Early toxic epidermal necrolysis syndrome post-intra-cranial tumor resection

Case report

Mrs KH, a 51-year-old migrant from Hong Kong was admitted to hospital for management of complex partial seizures secondary to a right temporal lobe lesion consistent with a meningioma; 100 mg of carbamazepine twice daily was commenced and the patient was electively admitted a fortnight later for craniotomy and resection of meningioma. On postoperative day three, Mrs KH was noted to have localized erythematous macular rash mainly in the left shoulder extending down to the arm initially treated with antihistamines; the aetiology of rash was thought to be contact dermatitis to hospital sheets. Two days later, medical staff noted that Mrs KH had developed some sloughing of the mucosa of the lips (Figure 1) in addition to progression of the previously noted rash (Figure 2). The dermatology and Burns teams were contacted. Early Toxic Epidermal Necrolysis (TEN) syndrome was suspected given areas of positive Nikolsky sign (Figure 3) with approximately 30% mucosal sloughing in bilateral upper and lower limbs, trunk and oral mucosa. A skin biopsy confirmed the diagnosis. The patient was commenced on intravenous immunoglobulin therapy and the carbamazepine treatment was discontinued. Histopathology of the skin biopsy showed artefactual splitting of the epidermis and dermis with upper dermal perivascular lymphohistiocytic infiltrate; necrosis of the epidermis throughout its full thickness was appreciated. Mrs KH remained in hospital for a total of 14 days and was discharged home following excellent improvement in skin integrity and resolution of excoriations. She also had an excellent outcome from the surgical resection of the right temporal meningioma.

Discussion

Stevens-Johnson Syndrome (SJS) and TEN are two rare self-limited but serious cutaneous drug reactions with significant morbidity and mortality. Mortality rates at six weeks are 12% for SJS, 29% for SJS/TEN overlap syndrome and 46% for TEN. ¹ There are many drugs associated with the condition such as allopurinol, carbamazepine, co-trimoxazole, lamotrigine, nevirapine, NSAIDS (oxicamtype), phenobarbital and phenytoin. Cephalosporins, macrolide, quinolones and tetracyclines also carry a moderate risk for SJS/TEN.^2–4

Significant morbidity is associated with fluid losses as with severe burns, electrolyte imbalance, immunology and haematological dysfunction, superimposed-infection, thermoregulatory problems and more importantly tracheo-bronchial tree involvement causing airway and breathing compromise.^1,2 Severity and prognosis can be rapidly evaluated using the SCORTEN score and is based on individual prognosis factors such as age, malignancy, body surface area detached, tachycardia, serum urea, serum glucose and serum bicarbonate. Patients with a SCORTEN score of 2 or more should be transferred to intensive care or burns units, if available.^1–4

There is vast documented evidence of carbamazepine-induced SJS/TEN in patients of Asian ethnicity mainly Han Chinese. This is due to the presence of the HLA allele B*1502 resulting in an immune-based reaction that leads to extensive mucosal sloughing. Tangamornsuksan et al. ⁶ have reported a strong relationship between HLA-B*1502 allele and carbamazepine-induced SJS and TEN in other Asian ethnic groups mainly Malaysians, Thais and Koreans. The risks of SJS and TEN are approximately 220-fold, 60-fold and 25-fold increases, respectively. ⁶ No clinical cases of HLA-B*1502-associated SJS or TENS have been recorded in Caucasians (no traces of Asian ancestry), hence ethnicity does matter.^1–5 The above racial differences may be also explained by the influence of other HLA alleles related to SJS and TEN. HLA-A*3501-associated carbamazepine-induced skin eruptions and immune reactions are approximately 26-fold higher for Europeans and 11-fold higher in Japanese. ⁶ OPEN IN VIEWER

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Figure 2.

Confluent purpuric macular rash involving the back and extremities in Stevens-Johnson and toxic epidermal necrolysis.

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Figure 3.

Nikolsky-positive skin and biopsy site.

The current treatment of TENS/SJS is divided into early management and symptom control. The immediate cessation of the culprit drug is quintessential.^1–4 Intravenous fluids should be administered judiciously with strict fluid balance assessment. Early referral of the patient to the intensive care unit or the Burns Unit for ongoing care significantly reduces morbidity rates from complications. The experienced Burns Unit allows for strict environmental factors control, appropriate nutritional supports, expert aseptic wound care and peripheral access management away from the affected sites.^2–4 Symptom control involves the use of respiratory adjuncts such as pulmonary aerosols and chest physiotherapy in the event of tracheobronchial involvement.

The role of corticosteroids in SJS/TENS both systemically and topical is debatable. There have been evidence to show that systemic corticosteroids do very little to halt the denuding of skin, may delay wound healing, mask early signs of sepsis and even result in superimposed infections.^2,4 Intravenous immunoglobulin (IVIG) on the other hand has been used more readily in centres around the world with promising outcomes.^1,3,4

Our recommendations include the practice of caution and HLA-B*1502 screening when using aromatic anticonvulsants such as carbamazepine in patients of high-risk South East Asian descent. HLA-B*1502 allele testing can be performed in Australia and the cost of the test is reimbursable under Medicare.