PURPOSE: To enhance the learner's competence with information about a wound bed preparation model of fragile skin for patients with epidermolysis bullosa (EB).

TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care.

OBJECTIVES: After participating in this educational activity, the participant should be better able to:

1. Differentiate between the types and subtypes of EB. 2. Apply EB assessment and treatment strategies to patient care scenarios.

ABSTRACT: Epidermolysis bullosa (EB) is a group of inherited diseases with 4 subtypes. This disorder is a model for fragile skin, with some affected individuals having chronic, difficult-to-heal wounds. The care of wounds in people with EB can be guided by the Wound Bed Preparation paradigm. The treatment of chronic EB wounds is outlined with a quick reference guide of 12 consensus recommendations created by a panel of 11 experts. These recommendations were reviewed by a computer-facilitated modified Delphi process where 15 external reviewers (68.8% of whom reported having 11 or more years' experience with EB care). Inclusion of recommendations was contingent on 80% agreement from reviewers.

INTRODUCTION

There are 2 key concerns surrounding transplantation procedures. First, the small number of individuals eligible for transplant may develop human leukocyte antigens from the allogeneic cells in the skin transplant, increasing the potential for rejection of a bone marrow transplant. Second, older individuals with RDEB (especially after age 20 years) are very susceptible to aggressive squamous cell carcinomas, and the immunosuppression associated with allogeneic stem cell transplantation may increase this.

This article summarizes the EB recommendations with a special emphasis on the wound healing component as outlined with the WBP paradigm and utilizes EB as a model for fragile skin.

TREAT THE CAUSE

1. Assess the patient's ability to heal.

2. Develop an individualized goal of care.

Epidermolysis Bullosa Simplex: The most common type of EB simplex is localized EB simplex with skin cleavage within the basal layer of the epidermis. The blisters are usually on the palms and soles, aggravated by heat and friction. The inheritance is autosomal dominant with mild disease. Mutations are present in keratins 5 or 14. A less common but also autosomal dominant type, Dowling-Meara, features clustered distal blisters with a string of pearl-like arrangement. Although painful keratoderma is noted with time, patients tend to be less severe with increasing age.

Junctional EB: Skin and mucosal cleavage occurs at the lamina lucida level of the basement membrane zone, including periorificial areas of skin, ocular, tracheolaryngeal, gastrointestinal, genitourinary, and renal systems. The mode of inheritance is usually autosomal recessive, with mutations in the genes encoding collagen XVII, [alpha]6[beta]4 integrin, or laminin 332. The Herlitz form is the most severe (exuberant granulation in the perioral area, around the nails, and denuded diaper area), with death in most cases in the first 1 to 2 years of life. The non-Herlitz form is often severe in infancy, but life expectancy is considerably longer.

Kindler Syndrome: This rare form of EB may result in cleavage at any of the 3 levels outlined above. Blisters in early childhood are gradually replaced by scarring, keratoderma (thickened palms and soles), poikiloderma (hypopigmentation and hyperpigmentation, telangiectasia, and atrophy), and photosensitivity. It is caused by mutations in the gene encoding kindlin 1, which is involved in basal layer keratinocyte adhesion at focal contacts.

Genetic Engineering

Until recently, care of patients with EB has consisted of trying to minimize trauma-induced blistering of the skin and supportive care of resulting wounds. However, there are some new and exciting therapies being proposed to target the cause of the skin fragility in these patients, including replacement of the abnormal protein (eg, collagen VII in RDEB) and bone marrow transplantation.

* increased blood loss through blisters and chronic wounds on the skin and in the gastrointestinal tract

* chronic inflammation leading to decreased production of red blood cells

* iron deficiency and increased iron utilization

* deficiencies of other vitamins and minerals including vitamin B₁₂ and folate.

Chronic wounds with large open areas are often stuck in the inflammatory stage of the healing process. Proinflammatory metalloproteases and elastases can be derived from both the host and critically colonizing bacteria. Antimicrobials have a known spectrum of antibacterial action, but some antimicrobials also have an anti-inflammatory action that can promote healing both by decreasing bacterial numbers in the wound but also by decreasing inflammation. In young infants, erythromycin is a reasonable agent for anti-inflammatory and antimicrobial effects, with trimethoprim (TMP) an appropriate alternative after 6 months of age. Tetracyclines should be reserved for older children after the emergence of permanent teeth.

It is important to obtain a good history of the presence and timing of itch, in order to tailor therapies to target or prevent triggers. For patients who experience nighttime itch, a sedating medication such as diphenhydramine may be beneficial. Uncommonly, diphenhydramine may produce paradoxical excitement instead of sedation or leave patients groggy in the morning. In these cases, hydroxyzine or doxepin may be helpful alternatives. Hydroxyzine syrup allows for very small doses to be administered, and the drowsiness is often less severe by morning, but the effect in the skin may last for up to 72 hours. For daytime itch, nonsedating antihistamines, such as cetirizine or loratadine, can be used; however, a small subset of patients may experience drowsiness with these products. Refrigeration of topical products used on the skin can also produce a cooling sensation and minimize itch.

4A. Consider activities of everyday living and restrictions.

Epidermolysis bullosa patients carry a large disease burden with impacts on all aspects of daily living. It is helpful to involve occupational and physiotherapists to maximize independence in activities of daily living, as well as leisure activities. It is also important to screen for concurrent anxiety or depression with appropriate referrals where indicated and provide psychosocial support with information about support and patient advocacy groups.

4B. Quality of life is affected by local wound care.

The frequency of dressing changes and time involved depends on the extent of the wounds and the dressings used. Although many foam dressings can be left in place for up to 7 days, most patients with severe EB require dressing changes every day to every 1 to 3 days. The amount of exudate from the wound along with odor or discomfort will often determine the frequency of dressing changes. If materials stick, dressing changes may be facilitated by bathtub bathing and soaking. Baths are preferred over showers that can cause extension of the blisters due to pressure from the water stream.

The dressing changes take time, and the dressings themselves can be hugely expensive. Community nurses are sometimes required to help with dressing changes, which adds a layer of scheduling inconveniences and system costs above those already mentioned. The dressing changes are often very painful, and if so, it is important to recommend that the patient take an analgesic approximately 30 minutes before the anticipated change. The need for dressing changes and limitations on mobility makes schooling and employment challenging for many of the more severe types of EB patients.

LOCAL WOUND CARE

5. Document the wounds and their ability to heal.

* Size: This is measured with the longest length and the widest width at right angles to the longest length.

* Exudate: Exudate is derived from the dermis or deeper structures and consists of varying amounts of serum, blood, or pus. The most predominant component should be listed first and then the subsequent component(s). For example, serosanguineous exudate has more serum than blood, or all 3 components may be present such as sero-pustular-sanguineous.

* Appearance: The wound base and the margin should be assessed. The base can have black, yellow, or red-pink tissue. Black tissue usually indicates necrosis or tissue death. Yellow can be fibrin in the wound base that may be healthy, and the lattice framework for pink buds of healthy granulation to appear. This needs to be distinguished from loose yellow slough that represents dead surface cells. Healthy granulation tissue is firm and pink. It needs to fill the wound base to the level of the wound edge for epithelium to migrate across the surface as quickly as possible. Unhealthy granulation tissue has a bright red color, is friable, and bleeds easily. When a dressing is removed, blood may be obvious on the inner aspects of the dressing, and punctate bleeding points are seen on the wound surface. This type of granulation is often associated with critical colonization of the wound surface and may respond to topical antimicrobial agents. The wound base can be characterized as having 50% healthy pink granulation and 30% unhealthy bright red friable granulation, with 20% yellow slough.

Once the old dressing has been removed, the area should be gently cleaned with solutions with low or no toxicity. Options include saline solution, water, or solutions with low concentrations of acetic acid (white vinegar-5% diluted 1 in 5 or 1 in 10), benzalkonium chloride, and/or chlorhexidine. Some patients may not tolerate the vinegar because of burning or stinging, and the cleansing agent should be rotated in these cases. The gauze can be saturated with the solution and applied as a soak to hydrate the wound surface with the net movement of liquid from the gauze to the wound surface. Alternately the same material can be squeezed or wrung out leaving damp gauze to apply to the wound, resulting in a compress that acts as an astringent (coagulates protein). The net movement from a compress is from the wound surface to the gauze and results in removal of surface debris. With both methods, the cloth should be changed every 30 to 60 seconds to complete the cleansing process. Irrigation is too harsh for the fragile skin associated with EB.

Dilute acetic acid will lower the pH of the wound surface, and this is often helpful to remove Pseudomonas or other gram-negative organisms from the wound surface that thrive in an alkaline environment. Pseudomonas has a lower virulence than most gram-positive organisms (eg, Staphylococcus aureus or Streptococcus) and can often be treated topically rather than with systemic antibiotics, and it is best to consider 2 topical antimicrobials (such as acetic acid with silver or iodine preparations).

7. Debridement.

If intact blisters are present, they should be punctured with a sterile needle and gentle pressure applied to remove the contents. The roof should be left to act as a natural biologic dressing. If crusts (scabs) have formed over the wound, they should be soaked and carefully lifted off as the presence of the eschar can impair healing and create a proinflammatory stimulus.

8. Assess and treat superficial critical colonization, deep and surrounding infection, or inflammation.

For deep infections, treatment will be based on empirical choices that should have broad-spectrum coverage, and then more specific anibiotics can be ordered based on the culture and sensitivity results.

9. Moisture balance-use silicone foams instead of adhesives.

The choice of dressing depends on the wound characteristics, but should be selected with a goal of optimal moisture balance. In EB patients, silicone foam dressings work well as they allow large amounts of fluid to be absorbed while providing protective padding and will not adhere strongly to the skin when removed preventing pain and trauma on removal.² Other nonadherent moisture balance dressings will also be useful with calcium alginates for areas of bleeding or hydrogels/hydrofibers for gentle moisture balance where fluid donation or fluid lock is required. Some highly exudative wounds require fluid lock technology with superabsorbent dressings with diaper-like technology.

10/11. Evaluate stalled but healable chronic wounds-edge effect: when to use advanced therapies.

Each new case requires a diagnosis and typing or subtyping assoon as possible. Healthcare systems need to build support networks such as the one established in the United Kingdom that provides ongoing support from knowledgeable practitioners. Families need to regroup, and healthcare providers need to be flexible to build trust and improve patient outcomes.

SUMMARY

Epidermolysis bullosa is a highly complex, multisystem disease, with severe EB types having devastating effects on the quality of life and life span of affected patients and their families. Wound care requires an interprofessional coordinated approach that addresses the patient as a whole. The authors have brought together experts in the field of EB, the science of wound care, and clinical wound care practice to provide the best available approaches for optimal wound care to people with EB. Until a definitive cure becomes available, these practice goals are to minimize suffering, improve wound healing, and prepare patients for potential corrective procedures, thereby improving the lives of affected individuals.

REFERENCES