Edward Eid

All Publications

• Natural history study of recessive dystrophic epidermolysis bullosa wounds and patient reported outcomes using mobile application home photography. Scientific reports Fulchand, S., Nazaroff, J., Harris, N., So, J. Y., Villanueva Gaona, R., Alvarez, E., Li, S., Lu, Y., Eid, E., Tang, J. Y. 2025; 15 (1): 28767

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, blistering genetic disease where wounding and wound pain are the most reported problems by patients. The natural history of RDEB wounds, specifically spontaneous wound closure between chronic open vs. recurrent wounds, has not been prospectively studied, thus limiting the design of clinical trial endpoints. We conducted a prospective observational study in which participants used a mobile application to upload weekly photographs of multiple target wounds for up to 6 months and reported associated wound pain and itch (Photo Cohort, N = 69 wounds). We also utilized a separate dataset of placebo-treated wounds from a previously completed trial (Validation Cohort, N = 57 wounds) to validate the 12-week definition of wounds and to determine their rate of spontaneous wound closure. We reveal that chronic open wounds were larger, more painful, and only 17% of were observed to have spontaneous wound closure during follow up. In contrast, 100% (P < 0.001) of recurrent wounds were observed to have spontaneous closure during the photo observation. These differences were confirmed in the Validation Cohort. The median time to wound closure for chronic open wounds was 14.6 vs. 8 weeks for recurrent wounds. Additionally, recurrent wounds had a 29-fold greater likelihood to close spontaneously. In conclusion, chronic open wounds have a lower rate of spontaneous wound closure and are associated with more pain and itch. Wound type is the most significant predictor of spontaneous wound closure and should be the key consideration in the selection of wounds in RDEB clinical trials.

  View details for DOI 10.1038/s41598-025-14413-1

  View details for PubMedID 40770062

  View details for PubMedCentralID PMC12328626

• Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial. Lancet (London, England) Tang, J. Y., Marinkovich, M. P., Wiss, K., McCarthy, D., Truesdale, A., Chiou, A. S., Eid, E., McIntyre, J. K., Bailey, I., Furukawa, L. K., Gorell, E. S., Harris, N., Khosla, R. K., Peter Lorenz, H., Lu, Y., Nazaroff, J., Grachev, I. D., Moore, A. J. 2025

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the COL7A1 gene encoding type VII collagen. Individuals with RDEB have fragile skin and most develop large, chronic wounds. The aim of the VIITAL study was to evaluate the efficacy and safety of a one-time surgical application of prademagene zamikeracel in wound healing.This randomised, open-label, intrapatient-controlled, phase 3 trial was conducted at two institutions in the USA. Eligible patients were aged 6 years or older, had a confirmed clinical and genetic diagnosis of RDEB, at least two chronic wounds (>20 cm2), had no evidence of an immune response to type VII collagen, and expressed the amino-terminal NC1 fragment of type VII collagen. Large, chronic wounds on the participants were matched in pairs by size, chronicity, and anatomical region and computer randomised (1:1) to treatment (prademagene zamikeracel) or control (standard of care). There was no masking. Prademagene zamikeracel is an autologous COL7A1 gene-modified cellular sheet that is sutured onto to a large, chronic RDEB wound. A maximum of six wounds could be treated with prademagene zamikeracel per patient. The coprimary endpoints were the proportion of wounds with at least 50% healing and pain reduction from baseline at week 24 in the intention-to-treat population of all patients and their randomised wounds. The safety analysis population included all patients and evaluated wounds, randomised and non-randomised. This completed trial was registered with ClinicalTrials.gov (NCT04227106).Between Jan 1, 2020, and March 31, 2022, 15 patients were screened and 11 were enrolled (43 randomised wound pairs). Four (36%) of 11 participants were male and seven (64%) of 11 participants were female, with a median age of 21 years (IQR 17-30). 86 wounds were matched and randomised: 43 (50%) to prademagene zamikeracel and 43 (50%) to control. At week 24, 35 (81%) of 43 treated wounds were at least 50% healed from baseline for prademagene zamikeracel compared with seven (16%) of 43 control wounds (mean difference 67% [95% CI 50 to 89]; p<0·0001). The mean change from baseline to week 24 in wound pain was -3·07 with prademagene zamikeracel and -0·90 in controls (mean pairwise difference -2·23 [-3·45 to -0·66]; p=0·0002). No serious treatment-related adverse events were observed.Prademagene zamikeracel improved wound healing and pain versus control and was well tolerated, supporting its potential to reduce wound burden in patients with large, chronic RDEB wounds.Abeona Therapeutics.

  View details for DOI 10.1016/S0140-6736(25)00778-0

  View details for PubMedID 40570869

• Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa. The British journal of dermatology Pathmarajah, P., Eid, E., Nazaroff, J., So, J., Mittal, V., Harris, N., Li, S., Lucky, A. W., Gorell, E. S., Peoples, K. G., Pope, E., Lara-Corrales, I., Paller, A. S., Wiss, K., Perman, M. J., Eichenfield, L. F., Levy, M. L., Morel, K. D., Garcia-Romero, M. T., McCuaig, C. C., Saber, M., Marinkovich, M. P., Oro, A., Bruckner, A. L., Tang, J. Y. 2025

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function. Three impact categories were postulated: genotypes that would likely cause a low impact on C7 function (splice B/missense, missense/missense), medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B] and high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants are predicted to cause downstream PTCs while splice B variants cause in-frame exon skipping and are therefore less deleterious. Severity of functional impact was significantly associated with history of gastrostomy tube placement, esophageal dilation, hand surgery, anemia, renal disease, chronic wounds, diffuse skin involvement and history of squamous cell carcinoma. Odds of death were 3.25 (1.24-8.50, p=0.02) higher in the high vs medium impact group. High impact group patients had worse clinical outcomes. Functional genotype categories are a feasible approach to risk stratify patients based on predicted C7 function.

  View details for DOI 10.1093/bjd/ljaf015

  View details for PubMedID 39790012

• Online, home-based dystrophic epidermolysis bullosa registry. Pediatric dermatology Mittal, V., Nazaroff, J., Eid, E., Li, S., Linos, E., Oro, A., Tang, J. Y. 2024

  Abstract

  Genetic testing is the gold standard for diagnosing different epidermolysis bullosa (EB) subtypes; however, testing rates are low. We conducted a pilot study to test feasibility of a novel, home-based registry that involved patients with EB submitting self-reported clinical symptoms using secure, online surveys (REDCap) and submitting buccal swabs for exome sequencing of EB-related genes (GeneDx). In total, 50 EB participants were enrolled, with an average age of 17 years and an average distance of 198 miles from EB specialty centers. All buccal swabs (N = 24) provided sufficient DNA for sequencing without causing mucosal trauma and 80% of participants were found to have pathogenic variants in COL7A1, the gene mutated in DEB. Participants with recessive dystrophic EB (RDEB) reported a higher prevalence of esophageal dilations (65.7% vs. 0%, p = .009) and mitten deformities of the feet (57.1% vs. 0%, p = .047) compared to non-RDEB participants.

  View details for DOI 10.1111/pde.15682

  View details for PubMedID 38943317

• Functional Genotype-Phenotype Associations in Recessive Dystrophic Epidermolysis Bullosa. Journal of the American Academy of Dermatology So, J. Y., Nazaroff, J., Yenamandra, V. K., Gorell, E. S., Harris, N., Fulchand, S., Eid, E., Dolorito, J. A., Marinkovich, M. P., Tang, J. Y. 2024

  Abstract

  Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB) have been difficult to elucidate.To investigate RDEB genotype-phenotype associations and explore a functional approach to genotype classification.Clinical examination and genetic testing of RDEB subjects, including assessment of clinical disease by RDEB subtype and extent of blistering. Genotypes were evaluated according to each variant's effect on type VII collagen (C7) function per updated literature, and subsequently categorized by degree of impact on C7 function as low-impact (splice/missense, missense/missense), medium-impact (premature termination codon [PTC]/missense, splice/splice), and high-impact (PTC/PTC, PTC/splice). Genotype-phenotype associations were investigated using Kruskal-Wallis and Fisher's exact tests, and age-adjusted regressions.83 participants were included. High-impact variants were associated with worse RDEB subtype and clinical disease, including increased prevalence of generalized blistering (55.6% for low-impact vs. 72.7% medium-impact vs. 90.4% high-impact variants, p=0.002). In age-adjusted regressions, participants with high-impact variants had 40.8-fold greater odds of squamous cell carcinoma compared to low-impact variants (p=0.02), and 5.7-fold greater odds of death compared to medium-impact variants (p=0.05).Cross-sectional design.Functional genotype categories may stratify RDEB severity; high-impact variants correlated with worse clinical outcomes. Further validation in larger cohorts is needed.

  View details for DOI 10.1016/j.jaad.2024.04.073

  View details for PubMedID 38735484

• Incidence of Nonkeratinocyte Skin Cancer After Breast Cancer Radiation Therapy. JAMA network open Rezaei, S. J., Eid, E., Tang, J. Y., Kurian, A. W., Kwong, B. Y., Linos, E. 2024; 7 (3): e241632

  Abstract

  Previous studies have suggested that radiation therapy may contribute to an increased risk of subsequent nonkeratinocyte (ie, not squamous and basal cell) skin cancers.To test the hypothesis that radiation therapy for breast cancer increases the risk of subsequent nonkeratinocyte skin cancers, particularly when these cancers are localized to the skin of the breast or trunk.This population-based cohort study used longitudinal data from the Surveillance, Epidemiology, and End Results (SEER) Program for January 1, 2000, to December 31, 2019. The SEER database includes population-based cohort data from 17 registries. Patients with newly diagnosed breast cancer were identified and were evaluated for subsequent nonkeratinocyte skin cancer development. Data analysis was performed from January to August 2023.Radiation therapy, chemotherapy, or surgery for breast cancer.The primary outcomes were standardized incidence ratios (SIRs) for subsequent nonkeratinocyte skin cancer development from 2000 to 2019 based on treatment type (radiation therapy, chemotherapy, or surgery), skin cancer site on the body, and skin cancer subtype.Among the 875 880 patients with newly diagnosed breast cancer included in this study, 99.3% were women, 51.6% were aged older than 60 years, and 50.3% received radiation therapy. A total of 11.2% patients identified as Hispanic, 10.1% identified as non-Hispanic Black, and 69.5% identified as non-Hispanic White. From 2000 to 2019, there were 3839 patients with nonkeratinocyte skin cancer, including melanoma (3419 [89.1%]), Merkel cell carcinoma (121 [3.2%]), hemangiosarcoma (104 [2.7%]), and 32 other nonkeratinocyte skin cancers (195 [5.1%]), documented to occur after breast cancer treatment. The risk of nonkeratinocyte skin cancer diagnosis after breast cancer treatment with radiation was 57% higher (SIR, 1.57 [95% CI, 1.45-1.7]) than that of the general population when considering the most relevant site: the skin of the breast or trunk. When risk at this site was stratified by skin cancer subtype, the SIRs for melanoma and hemangiosarcoma were both statistically significant at 1.37 (95% CI, 1.25-1.49) and 27.11 (95% CI, 21.6-33.61), respectively. Receipt of radiation therapy was associated with a greater risk of nonkeratinocyte skin cancer compared with chemotherapy and surgical interventions.In this study of patients with breast cancer, an increased risk of melanoma and hemangiosarcoma after breast cancer treatment with radiation therapy was observed. Although occurrences of nonkeratinocyte skin cancers are rare, physicians should be aware of this elevated risk to help inform follow-up care.

  View details for DOI 10.1001/jamanetworkopen.2024.1632

  View details for PubMedID 38457179

• Longitudinal remote monitoring of hidradenitis suppurativa: a pilot study. The British journal of dermatology Fonjungo, F. E., Barnes, L. A., Cai, Z. R., Naik, H. B., Eid, E. S., Aleshin, M. A., Nava, V., Johnson, T., Chren, M., Linos, E. 2023

  View details for DOI 10.1093/bjd/ljad385

  View details for PubMedID 37823362

• Risk of Multiple Primary Cancers in Patients With Merkel Cell Carcinoma: A SEER-Based Analysis. JAMA dermatology Eid, E., Maloney, N. J., Cai, Z. R., Zaba, L. C., Kibbi, N., John, E. M., Linos, E. 2023

  Abstract

  The risk of subsequent primary cancers after a diagnosis of cutaneous Merkel cell carcinoma (MCC) is not well established.To evaluate the risk of subsequent primary cancers after the diagnosis of a first primary cutaneous MCC.This cohort study analyzed data from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from January 1, 2000, to December 31, 2019. In all, 6146 patients diagnosed with a first primary cutaneous MCC were identified.The primary outcome was the relative and absolute risks of subsequent primary cancers after the diagnosis of a first primary MCC, which were calculated using the standardized incidence ratio (SIR; ratio of observed to expected cases of subsequent cancer) and the excess risk (difference between observed and expected cases of subsequent cancer divided by the person-years at risk), respectively. Data were analyzed between January 1, 2000, and December 31, 2019.Of 6146 patients with a first primary MCC diagnosed at a median (IQR) age of 76 (66-83) years, 3713 (60.4%) were men, and the predominant race and ethnicity was non-Hispanic White (5491 individuals [89.3%]). Of these patients, 725 (11.8%) developed subsequent primary cancers, with an SIR of 1.28 (95% CI, 1.19-1.38) and excess risk of 57.25 per 10 000 person-years. For solid tumors after MCC, risk was elevated for cutaneous melanoma (SIR, 2.36 [95% CI, 1.85-2.97]; excess risk, 15.27 per 10 000 person-years) and papillary thyroid carcinoma (SIR, 5.26 [95% CI, 3.25-8.04]; excess risk, 6.16 per 10 000 person-years). For hematologic cancers after MCC, risk was increased for non-Hodgkin lymphoma (SIR, 2.62 [95% CI, 2.04-3.32]; excess risk, 15.48 per 10 000 person-years).This cohort study found that patients with MCC had an increased risk of subsequently developing solid and hematologic cancers. This increased risk may be associated with increased surveillance, treatment-related factors, or shared etiologies of the other cancers with MCC. Further studies exploring possible common etiological factors shared between MCC and other primary cancers are warranted.

  View details for DOI 10.1001/jamadermatol.2023.2849

  View details for PubMedID 37703005