title: Genotype, Clinical Course, and Therapeutic Decision Making in 76 Infants with Severe Generalized Junctional Epidermolysis Bullosa.
abstract: Severe generalized junctional epidermolysis bullosa, a lethal hereditary blistering disorder, is usually treated by palliative care. Allogeneic stem cell transplantation (SCT) has been proposed as a therapeutic approach, yet without clinical evidence. Decision making was evaluated retrospectively in 76 patients with severe generalized junctional epidermolysis bullosa born in the years 2000-2015. The diagnosis was based on the absence of laminin-332 in skin biopsies. With an incidence of 1 of 150,000, severe generalized junctional epidermolysis bullosa occurred more often than published previously. Eleven as yet unreported mutations in the laminin-332 genes were detected. Although patients homozygous for the LAMB3 mutation c.1903C>T lived longer than the others, life expectancy was greatly diminished (10.8 vs. 4.6 months). Most patients failed to thrive. In two patients with initially normal weight gain, the decision for SCT from haploidentical bone marrow or peripheral blood was made. Despite transiently increasing skin erosions, the clinical status of both subjects stabilized for several weeks after SCT, but finally deteriorated. Graft cells, but no laminin-332, were detected in skin biopsies. The patients died 96 and 129 days after SCT, respectively, one of them after receiving additional skin grafts. Treatment of severe generalized junctional epidermolysis bullosa by SCT is a last-ditch attempt still lacking proof of efficacy.
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany. Electronic address: johanna.hammersen@uk-erlangen.de.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hammersen
authors.affiliation: Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Has
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Naumann-Bartsch
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stachel
authors.affiliation: Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Kiritsi
authors.affiliation: Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Söder
authors.affiliation: Dermatologie Pédiatrique, University Hospital Grenoble, Grenoble, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Tardieu
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.affiliation: Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.affiliation: Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Schneider
mesh_terms: D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003657:Decision Making; D016109:Epidermolysis Bullosa, Junctional / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D012867:Skin / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation / Q000379:methods*; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D004247:DNA; D007797:Laminin; D000097794:Kalinin; C400567:LAMC2 protein, human; C095567:laminin alpha 3