- Email: [email protected]
Mexiletine-induced severe skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction
Pain 73 (1997) 97–99
Clinical note
Mexiletine-induced severe skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction Kazuo Higa*, Kazuhiko Hirata, Kenjiro Dan Department of Anesthesiology, School of Medicine, Fukuoka University, 45–1, 7-chome, Nanakuma, Jonan-ku, Fukuoka 814–80, Japan Received 28 December 1996; revised version received 5 May 1997; accepted 22 May 1997
Abstract A 64-year-old man developed a severe generalized pruritic morbilliform skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction 30 days after ingestion of mexiletine, a sodium channel blocker, prescribed to treat postherpetic neuralgia. Following intravenous dexamethasone, body temperature normalized the next day. However, the skin eruption did not disappear completely for 4 weeks. The patch test was positive for mexiletine. Clinical features and the result of patch test indicated that the patient developed hypersensitivity syndrome, a severe adverse cutaneous drug reaction, caused by mexiletine. We propose that mexiletine be added to the list of drugs that can cause severe adverse cutaneous drug reactions and that patients receiving mexiletine be warned to stop taking the drug immediately if a skin eruption occurs. 1997 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Adverse drug reaction; Hypersensitivity syndrome; Mexiletine; Postherpetic neuralgia
1. Introduction
2. Case report
Sodium channel blockers, such as carbamazepine and phenytoin, are effective for treating patients with neuropathic pain (McQuay et al., 1995). Intravenous lidocaine and oral mexiletine, a congener of lidocaine, have also been increasingly used for such purposes (Dejgard et al., 1988; Tanelian and Brose, 1991; Backonja, 1994; Galer et al., 1996). However, adverse drug reactions to these drugs can occur (Campbell et al., 1978; Monk and Brogden, 1990; Avakian et al., 1991; Pelekanos et al., 1991; Roujeau et al., 1995). Carbamazepine and phenytoin can cause severe skin eruptions, which can be fatal (Avakian et al., 1991; Pelekanos et al., 1991; Roujeau et al., 1995). Severe skin eruption due to mexiletine has apparently not been reported (Monk and Brogden, 1990; Roujeau and Stern, 1994). One of our patients developed severe skin eruption and fever, accompanied by eosinophilia, atypical lymphocytosis, and liver dysfunction, 30 days after starting ingestion of mexiletine.
A 64-year-old otherwise healthy man who had no previous drug reactions suffered from herpes zoster over the right third thoracic dermatome 34 months before a severe adverse drug reaction occurred. The pain persisted and was controlled with amitriptyline 125 mg at bed-time and alprazolam 0.4 mg, three times a day, from 28 months after the onset of herpes zoster. The pain worsened, as it got cooler and cooler at the start of winter, 33 months after the onset of herpes zoster. Mexiletine, 100 mg three times daily, was then added and the pain decreased. Generalized pruritic morbilliform skin eruption developed 30 days after the initiation of mexiletine, and this drug was withheld. Sore throat, cough, and excess sputum were noted, and the body temperature rose to 38.1°C 5 days later. Amitriptyline and alprazolam were then withheld. The morbilliform skin eruption became confluent to erythema, which was marked on the face and trunk, 8 days after the onset of the skin eruption. The body temperature was 38.3°C. There were no skin bullae, purpuras, erosions on the mucous membranes, lymphadenopathy, or arthralgia. The patient was admitted to Fukuoka University Hospital. Blood pressure was 120/90 mmHg, and pulse rate 90 beats/
* Corresponding author. Tel.: +81 92 8011011 ext. 3512; fax: +81 92 8656032; e-mail: [email protected]
0304-3959/97/$17.00 1997 International Association for the Study of Pain. Published by Elsevier Science B.V. PII S0304-3959 (97 )0 0066-3
98
K. Higa et al. / Pain 73 (1997) 97–99
min. Laboratory examination (Table 1) revealed hemoconcentration (hemoglobin, 19.0 g/dl), leukocytosis (28.8 × 103/mm3) with eosinophilia (10.5%) and atypical lymphocytosis (9.5%), liver dysfunction (total bilirubin, 3.7 mg/dl; aspartate aminotransferase, 242 IU/l; alanine aminotransferase, 317 IU/l; lactic dehydrogenase, 2246 IU/l), and markedly elevated C-reactive protein (13.2 mg/ dl). Intravenous fluid and dexamethasone 8 mg a day for 3 days were prescribed. The body temperature decreased to 36.8°C the next day. The erythema of the face and trunk did not worsen from the third hospital day. On the fourth hospital day, intravenous dexamethasone was changed to oral prednisolone 30 mg a day; thereafter, it was decreased to 20 mg a day for 2 days, and 10 mg a day for another day. The skin eruption on the face and trunk almost disappeared, and exfoliation was noted on the eleventh hospital day (20 days after the onset of the skin eruption). Laboratory investigation showed the presence of marked eosinophilia (eosinophils, 51.0%), although the indices of liver function showed improvement. The skin eruption disappeared completely 4 weeks after the onset. The patch test was positive for mexiletine, but negative for amitriptyline and alprazolam. He was not re-challenged with oral mexiletine. Since his postherpetic neuralgia worsened 4 weeks after the onset of the adverse drug reaction, amitriptyline was resumed and gradually increased to 75 mg at bed-time. The postherpetic neuralgia improved. There was no recurrence of the morbilliform skin eruption.
3. Discussion Severe adverse cutaneous reactions to drugs include toxic epidermal necrolysis, Stevens–Johnson syndrome, hypersensitivity syndrome, and small-vessel vasculitis (Roujeau and Stern, 1994). Toxic epidermal necrolysis is characterized by confluent erythema, skin detachment of more than
30% of body surface area, fever, leukocytopenia, and a mortality rate up to 30%. Clinical features of Stevens–Johnson syndrome consist of small blisters, purpuric macules, and skin detachment of less than 10% of body surface area. The mortality rate is less than 10%. Both toxic epidermal necrolysis and Stevens–Johnson syndrome involve mucous membranes, and respiratory and gastrointestinal tracts. Symptoms develop 1–3 weeks after initiation of causative drugs. Hypersensitivity syndrome is characterized by severe skin eruption, fever, eosinophilia, atypical lymphocytosis, liver dysfunction, lymphadenopathy, and arthralgia, and occurs 2–6 weeks after initiation of drugs. The mortality rate is around 10%. Drug-related small-vessel vasculitis causes palpable purpuras on the lower limbs, gastrointestinal disturbances, neuritis, fever, and glomerulonephritis and occurs 1–3 weeks after initiation of causative drugs. The mortality rate is less than 5% (Roujeau and Stern, 1994). Sodium channel blockers, such as carbamazepine, phenytoin and mexiletine, are used to treat neuropathic pain (Dejgard et al., 1988; Tanelian and Brose, 1991; Backonja, 1994; McQuay et al., 1995; Galer et al., 1996). Skin eruptions after carbamazepine and phenytoin are not uncommon (Murphy et al., 1991; Pelekanos et al., 1991). These usually occur 2–3 weeks after initiation of the drug and usually disappear after withdrawal of the drug, in most patients (Pelekanos et al., 1991). However, toxic epidermal necrolysis, Stevens–Johnson syndrome, and hypersensitivity syndrome can occur as severe adverse cutaneous reactions to both drugs (Avakian et al., 1991; Roujeau and Stern, 1994; Roujeau et al., 1995), albeit extremely rarely. A recent review on severe adverse cutaneous reactions to drugs did not mention mexiletine as a drug that can cause severe skin eruptions (Roujeau and Stern, 1994). We could not find any reports of hypersensitivity syndrome to mexiletine through Medline search. There have been only a few reports of skin eruptions after mexiletine ingestion (Heger et al., 1980; Kikuchi et al., 1991).
Table 1 Laboratory data Normal value
Days after skin eruption −30
Hb WBC Eosinophils (%) Atypical lymphocytes (%) Total bilirubin AST ALT LDH ALP GGP CRP
(13.4–17.6 g/dl) (3.9–9.8 × 103/mm3)
(0.2–1.2 mg/dl) (,40 IU/l) (,40 IU/l) (200–520 IU/l) (75–290 IU/l) (,60 IU/l) (mg/dl)
16.9 7.0 2 0 0.4 33 36 346 239 89 0.5
0 17.2 7.3 3 1.0 0.7 235 252 815 574 420 5.6
8 19.0 28.8 10.5 9.5 3.7 242 317 2246 1280 613 13.2
20
30
41
15.4 12.7 51.0 0 1.3 82 194 651 700 348 1.4
12.9 8.2 19.0 0 0.8 38 69 493 767 154 1.4
13.4 10.4 2 0 0.5 27 36 442 535 96 0.6
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; GGP, gamma-glutamyl transferase; Hb, hemoglobin; LDH, lactic dehydrogenase; WBC, white blood cells.
K. Higa et al. / Pain 73 (1997) 97–99
Heger et al. (1980) reported a patient who developed a macular, erythematous skin eruption on the face, trunk, and limbs 2 days after taking mexiletine; it disappeared several days after withdrawal of mexiletine. Kikuchi et al. (1991) described a 77-year-old man who developed a generalized pruritic erythematous skin eruption 45 days after administration of mexiletine. He was given prednisolone orally, and the skin eruption disappeared completely a month later. The patch test was positive for mexiletine. Whether or not the patient had fever, eosinophilia, or liver dysfunction was not stated. Our patient developed a generalized pruritic morbilliform skin eruption and fever, accompanied by eosinophilia, atypical lymphocytosis, and liver dysfunction, 30 days after initiation of mexiletine. Although lymphadenopathy or arthralgia was nil, the temporal relationship between initiation of mexiletine and the development of generalized skin eruption, the clinical features, and the results of patch test positive for mexiletine but negative for amitriptyline and alprazolam indicate that he had hypersensitivity syndrome caused by mexiletine. It has been stated that hypersensitivity syndrome to a drug can be suppressed by adrenocorticosteroids and that the drug can be continued under adrenocorticosteroid treatment, even in the presence of hypersensitivity syndrome, in some patients (Murphy et al., 1991). When our patient was given intravenous dexamethasone, body temperature normalized the next day. However, since there have been no controlled clinical studies concerning the efficacy of adrenocorticosteroids on hypersensitivity syndrome and the mortality of the syndrome is around 10% (Roujeau and Stern, 1994), it is of the utmost importance to stop the drug immediately even while on adrenocorticosteroid treatment, if adverse skin reaction occurs. In conclusion, we have described a patient who developed hypersensitivity syndrome following ingestion of mexiletine. We propose that mexiletine be added to the list of drugs that can cause severe cutaneous drug reactions. Patients receiving mexiletine should be warned to stop taking this drug immediately, if skin eruption occurs.
Acknowledgements We thank Dr. Yukiko Nonaka for her help managing this patient and Ms. Sachiko Fujii and Ms. Yoshie Hirano for
99
secretarial assistance. Preparation of this article was supported by grant from the Ministry of Education, Science, Sports and Culture of Japan (Grants-in-Aid for General Scientific Research: No. 08671780).
References Avakian, R., Flowers, F.P., Araujo, O.E. and Ramos-Caro, F.A., Toxic epidermal necrolysis: a review, J. Am. Acad. Dermatol., 25 (1991) 69–79. Backonja, M.-M., Local anesthetics as adjuvant analgesics, J. Pain Symptom Manage., 9 (1994) 491–499. Campbell, N.P.S., Pantridge, J.F. and Adgey, A.A.J., Long-term oral antiarrhythmic therapy with mexiletine, Br. Heart J., 40 (1978) 796– 801. Dejgard, A., Petersen, P. and Kastrup, J., Mexiletine for treatment of chronic painful diabetic neuropathy, Lancet, 1 (1988) 9–11. Galer, B.S., Harle, J. and Rowbotham, M.C., Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study, J. Pain Symptom Manage., 12 (1996) 161– 167. Heger, J.J., Nattel, S., Rinkenberger, R.L. and Zipes, D.P., Mexiletine therapy in 15 patients with drug-resistant ventricular tachycardia, Am. J. Cardiol., 45 (1980) 627–632. Kikuchi, K., Tsunoda, T. and Tagami, H., Generalized drug eruption due to mexiletine hydrochloride: topical provocation on previously involved skin, Contact Dermatitis, 25 (1991) 70–72. McQuay, H., Carroll, D., Jadad, A.R., Wiffen, P. and Moore, A., Anticonvulsant drugs for management of pain: a systematic review, Br. Med. J., 311 (1995) 1047–1052. Monk, J.P. and Brogden, R.N., Mexiletine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias, Drugs, 40 (1990) 374–411. Murphy, J.M., Mashman, J., Miller, J.D. and Bell, J.B., Suppression of carbamazepine-induced rash with prednisone, Neurology, 41 (1991) 144–145. Pelekanos, J., Camfield, P., Camfield, C. and Gordon, K., Allergic rash due to antiepileptic drugs: clinical features and management, Epilepsia, 32 (1991) 554–559. Roujeau, J.C. and Stern, R.S., Severe adverse cutaneous reactions to drugs, N. Engl. J. Med., 331 (1994) 1972. Roujeau, J.-C., Kelly, J.P., Naldi, L., Rzany, B., Stern, R.S., Anderson, T., Auquier, A., Bastuji-Garin, S., Correia, O., Locati, F., Mockenhaupt, M., Paoletti, C., Shapiro, S., Shear, N., Schopf, E. and Kaufman, D.W., Medication use and the risk of Stevens–Johnson syndrome or toxic epidermal necrolysis, N. Engl. J. Med., 333 (1995) 1600–1607. Tanelian, D.L. and Brose, W.G., Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine, Anesthesiology, 74 (1991) 949–951.
Clinical note
Mexiletine-induced severe skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction Kazuo Higa*, Kazuhiko Hirata, Kenjiro Dan Department of Anesthesiology, School of Medicine, Fukuoka University, 45–1, 7-chome, Nanakuma, Jonan-ku, Fukuoka 814–80, Japan Received 28 December 1996; revised version received 5 May 1997; accepted 22 May 1997
Abstract A 64-year-old man developed a severe generalized pruritic morbilliform skin eruption, fever, eosinophilia, atypical lymphocytosis, and liver dysfunction 30 days after ingestion of mexiletine, a sodium channel blocker, prescribed to treat postherpetic neuralgia. Following intravenous dexamethasone, body temperature normalized the next day. However, the skin eruption did not disappear completely for 4 weeks. The patch test was positive for mexiletine. Clinical features and the result of patch test indicated that the patient developed hypersensitivity syndrome, a severe adverse cutaneous drug reaction, caused by mexiletine. We propose that mexiletine be added to the list of drugs that can cause severe adverse cutaneous drug reactions and that patients receiving mexiletine be warned to stop taking the drug immediately if a skin eruption occurs. 1997 International Association for the Study of Pain. Published by Elsevier Science B.V. Keywords: Adverse drug reaction; Hypersensitivity syndrome; Mexiletine; Postherpetic neuralgia
1. Introduction
2. Case report
Sodium channel blockers, such as carbamazepine and phenytoin, are effective for treating patients with neuropathic pain (McQuay et al., 1995). Intravenous lidocaine and oral mexiletine, a congener of lidocaine, have also been increasingly used for such purposes (Dejgard et al., 1988; Tanelian and Brose, 1991; Backonja, 1994; Galer et al., 1996). However, adverse drug reactions to these drugs can occur (Campbell et al., 1978; Monk and Brogden, 1990; Avakian et al., 1991; Pelekanos et al., 1991; Roujeau et al., 1995). Carbamazepine and phenytoin can cause severe skin eruptions, which can be fatal (Avakian et al., 1991; Pelekanos et al., 1991; Roujeau et al., 1995). Severe skin eruption due to mexiletine has apparently not been reported (Monk and Brogden, 1990; Roujeau and Stern, 1994). One of our patients developed severe skin eruption and fever, accompanied by eosinophilia, atypical lymphocytosis, and liver dysfunction, 30 days after starting ingestion of mexiletine.
A 64-year-old otherwise healthy man who had no previous drug reactions suffered from herpes zoster over the right third thoracic dermatome 34 months before a severe adverse drug reaction occurred. The pain persisted and was controlled with amitriptyline 125 mg at bed-time and alprazolam 0.4 mg, three times a day, from 28 months after the onset of herpes zoster. The pain worsened, as it got cooler and cooler at the start of winter, 33 months after the onset of herpes zoster. Mexiletine, 100 mg three times daily, was then added and the pain decreased. Generalized pruritic morbilliform skin eruption developed 30 days after the initiation of mexiletine, and this drug was withheld. Sore throat, cough, and excess sputum were noted, and the body temperature rose to 38.1°C 5 days later. Amitriptyline and alprazolam were then withheld. The morbilliform skin eruption became confluent to erythema, which was marked on the face and trunk, 8 days after the onset of the skin eruption. The body temperature was 38.3°C. There were no skin bullae, purpuras, erosions on the mucous membranes, lymphadenopathy, or arthralgia. The patient was admitted to Fukuoka University Hospital. Blood pressure was 120/90 mmHg, and pulse rate 90 beats/
* Corresponding author. Tel.: +81 92 8011011 ext. 3512; fax: +81 92 8656032; e-mail: [email protected]
0304-3959/97/$17.00 1997 International Association for the Study of Pain. Published by Elsevier Science B.V. PII S0304-3959 (97 )0 0066-3
98
K. Higa et al. / Pain 73 (1997) 97–99
min. Laboratory examination (Table 1) revealed hemoconcentration (hemoglobin, 19.0 g/dl), leukocytosis (28.8 × 103/mm3) with eosinophilia (10.5%) and atypical lymphocytosis (9.5%), liver dysfunction (total bilirubin, 3.7 mg/dl; aspartate aminotransferase, 242 IU/l; alanine aminotransferase, 317 IU/l; lactic dehydrogenase, 2246 IU/l), and markedly elevated C-reactive protein (13.2 mg/ dl). Intravenous fluid and dexamethasone 8 mg a day for 3 days were prescribed. The body temperature decreased to 36.8°C the next day. The erythema of the face and trunk did not worsen from the third hospital day. On the fourth hospital day, intravenous dexamethasone was changed to oral prednisolone 30 mg a day; thereafter, it was decreased to 20 mg a day for 2 days, and 10 mg a day for another day. The skin eruption on the face and trunk almost disappeared, and exfoliation was noted on the eleventh hospital day (20 days after the onset of the skin eruption). Laboratory investigation showed the presence of marked eosinophilia (eosinophils, 51.0%), although the indices of liver function showed improvement. The skin eruption disappeared completely 4 weeks after the onset. The patch test was positive for mexiletine, but negative for amitriptyline and alprazolam. He was not re-challenged with oral mexiletine. Since his postherpetic neuralgia worsened 4 weeks after the onset of the adverse drug reaction, amitriptyline was resumed and gradually increased to 75 mg at bed-time. The postherpetic neuralgia improved. There was no recurrence of the morbilliform skin eruption.
3. Discussion Severe adverse cutaneous reactions to drugs include toxic epidermal necrolysis, Stevens–Johnson syndrome, hypersensitivity syndrome, and small-vessel vasculitis (Roujeau and Stern, 1994). Toxic epidermal necrolysis is characterized by confluent erythema, skin detachment of more than
30% of body surface area, fever, leukocytopenia, and a mortality rate up to 30%. Clinical features of Stevens–Johnson syndrome consist of small blisters, purpuric macules, and skin detachment of less than 10% of body surface area. The mortality rate is less than 10%. Both toxic epidermal necrolysis and Stevens–Johnson syndrome involve mucous membranes, and respiratory and gastrointestinal tracts. Symptoms develop 1–3 weeks after initiation of causative drugs. Hypersensitivity syndrome is characterized by severe skin eruption, fever, eosinophilia, atypical lymphocytosis, liver dysfunction, lymphadenopathy, and arthralgia, and occurs 2–6 weeks after initiation of drugs. The mortality rate is around 10%. Drug-related small-vessel vasculitis causes palpable purpuras on the lower limbs, gastrointestinal disturbances, neuritis, fever, and glomerulonephritis and occurs 1–3 weeks after initiation of causative drugs. The mortality rate is less than 5% (Roujeau and Stern, 1994). Sodium channel blockers, such as carbamazepine, phenytoin and mexiletine, are used to treat neuropathic pain (Dejgard et al., 1988; Tanelian and Brose, 1991; Backonja, 1994; McQuay et al., 1995; Galer et al., 1996). Skin eruptions after carbamazepine and phenytoin are not uncommon (Murphy et al., 1991; Pelekanos et al., 1991). These usually occur 2–3 weeks after initiation of the drug and usually disappear after withdrawal of the drug, in most patients (Pelekanos et al., 1991). However, toxic epidermal necrolysis, Stevens–Johnson syndrome, and hypersensitivity syndrome can occur as severe adverse cutaneous reactions to both drugs (Avakian et al., 1991; Roujeau and Stern, 1994; Roujeau et al., 1995), albeit extremely rarely. A recent review on severe adverse cutaneous reactions to drugs did not mention mexiletine as a drug that can cause severe skin eruptions (Roujeau and Stern, 1994). We could not find any reports of hypersensitivity syndrome to mexiletine through Medline search. There have been only a few reports of skin eruptions after mexiletine ingestion (Heger et al., 1980; Kikuchi et al., 1991).
Table 1 Laboratory data Normal value
Days after skin eruption −30
Hb WBC Eosinophils (%) Atypical lymphocytes (%) Total bilirubin AST ALT LDH ALP GGP CRP
(13.4–17.6 g/dl) (3.9–9.8 × 103/mm3)
(0.2–1.2 mg/dl) (,40 IU/l) (,40 IU/l) (200–520 IU/l) (75–290 IU/l) (,60 IU/l) (mg/dl)
16.9 7.0 2 0 0.4 33 36 346 239 89 0.5
0 17.2 7.3 3 1.0 0.7 235 252 815 574 420 5.6
8 19.0 28.8 10.5 9.5 3.7 242 317 2246 1280 613 13.2
20
30
41
15.4 12.7 51.0 0 1.3 82 194 651 700 348 1.4
12.9 8.2 19.0 0 0.8 38 69 493 767 154 1.4
13.4 10.4 2 0 0.5 27 36 442 535 96 0.6
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; GGP, gamma-glutamyl transferase; Hb, hemoglobin; LDH, lactic dehydrogenase; WBC, white blood cells.
K. Higa et al. / Pain 73 (1997) 97–99
Heger et al. (1980) reported a patient who developed a macular, erythematous skin eruption on the face, trunk, and limbs 2 days after taking mexiletine; it disappeared several days after withdrawal of mexiletine. Kikuchi et al. (1991) described a 77-year-old man who developed a generalized pruritic erythematous skin eruption 45 days after administration of mexiletine. He was given prednisolone orally, and the skin eruption disappeared completely a month later. The patch test was positive for mexiletine. Whether or not the patient had fever, eosinophilia, or liver dysfunction was not stated. Our patient developed a generalized pruritic morbilliform skin eruption and fever, accompanied by eosinophilia, atypical lymphocytosis, and liver dysfunction, 30 days after initiation of mexiletine. Although lymphadenopathy or arthralgia was nil, the temporal relationship between initiation of mexiletine and the development of generalized skin eruption, the clinical features, and the results of patch test positive for mexiletine but negative for amitriptyline and alprazolam indicate that he had hypersensitivity syndrome caused by mexiletine. It has been stated that hypersensitivity syndrome to a drug can be suppressed by adrenocorticosteroids and that the drug can be continued under adrenocorticosteroid treatment, even in the presence of hypersensitivity syndrome, in some patients (Murphy et al., 1991). When our patient was given intravenous dexamethasone, body temperature normalized the next day. However, since there have been no controlled clinical studies concerning the efficacy of adrenocorticosteroids on hypersensitivity syndrome and the mortality of the syndrome is around 10% (Roujeau and Stern, 1994), it is of the utmost importance to stop the drug immediately even while on adrenocorticosteroid treatment, if adverse skin reaction occurs. In conclusion, we have described a patient who developed hypersensitivity syndrome following ingestion of mexiletine. We propose that mexiletine be added to the list of drugs that can cause severe cutaneous drug reactions. Patients receiving mexiletine should be warned to stop taking this drug immediately, if skin eruption occurs.
Acknowledgements We thank Dr. Yukiko Nonaka for her help managing this patient and Ms. Sachiko Fujii and Ms. Yoshie Hirano for
99
secretarial assistance. Preparation of this article was supported by grant from the Ministry of Education, Science, Sports and Culture of Japan (Grants-in-Aid for General Scientific Research: No. 08671780).
References Avakian, R., Flowers, F.P., Araujo, O.E. and Ramos-Caro, F.A., Toxic epidermal necrolysis: a review, J. Am. Acad. Dermatol., 25 (1991) 69–79. Backonja, M.-M., Local anesthetics as adjuvant analgesics, J. Pain Symptom Manage., 9 (1994) 491–499. Campbell, N.P.S., Pantridge, J.F. and Adgey, A.A.J., Long-term oral antiarrhythmic therapy with mexiletine, Br. Heart J., 40 (1978) 796– 801. Dejgard, A., Petersen, P. and Kastrup, J., Mexiletine for treatment of chronic painful diabetic neuropathy, Lancet, 1 (1988) 9–11. Galer, B.S., Harle, J. and Rowbotham, M.C., Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study, J. Pain Symptom Manage., 12 (1996) 161– 167. Heger, J.J., Nattel, S., Rinkenberger, R.L. and Zipes, D.P., Mexiletine therapy in 15 patients with drug-resistant ventricular tachycardia, Am. J. Cardiol., 45 (1980) 627–632. Kikuchi, K., Tsunoda, T. and Tagami, H., Generalized drug eruption due to mexiletine hydrochloride: topical provocation on previously involved skin, Contact Dermatitis, 25 (1991) 70–72. McQuay, H., Carroll, D., Jadad, A.R., Wiffen, P. and Moore, A., Anticonvulsant drugs for management of pain: a systematic review, Br. Med. J., 311 (1995) 1047–1052. Monk, J.P. and Brogden, R.N., Mexiletine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias, Drugs, 40 (1990) 374–411. Murphy, J.M., Mashman, J., Miller, J.D. and Bell, J.B., Suppression of carbamazepine-induced rash with prednisone, Neurology, 41 (1991) 144–145. Pelekanos, J., Camfield, P., Camfield, C. and Gordon, K., Allergic rash due to antiepileptic drugs: clinical features and management, Epilepsia, 32 (1991) 554–559. Roujeau, J.C. and Stern, R.S., Severe adverse cutaneous reactions to drugs, N. Engl. J. Med., 331 (1994) 1972. Roujeau, J.-C., Kelly, J.P., Naldi, L., Rzany, B., Stern, R.S., Anderson, T., Auquier, A., Bastuji-Garin, S., Correia, O., Locati, F., Mockenhaupt, M., Paoletti, C., Shapiro, S., Shear, N., Schopf, E. and Kaufman, D.W., Medication use and the risk of Stevens–Johnson syndrome or toxic epidermal necrolysis, N. Engl. J. Med., 333 (1995) 1600–1607. Tanelian, D.L. and Brose, W.G., Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine, Anesthesiology, 74 (1991) 949–951.