Acute skin rash
4. Fever > 38°C
5. Enlarged lymph nodes at ≥ 2 sites
6. Involvement of ≥ 1 internal organ
7. Blood count abnormalities (low platelets, raised eosinophils, or abnormal lymphocyte count)

DHS/DRESS investigation workup: ^[1]

• Skin biopsy: dense infiltration of lymphocytes + eosinophils, extravasated erythrocytes, oedema
• Blood tests:
  • Blood count (eosinophilia, atypical lymphocytes)
  • Biochemistry: LFT, RFT, muscle enzymes
  • Viral serology: Hepatitis B, C, EBV, CMV, HHV-6 (viral reactivation is characteristic)
  • Endocrine: thyroid function, glucose (autoimmune thyroiditis can develop as sequela)
• Patch testing: ~50% positive for anticonvulsants
• Lymphocyte transformation testing (LTT): available at QMH; can identify causative drug in majority of cases

DHS/DRESS management: ^[1]

• Immediate withdrawal of all suspect medicines
• Close monitoring and supportive care
• Supportive skin treatment: dressings, topical steroids, emollients, oral antihistamines
• Fluid, electrolytes, calorie intake; warm environment; expert nursing care
• Antibiotics only if secondary infection (NOT routine!)
• Systemic corticosteroids for severe cases (significant exfoliative dermatitis, pneumonitis, hepatitis)
  • Once effective, withdraw slowly — syndrome can recur as dose reduces
• Cyclosporin as alternative
• Other: IVIg, plasmapheresis

Prevention of DHS/DRESS: ^[1]

• Must avoid the causative drug in future
• Cross-reactions are common between the 3 main aromatic anticonvulsants: phenytoin, carbamazepine, phenobarbitone — patients who have experienced DHS with ANY one must avoid ALL THREE
• First-degree relative counselling: potentially increased risk due to genetic susceptibility

NF is a very serious bacterial infection of the soft tissue and fascia ^[1]. Bacteria multiply and release toxins/enzymes → thrombosis of blood vessels → destruction of soft tissues and fascia. The key mechanism is vascular compromise leading to tissue ischaemia and necrosis — antibiotics cannot penetrate dead tissue, hence surgical debridement is essential.

Fournier gangrene = NF affecting perineal, genital, and perianal regions — mortality up to 50% ^[1]

Risk factors for NF: ^[1] Advanced age, diabetes mellitus, immunosuppression, obesity, drug abuse, severe chronic illness, malignancy

Clinical progression: ^[1]

• Most common site: lower leg (also upper limb, perineum, buttocks, trunk, head/neck)
• Early phase (within 24 hours of minor injury):
  • Pain often very severe at presentation and worsens over time
  • Flu-like symptoms, general malaise
• Rapid progression over 3–4 days:
  • Swelling + purplish rash ± blisters with haemorrhagic fluid
  • Necrosis → area becomes blackened
  • Fine crackling sensation under skin (crepitus) = gas in tissues
  • Severe pain continues until necrosis destroys peripheral nerves → pain subsides (ominous sign!)
  • Toxic shock + metastatic abscess
• Positive finger test: A 2 cm vertical incision → finger passes through subcutaneous tissue without resistance = highly pathognomonic ^[1]

NF investigations: ^[1]

• Lab: CBC, LRFT
• Blood culture, deep tissue biopsy for gram stain and culture
• If S. aureus detected → MRSA sensitivity test
• Blood cultures usually negative for clostridial species
• Imaging: X-ray, CT, MRI → identify fluid collection, inflammation, gas within soft tissues

NF treatment: ^[1]

1. Hospitalisation: consult orthopaedic surgeon and ICU team
2. High dose IV antibiotics: initial choice includes penicillin, clindamycin, metronidazole, cephalosporins, carbapenems, vancomycin, linezolid → adjust after culture
3. Aggressive debridement of necrotic tissue — this is the most critical step
4. Supportive: IVF, O2, BP and I/O monitoring

• Up to 25% of patients will die from complications (renal failure, septicaemia, multiorgan failure)
• High mortality/poor prognosis if delay in diagnosis and treatment
• Other supportive options: vacuum-assisted/negative pressure wound device, hyperbaric oxygen, IVIg, skin graft

PG is a neutrophilic dermatosis — an autoinflammatory condition involving excessive neutrophil dysfunction, T lymphocytes, and cytokine dysregulation. It is not an infection despite the name. Key concept: pathergy — the tendency for skin lesions to worsen at sites of trauma. This means surgical debridement (the reflexive treatment for non-healing ulcers) will make PG worse.

PG clinical features: ^[1]

• Rapidly enlarging, very painful non-healing ulcer
• Full-thickness ulcer with blue/violaceous undermined borders
• Can be induced by pathergy
• Starts suddenly at site of minor injury — small pustule, red bump, or blood-blister (often misinterpreted as insect bite)
• Edge is purple and undermined; ulcer deepens and widens rapidly
• Deep ulcers heal with cribriform (criss-cross) or atrophic scarring

PG is frequently associated with internal disorders: ^[1]

• Inflammatory bowel disease (UC > > Crohn's)
• Rheumatoid arthritis, Behçet's disease
• GPA (Granulomatosis with Polyangiitis)
• PAPA syndrome
• Leukaemia
• Monoclonal gammopathy (usually IgA)
• Idiopathic

IBD-associated PG characteristics: ^[1]

• PG is one of common cutaneous manifestations of IBD (1–3%)
• More commonly a complication of UC >>> Crohn's
• More common in females; associated with mild IBD, erythema nodosum
• Underlying bowel disease active in > half of patients at time of PG episode
• Most often located on lower extremity; can be peri-stomal

PG diagnosis is by exclusion. ^[1]

• Delphi consensus 2018 criteria:
  • Major criterion (required): Histopathology of ulcer edge must show neutrophilic infiltrate
  • Minor criteria (need ≥ 4 of 8):
    1. Exclusion of infection
    2. Pathergy
    3. History of IBD or inflammatory arthritis
    4. History of papule/vesicle/pustule ulcerating within 4 days
    5. Peripheral erythema, undermining border, tenderness
    6. Multiple ulcers, ≥ 1 on anterior lower leg
    7. Cribriform or wrinkled paper scars
    8. Decreased ulcer size within 1 month of immunosuppressive medication

PG management: ^[1]

• Treatment is mainly non-surgical
• Wide surgical debridement should be AVOIDED during active phase — may enlarge the ulcer (pathergy!)
• Skin graft: may be performed when active phase has settled
• Topical: potent topical steroid ointment
• Wound care and pain control
• Oral anti-inflammatory antibiotics: doxycycline or minocycline
• Careful compression bandaging if tolerated
• Systemic treatment: prednisolone, cyclosporin, anti-TNF agents

Eczema herpeticum is a disseminated viral infection characterised by fever and clusters of itchy blisters or punched-out erosions ^[1]. It occurs because the impaired skin barrier in atopic dermatitis allows HSV to spread widely instead of remaining localised. The defective innate immune response in atopic skin (reduced antimicrobial peptides, cathelicidins) further facilitates viral dissemination.

Eczema herpeticum features: ^[1]

• Most often a complication of atopic dermatitis/eczema
• Most cases due to HSV type 1 or 2
• Usually arises during first episode of HSV infection (primary herpes)
• Signs appear 5–12 days after contact with infected individual
• Clusters of itchy and painful blisters, most often on face and neck
• Blisters on normal skin or previously affected by eczema
• Blisters are monomorphic (all appear similar)
• May be filled with clear yellow fluid or purulent material; often blood-stained
• Older blisters crust over → erosions
• Fever and swollen local lymph nodes
• Heal over 2–6 weeks; severe cases may leave small white scars

Eczema herpeticum diagnosis: ^[1]

• Viral culture
• Direct fluorescent antibody stain
• PCR (Polymerase Chain Reaction) sequencing
• Tzanck smear: showing epithelial multinucleated giant cells and acantholysis
• Bacterial swabs for microscopy and culture (may resemble impetigo; can be complicated by secondary bacterial infection)

Eczema herpeticum = dermatological emergency → admit to hospital ^[1]

• Prompt antiviral treatment:
  • Oral acyclovir 400–800 mg 5 times daily, or
  • Valaciclovir 1 g twice daily, for 10–14 days or until lesions heal
  • IV acyclovir if too sick or infection deteriorating
• Antibiotics for secondary bacterial infection
• Topical steroids not generally recommended but may be necessary for active atopic dermatitis
• Ophthalmology consult when eyelid/eye involvement is seen or suspected

SSSS results from exotoxins (epidermolytic toxins A and B) released by toxigenic strains of Staphylococcus aureus ^[1]. These toxins bind to Desmoglein 1 → cleave it → keratinocytes become detached at the granular layer of the epidermis. This is the same molecule targeted in pemphigus foliaceus, which is why SSSS and PF share superficial blistering and lack of mucosal involvement (mucous membranes express mainly Dsg 3, not Dsg 1).

SSSS demographics: ^[1]

• Mostly children < 5 years, particularly neonates — why?
  • Lack of specific immunity to toxins
  • Immature renal clearance system (toxins cleared through kidneys)
• Much less common in older children/adults — lifelong protective antibodies against staphylococcal exotoxins usually acquired in childhood
• At-risk adults: immunocompromised, renal failure
• Outbreaks in childcare facilities

SSSS signs and symptoms: ^[1]

• Starts with fever, irritability, widespread redness
• Within 24–48 hours: fluid-filled blisters form, rupture easily → area looks like a burn
• Tissue paper-like wrinkling of skin
• Blisters in axillae, groin, body orifices (nose, ears)
• In newborns: lesions in diaper area or around umbilical cord
• Nikolsky sign is positive (gentle strokes cause exfoliation)
• Tender and painful areas, weakness, dehydration

SSSS diagnosis: ^[1]

• History and physical examination
• Skin biopsy: intraepidermal cleavage at the granular layer (cf. TEN: full-thickness epidermal necrosis)
• Bacterial culture from skin, blood, urine, or umbilical cord

SSSS management: ^[1]

• Usually requires hospitalisation
• IV antibiotics — penicillinase-resistant anti-staphylococcal antibiotic: flucloxacillin
• Other: cephalosporin, clindamycin; vancomycin for MRSA
• Corticosteroids should NOT be given — can slow healing
• Supportive: paracetamol, fluid/electrolyte maintenance
• Skin care (skin is very fragile!) — petroleum jelly to keep moisturised
• Improvement within 5–7 days of starting treatment

SJS and TEN are rare but serious, rapidly progressive, and potentially fatal skin reactions with epidermal detachment and mucosal loss ^[1]. Nearly always caused by medications using current definitions. The mechanism:

1. Drug or metabolite → presented by specific HLA molecules to CD8+ cytotoxic T cells
2. Massive keratinocyte apoptosis via granulysin (the key cytotoxic mediator), Fas-FasL interactions, and perforin/granzyme B
3. Full-thickness epidermal necrosis → skin "peels off"

Most common causative drugs: ^[1]

• Antibiotics: sulfonamides (cotrimoxazole), beta-lactams (penicillins, cephalosporins)
• Anticonvulsants: lamotrigine, carbamazepine, phenytoin, phenobarbitone
• Allopurinol
• NSAIDs
• HLA associations: HLA-B1502 (carbamazepine), HLA-B5801 (allopurinol)

SJS/TEN clinical features: ^[1]

• Develops within first week of antibiotic therapy but up to 2 months after starting anticonvulsant
• Prodromal flu-like illness → fever > 39°C, sore throat, runny nose, cough, myalgia, sore red eyes
• Abrupt onset painful red rash starting on TRUNK → extending rapidly to face and limbs
• Skin lesions: maculopapular, erythroderma, flaccid blisters
• Blisters merge → sheets of skin detachment exposing red oozing dermis
• Nikolsky sign positive in areas of redness
• Mucosal involvement can be severe: eyes (conjunctivitis, corneal ulceration, anterior uveitis), lips/mouth (cheilitis, stomatitis), pharynx/oesophagus, genital area (urine retention due to painful voiding)

SJS/TEN classification: ^[1]

SJS/TEN complications: ^[1]

• Mortality: up to 10% for SJS, at least 30% for TEN
• Dehydration, acute malnutrition
• Skin infection → septicaemia
• Pneumonia/pneumonitis, ARDS
• Shock, acute renal failure, multiorgan failure
• Thromboembolism, DIC

SJS/TEN investigations: ^[1]

• Serum granulysin: raised in first few days — can be predictive of SJS/TEN
• Skin biopsy: keratinocyte necrosis, full-thickness epidermal necrosis, minimal inflammation (very mild lymphocytic infiltrate of superficial dermis)
• Direct immunofluorescence: NEGATIVE (distinguishes from autoimmune blistering diseases)
• Blood tests:
  • Deranged LFT, RFT, proteinuria
  • Anaemia
  • Lymphopenia (very common — 90%)
  • Neutropenia = bad prognostic sign
  • Eosinophilia and atypical lymphocytosis do NOT occur (differentiates from DHS/DRESS)

SCORTEN: predicts mortality in SJS/TEN ^[1]

• 1 point for each criterion present at admission:

1. Age > 40 years
2. Presence of malignancy
3. Heart rate > 120
4. Initial epidermal detachment > 10%
5. Serum urea > 10 mmol/L
6. Serum glucose > 14 mmol/L
7. Serum bicarbonate < 20 mmol/L

• SCORTEN ≥ 4 → mortality > 58.3%

SJS/TEN initial treatment: ^[1]

• Cessation of suspected causative drug ASAP
• Hospital admission — preferably ICU/burns unit (improves survival, reduces infection, shortens stay)
• Nutritional and fluid replacement (IV/NG) — review daily
• Temperature control — body temp regulation impaired
• Pain relief — pain can be extreme
• Sterile handling and reverse isolation
• Skin care:
  • Topical antiseptics (silver nitrate, chlorhexidine)
  • Dressings with petrolatum gauze
  • Avoid adhesive tapes and unnecessary removal of dead skin
  • Leave blister roof as "biological dressing"
• Eye and mouth care — proper nursing care, ophthalmology involvement

Erythroderma is defined as erythema and scaling affecting > 90% of BSA. It is not a diagnosis itself but a clinical presentation with multiple possible underlying causes. The lecture's take-home message explicitly mentions:

Erythroderma/sub-erythroderma — think of the 10 differential diagnoses and flare-up of pre-existing skin diseases ^[1]

From the lecture and supporting material ^[3]:

1. Psoriasis (erythrodermic psoriasis — often triggered by steroid withdrawal)
2. Eczema/atopic dermatitis flare
3. Drug eruption (DHS/DRESS reaching erythrodermic stage)
4. Cutaneous T-cell lymphoma (Sézary syndrome)
5. Pityriasis rubra pilaris
6. Pemphigus foliaceus
7. Seborrhoeic dermatitis (severe)
8. Contact dermatitis (severe generalised)
9. Lichen planus (rare cause)
10. Idiopathic

Take-home message from lecture: ^[1]

• Vital signs, hydration status/fluid replacement
• Rule out sepsis/bacteraemia but cautious with antibiotics!
• Stop the culprit drug immediately in suspected drug reactions
• Important to exclude drug, infection, and autoimmune causes
• Rare but can result in serious and potentially fatal sequelae