ABSTRACT
Tetrazepam is a benzodiazepine that is widely used in Spain as a muscle relaxant, with occasional cutaneous side effects. We report a patient who developed a generalized pruriginous cutaneous reaction compatible with acute generalized exanthematous pustulosis (AGEP) due to tetrazepam. Patch tests with bromazepam, diazepam, and tetrazepam were negative at 48 and 72 hours; however, the tetrazepam patch showed a positive reaction at 10 days. Immunohistochemical studies revealed a mononuclear infiltrate composed of CD4+ and CD8+ T lymphocytes. Analysis of interleukin (IL) 8 expression by quantitative polymerase chain reaction revealed increased IL-8 mRNA levels in patch test-positive skin. Lymphoblast transformation test (LTT) was positive with tetrazepam but not with diazepam. Positive patch test and LTT suggested that tetrazepam-specific lymphocytes might be responsible for a T cell-mediated reaction. These results support previous data suggesting an important role for IL-8 and drug-specific T cells in the pathogenesis ofAGEP and imply that the reaction was specific to tetrazepam with no cross-reactivity to other benzodiazepines.
Subject(s)
Benzodiazepines/adverse effects , Drug Eruptions , Drug Hypersensitivity/immunology , Erythema/chemically induced , Exanthema/chemically induced , Muscle Relaxants, Central/adverse effects , Arthralgia/drug therapy , Benzodiazepines/therapeutic use , Codeine/therapeutic use , Common Cold/drug therapy , Common Cold/immunology , Erythema/immunology , Exanthema/immunology , Female , Humans , Middle Aged , Muscle Relaxants, Central/therapeutic use , Skin TestsABSTRACT
BACKGROUND: Maculopapular exanthema has been reported to be the most frequently drug-induced cutaneous reaction. Although T lymphocytes are involved in the pathomechanism of this disease, little is know about the recruitment of these cells to the skin. OBJECTIVE: The aim of this work is to study the role of the chemokines TARC/CCL17 and MDC/CCL22 in the lymphocyte trafficking to affected skin in drug-induced exanthemas. METHODS: Real-time PCR was performed to quantify gene expression levels of CCL17, CCL22 and their receptor CCR4 in lesional skin biopsies and in peripheral blood mononuclear cells from patients. CCL27 and CCL22 proteins were detected in the skin by immunochemistry. Protein expression of CCR4 was determined by flow cytometry in peripheral blood lymphocytes. Functional migration assays to CCL17 and CCL22 were assessed to compare the migratory responses of peripheral blood lymphocytes from patients and healthy subjects. RESULTS: CCL17 and CCL22 were up-regulated in maculopapular exanthema-affected skin. CCR4 mRNA levels and protein expression were increased in peripheral blood mononuclear cells during the acute phase of the disease. The increased expression of the receptor was consistent with a higher response of peripheral blood lymphocytes to CCL17 and CCL22 compared with the migratory response in healthy donors. CONCLUSION: TARC/CCL17 and MDC/CCL22 might cooperate in attracting T lymphocytes to skin in drug-induced maculopapular exanthemas.
