Hereditary Dystrophic Ampullary Epidermolysis, case report

Summary

Dystrophic epidermolysis bullosa (DEB) is a form of inherited epidermolysis bullosa (EB), characterized by cutaneous and mucous fragility, which results in the formation of blisters and superficial ulcers that develop below the dense lamina of the cutaneous basement membrane. We report the case of a 16 year old female patient who presented the clinical characteristics and who underwent pathological study.

Authors: Johana Valeria Quilambaqui Andrade*, Lizbeth del Carmen Pogo Cueva*, Mayteé Celina Guerrero Cabrera*, Tatiana Fabiola Ordoñez Palacios*.

*General Practitioners in hospital functions Ecuador Public Health Ministry

Keywords: Dystrophic epidermolysis bullosa, inherited blisters, genetic skin disease.

Introduction

Epidermolysis bullosa (EB) constitute a group of inherited diseases characterized by excessive fragility of the skin to frictional forces resulting in the development of blisters. All of them are produce by alterations; now know, in proteins involved in the union of the epidermis with the dermis. According to the ultrastructural level at which blisters occur they are classified into four large groups: simple bullous epidermolysis (SBE) if the blister is located in the basal layer of the epidermis; joint bullous epidermolysis(JBE) if it is located at the level of the dermo-epidermal junction; Dystrophic bullous epidermolysis (DBE) if the separation occurs at the level of the dermis and Kindler syndrome that is clinically characterized by skin fragility, poikiloderma and photosensitivity1.

DBE is caused by mutations in the COL7A! (3p21.31) gene that encodes type VII collagen protein. Mutations alter function and reduce or interrupt the production of type VII collagen. This affects its assembly in the anchorage fibrils that maintain the basement membrane attached to the underlying dermis, reason why this disease occurs. This classification arises from consensus meetings held in 2013, which adds a subclassification depending on the molecular origin of each subtype that this disease presents2.

Clinical Case

We present the case of a female patient who has all the clinical and histopathological characteristics of this disease and who is in constant control by the dermatology service.

The patient’s mother refers that during pregnancy she had repeated urinary tract infections for which she received oral treatment for several occasions. The patient was born by eutocic delivery with respiratory distress whereby she was hospitalized for a week in the pediatric service and discharged with full and favorable recovery. The mother refers that her daughter at the age of 3 years old began to show scaly lesions on hands and feet so she went to the doctor who prescribed moisturizers and recommended avoiding sun exposure.

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At the age of 12 the patient is referred to the dermatology service by noticing the presence of clinical manifestations, requesting evaluation also by the genetic service. At the physical examination the following clinical characteristics where found: Diseminated dematosis predominantly on the forehead, hands (Figure 1), feet and heels characterized by tight blisters and vesicles with clear content found in healthy skin and lesions with serohematical scabs.

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Figure No. 1 Disseminated dermatosis

Family history: Mother of the patient refers that 20 years ago she had a male child with the same clinical characteristics as her daughter, who was hospitalized several times and died at the age of 5 years old due to the presence of generalized skin infection.

Histopathological exam:

Macroscopic Exam: (23-06-10) Section of skin that measures 0,6 x 0,5 x 0,2cm, presence of a vesicle on the surface 0,5 x 0,3cm.

Microscopic Exam: The cuts show skin and subcutaneous cellular tissue, at the basal level the skin shows blister formation due to epidermis / dermis detachment at the basal level, absence of cells in the lumen, the roof is form by the basal layer; the floor by the dermis, the latter presents mononuclear type infiltrate with few eosinophils of perivascular localization primarily, fibroblast augmentation; in another area the beginning of the detachment with the formation of a microvesicle is observed.

Diagnosis: Vesicle-bullous reaction pattern, subepidermal blister, BULLOUS EPIDERMOLYSIS subgroup DERMOLITIC (Dystrophic epidermolysis bullosa) in left arm.

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Discussion

Hereditary dystrophic epidermolysis bullosa is a serious skin disorder that begins at birth and is characterized by recurrent blisters at the level of the dense sublamina under the cutaneous basement membrane, this result in mutilating scars and contractures of the hands, feet and joints. Patients also developed gastrointestinal tract stenosis due to mucosal involvement which can lead to poor nutrition. Affected people have an increased risk of developing aggressive squamous cell carcinoma1.

In 1996 Christiano et al. reported four unrelated families in which five individuals had hereditary DEB they all presented at birth or shortly thereafter with blisters on the skin of the fingers, lips, oral mucosa and ears that became widespread. Older patient had multiple erosions, scars, deformities in hands due to fusion and joint contractures other features include nail loss and esophageal strictures. Electron microscopy showed hypoplastic anchor fibrils and excision at the level of the dense sublamin, consistent with Dystrophic EB1.

In 1991, the molecular part of this disease began to be studied, finding in a family with three affected siblings in which ligation studies excluded the participation of the collagenase locus in 11q22, Hovnanian et al. high levels of collagenase mRNA where found in only two of the three affected siblings, which suggests that it was not the primary defect in that family 2. By link studies, Colombi et al. In 1992, they also excluded the interstitial collagenase gene as responsible for severe dystrophic recessive epidermolysis bullosa. They also excluded stromelysin I and stromelysin II. The same family had other affected members with a form of cerebellar ataxia of postpubertal onset. All three genes, as well as fibronectin on chromosome 2, were excluded because they were involved in both phenotypes 3

Varki et al. In 2007, the COL7A1 gene was analyzed in 310 patients with dystrophic epidermolysis bullosa. Mutations were found in one or both alleles in 243 (78.4%) patients, comprising 355 mutant alleles of the 438 (81.1%) anticipated mutant alleles. The authors reviewed the spectrum of the COL7A1 mutation and genotype-phenotype correlations, noting that patients with severe recessive DEB tend to have truncated mutations, while those with milder dominant DEB tend to have glycine substitutions. Seven patients with characteristics of dominant and recessive forms of the disease were found to have dominant and recessive mutations 4.

Regarding to the treatment for this disease Wagner et al. In 2010, reported the results of allogeneic hematopoietic stem cell transplantation after immunomeloablative chemotherapy in 6 children with autosomal recessive dystrophic epidermolysis bullosa. They showed variable reductions in blistering formation between 30 and 130 days after transplantation. Two patients had a rapid and substantial clinical improvement, one had a slow improvement with a modest general benefit, one had a rapid improvement in short-term follow-up and one had a recurrence of blistering after an early period of almost none blisters.

A recipient died 183 days after transplant due to graft rejection and infection. The skin biopsies showed a substantial proportion of donor cells in the skin and mucosa. The cells seemed to have a hematopoietic origin, but their identity could not be fully determined. The authors suggested that the donor cells secreted type VII collagen that was subsequently incorporated into the dense lamina. The deposition of type VII collagen could be detected in skin biopsies after treatment, but the anchorage of the fibrils never seemed normal. These authors emphasized that bone marrow transplantation is a high-risk procedure, but point up that it can offer some benefits to patients with autosomal recessive dystrophic epidermolysis bullosa 5.

Conclusion

Dystrophic epidermolysis bullosa is a highly complex disease that requires appropiated diagnosis from the first signs of this disease, and also an adequate histopathological diagnosis in order to start treatment and reduce morbidity and mortality. Currently, with the advancement of technology, specific treatments are being carried out in relation to the genetic alteration and the results of the molecular studies, thus giving proper treatment for each of the sub-variants of this disease.

Similarly, observing the presence of this disease in both siblings of different sex and without a family history, it is believed that it presents an autosomal recessive inheritance pattern in whose parents are carriers of this disease. Molecular studies were requested from carriers of this disease that could not be performed due to economic situations.

Bibliography

  1. Atherton DJ. Epidermolysis Bullosa. En: Harper J, Oranje A, Prose N, editors. Texbook of Pediatric Dermatology. Oxford: Blackwell Science;2000. p.1075-1099.
  2. Fine JD, Bauer EA, McGuire J, Moshell A. Epidermolysis bullosa: clinical, epidemiologic, and laboratory advances, and the findings of the National Epidermolysis Bullosa Registry. Baltimore: Johns Hopkins University Press; 2013.
  3. Christiano, A. M., McGrath, J. A., Tan, K. C., Uitto, J. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance.
  4. Hovnanian, A., Duquesnoy, P., Amselem, S., Blanchet-Bardon, C., Lathrop, M., Dubertret, L., Goossens, M. Exclusion linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype.
  5. Colombi, M., Gardella, R., Zoppi, N., Moro, L., Marini, D., Spurr, N. K., Barlati, S. Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and fibronectin genes as the mutant loci in a family with recessive epidermolysis bullosa dystrophica and a form of cerebellar ataxia.
  6. Varki, R., Sadowski, S., Uitto, J., Pfendner, E. Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes. J. Med.
  7. Wagner, J. E., Ishida-Yamamoto, A., McGrath, J. A., Hordinsky, M., Keene, D. R., Woodley, D. T., Chen, M., Riddle, M. J., Osborn, M. J., Lund, T., Dolan, M., Blazar, B. R., Tolar, J. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa.