Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

Adolescent Adult Carbamazepine Female Humans Male Middle Aged Retrospective Studies Stevens-Johnson Syndrome / genetics Young Adult

Journal

Journal of the European Academy of Dermatology and Venereology : JEADV

ISSN: 1468-3083

Titre abrégé: J Eur Acad Dermatol Venereol

Pays: England

ID NLM: 9216037

Informations de publication

Date de publication:
Jul 2021

Historique:

received: 03 12 2020

accepted: 24 03 2021

pubmed: 10 4 2021

medline: 22 6 2021

entrez: 9 4 2021

Statut: ppublish

Résumé

Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). We sought to better describe adult IEN and understand the aetiology. This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

Sections du résumé

BACKGROUND BACKGROUND

Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]).

OBJECTIVE OBJECTIVE

We sought to better describe adult IEN and understand the aetiology.

METHODS METHODS

This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls.

RESULTS RESULTS

IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL.

CONCLUSIONS CONCLUSIONS

IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

Identifiants

DOI: 10.1111/jdv.17274 PMID: 33834541

pubmed: 33834541

doi: 10.1111/jdv.17274

doi:

Substances chimiques

Carbamazepine 33CM23913M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1569-1576

Informations de copyright

Références

Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. Lancet 2017; 390: 1996-2011.

Chaby G, Maldini C, Haddad C et al. Incidence of and mortality from epidermal necrolysis (Stevens-Johnson syndrome/toxic epidermal necrolysis) in France during 2003-16: a four-source capture-recapture estimate. Br J Dermatol 2020; 182: 618-624.

Bettuzzi T, Penso L, de Prost N et al. Trends in mortality rates for Stevens-Johnson syndrome and toxic epidermal necrolysis: experience of a single centre in France between 1997 and 2017. Br J Dermatol 2020; 182: 247-248.

Ingen-Housz-Oro S, Alves A, Colin A et al. Health-related quality of life and long-term sequelae in survivors of epidermal necrolysis: an observational study of 57 patients. Br J Dermatol 2020; 182: 916-926.

Fournier S, Bastuji-Garin S, Mentec H, Revuz J, Roujeau JC. Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection. Eur J Clin Microbiol Infect Dis 1995; 14: 558-559.

Mulvey JM, Padowitz A, Lindley-Jones M, Nickels R. Mycoplasma pneumoniae associated with Stevens Johnson syndrome. Anaesth Intensive Care 2007; 35: 414-417.

Schalock PC, Dinulos JGH. Mycoplasma pneumoniae-induced Stevens-Johnson syndrome without skin lesions: fact or fiction? J Am Acad Dermatol 2005; 52: 312-315.

Tankunakorn J, Sawatwarakul S, Vachiramon V, Chanprapaph K. Stevens-Johnson syndrome and toxic epidermal necrolysis-like lupus erythematosus. J Clin Rheumatol 2019; 25: 224-231.

Dumas M, Hua C, Hotz C et al. Epidermal necrolysis and autoimmune diseases: two more observations supporting the concept that « toxic » epidermal necrolysis can be « non-toxic ». J Eur Acad Dermatol Venereol 2018; 32: e360-e361.

Chaby G, Ingen-Housz-Oro S, De Prost N, Wolkenstein P, Chosidow O, Fardet L. Idiopathic Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevalence and patients’ characteristics. J Am Acad Dermatol 2019; 80: 1453-1455.

Ingen-Housz-Oro S, Duong T-A, Bensaid B et al. Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole national de diagnostic et de soins). Orphanet J Rare Dis 2018; 13: 56.

Sassolas B, Haddad C, Mockenhaupt M et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther 2010; 88: 60-68.

Larabi IA, Martin M, Etting I, Penot P, Fabresse N, Alvarez JC. Drug-facilitated sexual assault (DFSA) involving 4-methylethcathinone (4-MEC), 3,4-Methylenedioxypyrovalerone (MDPV), and doxylamine highlighted by hair analysis. Drug Test Anal 2018; 10: 1280-1284.

Alvarez JC, Etting I, Abe E, Villa A, Fabresse N. Identification and quantification of 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV) in hair by LC-MS/MS after chronic administration. Forensic Sci Int 2017; 270: 39-45.

Deschamps O, Ortonne N, Hüe S et al. Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation. Br J Dermatol 2020; 182: 355-363.

Rodriguez C, Jary A, Hua C et al. Pathogen identification by shotgun metagenomics of patients with necrotizing soft-tissue infections. Br J Dermatol 2020; 183: 105-113.

Toussaint C, Sanchez-Pena P, Titier K, Castaing N, Molimard M, Milpied B. Toxicological screening reveals toxic epidermal necrolysis likely carbamazepine-induced rather than idiopathic. J Allergy Clin Immunol Pract 2020; 8: 2075-2076.

Lavrik IN, Krammer PH. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ 2012; 19: 36-41.

Dickens LS, Boyd RS, Jukes-Jones R et al. A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell 2012; 47: 291-305.

Auquier-Dunant A, Mockenhaupt M, Naldi L et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol 2002; 138: 1019-1024.

Assier H, Bastuji-Garin S, Revuz J, Roujeau JC. Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995; 131: 539-543.

Giraud L, Bellon N, Costedoat I et al. Nécrolyse épidermique et érythème polymorphe majeur de l’enfant: caractéristiques épidémiologiques, cliniques et complications. Ann Dermatol Vénéréol 2019; 146: A192-A193.

Lavaud J, Rodriguez C, Ingen-Housz-Oro S et al. Dynamic study of microbial interactions in the skin microbiota of patients with epidermal necrolysis (DynaMiCut). 30th ECCMID European Congress of Clinical Microbiology and Infectious Diseases, Paris, France; 2020.

Zimmermann M, Koreck A, Meyer N et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol 2011; 127: 200-207.e10.

Leverkus M, Sprick MR, Wachter T et al. TRAIL-induced apoptosis and gene induction in HaCaT keratinocytes: differential contribution of TRAIL receptors 1 and 2. J Invest Dermatol 2003; 121: 149-155.

Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand. Am J Pathol 2003; 162: 1515-1520.

Kaplan MJ, Lewis EE, Shelden EA et al. The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. J Immunol 2002; 169: 6020-6029.

Miyagawa H, Yamai M, Sakaguchi D et al. Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus. Rheumatology (Oxford) 2008; 47: 158-164.

Downey A, Jackson C, Harun N, Cooper A. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol 2012; 66: 995-1003.

Lalevée S, Contassot E, Ortonne N et al. Advances in understanding of the pathophysiology of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis). Ann Dermatol Venereol 2020; 147: 475-481.