Metabolic predisposition to cutaneous adverse drug reactions. Role in toxic epidermal necrolysis caused by sulfonamides and anticonvulsants

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

“…In summary, although high SMX‐HA cytotoxicity toward patient PBMC has been previously attributed to a possible innate defect in drug detoxification, we found no evidence for an association between increased cytotoxicity and altered expression of genes known or hypothesized to be involved in sulfamethoxazole biotransformation. Instead, expression array analyses suggested other novel pathways that could contribute mechanistically to SMX‐HA cytotoxicity, and by extension, to sulfonamide HS in some populations.…”

“…However, we did not detect increased cytotoxicity in HS patients compared to TOL patients at this concentration for either method, which was a concern given the results of previous studies . The reported specificity of the LTA is quite high (78%‐99%), but sensitivity varies greatly (41%‐100%) . In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients.…”

“…22,32,56 The reported specificity of the LTA is quite high (78%-99%), but sensitivity varies greatly (41%-100%). 36,41,56,57 In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients. Additionally, the performance of the LTA in drug HS appears to vary with the severity of clinical presentation.…”

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

“…In summary, although high SMX‐HA cytotoxicity toward patient PBMC has been previously attributed to a possible innate defect in drug detoxification, we found no evidence for an association between increased cytotoxicity and altered expression of genes known or hypothesized to be involved in sulfamethoxazole biotransformation. Instead, expression array analyses suggested other novel pathways that could contribute mechanistically to SMX‐HA cytotoxicity, and by extension, to sulfonamide HS in some populations.…”

“…However, we did not detect increased cytotoxicity in HS patients compared to TOL patients at this concentration for either method, which was a concern given the results of previous studies . The reported specificity of the LTA is quite high (78%‐99%), but sensitivity varies greatly (41%‐100%) . In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients.…”

“…22,32,56 The reported specificity of the LTA is quite high (78%-99%), but sensitivity varies greatly (41%-100%). 36,41,56,57 In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients. Additionally, the performance of the LTA in drug HS appears to vary with the severity of clinical presentation.…”

Idiosyncratic toxicity associated with potentiated sulfonamides in the dog

“…Interestingly, this increased cytotoxicity can be documented months to years after the episode of hypersensitivity, and has also been observed in family members who have never been challenged with the drug (Shear et al. , 1986; Wolkenstein et al. , 1995b).…”

The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

“…In a study with a small group of HIV‐infected patients, Reilly et al questioned the validity of in vitro toxicity as a marker for in vivo hypersensitivity reactions. However, a large documented volume of evidence exists that support the observation that cells (BPMCs in these references) from Sulfa‐HS patients are more susceptible to in vitro insult with the SMX reactive metabolite (SMX‐HA) than cells from healthy control subjects . Correlation between in vitro cellular toxicity results and in vivo toxicity has long been established and used as a predictor of hazard of acute toxicity .…”

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

“…In summary, although high SMX‐HA cytotoxicity toward patient PBMC has been previously attributed to a possible innate defect in drug detoxification, we found no evidence for an association between increased cytotoxicity and altered expression of genes known or hypothesized to be involved in sulfamethoxazole biotransformation. Instead, expression array analyses suggested other novel pathways that could contribute mechanistically to SMX‐HA cytotoxicity, and by extension, to sulfonamide HS in some populations.…”

“…However, we did not detect increased cytotoxicity in HS patients compared to TOL patients at this concentration for either method, which was a concern given the results of previous studies . The reported specificity of the LTA is quite high (78%‐99%), but sensitivity varies greatly (41%‐100%) . In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients.…”

“…22,32,56 The reported specificity of the LTA is quite high (78%-99%), but sensitivity varies greatly (41%-100%). 36,41,56,57 In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients. Additionally, the performance of the LTA in drug HS appears to vary with the severity of clinical presentation.…”

Idiosyncratic toxicity associated with potentiated sulfonamides in the dog

“…Interestingly, this increased cytotoxicity can be documented months to years after the episode of hypersensitivity, and has also been observed in family members who have never been challenged with the drug (Shear et al. , 1986; Wolkenstein et al. , 1995b).…”

The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

“…In a study with a small group of HIV‐infected patients, Reilly et al questioned the validity of in vitro toxicity as a marker for in vivo hypersensitivity reactions. However, a large documented volume of evidence exists that support the observation that cells (BPMCs in these references) from Sulfa‐HS patients are more susceptible to in vitro insult with the SMX reactive metabolite (SMX‐HA) than cells from healthy control subjects . Correlation between in vitro cellular toxicity results and in vivo toxicity has long been established and used as a predictor of hazard of acute toxicity .…”

RNA expression profiling in sulfamethoxazole‐treated patients with a range of in vitro lymphocyte cytotoxicity phenotypes

“…In summary, although high SMX‐HA cytotoxicity toward patient PBMC has been previously attributed to a possible innate defect in drug detoxification, we found no evidence for an association between increased cytotoxicity and altered expression of genes known or hypothesized to be involved in sulfamethoxazole biotransformation. Instead, expression array analyses suggested other novel pathways that could contribute mechanistically to SMX‐HA cytotoxicity, and by extension, to sulfonamide HS in some populations.…”

“…However, we did not detect increased cytotoxicity in HS patients compared to TOL patients at this concentration for either method, which was a concern given the results of previous studies . The reported specificity of the LTA is quite high (78%‐99%), but sensitivity varies greatly (41%‐100%) . In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients.…”

“…22,32,56 The reported specificity of the LTA is quite high (78%-99%), but sensitivity varies greatly (41%-100%). 36,41,56,57 In the relatively small numbers of patients recruited for expression arrays in our study, the lack of sensitivity reported by some groups could have led to poor discrimination between HA and TOL patients. Additionally, the performance of the LTA in drug HS appears to vary with the severity of clinical presentation.…”

Idiosyncratic toxicity associated with potentiated sulfonamides in the dog

“…Interestingly, this increased cytotoxicity can be documented months to years after the episode of hypersensitivity, and has also been observed in family members who have never been challenged with the drug (Shear et al. , 1986; Wolkenstein et al. , 1995b).…”

The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

“…In a study with a small group of HIV‐infected patients, Reilly et al questioned the validity of in vitro toxicity as a marker for in vivo hypersensitivity reactions. However, a large documented volume of evidence exists that support the observation that cells (BPMCs in these references) from Sulfa‐HS patients are more susceptible to in vitro insult with the SMX reactive metabolite (SMX‐HA) than cells from healthy control subjects . Correlation between in vitro cellular toxicity results and in vivo toxicity has long been established and used as a predictor of hazard of acute toxicity .…”