Correspondence
Case 26-1996: Hypersensitivity to Carbamazepine
N Engl J Med 1997; 336:376-377January 30, 1997
- Article
To the Editor:
In his discussion of the differential diagnosis of Case 26-1996 (Aug. 22 issue),1 Gorlin states that “neurocysticercosis (infection with tapeworm after the ingestion of raw pork) should be considered, despite the parents' statement that the boy had not eaten raw meat.” The concept that neurocysticercosis is acquired through the ingestion of raw pork is erroneous and frequently leads many physicians away from the diagnosis in the absence of this history. Ingestion of raw or poorly cooked pork results only in intestinal infection with the adult Taenia solium tapeworm, not in neurocysticercosis.2 Neurocysticercosis is defined as infection with the larval stage of T. solium and is acquired through the ingestion of the embryonated eggs of the tapeworm from fecally contaminated food or water. Once the eggs hatch in the small intestine, the larvae migrate throughout the body and form cysticerci in tissues such as the brain, muscle, and eye. Although it is possible for people with adult tapeworms to inoculate themselves, the ingestion of pork is not necessary for the development of neurocysticercosis.
Gorlin also states that most patients with neurocysticercosis have elevated eosinophil counts in the cerebrospinal fluid. This has not been the experience in most large series of cases of neurocysticercosis, with eosinophils occurring in cerebrospinal fluid in only 20 percent of cases or fewer.3,4 Cerebrospinal fluid eosinophilia is typically seen only when the cysticerci are adjacent to the meninges or ventricles. Sotelo et al. reported that of 358 patients with exclusively parenchymal lesions, only 4 percent had cerebrospinal fluid eosinophils.5
5 ReferencesDavid C. Waagner, M.D.
Texas Tech University Health Sciences Center, Lubbock, TX 794301
Case Records of the Massachusetts General Hospital (Case 26-1996)
Full Text | Web of Science | Medline2
Katz M, Despommier DD, Gwadz RW. Parasitic diseases. 2nd ed. New York: Springer-Verlag, 1989:70-81.
3
McCormick GF ,Zee CS ,Heiden J . Cysticercosis cerebri -- review of 127 cases. Arch Neurol 1982;39:534-539
Web of Science | Medline4
Nash TE ,Neva FA . Recent advances in the diagnosis and treatment of cerebral cysticercosis. N Engl J Med 1984;311:1492-1496
Full Text | Web of Science | Medline5
Sotelo J ,Guerrero V ,Rubio F . Neurocysticercosis: a new classification based on active and inactive forms: a study of 753 cases. Arch Intern Med 1985;145:442-445
CrossRef | Web of Science | Medline
To the Editor:
A person with neurocysticercosis may not have been exposed to pork at all, as was recently exemplified by a report of neurocysticercosis in several members of an Orthodox Jewish community in New York City.1 The main risk factor for infection in most of these patients was contact with persons infected with the pork tapeworm T. solium.
1 ReferencesKlaus E. Mönkemüller, M.D.
University of Alabama at Birmingham, Birmingham, AL 35294-0007J. Howard Jaster, M.D.
University of Tennessee, Memphis, TN 381631
Schantz PM ,Moore AC ,Munoz JL , et al. Neurocysticercosis in an Orthodox Jewish community in New York City. N Engl J Med 1992;327:692-695
Full Text | Web of Science | Medline
To the Editor:
Gorlin provided an excellent summary of the biology and pathophysiology of eosinophils. However, we noted an oversimplification concerning the diurnal variation of peripheral-blood eosinophil counts. Gorlin states that “a diurnal variation has been noted, with higher counts in the morning.” The accepted view of the diurnal variation of peripheral-blood eosinophil counts is that the number is greatest at night during sleep, decreases throughout the morning, and then rises in midafternoon.1 The best and largest study of this phenomenon was performed by Rud,2 and the majority of subsequent studies agree with these findings.1,3 The way we remember the pattern of this phenomenon is by recalling that the administration of glucocorticoids causes a fall in peripheral-blood eosinophil counts 4 and that the count varies inversely with the diurnal variation of blood cortisol levels.
4 ReferencesAaron M. Levy, M.D.
Gerald J. Gleich, M.D.
Mayo Clinic, Rochester, MN 559051
Numbers in blood and marrow. In: Beeson PB, Bass DA, eds. The eosinophil. Vol. 14 of Major problems in internal medicine. Philadelphia: W.B. Saunders, 1977:10-4.
2
Rud F . The eosinophil count in health and in mental disease: a biometrical study. Acta Psychiatr Neurol Suppl 1947;40:1-4433
Winkel P ,Statland BE ,Saunders AM ,Osborn H ,Kupperman H . Within-day physiologic variation of leukocyte types in healthy subjects as assayed by two automated leukocyte differential analyzers. Am J Clin Pathol 1981;75:693-700
Web of Science | Medline4
Butterfield JH, Gleich GJ. Anti-inflammatory effects of glucocorticoids on eosinophils and neutrophils. In: Schleimer RP, Claman HN, Oronsky AL, eds. Anti-inflammatory steroid action: basic and clinical aspects. San Diego: Academic Press, 1989:151-98.
To the Editor:
Gorlin thought that hypersensitivity to carbamazepine was an unlikely possibility in Case 26-1996 because the symptoms progressed after the anticonvulsant therapy had been discontinued. However, it is not unusual for hypersensitivity syndromes to persist for several weeks after treatment has stopped1,2 (and unpublished data).
Gorlin emphasized the clinical similarities between acute Epstein–Barr virus infection and the hypersensitivity syndrome — namely, the occurrence of rashes, lymph-node enlargement, and hepatosplenomegaly. The immune reactions are also similar. In both diseases, activated lymphocytes can be found in the circulation. Like replicating viruses, drugs such as penicillins, phenytoin, carbamazepine, and sulfamethoxazole stimulate both major T-cell subgroups, and drug-specific T-cell clones (CD4+ or CD8+) may be generated.3,4 Thus, it is possible to detect a carbamazepine-specific immune reaction in patients with a hypersensitivity syndrome,2,3 a finding that might have supported the purely clinical diagnosis in the patient described.
A further similarity is the oligoclonality of the T-cell response (the use of only certain Vβ genes of the T-cell receptor). Drug-specific T-cell responses as well as the immune response in acute infection with Epstein–Barr virus or human immunodeficiency virus can be oligoclonal.3-5 The prominent eosinophilia, however, is a feature of drug allergy, but not of Epstein–Barr virus infections. Thus, it is of particular interest that drug-specific T cells in vitro secrete an unusually high amount of interleukin-5, which is the chief cytokine involved in the maturation of eosinophils.3
5 ReferencesWerner J. Pichler, M.D.
Benno Schnyder, M.D.
Martin Zanni, M.Sc.
University of Bern, CH-3010 Bern, Switzerland1
Vittorio CC ,Muglia JJ . Anticonvulsant hypersensitivity syndrome. Arch Intern Med 1995;155:2285-2289
CrossRef | Web of Science | Medline2
De Vriese AS ,Philippe J ,Van Renterghem DM , et al. Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature. Medicine (Baltimore) 1995;74:144-151
CrossRef | Web of Science | Medline3
Mauri-Hellweg D ,Bettens F ,Mauri D ,Brander C ,Hunziker T ,Pichler WJ . Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine. J Immunol 1995;155:462-472
Web of Science | Medline4
Mauri-Hellweg D ,Zanni M ,Frei E , et al. Cross-reactivity of T cell lines and clones to β-lactam antibiotics. J Immunol 1996;157:1071-1079
Web of Science | Medline5
Pichler WJ ,Mauri-Hellweg D ,Baumann K ,Bettens F . Selective expression of T-cell receptor-V β in acute infectious mononucleosis. Arch Intern Med 1995;155:1555-1556
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Gorlin replies:
To the Editor: I am grateful to Drs. Levy and Gleich for their clarification of the exact nature and origin of the diurnal cycle of the peripheral-blood eosinophil concentration. I want to credit Dr. Gleich as the source of the observation about the eosinophilic ramifications of therapy with granulocyte–macrophage colony-stimulating factor.
Drs. Mönkemüller and Jaster and Dr. Waagner provide several salient references documenting that neurocysticercosis follows the ingestion of T. solium eggs, not the intact tapeworm, and hence, clinical cases typically result from contamination by an infected food-handler with poor hygiene. Therefore, my admonition that the absence of the ingestion of raw pork does not rule out neurocysticercosis is correct. Nonetheless, I apologize for contributing to the confusion about the different pathways for contracting intestinal as opposed to central nervous system disease. The infectious-disease manual of the American Academy of Pediatrics distinguishes taeniasis from cysticercosis.1 The former is acquired from raw beef or pork, produces intestinal infection, and hence, may yield a positive test for ova and parasites. The latter, when it results in neurocysticercosis, must be diagnosed by computed tomography or some other method of neuroimaging.
Pichler and colleagues alert us to the potential for laboratory-based confirmation (by the demonstration of a T-cell clonal response to the drug) of the clinical diagnosis of hypersensitivity to carbamazepine. Unfortunately, such testing is beyond the spectrum of clinically available tests, even at a research-oriented institution. It would be useful to establish laboratory evidence to confirm the diagnosis of hypersensitivity to carbamazepine. As it stands, in the case I discussed, both the child's “meningoencephalitis” — the seizure and fever that were the presenting symptoms — and the drug sensitivity are diagnoses of exclusion.
1 ReferencesJed B. Gorlin, M.D.
Children's Hospital, Boston, MA 02115
