Codeine phosphate-induced hypersensitivity syndrome

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.