Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity.

BACKGROUND: Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. OBJECTIVES: To assess the clinical and biological features, genetic basis and therapeutic management, to better characterize this rare genodermatosis. METHODS: We have conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, immunohistopathological findings and biological characteristics and management of patients with dystrophic epidermolysis bullosa pruriginosa. This study was conducted in the Department of Dermatology at Saint-Louis Hospital and the Department of Genetics at Necker Hospital (Paris, France). All patients with a diagnosis of DEB-Pr seen between 2010 and 2020 were included. RESULTS: Seven patients were included, the average age of 50.1 years [range 36-76]. Pruriginous-lichenified papules, plaques or nodules appeared at 27.6 years on average [range 7-66] on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple treatments, but none could sustainably reduce pruritus. Immunohistopathological analysis of lesion skin revealed subepidermal blister with fibrosis, milia and mast cell infiltration. Serum TNFα, IL1ß and IL6 levels were elevated in 2/6 patients. Total serum IgE levels were increased in 7/7 patients, with no history of atopy. Immunophenotyping of circulating T-cells revealed an increased Th2 subset in 4/4 patients, with reduced Th1 and Th17 subpopulations. Genetic analysis of COL7A1 identified 7 distinct causative mutations, six of which were new. Intra-familial clinical variability was documented in 5/7 patients and was associated with the co-inheritance of a recessive COL7A1 mutation or an FLG2 mutation in 2 families. CONCLUSION: Our study confirms the stereotyped presentation of DEB-Pr with large intra-familial variability in disease expression. Mast cell infiltration, elevated IgE and increased Th2 subset without atopy strongly support a role of Th2-mediated immunity in DEB-Pr, and further argue for new targeted therapeutic options such as dupilumab.

High-frequency (20-50 MHz) ultrasonography of pseudoxanthoma elasticum skin lesions.

BACKGROUND: In most patients pseudoxanthoma elasticum (PXE) manifests with yellowish cutaneous papules and dermal elastorrhexis on skin biopsy. In a small number of cases there are no skin manifestations on clinical examination, and establishing a diagnosis of PXE in such patients is challenging. High-frequency ultrasonography (HFUS) may be of use in predicting skin areas that would yield a biopsy specimen positive for elastorrhexis. OBJECTIVES: To describe characteristics of clinically visible PXE skin using HFUS, and to evaluate its relevance for diagnosis. METHODS: HFUS was performed in a cohort of patients with PXE and in controls at a referral centre. HFUS images of PXE skin were compared with those of other conditions. Five operators blind-scored multiple HFUS images of photoprotected or photoexposed skin from patients with PXE and controls. The diagnostic indices (sensitivity, specificity, likelihood ratios, interobserver agreement) were calculated. RESULTS: The HFUS changes considered as diagnostic for PXE were primarily oval homogeneous hypoechogenic areas in the mid-dermis. The size of these areas closely matched the extent of the histological changes. The sensitivity and specificity of the diagnostic items and interobserver agreement were high, particularly in photoprotected skin. Dermal hypoechogenicity in PXE could be related to high hydration of connective tissue due to the presence of glycosaminoglycans despite elastic fibre mineralization. CONCLUSIONS: HFUS provides suggestive images of PXE skin lesions. HFUS should now be studied to determine whether it is a potentially valuable technique for the noninvasive identification of elastorrhexis in patients with PXE in whom skin involvement is clinically minimal or absent.

Positive Seatbelt Sign with Avulsed Leiomyoma following Motor Vehicle Accident Leading to Hemoperitoneum.

A positive seatbelt sign following a motor vehicle accident is associated with an increased risk of intra-abdominal injury and hemoperitoneum. Injury to the uterus in reproductive-age women can also occur. In this report, we describe a 29-year-old nulligravida female who presented to the emergency room following a motor vehicle accident at freeway speeds. A positive seatbelt sign was noted, and a focused assessment with sonography for trauma revealed hemoperitoneum with an incidental finding of uterine leiomyomata. Upon exploratory laparotomy, a free-floating intraperitoneal mass was identified as an avulsed uterine leiomyoma. A uterine laceration containing a subserosal leiomyoma was also identified. The gynecological team was consulted, and a myomectomy of the subserosal leiomyoma followed by a closure of the uterine laceration was performed. The patient was transfused with a total of three units of packed red blood cells and two units of fresh frozen plasma. The postoperative course was without major complication. A positive seatbelt sign and hemoperitoneum in a reproductive-age woman with leiomyomata should increase the clinical suspicion for uterine injury and decrease the threshold for obtaining a gynecological consultation.

Cardiac Dose and Survival After Stereotactic Body Radiotherapy for Early-stage Non-Small-cell Lung Cancer.

INTRODUCTION: Recent analyses have identified cardiac dose as an important predictor of overall survival (OS) after chemoradiation for locally advanced non-small-cell lung cancer (NSCLC). However, the survival influence of the cardiac dose after stereotactic body radiotherapy (SBRT) is unknown. We performed a dose-volume histogram (DVH) analysis of patients treated with SBRT for early stage NSCLC to examine survival and cardiac toxicity. MATERIALS AND METHODS: We reviewed the medical records of patients who had undergone SBRT for early-stage NSCLC from June 2007 to June 2015 and documented the cardiac DVH parameters, including the maximum and mean dose and percentage of volume receiving >5, >10, >20, and >30 Gy (V5, V10, V20, and V30, respectively). The biologically effective doses and 2-Gy equivalent doses were also calculated. The DVH parameters were assessed as predictors of OS using Cox regression analysis. RESULTS: We identified 102 patients with 118 treated tumors. At a median follow-up period of 27.2 months (range, 9.8-72.5 months), the 2-year OS estimate was 70.4%. The cardiac DVH parameters were as follows: maximum dose, median, 14.2 Gy (range, 0.3-77.8 Gy); mean dose, median, 1.6 Gy (range, 0-12.6 Gy); and V5, median, 8.7% (range, 0%-96.4%). We identified no correlation between OS and any cardiac dose parameter. No patient developed acute (within 3 months) cardiac toxicity. Four patients died of cardiac causes; all had had preexisting heart disease. CONCLUSION: In our cohort, cardiac dose was not a predictor of OS after lung SBRT, despite a subset of patients receiving high maximum cardiac doses. The findings from our limited cohort showed that high doses to small volumes of the heart appear safe. Analyses of larger patient cohorts with longer follow-up durations are needed to better delineate the safe cardiac DVH constraints for SBRT.