Itching, blistering, and dry skin is only a reality for most after a sunny day at the beach, but for others, it is their daily reality. Something as simple as moving your arm or making contact with another person causes blisters to form on the skin of those suffering from a rare, genetic skin condition called Epidermolysis Bullosa (EB). Yet, while someone with a sunburn can feel better after a cool shower and applying aloe to their skin, those with EB suffer daily with no effective treatment for improving the condition of their skin.
Epidermolysis Bullosa (EB) is a rare, genetic condition that causes the skin to be very fragile and blister easily. The blisters can be caused by a number of minor things such as: scratching the skin, friction, or exposure to heat (Mayo Clinic Staff 2022). Because of the blisters caused by this condition, people with EB often have reoccurring wounds that impact them for their entire life. Blisters caused by EB are typically found on palms and feet, the face, and arms and legs (Murrell et al. 2020, 2).
EB affects approximately 25,000 to 50,000 people in the United States (Mayo Clinic Staff 2022). Yet, despite the severity of this disease and number of those impacted, there are no viable treatment options, and no cure. Current treatments are meant to manage symptoms, frequently through medication, but in more severe cases may be through surgery or physical therapy (Mayo Clinic Staff 2022). It is evident that there is a need for effective treatment options for EB.
This realization resulted in a study being conducted to assess the efficacy of a topical treatment made by Amicus Therapeutics. The topical treatment was in the form of a cream. This phase of the study was called ESSENCE Phase 3 clinical trial, and, as the name suggests, involved using people suffering from EB to test how well the cream worked in reducing wounds caused by EB. It was expected that the cream would speed up wound closure in EB patients, but what happens when the placebo in a study is just as effective as the experimental cream?
The study was conducted on 169 patients over the course of three months, with half receiving a treatment with six percent of an active ingredient called allantoin within a lotion base, and the other half receiving a placebo cream, which was the same lotion without the active ingredient. The experiment was double blind, meaning neither the patients, nor the experimenters knew which patients were receiving the active lotion, and which were receiving the placebo. Criteria to be a patient for the study included: being older than one month old; having either EB simplex, recessive dystrophic EB, or intermediate junctional EB; and having a wound on the skin between ten and fifty centimeters squared that was present for at least twenty-one days. For ninety days, a thin layer of lotion was applied to the whole body of patients, followed by bandages changes every day. The goal of the study was to identify how effective and safe the active ingredient, allantion, was in reducing wounds caused by EB. The method for this study was described clearly and would be easily replicable if given the resources, giving the study credibility.
So, what differentiates forms of EB from one another? Since people with EB vary greatly in their severity of the condition, there is a spectrum of forms in which EB may manifest, each with its own name to differentiate characteristics. EB simplex is the most prevalent form of EB as it impacts 70% of those known to have the condition. EB simplex causes blisters to form on the epidermis layer of skin but is generally known to be a mild form of EB. Recessive dystrophic EB is the second most prevalent form of EB as it accounts for 25% of cases. In this form, any movement could cause blisters to form on the skin. This is due to delicate connections being made between layers of skin. From a visual standpoint, it is identifiable by fused fingers and toes, and scarring on the skin as a result of blisters. People suffering from this form of EB have a higher risk of developing skin cancer. Intermediate junctional EB is less severe than some other forms and is characterized by blistering, like all other forms of EB. These types are all passed down genetically and were the three types of EB that were included in the study.
The researchers assessed results for the experiment on four main criteria. First, was how long it took for the identified wound to close (if at all). Second, was the proportion of patients who experienced wound closure. Third, was how much of the body was still covered in wounds caused by EB (measured as a percentage of total skin). Lastly, was the amount of pain and itchiness patients experienced (measured using a device for patients younger than four and measured on a scale for those four and older).
There were 169 total patients in the study, and only eighty of the eighty-seven in the control group completed the study. The average time for a wound to close in the control group was 53.6 days. Additionally, the proportion of patients who experienced wound closure increased from 7.1% at fourteen days to 56.6% by the end of the study. The average amount of the body still covered in wounds was decreased by five percent and patients also experienced a reduction in pain and itchiness caused by EB by the end of the study. These results were quite surprising to researchers as these positive outcomes came from their placebo group for the experiment. The companion paper to this study expressed results from the experimental group and found there was no statistically significant difference between the placebo and the experimental group Paller et al. 2020, 2). This further exemplified the significance of the results from the placebo.
Because this research was meant to describe the effects of the experimental group and not the control group, authors were quick to admit limitations in the study. The study noted that the success of the control group could have been impacted by overall improved wound care, more specifically though appointments with physicians and daily dressing changes. Also, it was notable that there was no control group for the control group (in which patients receive no lotion and no daily dressing changes) to measure the outcomes of regular wound care. It was additionally found that there was poor age distribution in the study (only six of the eighty-seven control participants fell between the age of one month to two years). Finally, there was a disproportionally high number of patients with recessive dystrophic EB. Another interesting limitation to note is it is unknown how much of an impact how one cares for a wound affects how well/quickly they heal (in this case the daily bandage changes was how wounds were cared for).
After the results of the control brought about a notable positive outcome, researchers were left wondering what factors may have contributed to this. Did the control group’s cream have an ingredient that was aiding in wound closure? Did the daily dressing changes and application of a cream daily contribute to the findings? Did patients have a more positive outlook on their condition, causing wounds to improve? It seems like any of these options are viable and could be the reason behind this positive outcome, which brings about the idea of larger implications of this research.
The larger implication of this research could suggest that the mindset of a patient participating in a study may contribute to improved outcomes (in this case, the attention EB patient’s wounds were given over the course of the study may psychologically impacted the patients in a way that positively impacted the outcome). This idea could contribute to a conversation on the impact of mindset on the outcome of things. The narrower implication of this research begins to bring up the idea that how an EB wound is treated, may be just as important as what it is treated with.
Overall, the outcome of this study found that both ingredients in a topical cream and how wounds are treated could be vital in alleviating symptoms associated with EB. This study is greatly beneficial and brings up a number of things that could be further researched in the future. Those suffering from EB need a viable treatment option for a skin condition that impacts their lives daily. Studies like these give hope that one day EB will be as easy to treat as a sunburn.
References
Mayo Clinic Staff. 2022. Epidermolysis bullosa – Symptoms and causes. [accessed 2022 Sep 19]. https://www.mayoclinic.org/diseases-conditions/epidermolysis-bullosa/symptoms-causes/syc-20361062.
Epidermolysis Bullosa Clinic Frequently Asked Questions. Dermatology. [accessed 2022 Sep 19]. https://med.stanford.edu/dermatology/resources/gsdc/eb_clinic/eb-faqs.html#:~:text=severely%20affected%20individuals),How%20common%20is%20EB%3F,the%20United%20States%20have%20EB.
Murrell DF, Paller AS, Bodemer C, Browning J, Nikolic M, Barth JA, Lagast H, Krusinska E, Reha A, on behalf of the ESSENCE Study Group. 2020. Wound closure in epidermolysis bullosa: Data from the vehicle arm of the phase 3 ESSENCE Study. Orphanet Journal of Rare Diseases 15:1-10. [accessed 2022 Sep 19] 15:190. https://doi.org/10.1186/s13023-020-01435-3.
Paller AS, Browning J, Nikolic M, Bodemer C, Murrell DF, Lenon W, Krusinska E, Reha A, Lagast H, Barth JA, on behalf of the ESSENCE Study Group. 2020. Efficacy and tolerability of the investigational topical cream SD-101 (6% allantoin) in patients with epidermolysis bullosa: a phase 3, randomized, double-blind, vehicle-controlled trial (ESSENCE study). Orphanet Journal of Rare Diseases 15:1-11. [accessed 2022 Sep 19] 15:158. https://doi.org/10.1186/s13023-020-01419-3.
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