Valproic acid and Stevens‐Johnson syndrome: a systematic review of descriptive studies

Abstract

Valproic acid (VPA) is a commonly used antiepileptic drug (AED). Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis are the rare but fatal cutaneous adverse drug reactions for VPA. We aimed to identify and critically evaluate all the literature of SJS in association with VPA and to describe the clinical features of the condition. A literature search was conducted in MEDLINE/PubMed from inception to December 2017 and updated in July 2018 without any restrictions, and the references of included studies were also searched. The descriptive studies discussing any patients who experienced SJS followed by the use of VPA alone or along with any other AED for its main indication were included. Two authors were independently involved in the study selection and data extraction. Disagreements were resolved by consensus or by the discussion with a third reviewer. A total of 19 studies including 17 case reports and two case series of 98 were included in the review. In all studies, the dose of VPA ranged from 100 mg/day to a maximum dose of 1,000 mg/day and was administered for indications including epilepsy, seizures, schizophrenic affective disorders, and bipolar disorder. The mortality seen with severe cutaneous adverse drug reactions can be decreased by immediate withdrawal of opposing medications, providing symptomatic relief, and offering supportive care, all of which are the mainstay of controlling the condition. It is essential for healthcare professionals to be aware of the importance of monitoring SJS or any other cutaneous reactions followed by the use of valproic acid even though the incidence is low, but it is injurious to the patient.

Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies

“…In leucocytoclastic vasculitis, the drug stimulates antibody production and forms an immune complex that deposits in postcapillary venules and thereby activates the immune complex, leading to vascular damage [21]. There is an accumulation of arene oxide metabolite due to hepatic enzyme inhibition and genetic predisposition in SJS and TEN [6].…”

“…Proper monitoring of the risk group for laboratory parameters could help in the prevention of CADRs, and dose titration, immediate withdrawal of AEDs, choosing better alternative and providing wound care can help in better patient care. Supportive care to manage the adverse reaction include measures that healthcare professionals should be aware of to decrease morbidity and mortality due to CADRs [6]. Healthcare professionals should consider the AEDs with utmost care and caution to avoid such reactions [37] and the slow-dose rechallenge can be considered if the reactions are limited locally and completely resolved with an utmost caution [38].…”

“…Commonly known adverse effects of LEV include somnolence, headache, dizziness, asthenia, infection, pharyngitis, anorexia, cough and rash [5]. Toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic T symptoms syndrome (DRESS) are the serious fatal cutaneous reactions associated with AEDs such as lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHY), valproic acid (VPA) and rarely associated with second-line drugs such as LEV as per the post-marketing surveillance reports and these cutaneous adverse drug reactions (CADRs) are most commonly seen with aromatic AEDs [6][7][8].…”

“…DRESS has an annual incidence rate of 1 in 10 cases and is more common among the African American males, believed to be due to vitamin D deficiency which causes inflammation [12,13]. Human leucocyte antigen (HLA) alleles such as HLA-B*15:02 and HLA-A*31:01 are associated with SJS induced by VPA and CBZ [6]. Severe dermatologic reactions such as SJS/TEN and DRESS are less common than the maculopapular rash (MPE) in patients on LEV.…”

Phenotypic Overlap between Atopic Dermatitis and Autism

“…We assessed here the potential basis for the baseline association of AD with ASD in neonatal offspring of pregnant mice, who had been exposed to the anti-seizure medication, valproic acid (VPA) at 12.5d of fetal age, a standard ASD animal model [4,[45][46][47][48]. Pertinently, exposure of pregnant and neonatal humans to potential neurotoxins, like VPA and gabapentin, has been linked to severe hypersensitivity reactions [50,71,72], and the subsequent development of ASD [4,73]. Although the neuropathology resulting from toxin exposure has been assessed in this mouse model (e.g., [47,74]), the likely presence of parallel cutaneous abnormalities has been missed, likely due to the animals' furry pélage.…”