Validation and Repeatability of the Epidermolysis Bullosa Eye Disease Index in Dystrophic Epidermolysis Bullosa.

PURPOSE: Dystrophic epidermolysis bullosa (DEB) is a devastating condition that causes painful corneal abrasions and vision loss. Epidermolysis Bullosa Eye Disease Index (EB-EDI) for the first time captures and quantifies EB-specific assessment of ocular symptoms and activities of daily living scales. This survey will become critical in developing new interventions on patients' quality of life. METHODS: Three-part set of the EB-EDI baseline, EB-EDI interval, and Ocular Surface Disease Index (OSDI) survey was distributed to 92 patients with DEB who previously reported eye symptoms on previous surveys. It was then posted online through several EB patient organizations. We compared the EB-EDI with the gold standard OSDI and examined the repeatability of the EB-EDI over a 7- to 15-day interval. RESULTS: Of the 45 individuals who initially responded, 30 of 45 (67%) completed the surveys sent 7 to 15 days later. The age of participants ranged from 6 to 51 years (mean 21 ± 15 years), and 60% (18 of 30) of participants were younger than 18 years. The overall Cronbach alpha values for the subscales of EB-EDI baseline and interval tools presented a good internal consistency (≥0.7). From 2 visits, the domain scores of EB-EDI baseline (0.94) and interval tools (0.83) were shown to have excellent test-retest reliability (intraclass correlation coefficient >0.8). By comparison, OSDI had the intraclass correlation coefficient score of 0.72 ± 0.11. The convergent validation analysis showed that correlations between the domain scores of EB-EDI baseline and interval tools and the subscales of the OSDI reached the hypothesized strength. CONCLUSIONS: Based on a 30-person repeated-measures study, we found that the EB-EDI has excellent reliability and validity specifically in patients with DEB.

Opioid-Associated Amnestic Syndrome.

A 31-year-old male with a history significant for obesity, attention deficit hyperactivity disorder, methamphetamine use, and IV drug use was evaluated for unexplained global amnesia greater than 24 h. The patient had been in recovery for opioid use disorder for about a year, but he relapsed on IV fentanyl in the week prior to presentation. On exam, he was alert and fully oriented but had no spontaneous recall of three objects after five minutes. General medical and neurological examinations were otherwise unrevealing. Urine fentanyl and norfentanyl were positive. CT and MRI imaging demonstrated isolated bilateral hippocampal injury. Given the totality of his presentation and the contributing variables, his medical team considered this to be a case of the newly characterized opioid-associated amnestic syndrome (OAS). This case is significant because of the relative absence of potentially confounding variables on presentation, including antecedent cardiorespiratory failure. Further reporting of these cases may have implications for understanding opioid toxicity and clarifying the functional role of the hippocampus.

Anterior-segment spectral domain optical coherence tomography in epidermolysis bullosa.

PURPOSE: Assess epidermolysis bullosa (EB)-related corneal pathology using anterior segment optical coherence tomography (AS-OCT) and correlate imaging with clinical metrics in EB patients versus age-matched controls. METHODS: EB patients and controls were recruited during an EB conference (July 2018) and at Tufts Medical Center (June-August 2019). Subjects completed a questionnaire, had best corrected visual acuity (BCVA) tested, and underwent AS-OCT scanning. Stromal and epithelial thickness were measured. Depth, length, and type of the three largest lesions were assessed by a masked examiner using a novel pathology grading system. Multivariate analysis of AS-OCT findings and clinical metrics was performed. RESULTS: 62 EB patients and 60 age-matched controls were enrolled. Mean BCVA was 1.8 lines worse in patients (p < 0.001). Vision loss was associated with increased stromal thickness. Discrete lesions were seen in 60.2% of patient eyes, averaging 1.71 ± 1.75 lesions in patients and 0.14 ± 0.42 in controls (p < 0.001). Mean primary lesion depth was 151.88 ± 97.49 µm in patients. Patients showed significant stromal thickening versus controls and lesions were most common in the periphery and inferiorly. Differences in frequency and duration of abrasions and severity of pain were all statistically and clinically significant in patients versus controls (p < 0.001). CONCLUSIONS: AS-OCT can visualize and quantify differences in the corneas of EB patients compared with age-matched controls. Novel findings include quantification of average depth, length, and severity of discrete lesions, and sparing of the superior quadrant from stromal thickening in EB patients. These results support use of AS-OCT and a questionnaire in clinical trials for new EB therapies.

Long-Term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab.

BACKGROUND: We successfully used omalizumab to facilitate peanut oral immunotherapy (OIT) in children with reactivity to ≤50mg peanut protein and with high peanut IgE (median, 229 kU/L). OBJECTIVE: We report on long-term OIT outcomes in these patients, including dosing changes, adverse events, peanut immunoglobulin changes, and quality of life (QoL). METHODS: Patients were followed for up to 72 months (67 months of maintenance). Outcomes were collected on peanut dose amount, form, and frequency, as well as adverse events, (QoL), and laboratory studies. RESULTS: Of 13 patients initially enrolled, 7 patients (54%) continued on peanut OIT through month 72; 6 (46%) discontinued therapy because of adverse reactions. Maintenance peanut protein dose varied between 500 and 3500mg. Most patients consumed different peanut-containing products. All patients experienced at least 1 adverse event, and 1 patient developed eosinophilic esophagitis. Peanut-IgE, Arah1-IgE and Arah2-IgE, peanut-SPT, peanut-IgE:IgE ratio, and Arah2-IgE:Arah2-IgG4 ratio decreased on OIT. Peanut-IgG4, Arah1-IgG4, and Arah2-IgG4 initially increased on OIT and then decreased, though not falling to baseline levels. In patients who stopped OIT, there was a trend for reversal of these biomarker changes. Higher peanut-IgE and Arah2-IgE at study month 12 were associated with discontinuation. Patient and parent QoL improved from baseline, even in patients who discontinued OIT. CONCLUSIONS: Although adjunctive omalizumab allowed for faster and successful desensitization in patients with high peanut-IgE, almost half of patients discontinued OIT within 72 months because of reactions. Patients who stopped therapy had higher month 12 peanut-IgE and Arah2-IgE. It is possible that these patients might benefit from longer omalizumab administration.