Anticonvulsant hypersensitivity: an unfortunate case of triple exposure to phenytoin

Journal of Family Practice, Nov, 1997 by Cara E. Brown, Gregory D. Smith, Thomas Coniglione

Anticonvulsant hypersensitivity manifests 2 to 12 weeks after patients start taking phenytoin, phenobarbital, or carbemazepine. The syndrome begins with fever followed by a rash that can progress to erythema multiforme, toxic epidermal necrolysis, and multi-organ system involvement. Other common manifestations include lymphadenopathy, facial edema, eosinophilia, and elevated transaminase levels. Anticonvulsant hypersensitivity can be fatal in 5% to 50% of patients if hepatic involvement or toxic epidermal necrolysis occurs. Most evidence regarding the etiology points to a genetically related defect in the detoxification enzyme. Early recognition is important in order to discontinue drug therapy. Continuity of care assists in prevention of re-exposure. Treatment includes supportive measures and steroids. All patients with anticonvulsant hypersensitivity should wear a medical identification bracelet.

KEY WORDS. Anticonvulsants; drug hypersensitivity; continuity of patient care; family practice. (J Fam Pract 1997; 45:434-437)

Anticonvulsant hypersensitivity usually manifests 2 to 4 weeks after initiating treatment with phenytoin, phenobarbital, or carbemazepine, but can begin as late as 3 months. This reaction occurs in 1 in 1000 to 1 in 10,000 patients exposed to these drugs, and is more common in African Americans.[1] The syndrome usually involves fever, rash, lymphadenopathy, leukocytosis with eosinophilia, and elevation of transaminase levels.

CASE REPORT

A 62-year-old African American woman arrived unaccompanied at the emergency department (ED) in status epilepticus. After receiving diazepam to stop her seizure activity, she was given a loading dose of phenytoin. The patient could not communicate her medical history or drug allergy to the ED physician even after the seizure abated because she has profound dementia resulting from a cerebrovascular accident. When her medical chart arrived in the ED, the physician noted that she was being treated with carbemazepine. He therefore checked her carbemazepine level and found it to be subtherapeutic at 2.8 [micro]g/mL.

Within 6hours, her temperature was 101.2 [degrees] F (39 [degrees] C). By the next morning, a diffuse, warm erythema appeared on the skin of her ventral arms, axillas, and face. Therapy with prednisone was initiated for suspected anticonvulsant hypersensitivity, and phenytoin was discontinued. The fever resolved. By hospital day 3, the erythema spread to her shoulders, chest, and extensor surfaces of her legs. On day 5, approximately 12 target lesions appeared mostly on her legs, ranging in size from 3 to 10 centimeters, accompanied by two bullous lesions with epidermal desquamation and Nikolsky's sign (Figure 1). Her lips became dry, crusted, and fissured. No lymphadenopathy was appreciated. Maximal white blood count (WBC) was 10,100/[mm.sup.3] without eosinophilia. Seventeen days after administration of the phenytoin, the skin lesions were resolving.

[Figure 1 ILLUSTRATION OMITTED]

Throughout her lengthy chart (the "old" chart that the ED physician received), "no known drug allergies" were noted, except on the first history and physical examination when a "skin rash to unknown anti-convulsant" had been reported by her family. On review of her previous hospital records, toxic epidermal necrolysis that began developing with 24 hours of a phenytoin bolus was confirmed; therefore, it is likely that she had been exposed at least one more time previously.

During the past 1 1/2 years this patient received continuity of care in our family practice residency's internal medicine clinic. Four months after the hospitalization detailed above, the patient came for her monthly checkup and was found to have been discharged from another hospital for status epilepticus. Again, she was given a loading dose of phenytoin in the ED and continued to receive phenytoin during the 2-day admission. In our clinic that day, she displayed target lesions and areas of epidermal sloughing that were more extensive than previously noted (Figure 2). The phenytoin level was 2.5 [micro]g/mL; liver function tests, blood urea nitrogen, and WBC count with differential were within normal limits. Fortunately, her discharge phenytoin prescription from that hospital was not filled.

[Figure 2 ILLUSTRATION OMITTED]

Unfortunately, her family rarely accompanies her to the ED and neglects to direct the ambulance service to our hospital for continuity of care. In addition, despite multiple reminders, her family fails to remember her drug allergy, and despite repetitive counseling regarding the importance of regularly giving the patient her anticonvulsant administration, the patient continues to have break-through seizures related to subtherapeutic levels. At this point, it became sadly clear that we could not rely on her family to convey her life-threatening drug allergy or that her family would strive to keep her care within the same group of physicians who knew her allergy. Therefore, as her advocates, we obtained a MedicAlert identification bracelet for her protection. In addition, our social services helped us to honor her wishes to remain with her family by placing her in a daytime activity center, where she could receive her anticonvulsant medication regularly.