Orofacial Anomalies in Kindler Epidermolysis Bullosa
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JAMA Dermatol. 2024 Mar 20:e240065. doi: 10.1001/jamadermatol.2024.0065. Epub ahead of print. PMID: 38506824; PMCID: PMC10955352.

Orofacial Anomalies in Kindler Epidermolysis Bullosa

Authors: Susanne Krämer 1 2Anna Lena Hillebrecht 3Yao Wang 1Mihail-Alexandru Badea 4Jose Ignacio Barrios 5Sorina Danescu 6Ignacia Fuentes 7 8 9Demet Kartal 10Alfred Klausegger 11Enrique Ponce de León 2Reinhard Schilke 12Ivelina Yordanova 13Agnes Bloch-Zupan 14 15 16 17Cristina Has 1

Affiliation:

  1. Department of Dermatology, Medical Faculty and Medical Center, University of Freiburg, Freiburg, Germany.
  2. Special Care Dentistry Unit, Facultad de Odontologia, Universidad de Chile, Santiago, Chile.
  3. Department of Prosthetic Dentistry, Centre for Dental Medicine, Medical Centre, University of Freiburg, Freiburg, Germany.
  4. Dermatology Department, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Targu-Mures, Targu-Mures, Romania.
  5. Maxillo Facial Department, Clinica Alemana, Santiago, Chile.
  6. Department of Dermatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  7. Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
  8. DEBRA Chile, Santiago, Chile.
  9. Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile.
  10. Faculty of Medicine, Department of Dermatology and Venereology, Erciyes University, Kayseri, Turkey.
  11. EB House Austria, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
  12. Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany.
  13. Department of Dermatology and Venerology, Medical University Pleven, Pleven, Bulgaria.
  14. Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France.
  15. Université de Strasbourg, Institut d’études Avancées, Strasbourg, France.
  16. Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-dentaires, Hôpital Civil, Centre de Référence des Maladies Rares Orales et Dentaires, O-Rares, Filière Santé Maladies rares TETE COU, European Reference Network ERN CRANIO, Strasbourg, France.
  17. Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U1258, CNRS-UMR7104, Illkirch, France.

Abstract:

Importance: Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported.

Objective: To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa.

Design, settings, and participants: This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa.

Main outcomes and measures: The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma.

Results: The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients).

Conclusions and relevance: These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.

Download: https://jamanetwork.com/journals/jamadermatology/article-abstract/2816026