Successful kidney transplantation in a patient with neonatal-onset ILNEB.

BACKGROUND: ILNEB constitute an autosomal recessive disorder caused by homozygous or compound heterozygous mutation of the gene for the ITGA3. To date, 8 ILNEB patients have been reported, but all 6 neonatal-onset ILNEB patients suffered early death within 2 years. The most common cause of death among previously reported ILNEB patients was exacerbation of the respiratory condition. METHODS: In this study, we describe a case of ILNEB with neonatal onset in a female patient and the genetic and histopathological testing performed. RESULTS: Our patient had a compound heterozygous mutation in ITGA3. Compared to previously reported patients, this patient exhibited milder clinical and histopathological characteristics. After experiencing a life-threatening respiratory infection at 8 months old, the patient started periodic subcutaneous immunoglobulin treatment once every 1-2 weeks for nephrotic-range proteinuria-induced secondary hypogammaglobulinemia. At the age of 3 years, proteinuria gradually increased with severe edema despite strict internal management. Therefore, our patient underwent unilateral nephrectomy and insertion of a peritoneal dialysis catheter followed by another unilateral nephrectomy. One month later, she underwent an ABO-compatible living-donor kidney transplantation at the age of 4 years. CONCLUSIONS: Our patient is a neonatal-onset ILNEB patient who survived for more than 2 years and underwent successful kidney transplantation.

Bioingeniería de tejidos: cultivo de queratinocitos humanos en el tratamiento de la epidermólisis bullosa / Treatment of epidermolysis bullosa with allogeneic human cultured queratinocytes

Background: Epidermolysis bullosa (EB) or "crystal skin" is a group of inherited disorders that affect the protein that forms the anchor between dermis and epidermis, producing blister injuries. Case report: We report a four years old boy with junctional EB and lesions in 80 percent of the body lasting 48 months. His right lower limb was treated with allogeneic human cultured queratinocytes during five weeks. After the treatment period, a re-epithelization of 90 percent of the intervened limb was observed. Its diameter increased from 23 to 27 cm, the wound assessment scale score decreased from 30 to 13 and the visual analogue pain assessment score decreased from eight to two. Therefore allogeneic human cultured queratinocytes are a novel therapeutic alternative for EB.

Introducción: La epidermólisis Bullosa (EB) o "piel de cristal" es un grupo de trastornos hereditarios, el cual afecta las proteínas que forman la unión dermo-epidérmica de piel y mucosas, lo que lleva a la formación de lesiones ampollares. Objetivo: Comunicar la primera intervención con cultivos de queratinocitos humanos alogénicos (CQHA) en el tratamiento de la EB, en un centro de salud familiar de Chile el año 2013. Metodología: Se presenta el caso de un paciente de 4 años, quien presentaba lesiones en el 80 por ciento del cuerpo de 48 meses de evolución. Se realizó una intervención de la extremidad inferior derecha con el 90 por ciento comprometido con CQHA durante 5 sem con el fin de lograr la reepitelización y formación de piel indemne. Resultados: Posterior a las 5 sem del tratamiento se logró reepitelización del 90 por ciento de la extremidad intervenida, incremento del diámetro de la pierna de 23 a 27 cm., en la escala de valoración de heridas se reduce de 30 a 13 puntos y en la escala de valoración análoga del dolor de 8 a 2 puntos. Conclusión: Se presenta una alternativa terapéutica para pacientes con EB.

Successful therapeutic transplantation of revertant skin in epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is a group of genetic blistering diseases. Despite many efforts, treatment for EB remains symptomatic. Revertant mosaicism, coexistence of cells carrying disease-causing mutations with cells in which the inherited mutation is genetically corrected by a spontaneous genetic event (revertant cells) in 1 individual, can be found in EB. The naturally corrected revertant keratinocytes provide an opportunity for autologous cell therapy. OBJECTIVE: We sought to locally treat EB by transplantation of revertant skin. METHODS: Persistent ulcers in a patient with non-Herlitz junctional EB caused by mutations in the LAMB3 gene were treated by transplantation of split-thickness biopsy specimens from one of his revertant patches. RESULTS: All transplanted biopsy specimens were accepted and complete re-epithelialization occurred within 14 days. During 18 months of follow-up, the patient never experienced blisters or wounds in the grafted area, nor in the healed donor site. Immunofluorescence and DNA sequencing showed that acceptor sites healed with transplanted revertant keratinocytes. LIMITATIONS: Punch grafting allows only limited expansion of revertant skin. CONCLUSIONS: We demonstrate that phenotypical and genotypical correction of skin in patients with revertant mosaicism by expansion of revertant skin might be a promising therapeutic option for cutaneous manifestations of EB.

Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa.

Non-Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive genodermatosis characterized by skin fragility and blistering. It is usually caused by mutations in the genes encoding the basement membrane proteins laminin 5 or type XVII collagen. Clinically, impaired wound healing and chronic erosions cause major morbidity in affected patients. Previously it was thought that these individuals, unlike patients with dystrophic EB, did not have an increased risk of developing skin cancer. However, we describe three patients with non-Herlitz JEB (aged 42, 56 and 75 years) who developed cutaneous squamous cell carcinomas (SCCs). The tumours were well-differentiated in two cases, but one patient had multiple primary SCCs that were either well- or moderately differentiated. Most cases of SCC in non-Herlitz JEB described have occurred in those with laminin 5 defects and on the lower limbs. These clinicopathological observations have important implications for the management of patients with this mechanobullous disorder as well as providing further insight into the biology of skin cancer associated with chronic inflammation and scarring.

Outcome after surgical repair of junctional epidermolysis bullosa-pyloric atresia syndrome: a report of 3 cases and review of the literature.

BACKGROUND: Junctional epidermolysis bullosa-pyloric atresia syndrome is recognized as a distinct autosomal recessive entity. Affected infants present with skin fragility and inability to feed due to intestinal obstruction. Despite successful surgical repair of the anatomical defect, the outcome is poor owing to poor feeding, malabsorption, failure to thrive, and sepsis. OBSERVATIONS: In 70 cases of intestinal obstruction and epidermolysis bullosa reported in the medical literature and the 3 reported here, surgical intervention was attempted 51 times. In all except 16 infants, death occurred before age 11 months (mean age, 70 days). Renal involvement and continued failure to thrive accompanied the skin disease in survivors, who ranged in age from 30 days to 16 years (mean age, 4.0 years). CONCLUSIONS: The poor prognosis of this condition must be considered when decisions are made regarding surgical correction. Attempting surgical correction may be warranted in individual circumstances, but withholding surgical intervention and providing palliative support is an acceptable alternative.

Treatment of epidermolysis bullosa with human cultured epidermal allografts.

Junctional epidermolysis bullosa letalis type Herlitz Pearson is a genetically determined, life-threatening disease. Effective therapy has been lacking to date. Therefore any therapy that improves wound healing would be beneficial for these patients. Cultured epidermal grafts are known to enhance wound epithelialization and have been used with success in some epidermolysis bullosa disorders. Encouraged by these reports, we grafted cultured allogeneic keratinocytes to an infant with a junctional epidermolysis bullosa letalis type.

Management of urinary tract in children with epidermolysis bullosa.

Epidermolysis bullosa is a group of rare genetic disorders characterized by noninflammatory blistering lesions of the skin occurring after minor mechanical trauma. In association with junctional epidermolysis bullosa, a syndrome of pyloric atresia has occasionally been noted in the literature. Several infants who had this combined disorder have been reported to have severe genitourinary tract involvement. Most of these patients have died at an early age because of severe urinary tract involvement. We describe a rare survivor who was initially treated with urinary diversion. Subsequent attempts at undiversion of this patient were unsuccessful. He is presently stable following rediversion. The entities of e. bullosa and e. bullosa/pyloric atresia are reviewed with emphasis on urologic associations.