Accelerated Aging and Microsatellite Instability in Recessive Dystrophic Epidermolysis Bullosa-Associated Cutaneous Squamous Cell Carcinoma.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severely debilitating disorder caused by pathogenic variants in COL7A1 and is characterized by extreme skin fragility, chronic inflammation, and fibrosis. A majority of patients with RDEB develop squamous cell carcinoma, a highly aggressive skin cancer with limited treatment options currently available. In this study, we utilized an approach leveraging whole-genome sequencing and RNA sequencing across 3 different tissues in a single patient with RDEB to gain insight into possible mechanisms of RDEB-associated squamous cell carcinoma progression and to identify potential therapeutic options. As a result, we identified PLK-1 as a possible candidate for targeted therapy and discovered microsatellite instability and accelerated aging as factors potentially contributing to the aggressive nature and early onset of RDEB squamous cell carcinoma. By integrating multitissue genomic and transcriptomic analyses in a single patient, we demonstrate the promise of bridging the gap between genomic research and clinical applications for developing tailored therapies for patients with rare genetic disorders such as RDEB.

Characterization of wound microbes in epidermolysis bullosa: A focus on Pseudomonas aeruginosa.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

Transition of care in patients with epidermolysis bullosa: A survey study.

There are little published data on the transition of care in EB. We conducted a survey study recruiting EB patients from the Dystrophic EB Research Association (debra) website and centers caring for high numbers of EB patients in the United States and internationally from Sept 17, 2019 to Nov 3, 2021. The majority of participants had not discussed the transition of care with their healthcare providers, nor the healthcare needs to be required as an adult. Ongoing pediatric subspecialty care was reported by 12% of adults, most commonly in pediatric dermatology. Identified barriers to transition included the perceived lack of adult providers' knowledge about EB patient healthcare needs. The results suggest the need for transition guidelines, early discussions with families about transition, and practical information for the adult providers accepting care.

A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa.

BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Cutaneous findings in Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a genetic disorder that results in bone marrow failure, physical abnormalities, and solid organ malignancies. The diagnosis of FA is often delayed because the early disease characteristics have not been well established. OBJECTIVE: To outline the spectrum of cutaneous findings seen in patients with FA. METHODS: A cross-sectional study in which patients with FA received a full-body skin examination. Patient characteristics are summarized with mean (SD) for continuous and count (%) for categorical variables. Poisson regression and logistic regression models were used to examine the relationships between pigmentary changes and patient characteristics. RESULTS: At least 1 cutaneous pigmentary alteration was present in 96.8% of patients, most arising before the teenage years. The most common finding was café-au-lait macules. Other findings included hypopigmented macules, skin-fold freckle-like macules, extensive sun-exposed freckling, and both hypopigmented and hyperpigmented pigment macules. LIMITATIONS: Patients received a single assessment, so the number of pigmentary changes could not be assessed over time. CONCLUSIONS: Characteristic morphology of FA includes faint and ill-defined café-au-lait macules, hypopigmented skin-fold freckle-like macules and the concurrence of hypopigmented and hyperpigmented macules. The recognition of these findings could aid clinicians in making earlier diagnoses.

Characterization of wound microbes in epidermolysis bullosa: Results from the epidermolysis bullosa clinical characterization and outcomes database.

BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require care of wounds that are colonized or infected with bacteria. A subset of EB patients are at risk for squamous cell carcinoma, and bacterial-host interactions have been considered in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the United States and Canada. Access to this resource enabled broad-scale analysis of wound cultures. METHODS: A retrospective analysis of 739 wound cultures from 158 patients from 13 centers between 2001 and 2018. RESULTS: Of 152 patients with a positive culture, Staphylococcus aureus (SA) was recovered from 131 patients (86%), Pseudomonas aeruginosa (PA) from 56 (37%), and Streptococcus pyogenes (GAS) from 34 (22%). Sixty-eight percent of patients had cultures positive for methicillin-sensitive SA, and 47%, methicillin-resistant SA (18 patients had cultures that grew both methicillin-susceptible and methicillin-resistant SA at different points in time). Of 15 patients with SA-positive cultures with recorded mupirocin susceptibility testing, 11 had mupirocin-susceptible SA and 6 patients mupirocin-resistant SA (2 patients grew both mupirocin-susceptible and mupirocin-resistant SA). SCC was reported in 23 patients in the entire database, of whom 10 had documented wound cultures positive for SA, PA, and Proteus species in 90%, 50%, and 20% of cases, respectively. CONCLUSIONS: SA and PA were the most commonly isolated bacteria from wounds. Methicillin resistance and mupirocin resistance were reported in 47% and 40% of patients tested, respectively, highlighting the importance of ongoing antimicrobial strategies to limit antibiotic resistance.

Characterizing online searches in pediatric dermatology.

The use of online medical information is a common trend but little is known about these searches and implications in pediatric dermatology. Through a convenience sample of 95 parents/guardians and patients in pediatric dermatology at the University of Minnesota, 38.9% of participants reported that they had used an online search tool prior to their appointment. Google was the most common tool used (91.4%), and eczematous conditions were the most common patient-suspected diagnosis (32.4%). Of interest, 13.9% of individuals became more concerned and 16.7% made an appointment earlier because of their online findings.

Skin cleansing and topical product use in patients with epidermolysis bullosa: Results from a multicenter database.

BACKGROUND/OBJECTIVES: Epidermolysis bullosa (EB) comprises a group of inherited skin blistering diseases. There is currently no cure, and management includes skin protection and prevention of infection. To date, there has been no systematic investigation of home skin care practices among EB patients on a multicenter scale. METHODS: This cross-sectional, observational study included data collected from patients with EB enrolled in the Epidermolysis Bullosa Characterization and Clinical Outcomes Database (EBCCOD) who provided answers to a patient-directed questionnaire between January 1, 2017, and December 31, 2017. RESULTS: Of 202 respondents, 130 (64.4%) had dystrophic EB, 51 (25.2%) had EB simplex, 21 (7.4%) had junctional EB, 3 (1.5%) had Kindler syndrome, and 3 (1.5%) had an unspecified subtype. Seventy-eight patients reported cleansing in plain water only (39%). Of those who used an additive in their cleansing water, 75 (57%) added salt, 71 (54%) added bleach, 36 (27%) added vinegar, and 34 (26%) endorsed the use of an "other" additive (multiple additives possible). Reported concentrations of additives ranged widely from 0.002% sodium hypochlorite and 0.002% acetic acid solutions, which are thought to have negligible effects on microbes, to 0.09% sodium hypochlorite and 0.156% acetic acid, concentrations shown to be cytotoxic. One hundred eighty-eight patients answered questions regarding topical product use (93%). Of those, 131 reported topical antimicrobial use (70%). Mupirocin and bacitracin were the most commonly reported topical antibiotics (59, 58 [31.4%, 30.9%], respectively). CONCLUSIONS: These findings highlight the variety of skin care routines and frequent use of topical antimicrobials among EB patients and have potential implications for antibiotic resistance. The reported range of bleach and vinegar additives to cleansing water, including cytotoxic concentrations, emphasizes the need for clear and optimized skin cleansing recommendations.

Tinea capitis: A single-institution retrospective review from 2010 to 2015.

BACKGROUND/OBJECTIVE: Tinea capitis is a common infection of scalp hair in children. The prevalent etiologic organism has changed significantly over time, which may reflect the complex interaction of environmental factors, genetic predisposition, and movement of populations. We evaluate the prevalence of different infectious organisms causing tinea capitis and describe the clinical characteristics. METHODS: A retrospective chart review of patients diagnosed with tinea capitis with tissue culture confirmation, who were seen in pediatric dermatology at a tertiary care center from 2010 to 2015. Patient demographics, culture data, and clinical characteristics were evaluated. Inflammatory pattern, characterized by presence of pustules, bogginess, or lymphadenopathy, was noted. RESULTS: Forty-six patients with culture-positive tinea capitis were identified. In the 18 (42.9%) patients who were infected with either Trichophyton violaceum or Trichophyton soudanenese, all were of African ethnicity. In contrast, Trichophyton tonsurans was identified in a minority of African patients (3.8%), revealing a statistically significant difference between ethnicity and infective species (P-value < 0.001). T tonsurans was significantly more likely than T violaceum to exhibit an inflammatory pattern (68% vs 22%, P value < 0.027). CONCLUSIONS: While T tonsurans remained the most common cause of tinea capitis, T violaceum and T soudanense have increased in prevalence. As these latter agents are less inflammatory, clinical diagnosis may be delayed. Studying changes in the infectious cause of tinea capitis can help us create a snapshot to better understand the evolution of our population make-up, allowing us to provide crucial quality health care to all.

Assessment of the Timing of Milestone Clinical Events in Patients With Epidermolysis Bullosa From North America.

Importance: Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB. Objectives: To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression. Design, Setting, and Participants: This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study. Exposures: Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS). Main Outcomes and Measures: Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB. Results: Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died. Conclusions and Relevance: The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.

Perceptions and Practices Regarding Atopic Dermatitis: A Survey.

Parents (N = 392) completed a survey at the Minnesota State Fair in August and September 2015 addressing knowledge regarding the pathogenesis of atopic dermatitis (AD), basic skin care practices, and the perceived role of infection and food allergies in AD. Of participating parents, 82% identified food allergy or sensitivity in AD pathogenesis, whereas only 42% identified bacterial infection as an important factor in AD severity. Participants most often received education on skin health from their pediatrician (49%), followed by Internet-based sources (23%), rather than a dermatologist or pediatric dermatologist. Parents of children with AD overestimate the role of food allergies in this condition and are not as aware of the role of bacterial infection. Future educational directions from our specialty should focus on resources for pediatricians and families that emphasize these factors.

Overgrowth syndromes with vascular malformations.

This review provides a clinically-oriented summary of the most commonly encountered overgrowth syndromes associated with vascular malformations. This manuscript will outline morphologic features, clinical evaluation and management of this complex group of patients. Recent genetic advances have aided in classification and help to explain overlapping clinical features in many cases.

Toxic Epidermal Necrolysis in Recessive Dystrophic Epidermolysis Bullosa following Bone Marrow Transplantation.

A 3-year-old child with recessive dystrophic epidermolysis bullosa treated with bone marrow transplantation subsequently developed body-wide epidermal detachment distinct from his epidermolysis bullosa. Toxic epidermal necrolysis was diagnosed by examination and skin biopsy. Although graft-vs-host disease was considered, he had no features of this diagnosis by laboratory studies or skin biopsy, and he improved without addition of further immune suppressants. Throughout the episode, the patient was maintained on cyclosporine A, a component of his transplant regimen, and also a reported therapy for toxic epidermal necrolysis. He had full recovery. Re-epithelialization occurred in a unique folliculocentric pattern, which we postulate was related to the patient's mesenchymal stem cell infusion, received as an adjunct to his marrow transplantation.

Transplacental Transmission of Pemphigus Herpetiformis in the Setting of Maternal Lymphoma.

Pemphigus herpetiformis (PH) is characterized by grouped vesicular or papular pruritic lesions with histologic and immunopathologic features of pemphigus. PH can manifest at any age, and paraneoplastic cases have been reported. We describe a healthy boy born with acral crateriform erosions of the hands and feet whose 35-year-old mother had similar lesions. Biopsies from both patients were most consistent with PH. The mother was diagnosed with high-grade B-cell non-Hodgkin lymphoma and began chemotherapy with dexamethasone, and her lesions quickly improved. The infant had no additional lesions after 3 weeks of age and his acral erosions healed. To our knowledge, this is the first report of a diagnosis of PH in an infant and the first case of transplacental transmission of PH. This is also the first report of paraneoplastic PH in lymphoma. This case adds to the growing differential diagnosis of skin disease in postpartum women and their neonates.

Cutaneous vascular anomalies in the neonatal period.

Vascular birthmarks can be difficult to diagnose in the perinatal period due to varied growth characteristics and similar initial appearances. Location and type of birthmark can provide signals that extracutaneous involvement may be a concern. This article provides a baseline framework that can help diagnose, define associations and guide workup and treatment in these neonates.

Approach to the neonate with ecchymoses and crusts.

Premature and systemically ill infants have a high risk of developing dermatologic infectious complications, displaying the consequences of skin barrier immaturity. Opportunistic infections are an increasing concern in neonates, with cutaneous fungal infections (Aspergillus, Rhizopus, Mucor, Fusarium) observed more commonly as pathogens. Neonates are especially susceptible due to stresses of the perinatal transition to ex-utero life, stratum corneum immaturity, and medical intervention during early life including intravenous catheters, non-sterile adhesive dressings, broad spectrum antibiotic use, and systemic corticosteroids for lung disease. Cutaneous presentations of these infections encompass a broad set of morphologies: papules, vesicles, pustules, ecchymoses, and necrotic, pupuric plaques. There are many etiologies that present as ecchymoses and scaly or crusted lesions. The presentation, diagnosis, and treatment options in the neonatal patient presenting with ecchymoses and crusts will be discussed.