Successful Treatment of a Paroxysmal Kinesigenic Dyskinesia Patient with Carbamazepine-Induced Stevens-Johnson Syndrome Using Oxcarbazepine Monotherapy: A Case Report

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

Download Full-text

A rare case of toxic epidermal necrolysis in pregnancy

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20200391 ◽

2020 ◽

Vol 9 (2) ◽

pp. 846

Author(s):

Reena Yadav ◽

Astha Srivastava ◽

Preeti Pawar ◽

Vibhu Mendiratta ◽

Prerna Tayal

Keyword(s):

Toxic Epidermal Necrolysis ◽

Perinatal Outcome ◽

Rare Case ◽

Rare Condition ◽

Stevens Johnson Syndrome ◽

Successful Pregnancy ◽

Johnson Syndrome ◽

Mucous Membranes ◽

Epidermal Necrosis ◽

In Pregnancy

Stevens-Johnson syndrome (SJS) is a group of toxic necrolytic group of disorder of skin and mucous membrane with significant morbidity and mortality. It is a highly serious allergic reaction to medications affecting the skin and mucous membranes. Pregnant women with SJS or toxic epidermal necrolysis (TEN) are a unique subset, and both conditions can simultaneously affect the mother and fetus. It is a rare condition with a reported incidence of one case per million people per year. Till date, few cases of pregnancy with SJS/TEN have been reported. We are reporting a case of 20-year-old primigravida with 31+3 weeks of gestation presenting with extensive toxic epidermal necrosis. Attack of SJS developing in pregnancy can be fatal because immunity is compromised. This patient was managed in our institute with involvement of multidisciplinary team and had a successful pregnancy outcome. Perinatal outcome was also good in this case.

Download Full-text

Human Leukocyte Antigen Gene Testing and Carbamazepine-Induced Toxic Epidermal Necrolysis: A Study of Pediatric Practice

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475420952422 ◽

2020 ◽

pp. 120347542095242

Author(s):

Jessica M.S. Asgarpour ◽

Lauren M. Lam ◽

Tina K. Vogel ◽

Helly R. Goez ◽

Loretta Fiorillo

Keyword(s):

At Risk ◽

High Risk ◽

Toxic Epidermal Necrolysis ◽

Therapeutic Interventions ◽

Stevens Johnson Syndrome ◽

Drug Induced ◽

Realistic Potential ◽

Gene Testing ◽

Johnson Syndrome ◽

Standard Of Practice

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug-induced dermatologic conditions. SJS/TEN occurs in 1-10 per 10 000 patients taking carbamazepine (CBZ) (Pratt VM, McLeod HL, Rubinstein WS et al. Medical Genetics Summaries. National Center for Biotechnology Information US; 2018: 1-527). The development of SJS/TEN is associated with variable drug metabolism and presence of an at-risk HLA haplotype. HLA-B*15:02 and HLA-A*31:01 haplotypes can produce a hyperimmune response in the setting of CBZ use in patients of Asian and European descent, respectively (Schneider JA, Cohen PR. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017; 34:1235-1244). Objective The US Food and Drug Administration (FDA) and the Canadian pharmacogenomics Network for Drug Safety (CPNDS) recommend that patients with high-risk ethnic backgrounds should be genetic tested before initiating CBZ (Sukasem C, Chaichan C, Nakkrut T et al. Association between HLA-B Alleles and Carbamazepine-induced maculopapular exanthema and severe cutaneous reactions in Thai patients. Journal of Immunology Research. 2018; 1-11).We sought out to assess the awareness of this in prescribing practitioners and their standard of practice. Materials and methods We created a 15-question survey and distributed to pediatric neurologists and pediatricians at the University of Alberta. We hypothesized that there was a discordance between the standard of practice and the recommendation by the FDA and CPNDS. Results The survey results indicated a lack of awareness of the at-risk ethnicities for CBZ-induced SJS/TEN. HLA gene testing was rarely done prior to initiation of CBZ in high-risk patients. In addition, there was a lack of awareness for standard of care for genetic testing in Canada and worldwide. Conclusions Our results demonstrate an evident gap between current prescriber practices and existing FDA and CPNDS recommendations to screen for HLA genotypes. We hope that this study captures the realistic potential to improve patient outcomes.

Download Full-text

Paroxysmal Movement Disorders

Frontiers in Neurology ◽

10.3389/fneur.2021.659064 ◽

2021 ◽

Vol 12 ◽

Author(s):

Susan Harvey ◽

Mary D. King ◽

Kathleen M. Gorman

Keyword(s):

Next Generation Sequencing ◽

Movement Disorders ◽

Clinical Phenotype ◽

Single Gene ◽

Copy Number Variant ◽

Genomic Research ◽

Next Generation ◽

Causative Gene ◽

Gene Testing ◽

Generation Sequencing

Paroxysmal movement disorders (PxMDs) are a clinical and genetically heterogeneous group of movement disorders characterized by episodic involuntary movements (dystonia, dyskinesia, chorea and/or ataxia). Historically, PxMDs were classified clinically (triggers and characteristics of the movements) and this directed single-gene testing. With the advent of next-generation sequencing (NGS), how we classify and investigate PxMDs has been transformed. Next-generation sequencing has enabled new gene discovery (RHOBTB2, TBC1D24), expansion of phenotypes in known PxMDs genes and a better understanding of disease mechanisms. However, PxMDs exhibit phenotypic pleiotropy and genetic heterogeneity, making it challenging to predict genotype based on the clinical phenotype. For example, paroxysmal kinesigenic dyskinesia is most commonly associated with variants in PRRT2 but also variants identified in PNKD, SCN8A, and SCL2A1. There are no radiological or biochemical biomarkers to differentiate genetic causes. Even with NGS, diagnosis rates are variable, ranging from 11 to 51% depending on the cohort studied and technology employed. Thus, a large proportion of patients remain undiagnosed compared to other neurological disorders such as epilepsy, highlighting the need for further genomic research in PxMDs. Whole-genome sequencing, deep-sequencing, copy number variant analysis, detection of deep-intronic variants, mosaicism and repeat expansions, will improve diagnostic rates. Identifying the underlying genetic cause has a significant impact on patient care, modification of treatment, long-term prognostication and genetic counseling. This paper provides an update on the genetics of PxMDs, description of PxMDs classified according to causative gene rather than clinical phenotype, highlighting key clinical features and providing an algorithm for genetic testing of PxMDs.

Download Full-text