Toxic Epidermal Necrolysis of the Scalp Following Anticonvulsant Use and Cranial Irradiation

apd: 31 October 2001     

Toxic Epidermal Necrolysis Associated with Klebsiella Pneumoniae Sepsis

Abstract: Toxic epidermal necrolysis (TEN) is a rare condition In childhood usually attributed to drugs. We describe a 4-month-old infant who developed typical clinical and histologic findings of TEN concomltantly with Klebsiella pneumoniae sepsis. We emphasize that in cases of acute, severe exfoliative disease in infants, apart from staphylococcal infection, gram-negative bacterial sepsis must also be considered.     

Allopurinol-induced Toxic Epidermal Necrolysis

ABSTRACT: An erythematous eruption with itching developed in an 84-year-old man 4 days after therapy with allopurinol was initiated. The diagnosis of toxic epidermal necrolysis, suspected when separation of the epidermis was noted, was confirmed by skin biopsy. This is the third reported case that can be attributed exclusively to allopurinol and the first patient who did not die.     

Drug-Induced Toxic Epidermal Necrolysis Treated with Cyclosporin

A 35-year-old woman developed toxic epidermal necrolysis secondary to phenytoin. Because the life-threatening eruption was resistant to prednisone and high-dose methylprednisolone therapy, cyclosporine therapy was initiated. Within 24-48 hours, the eruption stabilized and the patient improved.     

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Overlap due to Oral Temozolomide and Cranial Radiotherapy

A 46-year-old man developed Stevens-Johnson syndrome and toxic epidermal necrolysis overlap, with severe localized denudation of the skin on the head and neck, following radiotherapy and oral temozolomide therapy for cranial glioblastoma multiforme. He also had a primary malignant fibrous histiocytoma of the thigh that was amputated 5 years earlier. A rash developed after 7 days of radio- and chemotherapy. It was an extensive maculopapular rash that started over the temporal area of the head and rapidly spread, sparing only the distal limbs. Radiotherapy and temozolomide were stopped on the tenth day but the rash rapidly progressed for the next 4–6 days. Following this, the spread halted and complete recovery was observed within the next 2 weeks. The peculiarity of the presentation in this case was that the brunt of the disease with severe skin denudation was localized to the surrounding areas of cranial radiotherapy. The patient was also receiving oral phenytoin, diclofenac, and parenteral dexamethasone before chemotherapy was started. These medications were continued, even after development of the skin rash, until well after full recovery from the skin lesions. After critical evaluation of disease onset, progression, and recovery, and their relationship to the introduction and withdrawal of different medicines, it appeared that either temozolomide alone or in combination with radiotherapy most probably triggered the condition.     

Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare (occurring in approximately 2 to 3 people/million population/year in Europe and the US), life-threatening, intolerance reaction of the skin. It is most often caused by drugs (most commonly sulfonamides, nonsteroidal anti-inflammatory drugs, antimalarials, anticonvulsants, and allopurinol). SJS/TEN is characterized by a macular exanthema (‘atypical targets’) which focusses on the face, neck, and the central trunk regions. Lesions show rapid confluence, a positive Nikolsky’s sign, and quickly result in widespread detachment of the epidermis and erosions. Mucosal, conjunctival, and anogenital mucous membranes are prominently involved. Histopathology shows satellite cell necrosis in the early stages progressing to full thickness necrosis of the epidermis, contrasting with rather inconspicuous inflammatory infiltrates of the dermis. Damage to the skin is thought to be mediated by cytotoxic T lymphocytes and mononuclear cells which induce apoptosis in keratinocytes expressing drug-derived antigens at their surfaces. No guidelines for the treatment of SJS/TEN exist since no controlled clinical trials have ever been performed. The controversy over whether systemic corticosteroids should be used to curtail progression is still unresolved; while many authors agree that corticosteroids do in fact suppress progression, it is obvious that they also greatly enhance the risk of infection, the complication which most frequently leads to a fatal outcome. It appears reasonable to only administer corticosteroids in the phase of progression and to withdraw them as soon as possible, and to add antibacterials for prophylaxis. Recently, in a small series of patients, intravenous immunoglobulins were presumed to be effective by the blockade of lytic Fas ligand-mediated apoptosis in SJS/TEN. However, these results have to be confirmed by large clinical trials. Supportive treatment and monitoring of vital functions is of utmost importance in SJS/TEN, and out-patient treatment is unacceptable. Recovery is usually slow, depending on the extent and severity and the presence of complications, and may take 3 to 6 weeks. Skin lesions heal without scars as a rule, but scarring of mucosal sites is a frequent late complication, potentially leading to blindness, obliteration of the fornices and anogenital strictures. There is no reliable laboratory test to determine the offending drug; diagnosis rests on the patient’s history and the empirical risk of drugs to elicit skin SJS/TEN. Provocation tests are not indicated since re-exposure is likely to elicit a new episode of SJS/TEN of increased severity.     

Toxic Epidermal Necrolysis in a 6-week-old Infant

Toxic epidermal necrolysis was documented in a 6-week-old infant with Klebsiella pneumoniae sepsis who received many medications. We inoculated infant mice with the K. pneumoniae isolate but were unable to produce histologic changes resembling those seen in our patient. This condition should be included in the differential diagnosis of severe drug reactions in very young infants with clinical scalded-skin syndromes.     

Toxic Epidermal Necrolysis in a Child Successfully Treated with Infliximab

A 7‐year‐old boy developed severe toxic epidermal necrolysis (TEN) secondary to carbamazepine and was transferred to our center after further deterioration despite receiving one dose of intravenous immunoglobulin. After administration of one dose of infliximab, there was a clear halting of progression of blistering and an apparent dramatic improvement. We consider it likely that the administration of infliximab led to the improvement in this child and that anti‐tumor necrosis factor‐alpha therapy may be a logical treatment for TEN, given the possible underlying pathologic process. Well‐conducted studies on the safety and efficacy of any such treatment are urgently required.     

A Case of Generalized Seizure after Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a severe mucocutaneous adverse reaction characterized by extensive necrosis and epidermal detachment involving more than 30% of the body surface area (BSA). It is commonly triggered by antiepileptics, sulfonamide antibiotics, and non-steroidal anti-inflammatory drugs. A 22-year-old female without any underlying medical history presented with painful multiple erythematous bullae and plaques of varied sizes throughout the body for 1 day. On the second hospitalization day (HD), the bullae progressively coalesced, leading to epidermal detachment involving 60% of the BSA. On the fifth HD, the patient had a tonic–clonic seizure with eyeball deviation for 5 minutes. She was transferred to the intensive care unit (ICU) and administered lorazepam 4 mg and levetiracetam 1,500 mg. Brain computed tomography, magnetic resonance imaging, and cerebrospinal fluid examination showed no abnormalities. Although the patient had delirium and additional seizures while in the ICU, her condition improved without any complications after 5 weeks of inpatient treatment. Several complications of TEN such as dehydration, malnutrition, sepsis, and ophthalmic and pulmonary complications have been reported; however, seizures have not been reported yet. Herein, we report a case of seizure in a patient during treatment for TEN.