Apoptosis in ibuprofen-induced Stevens–Johnson syndrome

doi:10.1016/j.trsl.2006.12.005

Translational Research

Volume 149, Issue 5, May 2007, Pages 254-259

https://doi.org/10.1016/j.trsl.2006.12.005 Get rights and content

Cytokines play a role in the immunopathological and molecular mechanisms of drug-induced hypersensitivity reactions (HSR). The objective of the current report was to analyze the reliability and correlation between the clinical symptoms observed in a patient that presented an ibuprofen-induced Stevens–Johnson Syndrome (SJS), her lymphocyte toxicity assay to the incriminated drug, and the cytokine secretion in the patient’s sera. In her skin biopsy, the apoptotic keratinocytes is shown. Clinically, the patient presented a triad that characterizes “true” HSR (rash, fever, and liver involvement). The pro-inflammatory cytokines were significantly higher in sera from the patient than in sera from control patients (analyzed previously in the authors’ laboratory). More specifically, the high level of tumor necrosis factor alpha (TNF-α) is as high as in patients found to have toxic epidermal necrolysis (TEN) and presenting “true” HSR, eg, rash, fever, and organ involvement. The same is the case with the apoptotic markers Fas, caspase activity, and M30. T-cell cytokines control the pathogenesis of SJS/TEN contributing to apoptotic processes in the liver and in the skin.

Section snippets

Case report

A 7-year-old African-American girl was hospitalized with rash, pruritus, and fever. Previously, the girl was given ibuprofen, as medication for fever. Viral determinations showed no signs of viral infection. The vesicular eruptions became bullous, coalescent, and led to desquamation of the skin. Based on the clinical manifestation, the hospital dermatologist made the diagnosis of SJS. A biopsy was taken during the SJS episode. During the hospitalization she developed high alanine

Results

In controls, LTA shows normal ranges of toxicity for ibuprofen. This patient presented a high level of cytotoxicity to ibuprofen as compared with controls with a result of 33%. The normal level or cut-off for this ibuprofen-LTA on patients is 15% (10 ± 5). In immunocompetent individuals found to have SJS or TEN, the LTA ranges between 24% and 35%. The immunocompetent person is defined as not presenting acquired or hereditary immunodeficiency, and as not being under immunosupressive drugs or

Discussion

Current investigations contribute to the understanding of the underlying adverse drug reaction that caused the SJS/TEN, providing clues to their immunopathogenesis.

Clinical symptoms of rash, fever, and organ involvement that occur in HSRs and specifically in a patient’s TEN may be due to the involvement of cells such as neutrophils, monocytes, and macrophages, as well as to specialized cells such as keratinocytes. However, excluding neutrophils, these cells are also antigen-presenting cells and

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Citation Excerpt :
IL-6 stimulates most acute-phase proteins, while IL-10 is a prototype anti-inflammatory cytokine that regulates B-cell function.16 Moreover, Fas was shown to be dysregulated in SJS/TEN.55,67 T-cell memory is responsible for the recognition of “stress” signals represented by the exposure of lymphocytes to the insulting drug.
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Original articleApoptosis in ibuprofen-induced Stevens–Johnson syndrome

Section snippets

Case report

Results

Discussion

J Allergy Clin Immunol

Lancet

Clin Biochem

Am J Pathol

Blood

Frequency and cost of serious adverse drug reactions in a department of general medicine

Br J Clin Pharmacol

Cutaneous drug reactions

Pharmcol Rev

Incidence of adverse drugs reactions in hospitalized patients

JAMA

Toxic epidermal necrolysis: an eruption resembling scalding of the skin

Br J Dermatol

Toxic epidermal necrolysis (an eruption resembling scalding of the skin) a repraisal

Br J Dermatol

Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiformae

Arch Dermatol

Idiosyncratic drug reactions: a mechanistic evaluation of risk factors

Br J Clin Pharmacol

Severe cutaneous drug reactions to drugs

N Engl J Med

Original article
Apoptosis in ibuprofen-induced Stevens–Johnson syndrome