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Epidermolysis Bullosa (epidermolysi + bullosa)
Kinds of Epidermolysis Bullosa Terms modified by Epidermolysis Bullosa Selected AbstractsMutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosaEXPERIMENTAL DERMATOLOGY, Issue 7 2008Ningning Dang Abstract:, Dystrophic epidermolysis bullosa (DEB) is inherited in both an autosomal dominant DEB and autosomal recessive manner RDEB, both of which result from mutations in the type VII collagen gene (COL7A1). To date, 324 pathogenic mutations have been detected within COL7A1 in different variants of DEB; many mutations are clustered in exon 73 (10.74%) which is close to the 39 amino acid interruption region. Dominant dystrophic epidermolysis bullosa usually involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice-site mutations may underlie some cases. In recessive dystrophic epidermolysis bullosa, the mutations include nonsense, splice site, deletions or insertions, ,silent' glycine substitutions within the triple helix and non-glycine missense mutations within the triple helix or non-collagenous NC-2 domain. The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes. [source] Cholinergic control of epidermal cohesionEXPERIMENTAL DERMATOLOGY, Issue 4 2006Sergei A. Grando Abstract:, The non-neuronal cholinergic system of human epidermis includes the keratinocyte (KC) acetylcholine (ACh) axis composed of the enzymes mediating ACh synthesis and degradation, and two classes of ACh receptors, the nicotinic and muscarinic ACh receptors, mediating biological effects of the cutaneous cytotransmitter ACh. Regulation of KC cell,cell and cell,matrix adhesion is one of the important biological functions of cutaneous ACh. The downstream targets of ACh effects mediated by distinct ACh receptor subtypes include both the intercellular adhesion molecules, such as classical and desmosomal cadherins, and integrins mediating KC adhesion to a substrate. The signaling pathways include activation or inhibition of kinase cascades resulting in either up- or down-regulation of the expression of cell adhesion molecules or changes in their phosphorylation status, or both. The components of the KC ACh axis are involved in cutaneous blistering in patients with autoimmune pemphigus, junctional and dystrophic forms of epidermolysis bullosa, thermal burns, and mustard-induced vesication. Recent progress with the development of antiacantholytic therapies of patients with pemphigus using cholinomimetics indicates that cholinergic drugs may be a promising approach for other cutaneous blistering disorders. [source] Paternal germline mosaicism in Herlitz junctional epidermolysis bullosaEXPERIMENTAL DERMATOLOGY, Issue 5 2002Peter B. Cserhalmi-Friedman Abstract: We studied a single patient with the lethal (Herlitz) type of junctional epidermolysis bullosa (H-JEB). Screening for mutations in the LAMB3 gene in the patient revealed the previously described hotspot mutation R635X and a novel one basepair deletion in exon 10. The single basepair deletion 1094delA could be detected in the clinically unaffected mother, while the nonsense mutation R635X could not be found in the peripheral blood DNA of either parent. After excluding non-paternity by microsatellite analysis using random markers on chromosomes 3, 8 and 18, we determined that the mutation R635X in the proband was most likely the result of a de novo event or alternatively, germline mosaicism. The parents requested prenatal diagnosis for a second pregnancy, and while the maternal mutation 1094delA could not be detected in DNA from the fetus, unexpectedly, the mutation R635X was present in the chorionic villus DNA. These findings were most consistent with paternal germline mosaicism for the recessive mutation R635X. The results have had a significant impact on the genetic counseling in this family. To our knowledge, this study represents the first documented case of germline mosaicism in junctional epidermolysis bullosa, and serves as a reminder that germline mosaicism should be considered in cases in which a ,new' mutation is found in the offspring of a clinically and/or genetically unaffected parent. [source] Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex,HUMAN MUTATION, Issue 10 2010Ken Natsuga Abstract Plectin is a cytoskeletal linker protein which has a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC) cause two distinct autosomal recessive subtypes of epidermolysis bullosa: EB simplex (EBS) with muscular dystrophy (EBS-MD), and EBS with pyloric atresia (EBS-PA). Previous studies have demonstrated that loss of full-length plectin with residual expression of the rodless isoform leads to EBS-MD, whereas complete loss or marked attenuation of expression of full-length and rodless plectin underlies the more severe EBS-PA phenotype. However, muscular dystrophy has never been identified in EBS-PA, not even in the severe form of the disease. Here, we report the first case of EBS associated with both pyloric atresia and muscular dystrophy. Both of the premature termination codon-causing mutations of the proband are located within exon 32, the last exon of PLEC. Immunofluorescence and immunoblot analysis of skin samples and cultured fibroblasts from the proband revealed truncated plectin protein expression in low amounts. This study demonstrates that plectin deficiency can indeed lead to both muscular dystrophy and pyloric atresia in an individual EBS patient. © 2010 Wiley-Liss, Inc. [source] Sporadic dystrophic epidermolysis bullosa with albopapuloid and prurigo- and folliculitis-like lesionsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2009Yi-Ming Fan MD A case of sporadic dystrophic epidermolysis bullosa (DEB) with albopapuloid and prurigo- and folliculitis-like lesions is reported. Histopathology of the scalp biopsy showed hyperkeratosis, a subepidermal cleft near the orifice of a hair follicle, dermal fibrosis, and a moderate perivascular and perifollicular lymphohistiocytic inflammatory cell infiltrate in the papillary dermis, without neutrophilic infiltrate in the orifice of the hair follicle. It is uncertain whether the present case should be classified as DEB pruriginosa or represents a new subtype of DEB. [source] Pretibial epidermolysis bullosa: is this case a new subtype with loss of types IV and VII collagen?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2009Hong-sun Lee MD Pretibial epidermolysis bullosa (PEB) is an extremely rare subtype of dominant dystrophic epidermolysis bullosa (DDEB), in which recurrent blistering with scarring predominantly involves the pretibial skin. Nail dystrophy, albopapuloid lesions, and hypertrophic scars may also occur. In PEB, immunohistochemical and electron microscopic studies demonstrate the complete or partial loss of the anchoring fibril (AF) in the basement membrane zone, suggesting disturbed synthesis or excessive degradation of collagen VII, the main component of AF. Interestingly, we report a case of PEB with unusual results of joint loss of types IV and VII collagen. [source] Squamous cell carcinoma complicating epidermolysis bullosa in a 6-year-old girlINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2009Kanakapura Nanjundaswamy Shivaswamy MD Recessive dystrophic epidermolysis bullosa (RDEB) is a rare form of epidermolysis bullosa (EB) that presents with generalized blistering since birth. Squamous cell carcinoma (SCC) is the most common cutaneous malignancy seen in RDEB, starting from second decade onwards. We report a case of SCC complicating RDEB in a 6-year-old girl. [source] Basic science of epidermolysis bullosa and diagnostic and molecular characterization: Proceedings of the IInd International Symposium on Epidermolysis Bullosa, Santiago, Chile, 2005INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2007Ellen G. Pfendner PhD First page of article [source] Compound heterozygosity in sibling patients with recessive dystrophic epidermolysis bullosa associated with a mild phenotypeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2006Y. Shibusawa MD We describe two cases of a 3-year-old Japanese boy and his 1-year-old sister presenting recessive dystrophic epidermolysis bullosa; a relatively mild phenotype. Blistering and scarring were limited to the acral region, and some fingernails and toenails were lost. PCR-RFLP and DNA sequencing analyses revealed compound heterozygotes for a splice-site mutation (6573 +1GtoC) and a nonsense mutation (E2857X) in the type VII collagen gene (COL7A1). Both mutations caused a premature termination codon (PTC). The mutation E2857X was located behind the candidate cleavage site within the NC-2 domain required for the assembly of anchoring fibrils. This PTC position may explain their mild phenotype. [source] A Japanese case of Kindler syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2000Yasushi Suga MD A 25-year-old Japanese woman presented with contracture of the fingers and toes, and difficulty in opening her mouth. Her grandparents are first cousins, but none of the other members of the family are affected. Bulla formation started at birth on areas of the skin that received pressure, and in infancy and early childhood the lesions were limited only to the acral areas. She also had bilateral, incomplete syndactylies involving all web spaces ( Fig. 1a). The formation of blisters ceased after the age of 15 years, but a generalized progressive poikiloderma then appeared with accompanying cutaneous atrophy of the skin of the neck, trunk, and extremities ( Fig. 1b). The patient experienced mild photosensitivity of the face and neck. At age 18 years, surgical removal of the webbing of all her fingers was performed. Oral examination showed atrophy of the buccal mucosa, and an inability to fully open the mouth. The patient also suffered from poor dentition and easily bleeding gums, but had no symptoms of esophageal dysfunction. Figure 1. Clinical manifestations of the patient with Kindler syndrome. (a) Dorsal surface of the patient's hands. Note the marked cutaneous atrophy with a severely wrinkled appearance on the dorsal surface of the hands, as well as the proximal fusion of the fingers. (b) Lower left leg of the patient. Atrophic thinning of the skin and poikiloderma with reticular pigmentation are evident Histology of separate biopsy specimens, taken from the poikilodermatous pretibial and trunk skin, showed classical features of poikiloderma, namely epidermal atrophy with flattening of the rete ridges, vacuolization of basal keratinocytes, pigmentary incontinence, and mild dermal perivascularization ( Fig. 2a). Interestingly, dyskeratotic cells ( Fig. 2b) and eosinophilic rounded bodies (colloid bodies) ( Fig. 2c) were frequently found at the basal keratinocyte layer and in the upper dermis, respectively. Pigment was also present in the upper epidermis. Figure 2. Hematoxylin and eosin staining of a biopsy specimen taken from pretibial skin. (a) Epidermal atrophy with flattening of the rete ridges. Note the dyskeratotic cells (arrowheads) and vacuolar degeneration of the basal layer in the epidermis. Bar = 50 ,m. (b) Higher magnification of dyskeratotic cells (arrowheads). Bar = 10 ,m. (c) Higher magnification of colloid bodies (arrowheads) in the superficial dermis. Bar = 10 ,m To rule out the possibility of a congenital epidermolysis bullosa, ultrastructural and immunofluorescence studies were performed. Ultrastructural studies demonstrated the reduplication of the basal lamina with branching structures within the upper dermis and cleavage between the lamina densa and the cell membrane of the keratinocytes ( Fig. 3a). The numbers of associated anchoring fibrils did not seem to be reduced, and colloid bodies and dyskeratotic cells were detected. Immunofluorescence studies with the antibody against type VII collagen (LH 7 : 2) were subsequently carried out. The results showed extensive broad bands with intermittently discontinuous and reticular staining at the dermo-epidermal junction (DEJ) ( Fig. 3b), whereas a linear distribution is typically seen in healthy tissue (data not shown). Interestingly, direct immunofluorescence studies revealed intracellular accumulation of immunoglobulin G (IgG), IgM, IgA, and C3 in colloid bodies under the basement membrane ( Fig. 3c). Figure 3. Ultrastructural and immunohistochemical findings of the patient with Kindler syndrome. (a) Ultrastructural study of the dermo-epidermal junction. The branching structures of the lamina densa (arrowheads) were frequently seen. The asterisks show the cleavage in the lamina lucida. Bar = 1 ,m. (b) Immunohistochemical studies with the antibody to type VII collagen (LH 7 : 2). An extensive broad band with reticular patterns is evident. Bar = 50 ,m. E, epidermis; D, dermis. (c) Direct immunofluorescence study. Intracytoplasmic deposition of IgM in the basal keratinocytes is evident (arrowheads). Bar = 50 ,m. E, epidermis; D, dermis [source] Acellular dermal matrix allograft used to gain attached gingiva in a case of epidermolysis bullosaJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2003Eralp Buduneli Abstract Background: Epidermolysis bullosa (EB) is an acquired disease or inherited as either autosomal dominant or recessive with an incidence of 1/50,000. The prominent clinical characteristic of the disease is the development of bullae or vesicles in mucosa or skin in response to minor trauma. Aim: A female patient with a dystrophic type of EB had been put in a maintenance regimen after completion of the initial phase of periodontal therapy and followed for 7 years. The purpose of this report is to document acellular dermal matrix allograft application to increase the width of the attached gingiva in this patient experiencing difficulty in chewing and performing plaque control due to the dramatic loss of attached gingiva after 7 years of supportive periodontal therapy. Methods: Under local anaesthesia and antibiotic coverage, the acellular dermal matrix allograft was applied in the anterior region of the upper jaw in order to increase the width of attached gingiva, thereby improving patient comfort. Results: The healing was uneventful and a significant gain in attached gingiva dimensions was observed 9 months after the periodontal surgery. The procedure avoided a second surgical site, provided satisfactory results from an aesthetic point of view, and improved patient comfort. Conclusion: Acellular dermal matrix allograft may be regarded as an alternative in the treatment of EB cases to increase the width of attached gingiva and facilitate maintenance of the dentition. Zusammenfassung Hintergrund: Die Epidermolysis bullosa (EB) ist eine erworbene oder eine autosomal dominant oder rezessiv vererbte Krankheit mit einer Incidenz von 1:50,000. Die hervorstechenden klinischen Symptome dieser Erkrankung sind die Entwicklung von Blasen oder Vesikeln in der Mukosa oder in der Haut auf geringste Traumen. Ziel: Eine Frau mit dem dystrophischen Typ von EB wurde in der Erhaltungsphase seit 7 Jahren geführt, nachdem die initiale Phase der parodontalen Therapie beendet worden war. Der Zweck dieser Studie ist die Dokumentation der Applikation eines azellulären Hautmatrixtransplantats für die Verbreiterung der fest angewachsenen Gingiva bei dieser Patientin, die nach 7 Jahren der erhaltenden parodontalen Therapie Probleme beim Kauen und bei der Durchführung der Plaquekontrolle durch einen starken Verlust an fest angewachsener Gingiva hatte. Methoden: Unter lokaler Anästhesie und antibiotischer Abschirmung wurde das azelluläre Hautmatrixtransplantat in die anteriore Region des Oberkiefers appliziert, um die Breite der fest angewachsenen Gingiva zu vergrößern und so das Befinden der Patientin zu verbessern. Ergebnisse: Die Heilung war komplikationslos, und ein signifikanter Gewinn an fest angewachsener Gingiva 9 Monate nach der parodontalen Operation wurde beobachtet. Die Methode vermied eine zweite chirurgische Region, erbrachte zufriedenstellende Ergebnisse aus ästhetischer Sicht und verbesserte das Befinden der Patientin. Schlussfolgerung: Das azelluläre Hautmatrixtransplantat kann als eine Alternative in der Behandlung von EB betrachtet werden, um die Breite der fest angewachsenen Gingiva zu vergrößern und zur Möglichkeit der Erhaltung der Dentition beizutragen. Résumé La bullose épidermolysie (EB) est une maladie contractée ou héritée qui peut être aussi bien autosomale dominante que récessive avec une fréquence de 1/50,000. La caractéristique clinique importante de la maladie est le développement de bulles ou de vésicules au niveau de la muqueuse ou de la peau comme réponse à un traumatisme mineur. Une femme avec un type dystrophique de EB a été placée dans un régime de maintenance après la fin de la phase initiale du traitement parodontal et suivie durant sept années. Le but de ce rapport est de documenter le placement d'un allographe de la matrice dermique acellulaire visant à augmenter la largeur de la gencive attachée chez cette patiente qui avait des problèmes aux niveaux masticatoire et du contrôle de la plaque dentaire vu la perte dramatique de la gencive attachée après sept années de maintenance parodontale. Sous anesthésie locale et sous couverture antibiotique, l'allographe de la matrice dermique acellulaire a été placé dans la région antérieure de la mâchoire supérieure pour augmenter la largeur de la gencive attachée afin d'améliorer le confort de la patiente. La guérison s'est déroulée sans problème et un gain significatif de gencive attachée a été observé neuf mois après la chirurgie parodontale. Ce processus chirurgical élimine la nécessité d'avoir un site donneur, apporte des résultats satisfaisants du point de vue esthétique et améliore le confort du patient. L'allographe de la matrice dermique acellulaire peut donc être considéré comme une alternative dans le traitement des cas de EB afin d'augmenter la largeur de la gencive attachée et faciliter le maintien de la dentition. [source] Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2004S Ingen-Housz-Oro ABSTRACT Background, In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. Objective, In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. Methods, Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. Results, Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36,70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. Conclusion, Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood. [source] Increased risk of squamous cell carcinoma in junctional epidermolysis bullosaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2004R Mallipeddi ABSTRACT 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. [source] Review article: Perioperative care of patients with epidermolysis bullosa: proceedings of the 5th international symposium on epidermolysis bullosa, Santiago Chile, December 4,6, 2008PEDIATRIC ANESTHESIA, Issue 9 2010FAAP, KENNETH GOLDSCHNEIDER MD Summary Epidermolysis bullosa (EB) has become recognized as a multisystem disorder that poses a number of pre-, intra-, and postoperative challenges. While anesthesiologists have long appreciated the potential difficult intubation in patients with EB, other systems can be affected by this disorder. Hematologic, cardiac, skeletal, gastrointestinal, nutritional, and metabolic deficiencies are foci of preoperative medical care, in addition to the airway concerns. Therefore, multidisciplinary planning for operative care is imperative. A multinational, interdisciplinary panel of experts assembled in Santiagio, Chile to review the best practices for perioperative care of patients with EB. This paper presents guidelines that represent a synthesis of evidence-based approaches and the expert consensus of this panel and are intended to aid physicians new to caring for patients with EB when operative management is indicated. With proper medical optimization and attention to detail in the operating room, patients with EB can have an uneventful perioperative course. [source] Aplasia Cutis Congenita in a Defined Population from Northwest SpainPEDIATRIC DERMATOLOGY, Issue 6 2006Soledad Martinez-Regueira M.D. It may occur as an isolated defect or associated with other anomalies. This study sought to determine the frequency of this condition over a 10-year-period at the single hospital for a well-defined population. A literature review of potential mechanisms implicated in the development of this condition was also conducted. A retrospective review of all case records of patients diagnosed with aplasia cutis congenita between January 1994 and December 2003 at Hospital Xeral-Calde, in the Lugo region of northwest Spain was undertaken. During the period of study four patients were diagnosed with this condition. Three of them were of the gypsy race. These three had aplasia cutis congenita associated with epidermolysis bullosa and deformed nails. The incidence of aplasia cutis congenita in our region was 2.8 cases per 10,000 newborns. It was found that the incidence of this disorder in northwest Spain was similar to that described in the literature. Careful study due to the frequent association of aplasia cutis congenita with other congenital anomalies and a complete obstetric and family history of all affected individuals are required to identify possible specific teratogens, intrauterine infections, chromosomal abnormalities, or history of this condition among relatives. [source] Herpetic Infection in Epidermolysis BullosaPEDIATRIC DERMATOLOGY, Issue 4 2006Adam I. Rubin M.D. Standard wound care practices advocate the use of special dressings on open erosions as well as antibiotic topical medications to treat and prevent cutaneous infections. We report a child with recessive dystrophic epidermolysis bullosa admitted to our institution because of fevers at home. She was treated with multiple antibiotics for a cutaneous infection of the right hand. During her hospital stay, she sustained persistent fevers, and oral erosions developed, with progressive hemorrhagic crusting. Viral culture of the lip grew herpes simplex virus type 1, consistent with a diagnosis of herpetic gingivostomatitis. We present this patient to illustrate the importance of investigating wounds of epidermolysis bullosa patients for viral agents when faced with managing a child with an unclear source of fever. To the best of our knowledge, although this is the first report of herpetic gingivostomatitis in association with epidermolysis bullosa, it is likely to be more prevalent than the literature could suggest. [source] Large Atypical Melanocytic Nevi in Recessive Dystrophic Epidermolysis Bullosa: Clinicopathological, Ultrastructural, and Dermoscopic StudyPEDIATRIC DERMATOLOGY, Issue 4 2005Fernando Gallardo M.D. The lesion was clinically atypical and fulfilled the criteria for a malignant melanocytic proliferation. A complete surgical excision was performed. Histopathologic examination disclosed a compound melanocytic nevus without melanocytic atypia. Ultrastructural examination showed melanocytic cells located both at the roof and the floor of the blister. Several months later, three pigmentary lesions with a similar clinical appearance developed. Periodic clinical and dermoscopic examinations were recommended. Dermoscopic examination disclosed a globular pattern with brown globules and black dots distributed all over the lesions. The lesions also exhibited blue-greyish dots and multiple rounded white structures corresponding to milia-like cysts. No dermoscopic features suggestive of malignancy were noted. Acquired melanocytic nevi showing atypical clinical features have been reported to occur in areas of blistering in patients with epidermolysis bullosa. These nevi appear as large, asymmetrical pigmentary lesions with irregular borders. Initially, they are very dark in pigmentation, with color variegation and loss of pigment, and even becoming papillomatous over time. Histopathologic examination can show features of compound/junctional nevus as well as persistent/recurrent nevus. The concept of "epidermolysis bullosa nevus" has been proposed to define these peculiar lesions. The clinical, histopathologic and ultrastructural features of these nevi are reviewed. The usefulness of dermoscopic examination in the routine diagnosis and follow-up of these lesions are stressed. [source] Junctional epidermolysis bullosa with pyloric stenosisPEDIATRIC DERMATOLOGY, Issue 6 2001Dean S. Morrell MD No abstract is available for this article. [source] Epidermolysis bullosa nevus arising in a patient with Dowling,Meara type epidermolysis bullosa simplex with a novel K5 mutationTHE JOURNAL OF DERMATOLOGY, Issue 8 2009Hiroko SUGIYAMA-FUKAMATSU Abstract We report herein a 4-year-old girl with Dowling,Meara type epidermolysis bullosa (EB) who presented with peculiar pigmented nevi. Blister formation had repeatedly occurred on the erythematous plaques in a circinate fashion since birth, and marked hyperkeratosis was observed on the palms and soles associated with nail deformity. Her mother and maternal grandmother also had similar symptoms. In addition to the blistering lesions, the patient had three large, asymmetrical, pigmented plaques with color variegation. Light and electron microscopic findings of the blistering lesions showed a subepidermal blister with intracytoplasmic granules in keratinocytes as well as degeneration of basal cells and aggregation of tonofilaments. The pigmented lesions revealed histopathological features of compound nevus without malignant changes. Gene analysis revealed an E478K (Glu to Lys) mutation in exon 5 of the keratin 5 (K5) gene. These findings, together with clinical features, were consistent with those of Dowling,Meara type EB associated with so-called EB nevus. [source] Recessive dystrophic epidermolysis bullosa: Case of non-Hallopeau,Siemens variant with premature termination codons in both allelesTHE JOURNAL OF DERMATOLOGY, Issue 11 2006Nozomi YONEI ABSTRACT Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding collagen, the major component of anchoring fibrils. Premature termination codon (PTC) mutations in both alleles usually lead to the Hallopeau,Siemens variant that shows the most severe phenotype. We experienced a case of the non-Hallopeau,Siemens variant (nHS-RDEB), which had a mild clinical severity although it has PTC mutations in both alleles. Our patient was a compound heterozygote for a nonsense mutation (R669X) in exon 15 and a nonsense mutation (E2857X) in exon 116. But we confirmed the existence of some anchoring fibrils on electron micrograph. This suggested that a PTC close to the 3, end of COL7A1 does not completely abolish the collagen VII mRNA. We hypothesized that the truncated procollagen VII from the mutant allele with a nonsense mutation (E2857X) in exon 116 included two out of eight cysteines needed for disulfide bond formation, and hence a few functional anchoring fibrils could be formed. [source] Tracheolaryngeal Complications of Inherited Epidermolysis Bullosa: Cumulative Experience of the National Epidermolysis Bullosa Registry,THE LARYNGOSCOPE, Issue 9 2007Jo-David Fine MD Abstract Objectives/Hypothesis: To accurately determine the frequency with which complications arise in the ears, noses, and throats of patients with inherited epidermolysis bullosa (EB) as well as the cumulative risk of tracheolaryngeal stenosis or stricture. Study Design: Cross-sectional study (3,280 patients) with a nested, randomly sampled longitudinal subcohort (n = 450), representing data collection, stratified by major EB subtype, of the National EB Registry, an epidemiologic project focused on enrolling all EB patients within the continental United States from 1986 to 2002, to permit generalization of findings to the entire American EB population. Methods: Systematic epidemiologic case finding and data collection were performed throughout the continental United States, followed by subclassification of patients by EB subtype. ENT complications were quantified via contingency tables (as frequencies) and lifetable analyses. Frequencies of surgical procedures were also determined. Results: The most important clinical ENT complication in inherited EB was tracheolaryngeal stenosis or stricture, arising during early childhood and primarily within infants and children with junctional EB (JEB) (cumulative risk of 39.8% and 12.8% in Herlitz and non-Herlitz JEB, respectively, by ages 6 and 9). Other uncommon complications included chronic otitis media, chronic otitis externa, and hearing loss. Conclusions: Given the potential risk for sudden airway occlusion and death, meticulous surveillance by a pediatric otolaryngologist is a critical part of the overall management of infants and children with EB, especially those with JEB and two rare subtypes of generalized EB simplex. Elective tracheostomy should be considered in EB infants and children with evidence of airway embarrassment. [source] Partial deletion of the LAMA3 gene is responsible for hereditary junctional epidermolysis bullosa in the American Saddlebred HorseANIMAL GENETICS, Issue 1 2009K. T. Graves Summary Laminin 5 is a heterotrimeric basement membrane protein integral to the structure and function of the dermal,epidermal junction. It consists of three glycoprotein subunits: the ,3, ,3 and ,2 chains, which are encoded by the LAMA3, LAMB3 and LAMC2 genes respectively. A mutation in any of these genes results in the condition known as hereditary junctional epidermolysis bullosa (JEB). A 6589-bp deletion spanning exons 24,27 was found in the LAMA3 gene in American Saddlebred foals born with the skin-blistering condition epitheliogenesis imperfecta. The deletion confirms that this autosomal recessive condition in the American Saddlebred Horse can indeed be classified as JEB and corresponds to Herlitz JEB in humans. A diagnostic test was developed and nine of 175 randomly selected American Saddlebred foals from the 2007 foal crop were found to be carriers of the mutation (frequency of 0.026). [source] Categorizing immunoflourescence mapping in epidermolysis bullosa with pyloric atresia: Use as a broad prognostic indicatorAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2010John W Frew ABSTRACT Epidermolysis bullosa with pyloric atresia is a form of junctional epidermolysis bullosa associated with gastrointestinal abnormalities, which may include pyloric atresia. Genotype phenotype correlation is poorly understood and prognosis is difficult, if not impossible, to predict. Immunoflourescence mapping is an ideal candidate for developing a broad prognostic indicator for epidermolysis bullosa with pyloric atresia without the need for genetic mutation analysis. However, the tool developed in this paper does have limitations due to the small number of cases available and the effects of deleterious mutations in highly conserved cysteine residues on the predicted length of survival. [source] A comparative study between electron microscopy and immunofluorescence mapping in the diagnosis of epidermolysis bullosaAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2006Eleni Yiasemides MBBS INTRODUCTION: The classification of epidermolysis bullosa (EB) into 3 main subtypes has been based on electron microscopy (EM) that is able to directly visualize and quantify specific ultrastructural features. Immunofluorescence antigenic mapping (IFM) is a technique that determines the precise level of skin cleavage by determining the site of binding of a series of antibodies. To date, no study has compared the accuracy of these two techniques in diagnosing the major types of EB. METHODS: A prospective cohort of 33 patients thought to have EB on clinical grounds had both EM and IFM. The sensitivity and specificity of EM and IFM were calculated using the genetic results as the ,gold standard'. Statistical analysis involved the determination of positive and negative predictive values, accuracies, positive and negative likelihood ratios and post-test probabilities of the IFM and EM diagnosis being correct compared to genetic diagnosis. RESULTS: 30/33 cases had a positive EB diagnosis. TEM subclassified EB into its three major forms in 24/30 cases (80%) and IFM in 29/30 cases (97%). Overall, TEM sensitivities and specificities when compared to genetic results were 71% and 81%, respectively. IFM sensitivities and specificities when compared to genetic results were 97% and 100% respectively. If a patient tested positive for EB by IFM, the likelihood ratio of having a particular type of EB was consistently greater than 20 against the reference standard (compared to a likelihood ratio less than 10 for TEM). CONCLUSION: These findings dispute the contention that EM and IFM are equally accurate and sensitive as diagnostic tests for the classification of the major types of EB. The results indicate that the diagnosis of EB is improved (sometimes substantially) by the use of IFM compared to TEM. [source] Branch point and donor splice-site COL7A1 mutations in mild recessive dystrophic epidermolysis bullosaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009B. Drera First page of article [source] Dystrophic epidermolysis bullosa pruriginosa is not associated with frequent FLG gene mutationsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008H. Schumann Summary Background, Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr; OMIM 604129) is a rare manifestation of dystrophic epidermolysis bullosa (DEB), characterized by pruritus, nodular prurigo-like lesions and fragility of the skin mainly in the extremities. Fewer than 40 patients with autosomal dominant or recessive inheritance, or sporadic DEB-Pr, have been described in the literature. Objectives, To disclose mutations in DEB-Pr and to elucidate the role of other pathogenic factors which may influence the pruriginous phenotype. Methods, Seven patients with typical clinical features of DEB-Pr were studied. Results, In all patients, mutations in the gene encoding collagen VII (COL7A1) were disclosed, two of them novel (p.G2623V, p.E2736K). Three mutations were dominant, three recessive and one de novo. In the families with dominant DEB there were one or more members with DEB-Pr, but also at least one affected sibling who did not develop DEB-Pr. In six of seven patients, the clinical history revealed factors that initially induced pruritus, such as atopy, pregnancy, thyroid hormone imbalance, diabetes, infections and contact sensitization. Common filaggrin mutations were ruled out in all patients and normal filaggrin staining was found in the skin samples. Conclusions, DEB-Pr develops as a result of COL7A1 gene mutations and acquired phenotype-modifying factors. Filaggrin mutations did not contribute to the pruriginous phenotype in the present patient cohort. [source] COL7A1 mutational analysis in Korean patients with dystrophic epidermolysis bullosaBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2007S-W. Oh First page of article [source] A child with laryngo-onychocutaneous syndrome partially responsive to treatment with thalidomideBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2006R.M. Strauss Summary Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered. [source] A novel indel COL7A1 mutation 8068del17insGA causes dominant dystrophic epidermolysis bullosaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006D. Sawamura No abstract is available for this article. [source] High frequency of the 425A,G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005M. Csikós Summary Background, Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives, Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods, All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1 -specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results, In this group of patients, the splice-site mutation 425A,G was observed frequently, in 11 of 86 alleles (12·8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C,A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions, High recurrence of the splice-site mutation 425A,G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype,phenotype correlations in different DEB subtypes. [source] | |||||||||||||