Current Treatment Landscape for Dystrophic Epidermolysis Bullosa: From Surgical Management to Emerging Gene Therapies and Novel Skin Grafts.

Epidermolysis bullosa is a genetic skin disorder characterized by blister formation from mechanical trauma. Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene presenting as generalized blisters from birth, which can result in extensive scarring, alopecia, esophageal stenosis, corneal erosions, and nail dystrophy. This disease also often leads to pseudosyndactyly of the digits from the closure of webspaces, progressing to a "mitten hand" deformity. Although traditional and current treatment for DEB is largely supportive with wound care and iterative surgical pseudosyndactyly release, emerging gene therapies and novel skin grafts may offer promising treatment. Studies published in the early 2020s have used HSV-1 vectors expressing missing COL7A1 genes to restore collagen function. One of these treatments, B-VEC, is an HSV-1-based topical gene therapy designed to restore collagen 7 by delivering the COL7A1 gene, leveraging a differentiated HSV-1 vector platform that evades the patient's immune system response. Other work has been performed to retrovirally modify autologous keratinocytes, but limitations of this process include increased labor in harvesting and engineering autologous cells. This article provides an overview of DEB treatment with an emphasis on emerging gene therapies and novel skin grafts, especially as they pertain to pseudosyndactyly treatment.

Hand surgery in recessive dystrophic epidermolysis bullosa: Our experience with dermal substitutes.

BACKGROUND: Deformities of the hands occur in most patients with recessive dystrophic epidermolysis bullosa. All structures of the hand may be involved. To restore hand function, it is necessary to identify the proper method of treatment. PATIENTS AND METHODS: We conducted a retrospective review of 18 patients for a total of 30 surgically treated hands. The data were collected between 1998 and 2016 at Hôpital Necker Enfants Malades (Paris, France) and Institut de la Main (Paris, France). The postoperative follow-up period ranged between 22 months and 168 months, with an average duration of 76 months. The procedure performed on all of these patients involved a first web release for the thumb and pseudosyndactyly release for the remaining digits. A full thickness skin graft was used at the level of the first commissure and palm of the hand, while acellular dermal substitutes (Integra® or Matriderm®) were used to cover the remaining commissures, digits, and the remainder of the hand, followed by a split thickness skin graft. Postoperative rehabilitation ensued. RESULTS: Long-term results are encouraging, demonstrating maintenance of function greater than 3 years in 57% of cases, and greater than 5 years in 33% of cases. CONCLUSION: We believe that good surgical technique followed by good rehabilitation, combined with an interdisciplinary overall management of these patients, allowed us to succeed in maintaining a very satisfactory, esthetic, and functional result exceeding 5 years for one-third of patients. The resultant psychological benefit is very important.

Release of pseudosyndactyly in recessive dystrophic epidermolysis bullosa using a dermal regeneration template glove: the Foggia experience.

BACKGROUND: Epidermolysis bullosa (EB) comprises a heterogeneous group of rare genetic diseases associated with skin blistering caused by minimal trauma. A major and common EB subtype, recessive dystrophic EB (RDEB), is characterized by altered wound healing, inflammatory dysbalance and fibrotic changes associated with reduced to absent collagen VII. Because of its exposed position and its continued use in daily activities, the hand is constantly at risk of microtrauma and is therefore one of the organs most affected by the disease with highly disabling deformities that represent a challenging field in hand surgery practice. METHODS: The authors present their experience in the microsurgical treatment of pseudosyndactylies comparing the classic dressing with vaseline gauze with an innovative "glove protocol" using Integra® dermal regeneration template. The endpoints analyzed were: healing times, hospital stay time, discomfort for the patient, free-recurrence interval, follow-up range and major complications. RESULTS: A total of 34 procedures were performed on 24 RDEB patients with hand deformities. Compared with the dressing with vaseline gauze, microsurgery followed by application of dermal regeneration template gloves allowed a significant reduction of hospital stay, healing time, and dressing pain as well as an increased recurrence-free interval. CONCLUSIONS: The microsurgical approach followed by our new protocol described in the study has been beneficial in providing consistent and successful long-term results for these patients.

An algorithmic approach for the management of hand deformities in dystrophic epidermolysis bullosa.

Treatment of hand deformities in epidermolysis bullosa patients represents a challenging field in hand surgery practice, thus a systematic approach by a team is mandatory for a successful result. A simple and practical algorithm for the surgical treatment of hand deformities in EB was employed by the authors where the deformities of each digit in EB patients was categorized according to pseudosyndactyly and interphalangeal joint contracture severity for guidance during the surgical treatment. The current study retrospectively reviewed the medical records and photographic data of 13 EB patients followed in our department, for whom a systematic approach to the management and treatment was used. Mild cases were treated by surgical release and secondary healing with non-adhesive dressing while moderate cases were treated with autologous dermal grafts harvested with a special technique that were fixed on denuded areas on the proximal interphalageal joints after release. The remaining areas were treated similarly to the mild group. Additional K-wires were applied for two weeks in severe cases. A total of 21 procedures were performed on 13 EB patients with hand deformities according to the proposed treatment strategy. Functional recovery was satisfactory for each patient and the outcomes were dependent upon the severity of deformity. A multidisciplinary and conscious approach followed by an algorithmic surgical treatment protocol described in the study has been beneficial in providing consistent and successful long-term results for these patients.

Suprathel(®) -assisted surgical treatment of the hand in a dystrophic epidermolysis bullosa patient.

Epidermolysis bullosa (EB) is a progressive familial disorder composed of dermal mucosal blisters, flexion contractures and pseudosyndactylies. Flexion contractures and pseudosyndactyly can be treated with surgery but usually require skin grafting. Because of poor wound healing, skin graft harvesting is a challenge in these patients. In order to prevent donor-site morbidities due to skin graft harvesting some alloplastic materials were introduced. In this study, we focused on Suprathel(®) as a new allograft material for covering the skin defects of a patient with dystrophic EB.

Pseudosindactilia y amputación como principales signos del síndrome de bandas amnióticas / Pseudosyndactyly and amputation as the main features of the amniotic band syndrome

Introducción. Las bandas amnióticas causan un espectro muy amplio de malformaciones fetales, desde labio-paladar hendido e hidrocefalia hasta estrangulación y amputación de extremidades; presenta una prevalencia que va de 1:1,200 a 1:15,000 nacimientos. El siguiente caso clínico se reporta con el objetivo de describir los principales signos del síndrome de bandas amnióticas. Caso clínico. Madre de 21 años, primigesta, con antecedente de vulvovaginitis en el primer trimestre, sin tratamiento; control prenatal irregular sin ultrasonidos obstétricos. El embarazo culminó en cesárea a las 30 semanas por presentar oligohidramnios severo. Se obtuvo producto femenino de 1,200 g y Apgar 7-8. A la exploración física se encontró pseudosindactilia con zona de anillo uniendo a las falanges por el vértice, pie equino varo izquierdo y pierna derecha amputada desde la región tibial media terminando en punta, con escara en porción distal. Además, en estudio radiológico se observaron las falanges del segundo, tercer y cuarto dedos unidas al centro en vértice y peroné hipoplásico. Conclusiones. Los anillos de constricción, la amputación de una o más extremidades y la pseudosindactilia son signos importantes y consistentes que apoyan el diagnóstico del síndrome de bandas amnióticas, con un mal pronóstico para la función aunque bueno para la vida.

Background. Amniotic band syndrome causes a wide spectrum of congenital defects such as cleft lip, hydrocephalus, and growth restriction of limbs, with or without amputation. The condition occurs in every 1:1,200 to 1:15,000 deliveries. The objective of this report is to define the most important features of amniotic band syndrome. Case report. We report the case of a 21 -year-old female with a first pregnancy. No prenatal care or ultrasound studies were carried out, but the patient reported experiencing vaginal discharge during the first trimester. The pregnancy resulted in cesarean section at 30 gestational weeks because of severe oligohydramnios. A 1200-g female was delivered with Apgar 7-8. The newborn presented congenital amputation of the right leg and pseudosyndactyly of the left hand with a ring constriction of the third phalange of the second, third and fourth finger, a left equinovarus foot and amputation of the right leg from the middle third of the tibial region. These findings were confirmed by x-ray. Conclusions. Constriction rings, limb amputation and pseudosyndactyly are important and consistent features with the amniotic band syndrome. Functional prognosis is nonfavorable, but prognosis for life productivity is good.