Correspondence

Carbamazepine and Fatal Eosinophilic Myocarditis

N Engl J Med 1997; 336:878-879March 20, 1997

Article

To the Editor:

We describe a 13-year-old boy with attention deficit–hyperactivity disorder in whom fever, rash, conjunctivitis, hepatitis, myocarditis, and eosinophilia developed and who died about two months after the start of carbamazepine therapy. The cardiopulmonary resuscitation (CPR) of this patient was reported in an article on transvenous right ventricular pacing during CPR in children with acute cardiomyopathy.1

The child was an inpatient on a psychiatric unit. His carbamazepine treatment (100 mg twice a day) was initiated for aggressive and impulsive behavior after he did not respond to methylphenidate and clonidine. The carbamaz-epine dose was gradually increased to 800 mg per day, which produced a therapeutic serum level of 9.4 mg per liter. Eosinophilia was first noted 17 days after the start of this treatment. Twenty-six days later, fever, rash, and nonexudative conjunctivitis were noted. A throat culture revealed group A streptococcus; oral penicillin was prescribed. However, the fever persisted, and on the eighth day of fever there was back pain and facial edema. The following day, the patient's temperature peaked at 40.3°C. He had a diffuse, erythematous, papular–miliary rash with palmar erythema, a strawberry tongue, and injected conjunctivae. His white-cell count was 20,400 per cubic millimeter, with 29 percent eosinophils. The aspartate aminotransferase level was 257 U per liter, and the creatine kinase level 7880 U per liter (the CK-MB fraction was 8.8 percent). Chest pain developed the following day, and the patient was admitted to the pediatric intensive care unit. Carbamazepine was discontinued. He had tachycardia, tachypnea, and hepatomegaly. Electrocardiography and 24-hour Holter monitoring showed ventricular tachycardia with frequent multiform ventricular ectopy. Echocardi-ography revealed decreased ventricular function, with a left ventricular shortening fraction of 25 percent. The following day the patient died from uncontrollable dysrhythmias.

At autopsy, examination of the myocardium showed severe eosinophilic myocarditis (Figure 1Figure 1Section of the Patient's Myocardium, Showing Diffuse Interstitial Infiltration by Eosinophils (Hematoxylin and Eosin, ×250; Inset, ×1000).). Viral cultures from the myocardium, spleen, and lymph nodes were negative. An antistreptolysin O titer was 166 Todd units (a titer above 200 is considered abnormal). No antinuclear antibodies were detected.

Hypersensitivity to carbamazepine has been well described.2 When it involves the myocardium, as in this patient, myocyte necrosis can be widespread and the outcome fatal. In a patient treated with phenytoin and carbamazepine, eosinophilic myocarditis was ascribed to phenytoin.3 Our patient had a hypersensitivity reaction to carbamazepine that initially mimicked scarlet fever. Fever, rash, and eosinophilia occurring weeks after the start of carbamazepine therapy should alert physicians to this diagnosis, and myocarditis should be considered a possible complication.

Mark B. Salzman, M.D.
Kaiser Permanente West Los Angeles Medical Center, Los Angeles, CA 90034

Elsa Valderrama, M.D.
Sunil K. Sood, M.D.
Schneider Children's Hospital, New Hyde Park, NY 11042

3 References

1. 1

   Greissman A, Silver P, Nimkoff L, Sagy M. Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy. Pediatr Emerg Care 1995;11:17-19
   CrossRef | Web of Science | Medline

2. 2

   Vittorio CC, Muglia JJ. Anticonvulsant hypersensitivity syndrome. Arch Intern Med 1995;155:2285-2290
   CrossRef | Web of Science | Medline

3. 3

   Taliercio CP, Olney BA, Lie JT. Myocarditis related to drug hypersensitivity. Mayo Clin Proc 1985;60:463-468
   Web of Science | Medline

Citing Articles (12)

Citing Articles

1. 1

   Nebojsa Arsenovic, Loraine Sheehan, David Clark, Ricardo Moreira. (2010) Fatal carbamazepine induced fulminant eosinophilic (hypersensitivity) myocarditis: Emphasis on anatomical and histological characteristics, mechanisms and genetics of drug hypersensitivity and differential diagnosis. Journal of Forensic and Legal Medicine 17:2, 57-61
   CrossRef

2. 2

   Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Rosenberg, Eric S., Cort, Alice M., Ebeling, Sally H.Peters, Christine C., Sabatine, Marc S., Poh, Kian-Keong, Mega, Jessica L., Shepard, Jo-Anne O., Stone, James R., Frosch, Matthew P., . (2007) Case 36-2007. New England Journal of Medicine 357:21, 2167-2178
   Full Text

3. 3

   Neil Archibald, Bryan Yates, Desmond Murphy, Fiona Black, James Lordan, John Dark, Paul A. Corris. (2006) Carbamazepine-induced interstitial pneumonitis in a lung transplant patient. Respiratory Medicine 100:9, 1660-1662
   CrossRef

4. 4

   Ugur Gonlugur, Tanseli Efeoglu Gonlugur. (2006) Non-allergic Eosinophilic Inflammation. Immunological Investigations 35:1, 29-45
   CrossRef

5. 5

   Julia Valencak, Susana Ortiz-Urda, Elisabeth Heere-Ress, Rainer Kunstfeld, Wolfgang Base. (2004) Carbamazepine-induced DRESS syndrome with recurrent fever and exanthema. International Journal of Dermatology 43:1, 51-54
   CrossRef

6. 6

   Reiko Ito, Takuma Sakon, Kiyoshi Yasui, Mari Iwamoto, Yukoh Aihara. (2003) Usefulness of eosinophilic cationic protein as a marker of eosinophilic myocarditis in a child. Allergology International 52:4, 219-224
   CrossRef

7. 7

   Finella Brito-Babapulle. (2003) The eosinophilias, including the idiopathic hypereosinophilic syndrome. British Journal of Haematology 121:2, 203-223
   CrossRef

8. 8

   Alvin M. Sanico, Hirohito Kita, Kristin M. Leiferman, Sarbjit S. Saini. (1999) Eosinophilia in a 23-year-old woman with asthma. Annals of Allergy, Asthma & Immunology 83:3, 193-199
   CrossRef

9. 9

   Mark R. Haase. (1999) Carbamazepine-Induced Hepatorenal Failure in a Child. Pharmacotherapy 19:5, 667-671
   CrossRef

10. 10

    A MORKUNAS, M MILLER. (1997) ANTICONVULSANT HYPERSENSITIVITY SYNDROME. Critical Care Clinics 13:4, 727-739
    CrossRef

11. 11

    F. Brito-Babapulle. (1997) Clonal eosinophilic disorders and the hypereosinophilic syndrome. Blood Reviews 11:3, 129-145
    CrossRef

12. 12

    &NA;. (1997) Carbamazepine. Reactions Weekly &NA;:644, 5
    CrossRef