QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Enomoto, M. Articles by Yamane, T. Search for Related Content PubMed PubMed Citation Articles by Enomoto, M. Articles by Yamane, T.

Codeine Phosphate–Induced Hypersensitivity Syndrome

Fellow, Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, Osaka, Japan

Masahiro Ochi, MD

Resident, Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School

Kayoko Teramae, MD

Assistant Professor, Department of Dermatology, Graduate School of Medicine, Osaka City University Medical School

Riei Kamo, MD

Assistant Professor, Department of Dermatology, Graduate School of Medicine, Osaka City University Medical School

Shinichi Taguchi, MD

Fellow, Division of Critical Care Medicine, Graduate School of Medicine, Osaka City University Medical School

Takahisa Yamane, MD

Associate Professor, Department of Clinical Hematology, Graduate School of Medicine, Osaka City University Medical School

Reprints: Masaru Enomoto MD, Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan, fax 81-6-6645-3813, enomoto-m{at}med.osaka-cu.ac.jp

OBJECTIVE: To report a case of drug-induced hypersensitivity syndrome related to codeine phosphate.

CASE SUMMARY: A 19-year-old Japanese man was prescribed codeine phosphate 10 mg 3 times daily and several other drugs for cold symptoms. About 20 days later, an erythematous, maculopapular rash appeared and progressed to erythroderma; a spiking fever also developed. He had splenomegaly and generalized lymphadenopathy on admission. Laboratory examinations showed atypical lymphocytosis, eosinophilia, and increased liver enzyme values. The platelet count slowly decreased after admission. The increased numbers of megakaryocytes in bone marrow and platelet-associated immunoglobulin (Ig) G antibodies in serum were compatible with a diagnosis of immune thrombocytopenic purpura. A significant increase in IgG antibodies to human herpesvirus 6 (HHV6) and transient viremia were helpful in diagnosing hypersensitivity syndrome. The results of patch tests were positive for codeine phosphate. An objective causality assessment revealed that an adverse drug event was probable.

DISCUSSION: Codeine is an opioid analgesic. Severe adverse cutaneous reactions rarely occur. As of March 3, 2004, our case is, to our knowledge, the first report of hypersensitivity syndrome attributed to codeine phosphate. Drug-induced hypersensitivity syndrome is an acute, potentially life-threatening, idiosyncratic adverse reaction caused mainly by aromatic anticonvulsants. It is characterized by the triad of fever, skin rash, and internal organ involvement. Reactivation of HHV6 is involved in the pathogenesis of this syndrome and may have also caused the immune thrombocytopenic purpura in our patient.

CONCLUSIONS: Codeine phosphate may rarely be associated with hypersensitivity syndrome. Clinicians should be aware that the potentially fatal syndrome can be caused by various drugs.

Key Words: codeine phosphate, human herpesvirus 6, hypersensitivity, immune thrombocytopenic purpura

Published Online, March 9, 2004. www.theannals.com, DOI 10.1345/aph.1D528