Life-threatening dermatoses

Toxic epidermal necrolysis and SJS

• Acute severe reactions characterised by extensive necrosis and detachment of epidermis defined by mucosal ulceration at two or more sites with cutaneous blistering
• More common in the elderly (more medications) and 100x more common in HIV 
• SJS affects <10% of body surface area
• TEN affects >30% of body surface area
• TNS/SJS overlap = 10-30% of BSA
• Erythema multiforme minor and major were once thought to be part of same disease process, but are now distinct clinical entities due to infection (vs. TEN/SJS usually due to medication)
• May be type II (cytotoxic) and type IV (cell-mediated) hypersensitivity driven

• Clinical features
  • Prodrome URTI symptoms, fever, malaise, vomiting and diarrhoea
  • Skin pain may herald onset of SJS/TEN
  • Symmetrical erythematous macules with dark purpuric centres, mainly on trunk and proximal limbs, evolves to atypical target lesions with central dusky purpura/bullae with surrounding macular erythema
  • Bullae coalesce 
  • Mucosal involvement is key (check mouth, eyes, nose,genitals, perianal)
    • At least 2 mucosal surfaces involved
    • GI and respiratory mucosa may also be involved
  • Nikolsky sign = Dislodgement of epidermis with lateral finger pressure in vicinity of a lesion causes erosion OR pressure on a bulla leads to lateral extension of blister

• Causes
  • Penicillins, sulfa antibiotics, NSAID’s (oxicams), sulfonamides, allopurinol, nevirapine, sodium valproate, lamotrigine and illicit drugs
  • Mycoplasma can rarely cause SJS
  • 50% of SJS is drug induced and 90% of TEN
• Investigations
  • FBC, U&E, LFT, BSL
  • ANA, ENA, anti-dsDNA, CRP, ESR, ani-skin antibodies, HIV and mycoplasma serology
  • Skin swabs for viral and bacterial PCR
  • CXR, urine and BC as indicated
  • Biopsy from edge of blister 
    • Hallmark is epidermal (keratinocyte) necrosis

• DDx
  • Drug hypersensitivity syndromes
  • Staphylococcal scalded skin (<5yo usually)
    • No mucosal involvement
  • Toxic shock syndrome
    • No mucosal involvement and clinically shocked
  • Erythema multiforme major
  • Mycoplasma
  • Bullous SLE
  • Paraneoplastic pemphigus

• Management
  • Analgesia
  • Cease causative agent
  • Prevent infection
  • Burns/ICU consult
  • Ophthalmology and ENT involvement for mucosal signs
  • Fluid resuscitation as per Parkland formula
  • Dressings with petroleum
  • Frequent eye lubrication
  • Mouthwashes
  • Genital care: Girls especially need urgent Gynae review to prevent labial fusion
  • IDC
  • DVT prophylaxis

• Prognosis
  • Acute phase lasts 8-12 days
  • Re-epithelialisation takes weeks
  • Long-term sequelae
    • Pigment changes
    • Scarring
    • Loss of nails
    • Scarred genitalia
    • Joint contractions
    • Lung disease e.g. bronchiolitis/bronchiectasis
    • Eye changes

• SCORTEN is a scoring system for TEN 
  • Variables
    • Age >40
    • HR >120
    • Cancer or haematological malignancy
    • >10% BSA on day 1
    • BUN >10
    • Glucose >14
    • Bicarb <20
  • Scores
    • Score 0-1: 3.2% mortality
    • Score 2: 12.1% mortality
    • Score 3: 35.3% mortality
    • Score 4: 58.3% mortality
    • 5 or greater: 90% mortality

• Prognosis
  • SJS mortality 5%
  • TEN mortality 40%

Erythema multiforme

• Acute, usually mild, self-limited cutaneous and/or mucosal syndrome with rapid onset of lesions favouring acral sites (extensor surfaces of limbs and hands/feet)
• Type IV hypersensitivity (cytotoxic T cell mediated)
• Mostly young men 20-40yo
• EM minor – Localised papular eruption with no or mild mucous membrane involvement
  • No epidermal detachment (vs SJS/TEN)
• EM major – Severe multisystem illness with one mucous membrane involved
  • Mucous membrane involvement is usually a few days after skin lesions

• Often mildly pruritic and painful papular/urticarial lesions + classic target lesions and iris lesions
• Mild prodrome may precede rash (less common in EM minor)
• Lesions show Kobner phenomenon (develop at sites of preceding trauma)
• Mostly due to HSV
  • In Mycoplasma pneumonia may only get mucositis without skin changes
  • Other viruses include varicella, hepatitis viruses, HIV, CMV, dermatophyte infections
  • Drugs (<10%): Barbiturates, NSAID, penicillins, sulfonamides, anticonvulsants
• Ix: FBC, UEC, LFT, CRP, HSV serology/swab and mycoplasma serology if respiratory symptoms

• Maculopapular rash arises on dorsum of hands/feet and extensor surfaces of extremities
• Rash becomes target lesions over next 24-48 hours
  • Three zones of colour: Centre dusky, pale pink and outer red
• Lesions develop in successive crops over a 2-4 week period and heal over 5-7 days
• DDx
  • Herpetic infection
  • Vasculitis
  • TEN
  • Primary blistering disorders
  • Urticaria
  • Kawasaki disease
  • Toxic and infectious erythema

• Management
  • Topical steroids, antihistamines, antiseptic mouthwash and local anaesthetic preparations for oral mucosal involvement
  • If severe, systemic prednisolone 0.5-1mg/kg/day
  • In recurrent EM due to HSV, oral antivirals are effective

Sweet’s syndrome

• Acute febrile neurophilic dermatosis
• May resemble severe EM in acute oedematous phase
• Presents with fever, arthralgia, neutrophilia and sterile painful pustules, plaques and nodules over head, trunks and arms
• Can be recurrent
• Associated with IBD, RA, haematological malignancy, pregnancy, streptococcal infection and Yersinia infection
• Highly responsive to systemic steroids 
• Need to Ix for underlying cause as above

DRESS

• Drug rash with eosinophilia and systemic symptoms
• Severe skin reaction with systemic manifestations that carries mortality rate of 10%
• Usually seen in first course of associated drug within 2-6 weeks of initiation
• Associated with phenytoin, carbamazepine, phenobarbital, lamotrigine, sulphonamides, allopurinol, terbinafine, abacivir and nevirapine
• 70% cross-reactivity among aromatic anticonvulsants (phenytoin, carbamazepine and phenobarbital)

• Fever and rash with initial maculopapular rash later becoming oedematous, exfoliative or erythrodermic
• If face involved, facial oedema and lymphadenopathy often occur and suggests more serious drug reaction
• 70% of cases have significant eosinophilia
• Can cause hepatitis, nephritis, pneumonitis, myocarditis, thyroiditis, encephalitis
• Can persist for months after drug withdrawal

• Investigations
  • Polymorphic rash and variable organ involvement makes diagnosis difficult
  • Skin biopsy can assist
  • Baseline FBC, UEC, LFT, EBV/CMV/HHV6/7 serology
• Management
  • Admission, withdrawal of suspect drug, systemic corticosteroids

Erythroderma

• Intense widespread reddening of skin often associated with exfoliation, usually due to underlying systemic or cutaneous disease
• Typically near 100% BSA involvement = skin failure
• Mostly adult males >40yo
• Tends to be a chronic condition but can arise acutely if associated with a drug, contact dermatitis or malignancy
• Causes
  • Eczema (40%)
  • Psoriasis (22%)
  • Drugs (15%) – Sulphonamides, penicillin, anticonvulsants, allopurinol, antimalarials
  • Cutaneous T cell lymphoma (10%)
  • Idiopathic (8%)
  • Systemic malignancy
  • HIV

• Generalised erythema and warmth but not tender
• Pruritis and flaking are universal
• Usually begins on face and upper trunk then spreads all over
• Complications seen like extensive burns

• Complications
  • High-output cardiac failure
  • Dehydration and renal impairment
  • Protein loss with oedema
  • Temperature dysregulation
  • Thrombophlebitis/DVT
  • Infection (cutaneous and respiratory – pneumonia is most common cause of death)
• Investigations
  • FBC, UEC, LFT, BC if >38 or appears unwell with rigors
  • Skin swabs for MCS and CXR
  • Biopsy if uncertain cause

• Management
  • Temperature control and avoiding hypothermia
  • IV fluid replacement
  • High protein diet
  • Chest physio
  • DVT prophylaxis
  • Bath oil
  • Paraffin over entire body q6h
  • Antibiotics for proven infection

Staphylococcal toxic shock syndrome

• Non-pruritic blanching macular erythroderma
• Usually diffuse erythroderma but sometimes confined to extremities and resemble sunburn
• Rash resolves in 3-5 days followed by desquamation 5-14 days later
• Erythroderma can be subtle

• Diagnostic criteria
  • Fever >38.9
  • Rash
  • Desquamation
  • Hypotension
  • 3 or more systems involved
• Lab criteria
  • Negative BC, throat or CSF cultures (blood can be positive for S. aureus)
  • Non-rising titres for RMSF, lepto or measles
• Probable case: 5 of 6
• Confirmed: 6/6

Streptococcal toxic shock syndrome

• Uncommon compared to staph
• Due to GAS (usually invasive deep tissue infection)
• Desquamation is less common
• Mortality as high as 36% (much higher)
• Same diagnostic criteria

Staph scalded skin syndrome

• Develops in patients with clinically minor/inapparent staph infections
• Mostly neonates and children <5yo
• Usually conjunctiva, nasopharynx or umbilicus infection
• No mucosal membrane involvement
• Three phases:
  • Erythroderma
    • Tender erythema globally with mucous membrane sparing
  • Exfoliative
    • Day 2 (Nikolsky sign)
    • Comes off in large sheets
  • Desquamative (recovery)
    • After day 3 to 5
    • Normal skin in 7-10 days

Purpura fulminans

• Severe and rapidly fatal form of acute DIC
• DDx
  • Septicaemia
  • Meningococcaemia
  • Inherited protein C deficiency
  • Typhoid
  • Disseminated varicella
  • Rickettsial infection
  • Plasmodium falciparum malaria
  • Snake bite
  • TTP
  • Warfarin-induced skin necrosis

Last Updated on October 13, 2021 by Andrew Crofton