Inherited epidermolysis bullosa dystrophica and squamous cell carcinoma- A case report

Epidermolysis bullosa dystrophica (EBD) is an inherited disease of the structural proteins in the upper dermis, characterized by blister formation at the site of trauma followed by scarring. Skin fragility and blistering are the hallmarks of this disease. Cutaneous squamous cell carcinoma (cSCC) is a dreadful complication in the epidermolysis bullosa (EB) patients and common cause of death. The recent advances in distinct tumor microenvironment explain the aggressive nature of SCC in recessive Recessive Dystrophic Epidermolysis Bullosa (RDEB) patients and the use of collagen VII re-expression as a possible therapeutic measure. Regular follow-up is a must in preventing complications.

Epidermolysis bullosa dystrophica with renal failure

Inherited epidermolysis bullosa (EB) is a family of diseases with blistering of skin and mucous membrane even with mild trauma. It has different subtypes based on the affected protein. Epidermolysis bullosa dystrophica (EBD) is associated with mutations in the COL7A1 gene encoding type VII collagen leading to the fragility of skin and mucosal membranes. EBD may be dominant or recessive. They should be distinguished because increased prevalence of SCC is associated with the recessive form. Here we are reporting a case at our hospital presented with various clinical features, history, clinical spectrum, renal biopsy and gene analysis giving appropriate diagnosis for the disorder. Treatment remains challenge. A multidisciplinary approach is needed for the effective management of EBD.

Mutation analysis of the COL7A1 gene in 4 cases of recessive dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective:To analyze gene mutations in and clinical phenotypes of 4 children with recessive dystrophic epidermolysis bullosa (RDEB) .Methods:Clinical data were collected from 4 children with RDEB, and DNA was extracted from peripheral blood samples of the children and their parents. A multi-gene panel targeting congenital epidermolysis bullosa was used for high-throughput sequencing. After identification of causative gene mutations, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents.Results:Genetic testing showed 8 compound heterozygous mutations in the COL7A1 gene in the 4 cases. Case 1 was diagnosed with moderate generalized RDEB, and inherited a paternal mutation c.7828C>T and a maternal mutation c.448G> A; case 2 was also diagnosed with moderate generalized RDEB, and inherited a paternal mutation c.3625_3635del and a maternal mutation c.2726_2728del; case 3 was diagnosed with localized RDEB, carrying a paternal mutation c.682+1G>A and an allelic mutation c.5532+1G>A, but the mutation c.5532+1G>A was not identified in the DNA extracted from the parental peripheral blood samples; case 4 was diagnosed with severe generalized RDEB, and inherited a paternal mutation c.5196delC and a maternal mutation c.500_501insAGGG. Among these mutations, c.2726_2728del and c.5196delC had not been reported previously.Conclusions:All the 4 children with RDEB carried compound heterozygous mutations in the COL7A1 gene, which may be the cause of RDEB. The phenotypes of biallelic frameshift mutation carriers appearred more severe than those of carriers of compound heterozygous mutations composed of biallelic splice site, missense and nonsense, frameshift and amino acid deletion or insertion mutations.

Reproductive alternatives for patients with dystrophic epidermolysis bullosa / Opções reprodutivas para pacientes com epidermólise bolhosa distrófica

ABSTRACT Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.

RESUMO O termo "epidermólise bolhosa" descreve um grupo de afecções cutâneas causadas por mutações em genes que codificam proteínas relacionadas à aderência dermoepidérmica. Nos Estados Unidos, estima-se a ocorrência de 50 casos de epidermólise bolhosa por 1 milhão de nascidos vivos, sendo 92% deles da forma simples, 5% da forma distrófica, 1% da forma juncional e 2% não classificados. A epidermólise bolhosa do tipo distrófica foi associada a padrões autossômicos, dominante e recessivo. A epidermólise bolhosa causa sérios impactos psicológicos, econômicos e sociais, e não há tratamento curativo atualmente − apenas controle dos sintomas. A seleção embrionária é disponível para portadores de epidermólise bolhosa, a fim de evitar a perpetuação da condição em seus descendentes.

Construction of living skin equivalents using mixed autologous and allogeneic skin cells for repairing scar contracture of the hand in a patient with recessive dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective To evaluate the effect of living skin equivalents (LSE) constructed of mixed autologous and allogeneic skin cells and human amnion which served as a matrix on repairing scar contracture of the hand in a patient with recessive dystrophic epidermolysis bullosa (RDEB).Methods Skin tissues were obtained from a patient with RDEB and her mother,and epidermal keratinocytes and dermal fibroblasts were isolated from these tissues and cultured in vitro separately.Human amnion was obtained from the placenta of an unrelated healthy parturient undergoing cesarean delivery,and served as a matrix of the LSE.The autologous and allogeneic fibroblasts were mixed and seeded on the stromal side of the amnion,and then the autologous and allogeneic keratinocytes were mixed and seeded on the epithelial side of the amnion,so as to construct the human amnion-LSE (AM-LSE).Histological examination was performed to observe the structure of the skin tissues obtained from the patient and her mother,and immunofluorescence staining was conducted to detect the expression of type Ⅶ collagen in the skin tissues of the patient and her mother and in the AM-LSE.The AM-LSE was grafted on the skin defects of the patient after release of scar contracture of the hand.After grafting,the survival status of the AM-LSE graft and repairing effect on the wounds were evaluated.Results The constructed AM-LSE consisted of dermis,multilayered and fully differentiated epidermis and well-developed basement membrane.Immunofluorescence examination revealed that type Ⅶ collagen was linearly distributed along the basement membrane.Half a year after grafting,the AM-LSE survived well,and no obvious rejection reaction was observed.No blisters or ulcers occurred at the recipient sites,and the scar contracture was mild.The grafted area showed normal skin color with soft texture.The patient could grab and hold things,which had met self-care requirements of daily living.Conclusions The AM-LSE constructed of mixed autologous and allogeneic skin cells have good histological structures,and can be grafted on the wounds after resection of the scars in a RDEB patient.After grafting,no obvious rejection reaction was observed,and the skin was not liable to develop blisters,ulcers or scar contracture due to friction.

Epidermólisis bullosa en el perú: estudio clínico y epidemiológico de pacientes atendidos en un hospital pediátrico de referencia nacional, 1993-2015 / Epidermolysis bullosa in peru: clinical and epidemiological study of patients treated in a national reference pediatric hospital, 1993-2015

RESUMEN Objetivos Describir las características clínicas y epidemiológicas de los pacientes diagnosticados con epidermólisis bullosa (EB), en el Instituto Nacional de Salud del Niño (INSN) en Lima, Perú; centro de referencia nacional para esta enfermedad. Material y métodos Estudio observacional, descriptivo y transversal. Se revisaron las historias clínicas y exámenes de laboratorio de los pacientes diagnosticados de EB atendidos en el INSN desde 1993 al 2015. Resultados Fueron registrados 93 pacientes. La edad promedio fue de 7,9 ± 5,6 años; el 53,8% (n=50) fueron hombres. Las formas clínicas correspondieron a EB distrófica con 41 (44,1%) casos, EB simple con 39 (41,9%) casos, EB de la unión con 8 (8,6%) y al síndrome de Kindler con 4 (4,3%) casos. No se pudo identificar la forma clínica en un caso. Procedían de Lima y Callao 48 casos (51,6%) y 45 casos (48,4%) de otras provincias del país. Entre las manifestaciones extracutáneas se registraron compromiso gastrointestinal (44,1%), ocular (37,6%), odontogénico (87,1%), nutricional (79,6%), además de pseudosindactilia (16,1%). Se halló desnutrición crónica (71,6%), desnutrición aguda (17,6%) y anemia en (62,4%). La mortalidad correspondió a 6 casos (6,5%). Conclusiones Se reportan 93 casos de EB en el INSN, la presentación clínica predominante fue la forma distrófica.

ABSTRACT Objectives To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Materials and methods Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. Results 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%), union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). Conclusions 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

Applications of electron microscopy in health: the example of epidermolysis bullosa / Aplicações da microscopia eletrônica em saúde: o exemplo da epidermólise bolhosa

ABSTRACT We report the case of a patient with dystrophic epidermolysis bullosa (DEB) diagnosed by transmission electron microscopy (TEM), emphasizing the applications and importance of this technique in the health area. The patient was a male, the only child of young and non-consanguineous parents without similar cases in the family. The patient underwent a cutaneous biopsy in which TEM revealed sub-basal membrane involvement, confirming the diagnosis of DEB. Despite technological advances, TEM continues to play an important role in diagnosis and clinical research and is considered the best option for confirmation of diagnosis and subtypes of diseases such as epidermolysis bullosa (EB).

RESUMO Relatamos o caso de um paciente com epidermólise bolhosa distrófica (EBD) diagnosticado por microscopia eletrônica de transmissão (MET), destacando aplicações e importância desta técnica na área da saúde. Paciente do sexo masculino, filho único de pais jovens não consanguíneos, sem histórico de caso familial. O paciente foi submetido à biópsia cutânea, na qual a MET revelou comprometimento da membrana sub-basal, confirmando o diagnóstico de EBD. Apesar dos avanços tecnológicos, a MET continua tendo papel importante no diagnóstico e na pesquisa clínica, sendo considerada a melhor opção para a confirmação do diagnóstico e dos subtipos de doenças como a epidermólise bolhosa (EB).

Mutation analysis of the COL7A1 gene and prenatal diagnosis in two families with recessive dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective To detect mutations of the COL7A1 gene in 2 families with recessive dystrophic epidermolysis bullosa (RDEB),and to perform prenatal diagnosis during the pregnancy of patients' mothers.Methods Clinical data were collected from 2 patients with RDEB.DNA was extracted from the peripheral blood samples from the patients,their parents and 100 unrelated healthy people who served as controls.PCR was performed to amplify all the 118 exons of the COL7A1 gene followed by DNA sequencing.After identification of pathogenic mutations,amniotic fluid cells were obtained by amniocentesis during the next pregnancy of the patients' mothers,and genomic DNA was extracted from uncultured or cultured amniotic fluid cells followed by amplification and DNA sequencing to detect mutations in the COL7A1 gene.The results were compared with patients' results for prenatal diagnosis.After delivery,venous blood samples were collected from the neonates to detect mutations in the COL7A1 gene.All the results were verified by bidirectional sequencing.Results Compound heterozygous mutations in the COL7A1 gene were identified in the 2 patients.Two heterozygous mutations (c.5453G ＞ A and c.6781C ＞ T) in the COL7A1 gene were found in case 1,which resulted in the p.G1818D mutation and the formation of a premature termination codon p.R2261Efs*25.Additionally,the c.5453G ＞ A and c.6781C ＞T mutations were inherited from his father and mother respectively.Another 2 heterozygous mutations (c.6205C ＞ T and c.8272_8272delG) in the COL7A1 gene were identified in case 2,which led to the p.R2069C and p.V2758Sfs*28 mutations in encoded proteins,and the c.6205C ＞ T and c.8272_8272delG mutations were inherited from the patient's father and mother respectively.None of the above mutations in the COL7A1 gene was found in the uncultured or cultured amniotic fluid cells,which were collected from the 2 patients' mothers during the next pregnancy.After birth,the neonates showed normal skin and mucosa without blisters,and genetic testing showed none of the above mutations in the COL7A1 gene in the neonates.Conclusion Compound heterozygous mutations in the COL7A1 gene were found in the 2 patients with RDEB,and prenatal diagnosis was successfully performed in the 2 patients' mothers during the next pregnancy.

Pretibial dystrophic epidermolysis bullosa

Abstract Epidermolysis bullosa is a group of mechano-bullous genetic disorders caused by mutations in the genes encoding structural proteins of the skin. Dystrophic epidermolysis bullosa is caused by mutations in the COL7A1 gene encoding collagen VII, the main constituent of anchoring fibrils. In this group, there are autosomal dominant and recessive inheritances. The pre-tibial form is characterized by the presence of blisters, milia, atrophic scars and lesions similar to lichen planus. The diagnosis is clinical and laboratory and subtypes are distinguished by means of immunohistochemical and ultrastructural studies, in addition to genetic differentiation. Electron microscopy and immunomapping are used in the diagnosis.

Mutation analysis of the COL7A1 gene in pretibial dominant dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective To explore the role of type Ⅶ collagen (COL7A1) gene in the pathogenesis of pretibial dominant dystrophic epidermolysis bullosa (DDEB-Pt).Methods Peripheral blood samples were obtained from a sporadic Chinese patient of Han nationality with DDEB-Pt,his parents and 100 healthy human controls.A modified salting-out method was used to extract genomic DNA from the blood samples,and PCR was performed to amplify 118 exons of the COL7A1 gene followed by DNA sequencing.Results A G→A mutation was identified at position 6109 (G6109A) in exon 78 of the COL7A1 gene in this patient,which caused a change from GCT to ACT at codon 2037 in the triple helix region,and resulted in the substitution of glycine (Gly) by arginine (Arg) (p.Gly2037Arg).Conclusion A novel glycine substitution mutation was identified in the COL7A1 gene in the patient with DDEB-Pt,which may be a pathogenic mutation.

Epidermolysis Bullosa Pruriginosa with Nail Dystrophy: A Rare Case Report.

Epidermolysis bullosa (DEB) pruriginosa is a type of dystrophic DEB wherein there is a mutation in gene COL VII A1, which encodes anchoring fibril protein Type VII collagen. Clinically, it is characterized by intensely pruritic linear lichenified or nodular prurigo like lesions over extremities with milia, nail dystrophy, and in some cases albopapuloid lesions over trunk. Here we report a case of an adult onset DEB pruriginosa with typical clinical features which was confirmed by histopathology. In any severely itchy skin lesion over pretibial region, DEB pruriginosa should be kept in mind, and DEB pruriginosa can occur for the first time in adulthood also.

Reabilitação com implantes dentários em paciente diagnosticado com epidermólise bolhosa distrófica dominante / Rehabilitation with dental implants of patient diagnosed with dominant dystrophic epidermolysis bullosa

Epidermólise bolhosa (EB) é caracterizada pela fragilidade excessiva da pele e membranas mucosas com formação de bolhas recorrentes, erosões e cicatrizes secundárias a traumas mecânicos e fricção. As manifestações bucais da EB dificultam a higienização e a realização de tratamentos restauradores, podendo levar à perda precoce da dentição, gerando quadros de edentulismo. O presente estudo relata um caso de reabilitação oral mandibular de paciente diagnosticado com EB distrófica dominante, utilizando prótese total implantossuportada, alternativa às próteses removíveis e implantomucossuportadas responsáveis por gerar fricção sobre a mucosa oral. Optou-se pela extração dos dentes remanescentes comprometidos e restauração da função mastigatória e estética do paciente, com uma prótese total suportada por quatro implantes instalados na região interforaminal. Foram realizados ajustes específicos à técnica anestésica e protocolo cirúrgico com o intuito de minimizar o trauma aos tecidos moles. A prótese definitiva foi instalada sete dias após a cirurgia. Com seis meses de acompanhamento, a paciente relatou melhora significativa da função mastigatória e redução das lesões orais, o que sugere que implantes dentários podem ser utilizados como forma de retenção para reabilitação protética em pacientes diagnosticados com EB, conferindo-lhes uma melhor qualidade de vida.

Epidermolysis bullosa (EB) is characterized by excessive fragility of the skin and mucosa, with repeated blistering, erosions and scar formation secondary to trauma and mechanical friction.The oral manifestations of EB hinder oral cleaning and restorative treatments, which may lead to early tooth loss. The present study reports a case of mandibular oral rehabilitation of a patient diagnosed with dominant dystrophic EB through the use of implant-supported prosthesis, avoiding dentures and overdentures that create frictioning on the oral mucosa. Compromised remaining teeth were extracted. Then, masticatory and esthetic functions were restored with a complete denture supported by 4 implants placed in the interforaminal region. Specific adjustments were made to the anesthetic and surgical protocol in order to minimize trauma to the soft tissues. The definitive prosthesis was installed 7 days after surgery. At 6 months of follow-up, the patient reported significant improvement on masticatory function and reduction of oral lesions, suggesting that dental implants can be successfully used as a means of retention for prosthetic rehabilitation in patients diagnosed with EB, giving them a better quality of life.

Scanning electron microscopy of a blister roof in dystrophic epidermolysis bullosa / Microscopia eletronica de varredura do teto de uma bolha de epidermolise bolhosa distrofica

In dystrophic epidermolysis bullosa the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane, with its consequent loss. We performed scanning electron microscopy of an inverted blister roof of a case of dystrophic epidermolysis bullosa, confirmed by immunomapping and gene sequencing. With a magnification of 2000 times a net attached to the blister roof could be easily identified. This net was composed of intertwined flat fibers. With higher magnifications, different fiber sizes could be observed, some thin fibers measuring around 80 nm and thicker ones measuring between 200 and 300 nm.

Na epidermólise bolhosa distrófica, o defeito genético das fibrilas ancorantes leva à clivagem abaixo da membrana basal, com sua consequente perda. Realizamos microscopia eletrônica de varredura do teto invertido de uma bolha de um caso de epidermólise bolhosa distrófica, cujo diagnóstico foi confirmado com imunomapeamento e com sequenciamento gênico. Com uma ampliação de 2.000 vezes, pôde ser facilmente identificada uma rede ligada ao teto da bolha. Essa rede era composta por fibras achatadas e entrelaçadas. Com grandes aumentos, fibras de diferentes tamanhos puderam ser observadas: algumas finas, medindo cerca de 80 nm, e outras mais largas, medindo entre 200 nm e 300 nm.

Inherited epidermolysis bullosa: clinical and therapeutic aspects / Epidermólise bolhosa hereditária: aspectos clínicos e terapêuticos

Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages.

A epidermólise bolhosa hereditária (EBH) compreende um grupo heterogêneo de desordens genéticas que têm em comum a fragilidade cutânea e, em alguns casos mucosa, predispondo ao desenvolvimento de bolhas e/ou erosões após fricção ou trauma mínimo. Crianças com história recorrente deste tipo de lesão ou neonatos que as apresentem na ausência de outra explicação plausível devem ser investigados. O diagnóstico deve se basear em achados clínicos e histopatológicos. Até o presente momento, o manejo da EBH consiste basicamente em evitar os traumas desencadeadores das lesões, bem como evitar a infecção e facilitar a cicatrização das feridas com o uso sistemático de curativos.

Light and transmission electron microscopy of generalized dystrophic epidermolysis bullosa (Pasini's albopapuloid subtype) / Microscopia óptica e eletrônica de transmissão da epidermólise bolhosa distrófica generalizada (subtipo albo-papulóide de Pasini)

Pasini's albopapuloid epidermolysis bullosa is a very rare subtype of generalized dystrophic dominant epidermolyis bullosa. A 30 year-old white female patient presented since her childhood disseminated small blisters and papules. Light microscopy of a blister showed dermal-epidermal cleavage; moreover, focal areas of dermal-epidermal splitting were also observed. Transmission electron microscopy also identified focal areas of cleavage, which were seen below the lamina densa. It is important to recognize this condition as a variant of epidermolysis bullosa, since the most important cutaneous findings are generalized papules and not blisters and erosions as in other forms of epidermolysis bullosa.

A epidermólise bolhosa albo-papulóide de Pasini é uma variante rara da forma generalizada de epidermólise bolhosa distrófica dominante. Uma paciente de 30 anos apresenta desde a infância pápulas e bolhas disseminadas. A microscopia óptica de uma bolha demonstrou clivagem dermo-epidérmica; além disso áreas focais de desprendimento dermo-epidérmico foram encontradas. A microscopia eletrônica de transmissão identificou a clivagem abaixo da lâmina densa. É importante que se reconheça essa variante de epidermólise bolhosa, já que o aspecto clínico predominante são pápulas disseminadas e não bolhas como nas outras formas de epidermólise bolhosa.

Clinical variability in dystrophic epidermolysis bullosa and findings with scanning electron microscopy / Variabilidade clínica em epidermólise bolhosa distrófica e achados de microscopia eletrônica de varredura

In dystrophic epidermolysis bullosa, the genetic defect of anchoring fibrils leads to cleavage beneath the basement membrane and its consequent loss. A 46 year-old female patient presented blisters with a pretibial distribution associated with nail dystrophy. Her two children had hyponychia and anonychia, which affected all toe nails and the thumb, forefinger and middle finger. DNA sequencing identified in exon 75 of COL7A1 gene a pathologic mutation: c.6235G>A (p.Gly2079Arg). Immunomapping of a blister demonstrated collagen IV (basal membrane) in the blister roof and collagen VII in its floor, confirming dystrophic epidermolysis bullosa. Scanning electron microscopy of an inverted blister showed net-forming collagen attached to the blister roof . The variability found in this family has already been reported and confirms, on a clinical basis, the nail subtype as a dystrophic variant.

Na epidermólise bolhosa distrófica, o defeito genético das fibrilas de ancoragem leva à clivagem abaixo da membrana basal com sua consequente perda. Uma paciente de 46 anos apresentava bolhas pré-tibiais associadas à distrofia ungueal. Seus dois filhos apresentavam hipo e anoníquia, afetando todas as unhas dos pododáctilos e dos primeiros, segundos e terceiros quirodáctilos. O sequenciamento de DNA identificou no exon 75 do gene COL7A1 uma mutação patológica: c.6235G>A (p.Gly2079Arg). O imunomapeamento identificou o colágeno IV no teto e colágeno VII no assoalho de uma bolha , confirmando o diagnóstico de epidermólise bolhosa distrófica. A microscopia eletrônica de varredura de um teto invertido de bolha demonstrou rede de colágeno aderida ao mesmo. A variabilidade clínica encontrada nessa família já foi escrita e confirma, que o subtipo ungueal das epidermólises bolhosas é uma forma distrófica.

Analysis of COL7A1 gene mutations in a family with recessive dystrophic epidermolysis bullosa inversa / 中华皮肤科杂志

Objective To observe the ultrastructural features of recessive dystrophic epidermolysis bullosa inversa(RDEB-Ⅰ)and to detect the mutations of COL7A1 gene in a family with RDEB-Ⅰ.Methods A 24-year-old male patient complained of recurrent vesicles in the skin for 24 years.The lesions began as generalized pruritic vesicles and bullae soon after birth,with a predilection for areas subject to friction,and showed a trend to be worse in summer but mild in winter.No photosensitivity was observed.When he was 3 to 4 years old,the lesions were decreased in number,with the only involvement of the trunk and abdomen;thereafter,the lesions were improved year by year.The patient suffered from nephritis at the age of 5 years,which progressed into renal failure at the age of 15 years.He received renal transplantation and was given long-term oral tacrolimus and mycophenolate mofetil,which leaded to an improvement in the lesions.The family history was unremarkable,and the marriage between her parents was not consanguineous.Dermatological examination revealed large areas of irregularly-marginated,hypopigmented,atrophic scar on the waist,back and abdomen with onychodystrophy involving multiple nails.No vesicles were observed.Immunofluorescence antigen mapping and transmission electron microscopy were conducted to observe the expression of type Ⅶ collagen in and ultrastructure of cutaneous lesions from the patient.Venous blood samples were obtained from the patient as well as his parents and 3 sisters,and drill biopsy specimens were obtained from the margin of vesicular lesions and unaffected anterior tibial skin of the patient.DNA specimens were obtained from the blood samples of the family members and 150 unrelated healthy controls,and RNA was extracted from the biopsy samples of the patient.PCR and direct sequencing were carried out to detect mutations in COL7A1 gene,and reverse transcription-PCR was conducted to confirm the mutation at mRNA level.Results Skin cleavage was observed under lamina densa in the dermis,with a decrease in anchoring fibrils and expression of type Ⅶ collagen in the lesions of the patient.A heterozygous synonymous mutation c.C5499T which created a new splicing site and leaded to a premature terminal codon,as well as a heterozygous missense mutation c.C6205T(C-T transition at codon 2069:CGT to TGT)which leaded to the substitution of arginine by cysteine,were identified in the COL7A1 gene of the proband and all of his sisters,but not in any of the unrelated controls.The c.C5499T and c.C6205T mutations were inherited from the patient's father and mother respectively.Conclusion The compound heterozygous mutations c.C6205T and c.C5499T may be responsible for RDEB-Ⅰ in this patient.

Nevo da epidermólise bolhosa: aspectos clínicos, dermatoscópicos e histológicos em um caso de portador da forma distrófica recessiva / Epidermolysis bullosa nevi: clinical, dermatoscopical and histological features in a case of recessive dystrofic form

As lesões melanocíticas adquiridas podem apresentar aspecto clínico não-usual em pacientes portadores de epidermólise bolhosa hereditária. Essas lesões são conhecidas como "nevos EB" e, muitas vezes, constituem um desafio diagnóstico ao dermatologista por apresentarem características clínicas, dermatoscópicas e histopatológicas semelhantes às encontradas no melanoma. Não são exclusivas de nenhuma forma de epidermólise bolhosa e têm sua frequência aumentada na infância. Relata-se o caso de um doente do sexo masculino, de 6 meses de idade, portador da forma distrófica recessiva da doença, com lesão pigmentada de rápido crescimento na coxa esquerda. Optou-se por seguimento clínico da lesão, considerando que os aspectos clínicos, dermatoscópicos e histológicos eram compatíveis com a descrição de outros casos de nevo EB previamente descritos.

Acquired melanocytic lesions may present unusual clinical features in all forms of hereditary epidermolysis bullosa. These lesions are known as "EB nevi", and often pose a diagnostic challenge for dermatologists given their resemblance - clinically, dermoscopically and histologically - to melanoma. The lesions have been reported in all types of hereditary EB, most of them in childhood. We report the case of a 6-month-old boy suffering from recessive dystrophic epidermolysis bullosa (RDEB) that presented as a large pigmented lesion on his left thigh. We decided to monitor the lesion closely since we considered that the clinical and pathological aspects of the lesion were compatible with the description of other previously reported cases of EB nevi.

Bart Syndrome: a rare entity / Síndrome de Bart: uma entidade rara

Introduction: Bart Syndrome is a rare inherited skin blistering disorder. It is also known as congenital transient mechano-bullous dermatosis and is one of the lesser known presentations of epidermolysis bullosa (EB). Case report: The objective of this report is to present a case of Bart Syndrome in a 3 day old newborn female baby. The skin lesions showed denuded areas with bullae rupturing easily to reveal painful eroded areas. Eroded lesions were distributed over the hands, feet, chest and on the face over the cheeks bilaterally. The lips were erythematous, eroded with tissue tags. Eroded, crustated lesions were seen on the labial mucosa and anterior palate. Histopathological examination revealed split localized to the epidermis. The epidermal layer above the spilt appeared to be normal. The basement membrane was intact, along with normal underlying connective tissue. Discussion: Management consisted of decompression of blisters followed by topical antibiotics. Oral corticosteroids were given for control of blistering, since they reduce collagenase activity. Avoidance of trauma is essential aspect of management: baby was nursed with care to prevent occurrence of new lesions. Therapy and counseling sessions were scheduled for the parents.

Introdução: A Síndrome de Bart é uma rara desordem hereditária cutânea bolhosa. Também conhecida comdermatose congênita transiente mecano-bolhosa, é uma das apresentações menos conhecidas de epidermólisebolhosa (EB). Relato de caso: O objetivo deste relato é apresentar um caso de Síndrome de Bart em um neonato(com três dias) do sexo feminino. As lesões de pele caracterizavam-se por áreas desnudas com lesões bolhosas derompimento fácil, revelando áreas erodidas dolorosas. As lesões erodidas estavam distribuídas pelos pés, mãos,peito e face, sobre as regiões malares. Os lábios estavam eritematosos e erodidos. Lesões erodidas e crostosasforam observadas na mucosa labial e no palato anterior. O exame histopatológico revelou fenda localizada naepiderme. A camada epidérmica acima da fenda apresentava normalidade. A membrana basal estava intactae o tecido conjuntivo subjacente normal. Discussão: O tratamento das lesões consistiu na descompressão dasbolhas seguida de uso de antibióticos tópicos. Foram administrados corticosteróides orais, para controle daslesões bolhosas, uma vez que estes reduzem a atividade da colagenase. Evitar o trauma é um aspecto essencialno tratamento desses casos. Assim, o bebê era manejado com cuidado para evitar novas lesões. Foram agendadassessões de terapia e aconselhamento aos pais.

Mutations of COL7A1 gene in three cases of dystrophic epidermolysis bullosa pruriginosa / 中华皮肤科杂志

Objective To detect the mutations of COL7A1 gene in three cases of dystrophic epidermolysis bullosa pruriginosa (DEBP). Methods Clinical data were collected from 3 patients with DEBP. Skin lesions were obtained from these patients and subjected to transmission electron microscopy. DNA was extracted from the peripheral blood of the 3 patients, their 16 relatives, and 150 unrelated normal human controls, and PCR was performed to amplify all the exons and flanking sequences of COL7A1 gene followed by sequencing.Results The patient 1 and 2 had family history, whereas the case 3 was sporadic. Transmission electron microscopy showed tissue cleavage beneath lamina densa in case 1 and slightly decreased anchoring fibrils in some areas of the lesions in case 1 and 3. Three heterozygous mutations of COL7A1 gene, i.e., c. G6734T, c.G6859A and c. G5318T, which leaded to three amino acid mutations, i.e., p. G2245V, p. G1773V and p. G2287R, were found in patient 1, 2 and 3 respectively. Of them, p. G2245V and p. G1773V were novel mutations. The mutations strictly cosegregated with the phenotype in the patients of family 1 and 2. No mutation was detected in the unaffected parents of patient 3 or the 150 unrelated healthy controls. Conclusions The p. G2245V, p. G2287Rand p. G1773V mutations of COL7A1 gene may be responsible for the phenotype of DEBP in the three cases,and of them, p. G2245V and p. G1773V have never been reported.