Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions

Abstract

Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN.

Exploring Chemical Routes Relevant to the Toxicity of Paracetamol and Its meta-Analogue at a Molecular Level

“…Albeit in therapeutic doses it is usually safe, overdoses can result in hepatic toxicity and are the most common cause of drug-induced liver injuries. 1−3 Moreover, while APAP toxicity is mainly associated with liver damage, other organs can also be affected including the auditory 4 and reproductive 5 systems, the epidermis, 6,7 and the brain. 8 Albeit there is evidence that at low doses it protects brain cells against oxidative stress, 9,10 APAP overdoses have been associated with increased oxidative and nitrosative stress in hepatic and renal tissues.…”

“…Paracetamol, also known as acetaminophen, or N -acetyl- p -aminophenol (APAP, Scheme ), is one of the most frequently used drugs as an analgesic and antipyretic. Albeit in therapeutic doses it is usually safe, overdoses can result in hepatic toxicity and are the most common cause of drug-induced liver injuries. − Moreover, while APAP toxicity is mainly associated with liver damage, other organs can also be affected including the auditory and reproductive systems, the epidermis, , and the brain . Albeit there is evidence that at low doses it protects brain cells against oxidative stress, , APAP overdoses have been associated with increased oxidative and nitrosative stress in hepatic and renal tissues. , Moreover, some studies show the beneficial effects of some antioxidants against APAP induced damage, which are assumed to arise from the deactivation of reactive oxygen and nitrogen species.…”

Is acetaminophen associated with a risk of Stevens–Johnson syndrome and toxic epidermal necrolysis? Analysis of the French Pharmacovigilance Database

“…We were able to apply ALDEN retrospectively using available data in 12 cases. Acetaminophen causality was ‘probable’ (ALDEN score = 4) in four cases , ‘possible’ (ALDEN score = 2–3) in five cases and ‘very unlikely’ (ALDEN score <0) in three cases . The ALDEN score was inapplicable in eight cases because of a lack of data on the delay between acetaminophen intake and index day .…”

“…Twenty case reports of SJS/TEN related to acetaminophen are available in the international literature , two of them with a positive rechallenge. We were able to apply ALDEN retrospectively using available data in 12 cases.…”

Chemical Protectors against the Toxic Effects of Paracetamol (Acetaminophen) and Its Meta Analogue: Preventing Protein Arylation

“…Although safe at therapeutic doses, APAP overdoses can be toxic. Such toxicity is considered the most frequent cause of drug-induced liver injuries − and is also known to affect other organs. − N -Acetyl- p -benzoquinone imine (NAPQI, Scheme ) is a metabolite of APAP, which has been identified as responsible for the APAP hepatotoxicity. , At APAP therapeutic doses, NAPQI is properly detoxified by glutathione (GSH). On the contrary, when APAP is consumed in excess, NAPQI accumulates and GSH is insufficient for preventing the associated injuries. ,,, Chemically speaking, such injures are characterized by the formation of NAPQI adducts with the thiol group in cysteine residues, which eventually result in the production of the oxidative species. , The adduct formation mainly involves covalent bonding between the thiol group in cysteine residues and the ortho position, with respect to the keto group, in NAPQI .…”