scholarly journals Epidermolysis bullosa in Greece: the patients’ journey so far

2018 ◽  
Vol 4 (3) ◽  
pp. 282
Author(s):  
Ioanna Verroiou ◽  
Vassiliki N. Tzanetakou ◽  
Alexandra Katsarou ◽  
Giovanna Zambruno ◽  
Daniele Castiglia ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Clinical Characteristics ◽  
Laboratory Diagnosis ◽  
Published Data ◽  
Laboratory Assessment ◽  
Inherited Disorders ◽  
Mucosal Involvement ◽  
Skin Fragility ◽  
Diagnostic Management ◽  
Adults And Children

<p class="abstract"><strong>Background:</strong> Hereditary epidermolysis bullosa (EB) represents a group of rare, inherited disorders with different penetrance patterns characterized by skin fragility and easy inducibility of blisters. Mucosal involvement of internal organs may occur. As no published data on EB in Greece exist, this study aimed to record demographics and clinical characteristics of EB patients. Another objective was to identify the associations among clinical characteristics of different types in connection with immunofluorescence mapping (IMF) findings and molecular analysis (MA) used for the laboratory diagnosis of the disease.</p><p class="abstract"><strong>Methods:</strong> This is a descriptive study conducted at the outpatient clinic of rare diseases of Andreas Sygros Hospital, Athens, Greece from March 2012 until February 2015. Adults and children presenting with EB were enrolled. Patients underwent a thorough clinical and laboratory assessment. Specific laboratory analyses were performed in Rome and two sets of data based on IFM and MA were collected.<strong></strong></p><p class="abstract"><strong>Results:</strong> In total, 41 patients were enrolled. Prevalence rate of EB was 0.024%. The most frequent type was dystrophic EB, as it affected 20 patients (48.8%). Twelve patients (29.3%) were diagnosed with EB simplex, 6 patients (14.6%) with Kindler syndrome and 3 (7.3%) with junctional EB. IFM was performed in 26 patients and MA in 8 patients. The concordance among clinical and laboratory diagnosis was 88.5%.</p><p class="abstract"><strong>Conclusions:</strong> This study is the first report on hereditary EB in Greece. Since there is a lack in diagnostic management of EB, we would strongly encourage an effort to perform the required laboratory tests in Greece.</p>

scholarly journals A Novel Phenotype of Junctional Epidermolysis Bullosa with Transient Skin Fragility and Predominant Ocular Involvement Responsive to Human Amniotic Membrane Eyedrops

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 716
Author(s):  
Daniele Castiglia ◽  
Paola Fortugno ◽  
Angelo Giuseppe Condorelli ◽  
Sabina Barresi ◽  
Naomi De Luca ◽  
...  
Keyword(s):  
Amniotic Membrane ◽  
Epidermolysis Bullosa ◽  
Ocular Involvement ◽  
Human Amniotic Membrane ◽  
Vitro Assay ◽  
Junctional Epidermolysis Bullosa ◽  
Mucosal Involvement ◽  
Skin Fragility ◽  
Laminin 332

Junctional epidermolysis bullosa (JEB) is a clinically and genetically heterogeneous skin fragility disorder frequently caused by mutations in genes encoding the epithelial laminin isoform, laminin-332. JEB patients also present mucosal involvement, including painful corneal lesions. Recurrent corneal abrasions may lead to corneal opacities and visual impairment. Current treatments are merely supportive. We report a novel JEB phenotype distinguished by the complete resolution of skin fragility in infancy and persistent ocular involvement with unremitting and painful corneal abrasions. Biallelic LAMB3 mutations c.3052-5C>G and c.3492_3493delCG were identified as the molecular basis for this phenotype, with one mutation being a hypomorphic splice variant that allows residual wild-type laminin-332 production. The reduced laminin-332 level was associated with impaired keratinocyte adhesion. Then, we also investigated the therapeutic power of a human amniotic membrane (AM) eyedrop preparation for corneal lesions. AM were isolated from placenta donors, according to a procedure preserving the AM biological characteristics as a tissue, and confirmed to contain laminin-332. We found that AM eyedrop preparation could restore keratinocyte adhesion in an in vitro assay. Of note, AM eyedrop administration to the patient resulted in long-lasting remission of her ocular manifestations. Our findings suggest that AM eyedrops could represent an effective, non-invasive, simple-to-handle treatment for corneal lesions in patients with JEB and possibly other EB forms.

scholarly journals Impaired Mitochondrial and Metabolic Function of Fibroblasts Derived from Patients with Recessive Dystrophic and Junctional Epidermolysis Bullosa

2020 ◽  
pp. 75-83
Author(s):  
Ilona Tietzová ◽  
Kirk Twaroski ◽  
Cindy Eide ◽  
Julie H. Ostrander ◽  
Peter Crawford ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Mitochondrial Function ◽  
Metabolic Stress ◽  
Mitochondrial Morphology ◽  
Energy Status ◽  
Inherited Disorders ◽  
Mitochondrial Energy Metabolism ◽  
Junctional Epidermolysis Bullosa ◽  
Skin Fragility ◽  
Skin Healing

Background: Recessive dystrophic epidermolysis bullosa (RDEB) and junctional EB (JEB) are inherited disorders characterised by fragility and blistering of epithelial tissues leading to pain, pruritus, and adherent scarring. The severity and chronic nature of the resultant skin wounds significantly reduces quality and length of life. Current therapies primarily consist of protective bandaging and nutritional supplementation; there is no cure for these disorders. Although the skin fragility results from a lack of C7 protein (RDEB) and laminin-332 (JEB), other serious aspects of these disorders, such as inflammation that interferes with healing and aggressive squamous cell carcinoma, have not been completely elucidated. Recent research has suggested that mitochondrial function plays a significant role in skin healing. Objective: To evaluate how mitochondrial function differs in patients with RDEB and JEB. Method: The energy status of RDEB and JEB patient-derived fibroblasts was determined by Seahorse analysis and metabolite production. The energetics and overall morphology of RDEB and JEB patient-derived fibroblasts were assayed as a measure of metabolic stress. Results: EB patient-derived fibroblasts showed impaired oxidative phosphorylation with concomitant compensation by glycolysis. Morphological parameters were altered in RDEB and JEB fibroblasts compared with controls. Conclusion: This is the first study to describe changes in mitochondrial energy metabolism, metabolic profile, and mitochondrial morphology of EB patients.

Structure, compositon and function of the dermal-epidermal junction: Relevance in cutaneous disease and diagnosis

1989 ◽  
Vol 47 ◽  
pp. 868-869
Author(s):  
K. A. Holbrook
Keyword(s):  
Basement Membrane ◽  
Epidermolysis Bullosa ◽  
Normal Skin ◽  
Lamina Densa ◽  
Inherited Disorders ◽  
Ultrastructural Studies ◽  
Type Iv ◽  
Type Vii Collagen ◽  
Attachment Structures ◽  
Matrix Components

The dermal-epidermal junction (DEJ), or basement membrane rone, is the boundary between the epithelial and mesenchymal compartments of the skin; epidermal and fibroblastic cells in these two regions collaborate to synthesire its components. Ultrastructural studies (TEM and SEM) have defined a series of planes or layers (basal epidermal, lamina lucida, lamina densa, sublamina densa) and the morphology and density of attachment structures (hemidesmosomes, anchoring filaments, anchoring fibrils and anchoring plaques) in this region of normal skin. Change in structure of the DEJ provides information about the history of the tissue; reduplication of the lamina densa, for example, indicates a site of cell detachment or migration, or remodelling that accompanies repair of focal damage. In normal skin the structure of the DEJ is stable; in pathologic conditions it can be compromised by the congenital absence of certain structures or antigens (e.g., in the inherited disorders, epidermolysis bullosa [EB]) or by enzymatic degradation (e.g., in tumor invasion). Dissolution of the DEJ can also occur normally during the formation of epidermal appendages (e.g., hair follicles) and as melanocytes and Langerhans cells migrate into the epidermis during development.Biochemical and immunohisto/cytochemical studies have identified more than 20 molecules at the DEJ. These include well known matrix molecules (e.g., types IV and V collagen, laminin and fibronectin) and skin-specific antigens. The latter have been identified by autoantibodies or specific polyclonal or monoclonal antibodies raised against the skin, cultured cells and other epithelia. Some of the molecules of the DEJ are are present in basement membrane zones of many epithelia and thus are considered ubiquitous components (type IV, V, laminin, fibronectin, nidogen, entactin, HSPG, LDA-1, CSP [3B3]). All of them (that have been investigated in developing skin) appear ontogenetically as early as human embryonic tissue can be obtained and their expression is typically normal in patients with EB. The known properties of many of these molecules (particularly the matrix components) suggest functions they might impart to the DEJ: support of an epithelium (type IV collagen), regulation of permeability (heparan sulfate proteoglycan) or facilitation of cell attachment (fibronectin) and movement (laminin). Another group of matrix components and antigens of the DEJ includes molecules that are skin-specific or characteristic of stratified squamous epithelia (type VII collagen=LH 7:2 antigen, bullous pemphigoid antigen, AA3, GB3, KF-1,19-DEJ-1, epidermolysis bullosa acquisita antigen [EBA], AF-1 and AF-2, cicatricial pemphigoid antigen [CPA]) . These molecules are expressed in the DEJ later in development than the first group of molecules, in conjunction with the morphologic appearance of the structure they represent. Their appearance is also coordinated with specific developmental events (e.g., epidermal stratification) and the expression of molecules of differentiation in the epidermis and dermis. One or more of them is typically absent or reduced in expression in the skin of patients with heritable disorders affecting this region. There is no apparent correlation between the location of molecules in the DEJ and the stability of their expression.

scholarly journals Gastrostomy for infants with severe epidermolysis bullosa simplex in neonatal intensive care

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
M. Marro ◽  
S. De Smet ◽  
D. Caldari ◽  
C. Lambe ◽  
S. Leclerc-Mercier ◽  
...  
Keyword(s):  
Intensive Care ◽  
Epidermolysis Bullosa ◽  
Neonatal Intensive Care ◽  
Nutrition Support ◽  
Epidermolysis Bullosa Simplex ◽  
Withdrawal Time ◽  
Multicentric Study ◽  
Nasogastric Tubes ◽  
Mucosal Involvement ◽  
Enteral Nutrition Support

Abstract Introduction Severe epidermolysis bullosa simplex (EBS sev) is a rare genodermatosis characterized by congenital generalized blistering and mucosal involvement. Increased needs and decreased intake quickly lead to nutritional imbalance. Enteral nutrition support is proposed, but classical nasogastric tubes are not well tolerated in these patients and gastrostomy is preferred. Objective and methods To report the experience with EBS sev in neonatal units of French reference centers for gastrostomy. In this retrospective multicentric study, we included all patients with EBS sev who had gastrostomy placement before age 9 months during neonatal care hospitalization. Results Nine infants (5 males/4 females) with severe skin and mucosal involvement were included. A gastrostomy was decided, at an early age (mean 3.7 months, range 1.4 to 8 months) in infants with mean weight 4426 g (range 3500 to 6000 g). Techniques used were endoscopy with the pull technique for 5 infants and surgery under general anesthesia for 4. Main complications were local but resolved after treatment. All infants gained weight after gastrostomy. The mean withdrawal time (n = 7) for the gastrostomy was 35.8 months (range 10.5 months to 6.5 years). Seven children had persistent oral disorders. Conclusions Gastrostomy in infants with EBS sev can be necessary in neonatal intensive care units. Both surgical and endoscopic pull techniques seem efficient, with good tolerance.

Mitochondrial Disorders of DNA Polymerase γ Dysfunction: From Anatomic to Molecular Pathology Diagnosis

2011 ◽  
Vol 135 (7) ◽  
pp. 925-934
Author(s):  
Linsheng Zhang ◽  
Sherine S. L. Chan ◽  
Daynna J. Wolff
Keyword(s):  
Dna Polymerase ◽  
Molecular Mechanisms ◽  
Clinical Laboratory ◽  
Laboratory Diagnosis ◽  
Molecular Study ◽  
Mitochondrial Disorders ◽  
Definitive Diagnosis ◽  
Inherited Disorders ◽  
Cooperative Effort ◽  
Dna Polymerase Γ

Abstract Context.—Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis. Objectives.—To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes. Data Sources.—Review of pertinent published literature and relevant Internet databases. Conclusions.—Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis.

scholarly journals A study of 235 cases of human brucellosis in Sana’a, Republic of Yemen

2001 ◽  
Vol 7 (1-2) ◽  
pp. 238-246 ◽  
Author(s):  
H. A. Al Shamahy ◽  
S. G. Wright
Keyword(s):  
Differential Diagnosis ◽  
Lymph Nodes ◽  
Clinical Examination ◽  
Clinical Picture ◽  
Laboratory Tests ◽  
Clinical Characteristics ◽  
Geographical Area ◽  
Human Brucellosis ◽  
Adults And Children ◽  
Spleen And Lymph Nodes

We studied the clinical characteristics of brucellosis among all patients with brucellosis referred to the Central Health Laboratory from the main hospitals in Sana’a during a 2-year period [1992-93] [235 adults and children]. A history was taken from each patient and clinical examination, general laboratory tests and brucellosis laboratory tests carried out. The overall clinical picture of brucellosis in this study is very similar to that reported by other workers in this geographical area. Awareness of the presenting features and the realization that brucellosis should be part of the differential diagnosis of febrile patients with enlarged liver, spleen and lymph nodes will lead to an increasing index of suspicion for this disease.

scholarly journals Mouse models for dominant dystrophic epidermolysis bullosa (DDEB) carrying common human point mutations recapitulate the human disease

2021 ◽  
Author(s):  
B. R. C. Smith ◽  
A. Nystrom ◽  
C. J. Nowell ◽  
I. Hausser ◽  
C. Gretzmeier ◽  
...  
Keyword(s):  
Mouse Models ◽  
Epidermolysis Bullosa ◽  
Severe Disease ◽  
Point Mutations ◽  
Missense Mutations ◽  
Dystrophic Epidermolysis Bullosa ◽  
Mild Phenotype ◽  
Growth And Survival ◽  
Skin Fragility ◽  
Collagen Vii

Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB) that is characterized by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of EB which frequently show early lethality and severe disease, these mouse models which to our knowledge are the first for DDEB show no reduction in growth and survival and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating EB.

scholarly journals Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa

2018 ◽  
Vol 115 (4) ◽  
pp. E705-E714 ◽  
Author(s):  
Alexander Nyström ◽  
Olivier Bornert ◽  
Tobias Kühl ◽  
Christine Gretzmeier ◽  
Kerstin Thriene ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epidermolysis Bullosa ◽  
Bacterial Colonization ◽  
Mouse Skin ◽  
Innate Immune ◽  
Macrophage Response ◽  
Skin Fragility ◽  
Human Validation ◽  
Spleen And Lymph Nodes ◽  
Collagen Vii

Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits. In genetic mouse models, loss of collagen VII increased bacterial colonization by diminishing levels of circulating cochlin LCCL domain. Intraperitoneal injection of collagen VII, which restored cochlin in the spleen, but not in the skin, reactivated peripheral innate immune cells via cochlin and reduced bacterial skin colonization. Systemic administration of the cochlin LCCL domain was alone sufficient to diminish bacterial supercolonization of RDEB mouse skin. Human validation demonstrated that RDEB patients displayed lower levels of systemic cochlin LCCL domain with subsequently impaired macrophage response in infected wounds. This study identifies an intrinsic innate immune dysfunction in RDEB and uncovers a unique role of the lymphoid extracellular matrix in systemic defense against bacteria.

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