American Journal of Therapeutics 23, e944–e946 (2016)
Rare Red Rashes: A Case Report of Levetiracetam-Induced Cutaneous Reaction and Review of the Literature Ryan T. Jones, BS,1* William Evans, PharmD,2 Tracey L. Mersfelder, PharmD, BCPS,3 and Kevin Kavanaugh, MD4
Cutaneous reactions secondary to medications are rare but can be serious events resulting in morbidity and mortality and can be caused by anticonvulsant medications. Levetiracetam has been considered relatively safe compared with other antiepileptics with regard to skin eruptions. We report a case of a cutaneous reaction secondary to levetiracetam. A 64-year-old man presented to the hospital with an altered mental status and aphasia. Imaging revealed a left basal ganglia mass. A biopsy of the lesion was obtained, and levetiracetam was started at 500 mg intravenously twice a day for seizure prophylaxis. After 13 doses, the patient developed a diffuse, erythematous, warm, blanching, morbilliform rash. Levetiracetam was discontinued, and methylprednisolone was started. After 4 days, the rash dissipated. Levetiracetam is an antiepileptic medication that has an unknown mechanism of action. To date, there are only 4 cases reported involving skin reactions from levetiracetam. Two of the cases were classified as Stevens–Johnson Syndrome: 1 as toxic epidermal necrolysis and 1 as erythema multiforme. Our case was classified as a morbilliform rash. A Naranjo score of 7 suggested a probable cause for a levetiracetam-induced skin reaction. Antiepileptic medications are used in certain cases to prevent seizures in patients with central nervous system tumors. Although levetiracetam seems to have fewer side effects than the traditional antiepileptic medications, it is important for the healthcare provider to continuously evaluate the need for all medications and discontinue unneeded ones to help avoid potential medication adverse effects. Keywords: levetiracetam, morbilliform, drug-induced rash, anticonvulsant reaction
INTRODUCTION Cutaneous reactions secondary to medications are rare but can be serious events resulting in morbidity and mortality. Anticonvulsant medications have been implicated in these reactions, and their effects range from erythema to more severe events such as
1
College of Osteopathic Medicine, Michigan State University, East Lansing, MI; 2College of Pharmacy, Ferris State University, Big Rapids, MI; 3College of Pharmacy, Ferris State University, Big Rapids, MI; and 4Department of Internal Medicine, Western Michigan University School of Medicine, Kalamazoo, MI. The authors have no conflicts of interest to declare. *Address for correspondence: 1000 Oakland Drive, Kalamazoo, MI 49008. E-mail: [email protected]
Stevens–Johnson syndrome and toxic epidermal necrolysis.1 Levetiracetam has been considered relatively safe compared with other antiepileptic medications with regard to skin eruptions. We report a case of a cutaneous reaction secondary to levetiracetam.
CASE REPORT A 64-year-old man presented to the hospital with an altered mental status and aphasia (Figures 1, 2). On evaluation in the emergency department, imaging revealed a left basal ganglia mass. Admission vital signs and pertinent laboratory data included the following: blood pressure, 132/82 mm Hg; heart rate, 76/min; respiratory rate, 16/min; white blood cells count, 5 3 109 per liter; procalcitonin, ,0.05 pg/mL; asparate aminotransferase, 21 U/L; alanine
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e945
Rare Red Rashes
values remained within normal limits. Apart from the rash described, the physical examination was negative for corneal ulcerations, oral cavity ulcerations or lesions, and there was no angioedema. Levetiracetam was discontinued, and methylprednisolone 125 mg intravenously every 8 hours was started. After 4 days, the rash dissipated, and methylprednisolone was changed to oral dexamethasone as part of his chemotherapy regimen.
DISCUSSION FIGURE 1. View of rash at anterior thorax.
aminotransferase, 17 U/L; and alkaline phosphatase, 46 U/L. The patient was admitted to the hospital with a neurosurgery consult. A biopsy of the lesion was obtained, and levetiracetam was started at 500 mg intravenously twice a day for seizure prophylaxis. The biopsy revealed diffuse large B-cell lymphoma and positive Epstein–Barr virus. The patient was seropositive for cytomegalovirus and was diagnosed with new-onset HIV-1 with a CD4 count of 64. After 13 doses of levetiracetam, the patient had a diffuse, erythematous, warm, blanching, morbilliform rash (Figures 1, 2). The vital signs, upon the discovery of the rash, showed a temperature of 38.7°C and a normal blood pressure and heart rate. Laboratory data showed a white blood cells count of 8.4 3 109 per liter, alanine aminotransferase increase to 64 U/L, and peripheral eosinophils had a minor increase to 3 3 109 per liter. Other current medications the patient was receiving at the time were dexamethasone, docusate/senna, and pantoprazole. All other
Levetiracetam is an antiepileptic medication that has an unknown mechanism of action but is believed to inhibit burst firing, thereby preventing propagation of seizure activity.2 Antiepileptic medications have been reported in the literature to result in cutaneous reactions; however, these cases reports rarely involve levetiracetam.1 To date, there are only 4 cases reported involving skin reactions and levetiracetam.3–5 Two of the cases were classified as Stevens–Johnson syndrome, 1 as toxic epidermal necrolysis, and 1 as erythema multiforme. The Naranjo score when provided for these cases was a 3, which suggested a possible correlation. The day of rash onset ranged from 9 to 26 days. The doses were only provided in 2 of the cases and were 1000 mg/d in one case and a recent increase to 30 mg$kg21$d21 in a second case. In our case, the onset of the rash was after only 7 days but was at a dose of 1000 mg/d. Similar to our case, one of the patients reported was HIV positive. Patients with HIV may have an increased risk of cutaneous drug reactions, which could have contributed to this adverse event.6 Other potential causes of the skin rash included the fact that our patient was positive for Epstein–Barr virus and cytomegalovirus.7,8 Because of the temporal association of the onset of the rash with the initiation of the medication, this makes it less likely. A Naranjo score was calculated to be 7, which suggests levetiracetam as being a probable cause for the skin reaction.9
CONCLUSIONS
FIGURE 2. Posterior view of rash. www.americantherapeutics.com
Antiepileptic medications are used in certain cases to prevent seizures in patients with CNS tumors. Even though levetiracetam seems to have fewer side effects including fewer reports of cutaneous reactions than the traditional antiepileptic medications, it is important for the healthcare provider to continuously evaluate the need for all medications and discontinue unneeded ones to help avoid potential medication adverse reactions. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e946
REFERENCES 1. Herbert AA, Ralston JP. Cutaneous reactions to anticonvulsant medications. J Clin Psychiatry. 2001;62(Suppl 14): 22–26. 2. Keppra [package insert]. Smyrna, GA: UCB, Inc; 2009. 3. Duong TA, Haddad C, Valeyrie-Allanore L, et al. Levetiracetam: a possible new inducer of toxic epidermal necrolysis and Stevens-Johnson syndrome in 2 cases. JAMA Dermatol. 2013;149:113–115. 4. Zou LP, Ding CH, Song ZJ, et al. Stevens-Johnson syndrome induced by levetiracetam. Seizure. 2012;21: 823–825.
American Journal of Therapeutics (2016) 23(3)
Jones et al 5. Yesilova Y, Turan E, Sonmez A, et al. A case of erythema multiforme developing after levetiracetam therapy. Dermatol Online J. 2013;19(2):12. 6. Coopman SA, Johnson RA, Platt R, et al. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328:1670–1674. 7. Lernia VD, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Derm. 2013;52:1177–1184. 8. Vitiello M, Echeverria B, Elgart G, et al. Erythema multiforme major associated with CMV infection in an immunocompetent patient. J Cutan Med Surg. 2011;15:115–117. 9. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Rare Red Rashes: A Case Report of Levetiracetam-Induced Cutaneous Reaction and Review of the Literature Ryan T. Jones, BS,1* William Evans, PharmD,2 Tracey L. Mersfelder, PharmD, BCPS,3 and Kevin Kavanaugh, MD4
Cutaneous reactions secondary to medications are rare but can be serious events resulting in morbidity and mortality and can be caused by anticonvulsant medications. Levetiracetam has been considered relatively safe compared with other antiepileptics with regard to skin eruptions. We report a case of a cutaneous reaction secondary to levetiracetam. A 64-year-old man presented to the hospital with an altered mental status and aphasia. Imaging revealed a left basal ganglia mass. A biopsy of the lesion was obtained, and levetiracetam was started at 500 mg intravenously twice a day for seizure prophylaxis. After 13 doses, the patient developed a diffuse, erythematous, warm, blanching, morbilliform rash. Levetiracetam was discontinued, and methylprednisolone was started. After 4 days, the rash dissipated. Levetiracetam is an antiepileptic medication that has an unknown mechanism of action. To date, there are only 4 cases reported involving skin reactions from levetiracetam. Two of the cases were classified as Stevens–Johnson Syndrome: 1 as toxic epidermal necrolysis and 1 as erythema multiforme. Our case was classified as a morbilliform rash. A Naranjo score of 7 suggested a probable cause for a levetiracetam-induced skin reaction. Antiepileptic medications are used in certain cases to prevent seizures in patients with central nervous system tumors. Although levetiracetam seems to have fewer side effects than the traditional antiepileptic medications, it is important for the healthcare provider to continuously evaluate the need for all medications and discontinue unneeded ones to help avoid potential medication adverse effects. Keywords: levetiracetam, morbilliform, drug-induced rash, anticonvulsant reaction
INTRODUCTION Cutaneous reactions secondary to medications are rare but can be serious events resulting in morbidity and mortality. Anticonvulsant medications have been implicated in these reactions, and their effects range from erythema to more severe events such as
1
College of Osteopathic Medicine, Michigan State University, East Lansing, MI; 2College of Pharmacy, Ferris State University, Big Rapids, MI; 3College of Pharmacy, Ferris State University, Big Rapids, MI; and 4Department of Internal Medicine, Western Michigan University School of Medicine, Kalamazoo, MI. The authors have no conflicts of interest to declare. *Address for correspondence: 1000 Oakland Drive, Kalamazoo, MI 49008. E-mail: [email protected]
Stevens–Johnson syndrome and toxic epidermal necrolysis.1 Levetiracetam has been considered relatively safe compared with other antiepileptic medications with regard to skin eruptions. We report a case of a cutaneous reaction secondary to levetiracetam.
CASE REPORT A 64-year-old man presented to the hospital with an altered mental status and aphasia (Figures 1, 2). On evaluation in the emergency department, imaging revealed a left basal ganglia mass. Admission vital signs and pertinent laboratory data included the following: blood pressure, 132/82 mm Hg; heart rate, 76/min; respiratory rate, 16/min; white blood cells count, 5 3 109 per liter; procalcitonin, ,0.05 pg/mL; asparate aminotransferase, 21 U/L; alanine
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e945
Rare Red Rashes
values remained within normal limits. Apart from the rash described, the physical examination was negative for corneal ulcerations, oral cavity ulcerations or lesions, and there was no angioedema. Levetiracetam was discontinued, and methylprednisolone 125 mg intravenously every 8 hours was started. After 4 days, the rash dissipated, and methylprednisolone was changed to oral dexamethasone as part of his chemotherapy regimen.
DISCUSSION FIGURE 1. View of rash at anterior thorax.
aminotransferase, 17 U/L; and alkaline phosphatase, 46 U/L. The patient was admitted to the hospital with a neurosurgery consult. A biopsy of the lesion was obtained, and levetiracetam was started at 500 mg intravenously twice a day for seizure prophylaxis. The biopsy revealed diffuse large B-cell lymphoma and positive Epstein–Barr virus. The patient was seropositive for cytomegalovirus and was diagnosed with new-onset HIV-1 with a CD4 count of 64. After 13 doses of levetiracetam, the patient had a diffuse, erythematous, warm, blanching, morbilliform rash (Figures 1, 2). The vital signs, upon the discovery of the rash, showed a temperature of 38.7°C and a normal blood pressure and heart rate. Laboratory data showed a white blood cells count of 8.4 3 109 per liter, alanine aminotransferase increase to 64 U/L, and peripheral eosinophils had a minor increase to 3 3 109 per liter. Other current medications the patient was receiving at the time were dexamethasone, docusate/senna, and pantoprazole. All other
Levetiracetam is an antiepileptic medication that has an unknown mechanism of action but is believed to inhibit burst firing, thereby preventing propagation of seizure activity.2 Antiepileptic medications have been reported in the literature to result in cutaneous reactions; however, these cases reports rarely involve levetiracetam.1 To date, there are only 4 cases reported involving skin reactions and levetiracetam.3–5 Two of the cases were classified as Stevens–Johnson syndrome, 1 as toxic epidermal necrolysis, and 1 as erythema multiforme. The Naranjo score when provided for these cases was a 3, which suggested a possible correlation. The day of rash onset ranged from 9 to 26 days. The doses were only provided in 2 of the cases and were 1000 mg/d in one case and a recent increase to 30 mg$kg21$d21 in a second case. In our case, the onset of the rash was after only 7 days but was at a dose of 1000 mg/d. Similar to our case, one of the patients reported was HIV positive. Patients with HIV may have an increased risk of cutaneous drug reactions, which could have contributed to this adverse event.6 Other potential causes of the skin rash included the fact that our patient was positive for Epstein–Barr virus and cytomegalovirus.7,8 Because of the temporal association of the onset of the rash with the initiation of the medication, this makes it less likely. A Naranjo score was calculated to be 7, which suggests levetiracetam as being a probable cause for the skin reaction.9
CONCLUSIONS
FIGURE 2. Posterior view of rash. www.americantherapeutics.com
Antiepileptic medications are used in certain cases to prevent seizures in patients with CNS tumors. Even though levetiracetam seems to have fewer side effects including fewer reports of cutaneous reactions than the traditional antiepileptic medications, it is important for the healthcare provider to continuously evaluate the need for all medications and discontinue unneeded ones to help avoid potential medication adverse reactions. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e946
REFERENCES 1. Herbert AA, Ralston JP. Cutaneous reactions to anticonvulsant medications. J Clin Psychiatry. 2001;62(Suppl 14): 22–26. 2. Keppra [package insert]. Smyrna, GA: UCB, Inc; 2009. 3. Duong TA, Haddad C, Valeyrie-Allanore L, et al. Levetiracetam: a possible new inducer of toxic epidermal necrolysis and Stevens-Johnson syndrome in 2 cases. JAMA Dermatol. 2013;149:113–115. 4. Zou LP, Ding CH, Song ZJ, et al. Stevens-Johnson syndrome induced by levetiracetam. Seizure. 2012;21: 823–825.
American Journal of Therapeutics (2016) 23(3)
Jones et al 5. Yesilova Y, Turan E, Sonmez A, et al. A case of erythema multiforme developing after levetiracetam therapy. Dermatol Online J. 2013;19(2):12. 6. Coopman SA, Johnson RA, Platt R, et al. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;328:1670–1674. 7. Lernia VD, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Derm. 2013;52:1177–1184. 8. Vitiello M, Echeverria B, Elgart G, et al. Erythema multiforme major associated with CMV infection in an immunocompetent patient. J Cutan Med Surg. 2011;15:115–117. 9. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
