Neonate with Severe Complications of Epidermolysis Bullosa and Bilateral Clubfoot : An Unusual Case Presentation and Treatment

Address for correspondence: Qëndresë Daka E-mail: qendrese.daka@uni-pr.edu 1Afërdita KrasniqiDaka, Department of Dermatovenereology, University Clinical Centre of Kosovo, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo, 2Teuta SejdiuHasbahta, Department of Paediatrics, University Clinical Centre of Kosovo, Prishtina, Kosovo, 3Antigona Gërqari, Department of Dermatovenereology, University Clinical Centre of Kosovo, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo, 4Merita Vuniqi-Krasniqi, Department of Gynaecology and Obstetrics, University Clinical Centre of Kosovo, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo, 5Qëndresë Daka, Department of Ophthalmology, University Clinical Centre of Kosovo, Prishtina, Kosovo, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo. Abstract


Introduction
E pidermolysis bullosa (EB) is a term for a heterogeneous group of rare disorders, characterized by extensive blistering of the skin and mucous membranes 1,2,3 .More than 30 subtypes of diseases have been classifi ed based on the pa ern of gene c inheritance, gene c muta on involved and morphology/topography of lesions 4 .All clinically dis nc ve phenotypes have skin manifesta ons as the major features, however, involvement of other systems that may severely aff ect the health of the pa ents are not unusual.EB may be associated with: muscular dystrophy, cardiomyopathy, pyloric atresion, urologic abnormali es, oral and eye manifesta ons, nail dystrophy, alopecia or tracheal epithelial erosion 5,6,7 .
Clubfoot is one of the most common congenital birth defects, characterized by a complex three-dimensional deformity of foot 8,9,10,11 .The cause of clubfoot is unknown and various theories have been proposed 9,11 .Most commonly, clubfoot is an idiopathic isolated birth defect of the musculoskeletal system, however, in approximately 20% of the cases it can be associated with congenital anomalies such as: spina bifi da, arthrogryposis, cerebral palsy, myotonic dystophy, myelomeningocele, amnio c band sequence, or trisomy 18 9,10,11 .
We are repor ng a case of a long-me hospitalised newborn with severe complica ons of EB, associated with bilateral clubfoot.

The Case
A newborn female, born at full-term, was hospitalized to NICU due to extensive dermal-mucous lesions.She was the sixth child of a non consanguineous couple who denied the presence of any hereditary or congenital abnormali es in the family.On admission, the baby was afebrile, normotonic, normorefl exsive and had vital func ons within normal limits.Dermatological examina ons revealed generalized bullous lesions fi lled with a thick and grey secret, wide-spread skin loss in both anterior crural regions, bleeding ulcera ons around major joints and dystrophic nails [Fig 1 & 2]; mul ple erosions and bulla on the oral and nasal mucosa.Systemic examina on including respiratory, cardiovascular, gastrointes nal and neurological systems revealed no pathological changes, whereas the orthopaedist confi rmed the presence of bilateral clubfoot.Laboratory inves ga ons showed leucopoenia, elevated C-reac ve protein, presence of streptococcus pneumoniae on the secret, and cleavage of the dermis on histological analysis of the lesional skin.Treatment with fresh frozen plasma, concentrated erythrocytes and human albumins was ini ated.Oral an bio cs were con nued, an myco c (nysta n sol.) was administrated preven vely.Topical an bio c and an epithelisa on ointment were applied locally.
Second month: Laboratory results were within normal limits.Candida albicans was grown on mouth and umbilical region.Fresh bulla were present on skin, there was a loss of fi nger and toenails [ Fig 4].Symptoma c treatment con nued and the baby was discharged.She was scheduled for clubfoot treatment at an orthopaedist.

Discussion
Although new knowledge about the muta ons of genes that encode structural proteins responsible for adhesion between cutaneous structures allows precise classifi ca on of pa ents in subcategories of EB 12,13 , in our case, we could not classify the type of EB and explain the possible connec on with clubfoot due to limited resources.
The diagnosis and classifi ca on of EB is made based on: clinical symptomatology, histopathology, electron microscopy, muta on analysis and immmunofl uorescence mapping.
However, in a resource limited se ng, the diagnosis is mainly clinical 14,15 .Medical surveillance for involvements of other systems should be a part of the rou ne evalua on.In children, complica ons such as: cutaneous losses, infec ons, anemia, respiratory failure, dehydra on or diges ve problems lead to impaired nutri on and growth and is some cases even death 4,12,16 .
Despite the progress on the knowledge about the cause of EB, currently, there is no sa sfactory treatment available and the long-term prognosis of the disease is poor.Gene, protein replacement and cell-based therapies are being inves gated, but these approaches are at the early stages of inves ga on, and there are a number of uncertain es surrounding them 13,17 .Treatment is primarily suppor ve and preven ve consis ng of: wound healing, infec on control, pain management, nutri onal support, adequate dressing and other therapies depending on the complica ons that arise 4,12,17 .
Our pa ent suff ered from severe complica ons, however, a er intensive care treatment, general condi on improved.Clubfoot treatment was scheduled a er healing of skin wounds, whereas parents were informed about the delicacy of the disease and instructed about bathing, skin treatment and con nuous regular follow-up visits.

Conclusion
We presented an unusual clinical case of neonatal EB associated with congenital clubfoot and other complica ons that needed long-me hospitaliza on and treatment.Due to our limited resources, we could not explain the possible connec on.Our case serves as a reminder for scien st that more research on neonatal EB is cri cal for be er quality of life and increased life expectancy of these pa ents.

Fig 3 :
Fig 3: Photograph showing improvement of wound healing a er one month of treatment.Fresh bulla, nail dystrophy and numerous crusts on the skin present.

Fig 4 :
Fig 4: Photograph showing loss of fi ngernails and fresh bulla a er two months of treatment.

First month :
Bo le feeding was commenced.Therapy improved wound closure, but blisters con nued to develop [Fig 3].Laboratory inves ga ons revealed: hypoalbuminemia; anemia; posi ve PCR; presence of providencia, citrobacter and pseudomonas on the bulla fl uid culture; sterile hemoculture and eleveated IgG levels for rubella on both mother and baby.Bilateral bronchopneumonia was detected in chest x-ray.