CASE STUDY
A 62-year-old woman presented to a walk-in clinic with a history of epidermolysis bullosa simplex (EBS) diagnosed by biopsy during her early childhood. Both her mother and sister have EBS because it is an inherited, autosomal dominant disorder. Chief complaint were large blisters under her axilla and palms of both hands caused by mechanical skin friction from having to utilize crutches because of a recent right knee meniscus tear. Chief concerns were twofold: the blisters could lead to infection and how she can prevent the mechanical skin friction, on the palms of hands and axilla, caused by the necessity of crutches (Figure 1).
The main objective was wound management/healing and prevention of further skin blistering. The patient was instructed to cleanse wounds with a low concentration of acetic acid. Polymen with silver patches (nonadhesive) were prescribed with elastic tube gauze for reinforcement of dressings. A knee scooter, with lamb skin covering, was recommended instead of crutches to prevent skin friction of the axilla and hands. The patient was instructed to take acetaminophen every 4 hours and be observant of signs and symptoms of wound infection.
BACKGROUND
EBS is a rare genetic condition where bullous lesions, larger than 0.5 cm, affect an area of the skin that is exposed to minimal trauma or mechanical friction (Bruckner et al., 2020). There are three major forms of heritable epidermolysis bullosa: simplex (70%), dystrophic (25%), and junctional (5%). All forms of EB are characterized by loss of tissue integrity in the upper dermis, in the dermoepidermal surface, and within the epidermis, respectively (Boeira et al., 2013).
EBS is the mildest form where blistering predominately affects the feet and hands; the two other forms are characterized by extensive skin and mucosal involvement, systemic complications, and disfigurement (Pope et al., 2013). The National Epidermolysis Bullosa Registry estimates the overall prevalence of EB in the Unites States is 11.1 per one million live births (Bruckner et al., 2020). Symptoms usually appear soon after birth, although lesions may not appear in some cases until adolescence (Bruckner et al., 2020).
EBS is an autosomal dominant inheritance, where one copy of the altered gene in each cell is sufficient to cause the disorder (Watkins, 2016). In some rare cases, EBS is inherited in an autosomal recessive pattern where two copies of the gene in each cell are altered (Brun et al., 2017). To appreciate the underlying mechanisms, one must understand the basic molecular organization of the dermal-epidermal membrane.
EBS is characterized by a disorder of keratinocytes, intraepidermal blistering with very minimal systemic involvement (Boeira et al., 2013). KRT5 or KRT14 genes provide instructions to cells for producing proteins, intrinsically organizing collections of molecules, and anchoring of complexes to facilitate cohesion (National Institutes of Health, 2020). The intraepidermal cleavage observed in EBS is the result of these mutations in the KRT5 or KRT14, which causes cells in the epidermis to become fragile and easily damaged (Boeira et al., 2013).
DIAGNOSTIC APPROACH
The diagnosis for EBS begins with a thorough history and physical examination, followed by a skin biopsy and DNA testing (Has, Liu, et al., 2020). Genetic testing of parents is recommended, whenever possible, if they have a family history of EBS. Diagnostic hallmark of all forms of EB involves blistering of the skin, a result of minor trauma, leading to nonhealing ulcers based on clinical and histopathological findings (Prodinger et al., 2019). Newborns and children with a recurrent history of blisters, occurring in the absence of another reasonable explanation, should be evaluated for EB with the extraction of genomic DNA (Has, Liu, et al., 2020). Ensuring the most accurate diagnosis, a fresh blister induced by mechanical friction should be biopsied (Pfendner & Bruckner, 2016).
To differentiate between the different forms of EB, skin biopsies must be examined by electron microscopy and/or indirect immune-fluorescent microscopy (Has, Liu, et al., 2020). The biopsy is critical to rule out differential diagnoses, such as staphylococcal scaled skin syndrome, candidiasis, herpes simplex, and bullous pemphigoid (Has, Liu, et al., 2020). Despite progress and a good understanding of molecular genetics and the mechanism pathways of EB, there remains no cure for EBS (Uitto et al., 2018).
TREATMENT
Currently, there are no approved treatments for EBS with management focusing primarily on blister prevention, wound care, pain reduction, and early recognition and treatment of infection (Bruckner et al., 2020). The basic underlying principle is to prevent blistering by meticulous skin protection from friction and averting infection via good wound care with nonadhesive hydrocolloid dressings (Uitto et al., 2018). In newly diagnosed patients, discussion should be focused on the extent of disease in conjunction with a dermatologist consultation along with genetic counseling (Pfendner & Bruckner, 2016). Dermatologists will provide preventative screening for squamous cell carcinoma, which can arise in any nonhealing area (Watkins, 2016).
Patients are educated to avoid long-distance walking, avoid bumps and scratches, wear loose fitting clothes, and obtain proper fitting shoes from a specialist (Watkins, 2016). Infants require greater care and control of environment to prevent trauma including gentle manipulation of infant, use of foam to cover bony prominences, and zinc oxide for skin under diapers (Watkins, 2016). Avoid rubbing the child's skin as much as possible, and discuss ways to lift child without causing friction to the skin. Older children will need foam over the knees to prevent blistering from falls. Contact sports should be avoided with recommendation of certain exercises such as swimming (Watkins, 2016).
Generally, if blisters occur, treatment entails a combination of wound management, infection support for chronic wounds, and surgical management if needed (Bruckner et al., 2020). In patients with EBS, wound healing and infection can be a continuous process composed of multiple factors including foreign bodies and bacteria (Pfendner & Bruckner, 2016). Open blisters allow penetration of microbes and accumulation of moisture from spontaneous or intentional nonsterile lancing of blisters, which further encourage bacterial growth (Pope et al., 2013). The most causative etiological agents are Streptococcus, although gram-negative pyogenes can proliferate (Boeira et al., 2013).
Puncturing blisters with sterile needles are preferred to prevent dissemination, and use of sterile dressings is a first-line treatment (Boeira et al., 2013). After sterile puncture, leaving the roof of blister is imperative allowing the loose skin to remain in place functioning as a biological dressing to prevent bacterial colonization (Boeira et al., 2013). Firm and easily torn edges of the skin require debridement to prevent maintenance of the inflammatory process (Garcia-Doval et al., 2013).
Wounds should be gently cleaned with saline solution, low concentrations of acetic acid, or chlorhexidine (Watkins, 2016). Silicone foam, not adhesives, is the most complete and effective type of coverage for the healing process (Watkins, 2016). This type of foam offers protection, fluid absorption, hydration of the lesions, and antimicrobial properties when combined with additives such as silver (Watkins, 2016). Hydrogel dressings and biosynthetic cellulose dressings are used mostly for dry wounds (Uitto et al., 2018). When removing old dressings, if crust is present, the dressings should be soaked and carefully lifted off as the presence of eschar can impair healing and subsequently generate a proinflammatory incitement (Watkins, 2016).
In addition to wound care, clinicians treating EBS need to address and support pain management. These patients experience neuropathic pain and local or topical pain. Furthermore, some patients have reported pruritis during the healing period of blisters, which can cause night wakening and exacerbation of skin friction because of scratching (Brun et al., 2017). Treatment recommendations include adhering to the World Health Organization pain ladder for nociceptive pain (Pope et al., 2013).
First-line pain treatment is acetaminophen, with subsequent addition of nonsteroidal anti-inflammatories. Tricyclics, gabapentin, and pregabalin are effective for neuropathic pain, which patients describe as burning, stinging, and shooting (Pope et al., 2013). Nonsedating H1 antihistamine in the morning combined with a sedating antihistamine, such as diphenhydramine, at night may assist with reduction in pruritus and neuropathic pain (Pope et al., 2013; Figure 2).
QUALITY OF LIFE
Patients with EBS live with a large disease burden that impacts activities of daily living and compels them to make difficult decisions and compromises regarding education, careers, and personal life (Bruckner et al., 2020). The effects of EBS can be far reaching with patients and caregivers making difficult life choices. Daily activities negatively affect patients with EBS interfering with ability to move around their home, bathe, eat, write, sleep, partake in sports and play, and procreate (Bruckner et al., 2020).
Coexistence of depression, anxiety, and behavioral disorders should be taken into consideration, as this may compromise treatment strategies and worsen symptoms (Boeira et al., 2013). Patients should be evaluated at every visit regarding coping abilities (Bruckner et al., 2020). Referrals for mental and behavioral treatment may be necessary along with patient advocacy groups (Boeira et al., 2013).
FINAL CONSIDERATIONS
EBS can require hours of care each day and impacts the lives of both patients and families, bringing physical and emotional suffering and limitations to their quality of life. Current trials are largely focused on treatment of other EB disorders and not EBS. In addition, concerns abound regarding the cost, delivery, and access of treatments (Has, South, & Uitto, 2020). It is believed most of the treatments on the horizon will complement strategies with the purpose of alleviating symptoms but not providing a cure (Has, South, & Uitto, 2020). With the absence of effective treatment and cures for blistering, it must be noted that management should be aimed at prevention, education, counseling, and comfort.
REFERENCES