Stevens Johnson syndrome and toxic epidermal necrolysis

• Stevens Johnson syndrome: Stevens & Johnson, 1922
• Toxic epidermal necrolysis : Lyell, 1956

Stevens Johnson syndrome, SJS, toxic epidermal necrolysis, TEN, Lyell syndrome, epidermolysis necroticans combustiformis, epidermolysis acuta toxica

Seldom, serious, potentially lethal, mucocutaneous disease, which is usually triggered by taking medication. It leads to detachment of the epidermis and the appearance of necrosis. Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) correspond to one clinical picture. Cheilitis and stomatitis occur in 100% of cases. The area of spread to the rest of the skin is different.

• Classification

  • Stevens Johnson syndrome: <10% of the body surface, mucous membranes are affected (eyes, oral cavity, genital).

  • SJS/TEN overlap syndrome: > 10% to < 30% of the body surface area, mucous membranes are affected (eyes, oral cavity, genital).

  • TEN: > 30% of the body surface area, mucous membranes are affected (eyes, oral cavity, genital).

• Incidence (for SJS, SJS/TEN and TEN): 2-7/1,000,000/per annum
• SJS:TEN = approx. 3:1
• 100-fold increased incidence in HIV-positive patients
• Women > men

• Frequently triggering medication: Mnemonic SATAN
  • Sulfonamide antibiotics: Sulfamethoxazole (Bactrim), sulfasalazine
  • Allopurinol
  • Tetracyclines & other antibiotics: Amoxicillin, cephalosporins, quinolones, etc.
  • Anticonvulsants: carbamazepine, lamotrigine, phenytoin, etc.
  • NSAIDs
  • Virostatics (HAART): nevirapine
• Infections
  • Mycoplasma pneumoniae
  • Cytomegalovirus infections
• Vaccinations
• Contrast media
• Food
• Bone marrow transplants
• Radiotherapy
• Predisposing factors
  • HIV infection
  • Genetics:
    • HLA: HLA-B*1502, HLA-A*3101, B*5801, HLA-B*1502, HLA-A*3101, HLA-B*5801.
    • Polymorphisms

• Prodromal stage:
  • Deteriorated AZ, fever
  • Influenza-like symptoms
    • Facultative:
      • Photophobia
      • Conjunctival pruritus
      • Pain when swallowing
      • Myalgias
      • Arthralgias
      • Purulent rhinitis
      • Joint complaints
      • Generalised lymphadenopathy
      • Liver and spleen involvement
• Mucocutaneous symptoms
  • Mostly appear after 1-3, but sometimes after up to 14 days
  • Lesions usually start on the face or trunk before spreading to other parts of the body
  • The capillitium is not affected, but palmoplantar involvement is also seen in some cases.
  • The duration of mucocutaneous symptoms is reported to be 8-12 days.
• Mucosa:
  • In 90% of cases, the oral mucosa is affected
    • Erosions and ulcerations
    • Haemorrhagic crusts on the lips.
  • The eyes (conjunctivitis, sometimes purulent) are almost always affected
    • Crusy lesions on the upper and lower eyelids.
    • Corneal ulcer, panophthalmitis, photophobia, synechiae, symblepharon.
  • Genital erosions
    • Synechiae and stenoses can develop in the labia and urethra.
    • Urethritis, urinary retention, cystitis
  • Involvement of the pharynx can be observed in almost all patients
  • Rarely, the trachea, bronchi, oesophagus and intestines may also be involved.

• Cutaneous manifestation:
  • Epidermal detachments, erosions and partly ulcers
  • Cocardiform plaques and maculae
  • Often scarlatiniform, stem-accentuated exanthema
  • Formation of vesicles and bullae
    • Nikolski phenomenon I (blisters can be triggered on healthy skin or non-blistered skin can be displaced when lateral pressure is applied)
    • Nikolski phenomenon II (existing blisters can be displaced by lateral pressure)
    • Asboe-Hansen sign (the blister expands laterally in response to pressure
  • Coarse lamellar desquamation/the skin peels off over a large area
  • Necroses
  • Onycholysis, if applicable
  • Reepithelialisation occurs after a few days

• Laboratory
  • Increased ESR, CRP, leukocytosis
  • Egg electrophoresis (increased α- & γ-globulin fraction)
  • Anaemia (approx. 15%)
  • Lymphopenia (frequent)
  • Neutropenia
    • Occurs in approx. 1/3 of all patients
    • Often masked by systemic glucocorticoids
    • Correlated with a poor prognosis
  • Eosinophilia (20%)
  • Elevated transaminases (approx. 15%)
  • Proteinuria and haematuria (5%)
  • Bacteraemia (approx. 27%)
  • Signs of a severe course:
    • Urea >10 mmol/L
    • Glucose >14 mmol/L
    • ALT (up to 2-3 times the value)

• Anamnesis (medication anamnesis)
• Clinical picture
• Biopsy
  • Rapid dermatopathological section! Important to differentiate from SSSS. Therefore has a pronounced therapeutic consequence!
  • Direct immunofluorescence
• With the "algorithm of drug causality for epidermal necrolysis" (ALDEN)
• Laboratory

  • Laboratory daily: BB, small coagulation status, chemogram incl. CRP, urea

    and bicarbonate, blood cultures if required, serum electrophoresis

  • Initial one-off: IgA quantitative in serum and HIV if necessary

• Bact. Swabs from skin and mucous membranes, blood cultures, cultures from urinary catheters and PEG probes should be repeated every 2 days if necessary!
• SCORTEN: Assess the severity using the SCORTEN (severity-of-illness) score* (if the score is >2, organise a burns IPS transfer (USZ)). Repeat daily
• Differentiation from: EEMM, SSSS, bullous autoimmune dermatoses, other severe drug reactions
• SJS/TEN: Disseminated, generalised, mucous membrane

  • Initial macular (dolent!), target lesions, blisters, "scalded skin"

  • Can affect internal organs: Pneumonitis, gastrointestinal tract

  • Fever, reduction in general condition

  • Lymphopenia

  • Histology: Epidermal necrosis

  • Begin after taking medication in case of new sensitisation: 1 - 4 weeks without pre-sensitisation

• AGEP: Disseminated, generalised, initially possibly flexural. Erythroderma, "pinprick pustules", possibly with confluence and fine lamellar desquamation
  • Can also affect internal organs (especially hepatopathy, nephropathy)
  • Frequently fever > 39°C. Neutrophilia
  • Histological subcorneal pustules.
  • Start after taking medication in case of new sensitisation: 5 - 7 days without sensitisation, 1 -2 days with sensitisation (1 day for antibiotics)
• DHS/DRESS: Generalised, centrofacial swelling

  • Polymorphic exanthema including isolated pustules and blisters possible, rare courses without exanthema

  • Hepatopathy, pneumonitis, lymphadenopathy, nephritis, cardiopathy.

  • Fever, reduction in general condition

  • Eosinophilia, atypical lymphocytes, cytopenias

  • Histological lymphocyte infiltrates

  • Begin after taking medication in the case of new sensitisation: 2 - 6 weeks without pre-sensitisation

• GBFDE (generalised bullous fixed drug exanthema): Generalised, mucosal, asymmetrically distributed

  • Livid maculae and plaques, blisters, intact skin in between

  • Internal organs not affected, slight fever possible. Normal blood count.

  • Histology epidermal necrosis

  • Begin after taking medication in case of new sensitisation: 5 - 7 days without sensitisation, 1 -2 days with sensitisation (1 day for antibiotics)

Subepidermal blister fissure, necrotic keratinocytes in the epidermis at the blister roof, otherwise unchanged str. corneum, ↑ eosinophils in the epidermis, spiny cells with ballooned degeneration. Lymphohistiocytic infiltrate in the corium, mainly arranged perivascularly.

• Hypoalbuminaemia
• Electrolyte imbalances
• Hypovolaemic shock
• Insulin resistance
• Catabolic metabolic state
• Multi-organ failure
• Bacterial infections
• Septic shock (frequently S. aureus and P. aeruginosa)
• Pneumonia or interstitial pneumonitis
• Necrosis of the oesophagus, small intestine and colon with perforation

• There are usually painful erosions in the area of the mucous membrane

• Estimation of the body surface infestation:
  • 1 palm of the patient corresponds to approximately 1% of the body surface area in children and adults
  • Rule of nines: rule for measuring body surface area
    • Head ≙ 9% of the body surface area
    • 1 arm ≙ 9% of the body surface area
    • Breast & stomach ≙ 9% & 9% (= 18%) of the body surface
    • 1 leg ≙ 18% (!) of the body surface area
    • Genital ≙ 1% of the body surface

• SCORTEN (severity of illness score for toxic epidermal necrolysis)
  • Scale designed to predict the probability of mortality
• Mortality (for SJS, SJS/TEN and TEN): approx. 30%
• Mortality (for SJS): 10%
• Mortality (TEN): >30%

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