A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review
Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring.
Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland.
Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.
KeywordsEpidermolysis bullosa Esophageal stricture Dysphagia Endoscopic dilatation
Body mass index
Dystrophic epidermolysis bullosa
Epidermolysis bullosa simplex
Junctional epidermolysis bullosa
Proton pump inhibitor
Transforming growth factor beta-1
Tumor necrosis alpha
Discussion and conclusions
In the 1886 German dermatologist Heinrich Koebner formed an idea of EB, a heterogenous group of genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EBS is the most common form in western countries and in general has less severe skin lesions in comparison to JEB or DEB. The herlitz subtype of JEB is less prevalent than the nonherlitz JEB, but both might involve enamel hypoplasia. Skin scarring is a crucial symptom of the herlitz JEB subtype. What is more, mucosal surfaces of the esophagus, upper airway and cornea might also be affected. On the other hand, extracutaneous manifestation is not typical for the nonherlitz JEB. Dominant form of DEB is associated with the formation of skin blisters at birth [3, 4]. Recurrent involvement of the esophagus with subsequent scarring and stenosis can be observed among these patients. Recessive form of DEB is the most severe type of EB and finally leads to disfiguring skin scars, hand and foot deformities, growth retardation and failure to thrive. In addition to skin blistering, photosensitivity and skin pigmentation are characteristic features of KS. EB might involve extra-cutaneous manifestation, leading to severe complications in the eye, nose, oral cavity, ear, larynx and upper respiratory tract. Genitourinary complications (scarring of the glans penis or vaginal vestibule, urethral strictures leading to hydroureter and hydronephrosis) together with musculoskeletal involvement reflected by joints contractures, muscular dystrophy and pseudosyndactyly due to extensive blistering and scarring in DEB are also possible [5, 6, 7]. Anemia, usually present in patients with JEB and recessive DEB, heart involvement caused by micronutrient deficiencies and transfusion related iron overload might result in cardiomyopathy. There is also a tendency to develop skin cancers (squamous cell carcinoma, basal cell carcinoma and melanoma) among patients with EB. Gastrointestinal manifestation might occur in several EB subtypes and the esophagus is the most commonly affected due to repeated blistering and scarring, eventually followed by stenosis. Dysphagia, odynophagia and malnutrition belong to the most typical symptoms. They can be even exacerbated by accompanying gastroesophageal reflux disease. Pyloric atresia, painful perianal blistering and anal canal stenosis together with constipation might also occur [8, 9, 10, 11, 12, 13, 14]. In presented patient an extra-cutaneous manifestation of EB was reflected by long-lasting esophageal involvement and its stenosis. It is worth emphasizing that this patient is to our knowledge the oldest one in Poland diagnosed with EB. Nowadays an effective therapy for curing EB does not exist. No drugs are known to correct the underlying molecular defects. Even an anti-collagenase strategy, investigated in various surveys, based on phenytoin or tetracyclines, did not improve the blistering or epithelial disadhesion in EB significantly or consistently. Other recent studies focus on the suppression of transforming growth factor beta-1 (TGF-β1) and reduction of fibrosis in this mechanism. Losartan, an angiotensin II type 1 receptor antagonist was proved to down regulate TGF-β1 activators (e. g. thrombospondin 1) and to improve the course of RDEB. Immunosuppressant drugs like cyclosporine, mycophenolate mofetil and tumor necrosis alpha (TNF-α) inhibitor etanercept were also trialled, however none of them was indicated in chronic therapy of EB. Numerous potential therapies based on cell therapies (allogeneic fibroblasts, mesenchymal stromal cells, bone marrow transplantation), protein replacement and genes modification have been explored. However, further investigations must still be conducted to clarify this issue [15, 16, 17, 18]. A modification of diet texture to soft, puree and liquids is the first step in the management of dysphagia in EB patients. If esophageal dilatation is required, endoscopic procedures are usually performed - with the use of a balloon catheter or a bougie. Nevertheless, in the most severe cases of esophageal stenosis, placement of a gastrostomy tube is recommended. Because of a broad range of complications, the treatment of EB patients must be based on a coordinated multidisciplinary approach and extend from psychological support together with dressings and padding blisters to the management of systemic complications [19, 20, 21, 22]. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.
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Availability of data and materials
All data generated or analyzed during this study are available from the corresponding author on reasonable request.
AM and BPK analyzed and interpreted the patient data, LB and MD performed radiological investigations, AM and HCL were major contributors in writing the manuscript. All authors read and approved the final manuscript
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The patient signed an informed consent form and agreed to present his medical history together with photos.
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