After the ‘pink clouds,’ he sees red
Mr. T receives lamotrigine for longstanding mood swings, hypomania, irritability, and anxiety. Two weeks later, a rash covers much of his body. Is the anticonvulsant to blame?
Figure: Did lamotrigine cause Mr. T’s rash?
Folliculocentric pustules around patient’s left elbow and throughout his left side.We have Mr. T come in that day for an emergency physical examination. At presentation, the rash appears infectious with isolated pustules throughout. We refer him to a dermatologist for same-day evaluation.
The authors’ observations
A rash is an immunologic reaction to an offending agent. If lamotrigine were causing the rash, lowering the dosage would not mitigate it.
We continued lamotrigine because the dermatologist could examine the rash within 24 hours of Mr. T’s complaint. Also, the agent was decreasing the patient’s mood, irritability, and anger. If we believed lamotrigine was causing the rash and could not obtain an immediate dermatology consult, we would have stopped the medication.
FOLLOW-UP: ‘Hot’ findings
During the patient history interview, the dermatologist discovers that Mr. T recently installed a whirlpool bath, and that the eruption occurred 3 to 5 days after the patient first used it. Physical examination shows groups of discrete folliculocentric pustules with surrounding erythema mainly on his extensor surfaces and left buttock. These findings and Mr. T’s history suggest a skin infection.
The dermatologist diagnoses hot tub folliculitis, an infection caused by exposure to contaminated whirlpools, hot tubs, or water slides. Cultures obtained that day grow Pseudomonas aeruginosa, confirming the diagnosis. The dermatologist tells Mr. T to stop using his whirlpool bath and prescribes topical gentamicin and ciprofloxacin, 500 mg bid for 10 days. We continue lamotrigine based on the dermatologist’s recommendation.
Two weeks later, Mr. T’s eruption resolves, and we increase lamotrigine to 100 mg/d, which improves his mood and achieves steady-state effectiveness.7 We continue escitalopram, 10 mg/d, then increase to 20 mg/d to treat his generalized anxiety. Mr. T begins experiencing anorgasmia 1 week after the escitalopram increase, so we switch to buspirone, 15 mg bid. After another 4 weeks, his anger, irritability, panic attacks, anxiety, and depression have diminished.
After 3 months, Mr. T’s hepatologist stops ribavirin and peginterferon because they are not helping his hepatitis C infection. Days later, Mr. T’s chills, sweats, and fatigue remit.
The hepatologist considers an experimental hepatitis C
medication.
We see Mr. T once monthly for supportive psychotherapy and medication management. Despite divorce proceedings and persistent mild depression he is optimistic, enjoys work, and rides his motorcycle safely twice a week.
The authors’ observations
Although Mr. T’s presentation and patient history clearly suggested an independent skin infection, distinguishing between an infection and anticonvulsant-induced rash can be difficult.
Lamotrigine and other antiepileptics (Table 1)8 have been associated with morbilliform eruptions, anticonvulsant hypersensitivity syndrome, erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), a severe form of SJS with a 20% to 30% mortality rate.9,10
Table 1
Estimated risk of severe rash among first-time antiepileptic users*
| Drug | Total new users† | Total SJS/TEN cases | Risk per 10,000 new users |
|---|---|---|---|
| Carbamazepine | 286,360 | 39 | 1.4 |
| Lamotrigine | 55,154 | 14 | 2.5 |
| Phenobarbital | 8,659 | 7 | 8.1 |
| Phenytoin | 36,171 | 30 | 8.3 |
| Valproic acid | 103,150 | 4 | 0.4 |
| * Researchers reviewed records of patients hospitalized between 1998 and 2001 with SJS or TEN after using an anticonvulsant. | |||
| † Estimates based on number of dispensed prescriptions, average prescribed dosages, and duration of anticonvulsant use as recorded in Germany’s Mediplus database. | |||
| SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis | |||
| Source: Adapted from reference 8 | |||
Although most lamotrigine-induced cutaneous eruptions are mild or self-limited, some are severe and potentially fatal. In clinical trials, approximately 10% of patients receiving lamotrigine for epilepsy developed cutaneous reactions.11 Among 3,348 patients with epilepsy who received lamotrigine, 11 (0.3%) required hospitalization for SJS or TEN.11
Anticonvulsant hypersensitivity syndrome, estimated to occur once per 1,000 to 10,000 exposures to anticonvulsants,12 can lead to fever, lymphadenopathy, hepatomegaly, and arthralgias. Although hypersensitivity to aromatic anticonvulsants such as phenytoin, carbamazepine, or phenobarbital is most common, hypersensitivity to lamotrigine also has been reported.13,14
Roughly 90% of patients with anticonvulsant hypersensitivity syndrome develop leukocytosis with eosinophilia, and some develop leukocytosis with agranulocytosis.15-17 Fulminant hepatitis can occur, which leads to most deaths associated with this syndrome.
4 steps to gauging rash
Taking a thorough history, examining the eruption, ordering liver function tests (LFTs) and a complete blood count (CBC), and referring the patient to a dermatologist are key to determining the seriousness of an eruption and planning treatment in patients taking anticonvulsants (Table 2). See the patient within 12 hours after he reports the rash, as SJS and TEN often progress rapidly.
