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?
Table 2
4 steps to determining rash severity and cause
| Take a thorough history | Find out when eruption occurred and when patient started the anticonvulsant |
| Ask about past rashes, other medicines, and family history of reactions to medications | |
| Find out if patient has had fever/chills, malaise, lymphadenopathy, or mucosal symptoms such as photophobia or dysuria | |
| Examine the eruption | Examine for mucosal involvement, facial edema, and blistering; describe the symmetry and extent of involvement |
| Look for systemic findings such as fever, chills, lymphadenopathy, and organomegaly | |
| Photograph the eruption for the dermatologist if possible | |
| Order laboratory tests | Order liver function tests and complete blood count with differentials; assess for eosinophilia |
| Closely monitor patient | Stop anticonvulsant if history, physical findings suggest a drug-induced eruption |
| Refer patient to a dermatologist |
STEP 1: Take a thorough history
Ask the patient:
What medications are you taking? Because more than 100 medications could cause SJS or TEN, a detailed drug history is critical to determining whether a medication has induced the eruption.
When did you start taking the potentially offending medication? True lamotrigine-induced eruptions usually occur 5 days to 8 weeks after the first dose.10 SJS and TEN generally take 1 to 2 weeks to develop.
What is your current dosage? Has it increased or decreased recently? Rapid lamotrigine dosage escalations or use of lamotrigine with valproic acid can cause severe rash.9,10,18 Valproic acid increases serum lamotrigine by inhibiting its hepatic metabolism, thereby raising side-effect risk. In clinical trials, 30% of patients who received both anticonvulsants developed a rash.10
Have any family members had rashes after taking an anticonvulsant? Compared with the general population, siblings and first-degree relatives of patients with anticonvulsant-related eruptions are at higher risk for this complication.19 Decreased epoxide hydrolase activity might negate these patients’ ability to detoxify the arene oxide metabolite, which can cause adverse effects if it accumulates.
Do you have other medical problems? Hepatitis C, for example, can theoretically increase lamotrigine’s half-life, thereby elevating side-effect risk.11
Watch for anticonvulsant-related adverse events in patients with hepatic insufficiency because hepatitis might hinder anticonvulsant metabolism.20 Other medical comorbidities—such as HIV infection and systemic lupus erythematosus—also could increase the risk of antiepileptic-induced rash.10
Have you had fever, chills, or other symptoms? Patients with SJS and TEN usually present with systemic symptoms such as malaise, rash, lymphadenopathy, mucosal lesions, and/or symptoms such as photophobia, difficulty swallowing, rectal erosions, or dysuria. Patients with anticonvulsant hypersensitivity syndrome typically have fever and associated arthralgias, skin pain, lymphadenopathy, or a burning sensation on their skin. These symptoms generally are absent in localized cutaneous infections.
STEP 2: Examine the eruption
Cutaneous SJS and TEN findings usually include abrupt onset of erythematous macules—which progress to targetoid lesions containing central bullae—followed by extensive epidermal necrosis. Superficial lip and mouth necrosis occur early, leading to severe stomatitis.
TEN and SJS can appear similar clinically, but TEN
covers >30% of body surface area, whereas SJS covers <10%.
Rashes that cover 10% to 30% of body surface suggest SJS-TEN overlap syndrome.
Anticonvulsant hypersensitivity syndrome usually manifests as
a morbilliform eruption on the face, arms, and/or torso. The
lesions might become edematous and progress to exfoliation or vesiculobullae. Facial edema is a hallmark of anticonvulsant hypersensitivity,15,16 and pustules and/or erythroderma might also appear. Other warning signs include symmetrical widespread eruption and organomegaly.
STEP 3: Order laboratory tests
Check liver function and order a CBC with differential to measure eosinophils. Eosinophilia and abnormal LFT results can signal anticonvulsant hypersensitivity.
Eosinophils. A normal eosinophil count ranges between 0% and 5% of peripheral blood leukocytes in adults, at a count of 350 to 650/cm. Although upper limits of normal vary, values >500/cm suggest hypereosinophilia.21
LFTs. Normal aspartate aminotransferase and alanine aminotransferase levels are 0 to 42 U/L and 0 to 48 U/L, respectively. Any LFT elevation could signal anticonvulsant hypersensitivity syndrome.
STEP 4: Closely monitor the patient
Discontinue the anticonvulsant if findings suggest a cutaneous drug reaction, and contact the patient’s primary care physician or dermatologist immediately. Early consultation with a dermatologist can help determine the eruption’s cause and reveal therapeutic options.
Dr. Pejic is chief resident in the adult psychiatry residency program, Louisiana State University Health Sciences Center and Ochsner Clinic Foundation, New Orleans.
Dr. Klinger is a third-year dermatology resident, Dr. Conrad is assistant professor of clinical psychiatry, and Dr. Nesbitt is chairman, department of dermatology, Louisiana State University Health Sciences Center.
