Toxic Epidermal Necrolysis: A Clinical and Therapeutic Review
Abstract
:1. Introduction
2. Materials and Methods
3. Discussion
3.1. Epidemiology
3.2. Aetiology
3.3. Pathophysiology
3.4. Clinical Presentation
3.5. Diagnosis
3.6. Differential Diagnosis
3.7. Treatment
3.7.1. General Measures
3.7.2. Wound Management
3.7.3. Corticosteroids
3.7.4. Antibiotics
3.7.5. Prevention and Management of Complications
3.7.6. Immunomodulation
3.8. Prognosis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Criteria | Value | Rules of Application | |
---|---|---|---|
Latency between drug administration and onset of symptoms (index day) | Suggestive | +3 | From 5 to 28 days. |
Compatible | +2 | From 29 to 56 days. | |
Probable | +1 | From 1 to 4 days. | |
Improbable | −1 | More than 56 days. | |
Excluded | −3 | Drug administered on index day. | |
NOTE: If there is a previous reaction to the same drug, it is considered “suggestive +3” from 1 to 4 days and “probable +1” from 5 to 56 days. | |||
Probability that the drug was present in the patient’s system | Definitive | +0 | Drug administered until index day or stopped less than 5 elimination half-lives before index day. |
Doubtful | −1 | Drug stopped more than 5 elimination half-lives before index day, with abnormal renal and/or hepatic functions or suspected pharmacological interactions. | |
Excluded | −3 | Drug stopped more than 5 elimination half-lives before index day, with normal renal and hepatic functions and no pharmacological interactions. | |
Prechallenge or rechallenge | Positive specifically for disease and drug | +4 | Occurrence of SJS/TEN 1 after the use of the same drug. |
Positive specifically either for disease or drug | +2 | Occurrence of SJS/TEN after the use of a similar drug or another adverse reaction to the same drug. | |
Positive non-specifically | +1 | Occurrence of another adverse drug reaction to a similar drug. | |
Unknown/not performed | +0 | No knowledge of previous exposure to the drug. | |
Negative | −2 | Previous exposure to the drug without any adverse reaction of any kind. | |
Dechallenge | Neutral | +0 | Drug stopped or unknown. |
Negative | −2 | Drug not stopped without worsening of clinical condition. | |
Drug notoriety | Strongly associated | +3 | High risk drug. |
Associated | +2 | Lower but proven risk drug. | |
Suspect | +1 | Ambiguous epidemiology; drug “under surveillance”. | |
Unknown | +0 | All other drugs, including new ones. | |
Not suspect | −1 | No evidence of association. | |
INTERMEDIATE SCORE = −11 to +10 | Sum of all previous criteria. | ||
Other possible aetiologies for the symptoms? | Possible | −1 | List all other administered drugs according to their intermediate score and if at least one > 3. |
Final Score | Classification |
---|---|
<0 | Very unlikely |
0–1 | Unlikely |
2–3 | Possible |
4–5 | Probable |
≥6 | Very probable |
Pharmacological Group | Strong Association | Less Strong Association | Weak Association |
---|---|---|---|
Antibiotics | Sulphonamides (especially cotrimoxazole) | Amoxicillin | Nitrofurantoin |
Cephalosporines | Vancomycin | ||
Macrolides | |||
Quinolones (typically, ciprofloxacin) | |||
Tetracyclines | |||
Antiepileptics | Carbamazepine (mainly in paediatric ages) | Valproate | |
Lamotrigine | |||
Phenobarbital | |||
Phenytoin | |||
Analgesic and anti-inflammatory drugs | NSAIDs 1 from ‘oxicam’ group | Acetic acid NSAIDs (e.g., diclofenac) | Acetaminophen (paracetamol) |
Ibuprofen | Tramadol | ||
Antidepressants | Sertraline | Fluoxetine | |
Mirtazapine | |||
Other | Allopurinol | Pantoprazol | Diltiazem |
Sulfasalazine | |||
Nevirapine |
Bullous Disease | Fever | Mucositis | Morphology | Onset | Other Characteristics |
---|---|---|---|---|---|
Erythema multiforme | Yes | No | Raised lesions Nikolsky neg. | Late | Lesions after HSV 1 or M. pneumoniae infections. |
SSSS 2 | Yes | No | Painful erythema with perioral crusts | Acute | Mainly in children younger than 5 y-o, but also in immunocompromised individuals or undergoing haemodialysis. |
Erythema Scarlatiniform | Yes | Yes | Erythema on flexures | Acute | Possible pharyngeal and lingual involvement. |
Toxic Shock Syndrome | Yes | No | Macular rash on palms and soles, with desquamation | Acute | Multisystemic involvement is more evident. |
Paraneoplastic Pemphigus | No | Yes, severe | Polymorphic lesions with flaccid bullae | Insidious | Linked to oncological diseases, primarily lymphomas. Refractory to treatment. |
GVHD 3 | Yes | Yes | Morbilliform erythema, bullae and erosions | Acute | Very similar to TEN. |
DRESS 4 syndrome | Yes | No | Rash without desquamation | Late | Marked eosinophilia and systemic symptoms. |
Therapeutic Options | Use and Recommendation | Notes | ||
---|---|---|---|---|
General measures | Fluid therapy | 1st line therapy. | At 2 mL/kg/%TBSA to ensure a UO ≥ 1 mL/kg/h. | |
Proton-pump inhibitors | Recommended. | For the prevention of gastric ulcers. | ||
Analgesics | Recommended. | For basal and procedure-induced pain. General anaesthesia may be needed. | ||
LMWH 1 | Recommended, unless contraindicated. | For the prevention of thromboembolic events. | ||
Corticosteroids | Not recommended. Can be useful in primordial stages of TEN. | A daily bolus of dexamethasone 1.5 mg/kg for 3 consecutive days may help reduce inflammation. | ||
Antibiotics | Recommended, if clinical or analytical signs of infection are present. | Prophylactic use is strongly discouraged. The empirical choice must cover for S. aureus, P. aeruginosa and Enterobacteriaceae. Adjust antibiotics to local flora and resistance patterns of the Burn Unit. | ||
Immunomodulation | Plasmapheresis | Recommended, in serious cases or if ineffective initial therapies. | Maximum usefulness in the first days of symptoms. | |
NAC 2 | Can be considered. | Till 1 g, 6 id. | ||
Pentoxifylline | Can be considered. | |||
G-CSF 3 | Can be considered. | Can be useful to minimise neutropenia. Filgrastim 5 µg/kg, 1 id. | ||
Zinc supplements | Can be considered. | At 150 mg, 2 id, for 6 weeks. | ||
Cyclosporin | Needs further clarification. | Empirical use not recommended, but at 3–5 mg/kg/day could help reduce inflammation. | ||
Cyclophosphamide | Not recommended. | |||
Anti-TNF 4 | Thalidomide | Absolutely contraindicated. | Associated with higher mortality. | |
Infliximab | Needs further clarification. | |||
Etanercept | ||||
IVIG 5 | Needs further and more thorough investigation. | It is safe at 1 g/kg/day for 3 consecutive days, but its efficacy is uncertain. |
Parameter | Reference Value |
---|---|
Age | >40 years. |
Oncological disease | Yes. |
Desquamative TBSA | >10%. |
Heart rate | >120 bpm. |
BUN | >28 mg/dL. |
Glycaemia | >252 mg/dL |
Serum bicarbonate | <20 mEq/L. |
SCORTEN | Estimated Mortality (%) |
---|---|
0–1 | 3.2 |
2 | 12.1 |
3 | 35.3 |
4 | 58.3 |
>5 | 90.0 |
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Canhão, G.; Pinheiro, S.; Cabral, L. Toxic Epidermal Necrolysis: A Clinical and Therapeutic Review. Eur. Burn J. 2022, 3, 407-424. https://doi.org/10.3390/ebj3030036
Canhão G, Pinheiro S, Cabral L. Toxic Epidermal Necrolysis: A Clinical and Therapeutic Review. European Burn Journal. 2022; 3(3):407-424. https://doi.org/10.3390/ebj3030036
Chicago/Turabian StyleCanhão, Gonçalo, Susana Pinheiro, and Luís Cabral. 2022. "Toxic Epidermal Necrolysis: A Clinical and Therapeutic Review" European Burn Journal 3, no. 3: 407-424. https://doi.org/10.3390/ebj3030036