Toxic epidermal necrolysis due to administration of celecoxib (Celebrex).

ABSTRACT

A 41-year-old woman was given celecoxib (Celebrex) for the treatment of carpal tunnel syndrome. An erythematous rash developed that progressed to exfoliative dermatitis, and the patient was diagnosed with toxic epidermal necrolysis. After transfer to the burn unit, she was treated with topical mupirocin calcium cream and bismuth tribromophenatein petrolatum gauze dressings. Her wounds healed well. This is the first case report of toxic epidermal necrolysis due to treatment with celecoxib of which we are aware.

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PATIENTS with toxic epidermal necrolysis (TEN) are frequently admitted for care at the burn center of Doctor's Hospital in Augusta, Ga. Toxic epidermal necrolysis is an allergic skin condition which, in this case, appears to be related to previous administration of oral celecoxib (Celebrex). This is the first such reported case of TEN that we found in reviewing the literature.

CASE REPORT

A 41-year-old woman had carpal tunnel syndrome, for which she was given celecoxib. She took the first dose in the morning 3 days before admission. She took a second dose that evening; after the second dose, severe itching developed. By the next day, the patient had a diffuse, erythematous skin eruption involving the thighs, chest, and back. She was seen at an emergency department in her home area and was treated with methylprenisolone sodium succinate and topical hydrocortisone cream. The following day, she was referred to the hospital burn unit because of extensive sloughing of the skin.

Her medical history revealed long-standing hypertension, a previous tubal ligation, and a cesarean section. On admission, she was taking felodipine, famotidine, prednisone, and hydroxyzine hydrochloride. She was a nonsmoker and drank alcohol occasionally. Family history was noncontributory. Physical examination revealed a well-developed, well-nourished black woman who was in no acute distress. Vital signs at presentation were temperature 98.4[degrees]F, pulse rate 120/min, respiratory rate 22/min, and blood pressure 128/66 mm Hg. On admission, the patient's skin revealed an erythematous rash, blistering, and areas of superficial skin slough covering 12% of her body. These lesions were thought to be consistent with TEN. The lesions were scattered over the chest, abdomen, back, neck, anterior and posterior thighs, and calves, but there were no lesions on the hands or feet. There were no mucosal or conjunctival lesions. The remainder of the physical examination was unremarkable. Hematocrit level was 32.7%, and w hite blood cell count was 18,600/[micro]L.

After removal of the blisters, the patient was treated with topical mupirocin calcium cream and bismuth tribromophenatein petrolatum gauze changed twice a day. The patient was seen in consultation by the dermatology and the medical services. Celecoxib had already been discontinued; steroids were also discontinued. Biopsy specimens showed erythema multiforme with inflammation and edema of the dermal tissue layer. A few scattered eosinophils were noted in the inflammatory infiltrate. A specimen was tested with antisera to immunoglobulin G, immunoglobulin A, immunoglobulin M, and complement component C3; no immunofluorescence was noted. This was believed to confirm the diagnosis of a drug reaction, and the negative immunofluorescence ruled out the diagnosis of bullous pemphigoid. The patient's wounds healed steadily, and she was discharged on the eighth day after admission. No new lesions were developing, and most of the older ones had healed. She continued to use mupirocin calcium cream and was to be followed o n an outpatient basis.

DISCUSSION

Toxic epidermal necrolysis is an entity that has been variously identified. It was originally called Lyell's syndrome, then TEN and Stevens-Johnson syndrome. (1,2) Erythema multiforme is an allergic skin eruption, usually due to medication. It is thought to be the preliminary form of a condition that may progress to the severe blistering and skin slough called TEN, which is histologically characterized by separation at the dermalepidermal junction leading to the development of slough. There can be severe systemic reactions as well; slough of the conjunctiva, gastrointestinal tract, and respiratory tract may develop. This entity is associated with a high death rate, reported to be as high as 70% of patients. (3) This disease must be distinguished from staphylococcal scalded-skin syndrome by biopsy, since the 2 entities appear similar clinically.

Because of the extensive open wounds and the intensive level of nursing care they require, patients with TEN are frequently treated on burn units. (3-5) The wounds may be treated with topical antibiotics of various sorts, application of silicone-based dressings (such as Biobrane), or the application of biological dressings (such as cadaver skin or porcine xenografts). The wounds usually heal without scarring. This patient was admitted and treated with mupirocin calcium cream because of the possibility of a cutaneous staphylococcal infection. Her wounds healed rapidly, and no new lesions developed. Systemic steroids were not given to the patient after admission to the burn center, since they are contraindicated in treating patients with TEN.

Toxic epidermal necrolysis usually develops after administration of medication. (6) Phenytoin, various sulfa drugs, a wide variety of antibiotics, and nonsteroidal anti-inflammatory drugs have been incriminated as the causative agents in the development of the syndrome. In this case, the patient had been taking several medications, but since her symptoms developed promptly after the initiation of treatment with celecoxib, it appears that this as the precipitating agent in the development of her symptoms. Celecoxib is a cyclo-oxygenase-2 (COX-2) inhibitor, a new class of nonsteroidal anti-inflammatory agent. (7) The drug contains a sulfa moiety, which may be a precipitating agent in the development of an allergic reaction. We are aware of no previous cases reported in the literature in which this agent has led to the development of TEN.

References

(1.) Chan HL, Stern RS, Arndt KA, et al: The incidence of erythema multiforme, Stevens-Johnson's syndrome, and toxic epidermal necrolysis: a population based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990; 126:43-47

(2.) Prendiville JS, Hebert AA, Greenwald MJ, et al: Management of Stevens-Johnson's syndrome and toxic epidermal necrolysis in children. J Pediatr 1989; 115:881-887

(3.) Adzick NS, Kim SH, Bondoc CC, et al: Management of toxic epidermal necrolysis in the pediatric burn center. Am J Dis Child 1985; 139:499-501

(4.) Heimbach DM, Engrav LH, Marvin JA, et al: Toxic epidermal necrolysis, a step forward in treatment. JAMA 1987; 257:2171-2173

(5.) Green D, Law E, Still JM: An approach to the management of toxic epidermal necrolysis in a burn center. Burns 1993; 19:411-414

(6.) Anderson JA: Allergic reactions to drugs and biological agents. JAMA 1992; 268:2844-2857

(7.) Davies NM, McLachlan AJ, Day RO, et al: Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclooxygenase-2 inhibitor. Clin Pharmacokinet 2000; 38:225-242

RELATED ARTICLE: KEY POINTS

* A 41-year-old woman who had been treated with celecoxib had an exfoliative dermatitis diagnosed as toxic epidermal necrolysis.

* The patient's wounds responded well to topical therapy.

* This is the first reported case of this condition, of which we are aware, due to celecoxib.

From the Joseph M. Still Burn Center, Doctor's Hospital, Augusta, Ga.

Reprint requests to Joseph M. Still, MD, Physicians' Multi-specialty Group, 1220 George C. Wilson Dr, PO Box 3726, Augusta, GA 30914-3726.