Recessive dystrophic forms of EB are burdened with a high psychological impact for patients and their families. A multidisciplinary approach to manage the disease is fundamental and surgery plays a critical role. “Mitten hands” compromise the functional development of the hands in children with EB. So, an early surgical approach is of paramount importance. Fine et al. showed that about 61% of recessive dystrophic EB patients require hand surgery, typically needing 5 or more operations .
Pseudosyndactylies in patients with this disease are characterized by high rates of recurrence [7, 9, 11,12,13, 15].
Surgical challenges include impaired wound healing and risk of iatrogenic trauma. In fact, the scar tissue of the hands can alter the anatomical structures, including the vascular-nerve pedicles; so minimal inadvertence during surgical procedures can cause local ischemia and subsequent partial or total skin necrosis.
Nevertheless, surgery is crucial to correct severe hand deformities, improving patient’s quality of life. In a study of 1995, Ciccarelli et al.  proposed these indications for surgery: palmar contracture, contracture of the proximal interphalangeal (IP) joint > 30°, severe small finger deformity, pseudosyndactyly extending to the proximal IP joint, severe impairment of daily activities.
Conventional surgical techniques for “mitten hand” are limited to the release of pseudosyndactylies and wound coverage, achieving optimal epithelialisation, beginning early mobilization, and providing long-term stability with minimal recurrence . Various methods are described, but no consensus exists.
Healing by secondary intention is described , but larger wounds require coverage to avoid infection, delayed healing with fibrosis and recurrence of contractures. In these cases, the use of skin graft (split-thickness or full-thickness), cultured keratinocytes, and cellular allograft dermal matrix (such as Apligraf) or acellular biosynthetic material (such as Biobrane or AlloDerm-GBR) has been described in the literature [7, 16,17,18,19,20,21,22,23,24,25,26].
Split-thickness skin grafts (STSG) provide coverage of wide areas, however, availability of healthy skin for autologous grafting and difficult healing at the donor site can be major problems in EB patients. Moreover, split-thickness skin graft usually provides unstable coverage with high risk of early recurrences [7, 11].
Full-thickness skin graft is useful in the first web space and delays recurrence of contracture as compared with STSG, but the donor sites are very limited.
The use of skin substitutes in patients with EB has been described in the literature; often in combination with skin grafts.
Recent studies focused on allogenic skin substitutes derived from human keratinocytes and fibroblasts. In particular, the studies of Fivenson  and Falabella , in the early 2000’s, demonstrated the successful results in the treatment of severe hand deformities of EB patients, using of an allogenic bilayer cellular skin equivalent called Apligraft®. Other studies analyzed the utility of other materials such as autologous and allogenic epidermal keratinocyte grafts, amniotic membrane grafts, and acellular dermal allograft [20, 21, 24, 25]. Although some disadvantages are described such as need autologous STSG harvesting, prolonged time healing, and high costs [20, 25], nevertheless the new dermal support created by the acellular dermal matrix can prevent recurrence of the pseudosyndactylies in the long term .
Hand function preservation and the time interval to relapse are the most important parameters in evaluating surgery efficacy.
Following a careful analysis of our surgical procedures, we were able to improve outcomes in our patients by combining the use of microsurgery with the application of Integra ® dermal regeneration template.
In fact, we believe that magnifying loupes have allowed us to preserve the vascular-nervous pedicles in these patients, especially if in paediatric age. The higher skills and expertise of the Surgeons using the microscopic lenses in the release of pseudosyndactylies also helped to gain better results avoiding surgical damages.
We believe that through our protocol using a bilayer dermal regeneration template it is possible to avoid skin grafting and therefore iatrogenic damage and further surgery.
Artificial dermis, as Integra®, is an acellular purely bilaminate synthetic construct consisting of an outer silicone (polysiloxane) semipermeable membrane and an inner porous matrix of collagen-glycosaminoglycan.
The outer layer serves as an epidermal substitute and provides mechanical protection, and heat and moisture modulation of the wound, prevents formation of wound granulation tissue and increases tear strength of the custom-made gloves.
On the other hand, the inner layer, composed of bovine tendon type I collagen cross-linked to chondroitin-6-sulfate, is a biologic-based acellular dermal scaffold and promotes cellular ingrowth (it is histioconductive/histioinductive and allows for fibroblast proliferation and migration into the dermal scaffold and capillary growth). In particular glycosaminoglycan provides elasticity to the matrix, controls the biodegradation rate, and maintains a more open pore structure that allows cell migration into the matrix.
The porous layer of the matrix is strictly applied to the wound bed at the first stage. It acts as a template for the ingrowth of host fibroblasts and endothelial cells and is gradually replaced by host (endogenous) collagen, forming a new dermal layer (neodermis).
Integra® dermal regeneration template has been originally designed for treatment of full thickness skin lesions in a two-step procedure, where the second step consists of peeling off the silicone layer and applying an autologous split-thickness skin graft on the neodermis [27, 28]. Importantly, in our protocol for EB hands we use the Integra®-glove as an advanced wound dressing avoiding the second phase of skin graft and obtaining an almost complete and spontaneous re-epithelialization.
On the other hand, the use of artificial dermis offers many advantages, such as: immediate availability, possibility to cover large defects, no donor-site morbidity, good scarring, and early recovery.
In addition, the anti-inflammatory properties and physical characteristics of INTEGRA® allowed us to perform pain-free dressing and achieve more stable coverage over time. The coverage of noble structures, such as vascular and nerve pedicles, has been found to perform well. We believe that coverage through our technique has allowed a lower rate of early recurrence. In fact, inter-digital spaces have had a reduced tendency toward fusion during the healing phase, probably thanks to the INTEGRA® layer. The severity of the primary disease, the degree of hand deformity and the age of the patients at their initial referral are also relevant factors, which need to be addressed in future studies.
Due to their reduced invasiveness, these surgical procedures can be carried out in local anaesthesia and sedation; in particular, we performed: regional anaesthesia (brachial plexus), or deep sedation with fentanyl and propofol plus local anaesthetic infiltration, or deep sedation with ketamine and fentanyl plus local anaesthetic infiltration . We avoid to perform general anaesthesia because of high risk of iatrogenic damage of intubation in this kind of patients. With our new protocol the medications are painless, so we don’t use anaesthesia.