BACKGROUND:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by skin fragility and systemic complications, including anemia, inflammation, and nutritional deficiencies. The prevalence and age of onset of monitoring laboratory tests remain poorly defined in the current literature. OBJECTIVE:To characterize the frequency of nutritional deficiencies and earliest age of laboratory abnormalities in a cohort of RDEB patients. METHODS:A retrospective chart review of 122 patients with RDEB seen at a tertiary care EB center (2010-2021) was conducted. Laboratory and anthropometric data from initial visits were stratified by age group and compared to institutional reference ranges. RESULTS:Inflammatory markers were frequently elevated: C-reactive protein (CRP) (100%, 74/74) and ESR (81%, 71/88), including in patients < 2 years. Anemia (86%, 98/114) and iron deficiency (84%, 80/95) were highly prevalent. Hypoalbuminemia was present in 69% of patients (77/112), particularly among those younger than 16 years. Thrombocytosis occurred in 41% (49/120). Anthropometric measures revealed early declines in weight-for-age and height-for-age percentiles and persistently low BMI. Mean height-for-age percentile decreased sharply from the 61st to the 30th %ile between ages 0-1.99 and 2-3.99 years. Vitamin D deficiency (using a 30 ng/mL cutoff) affected 49% (44/90), especially those > 8 years. Zinc and carnitine levels declined with increasing age, but the majority of patients had values within normal limits. Magnesium, selenium, phosphorus, and thyroid studies were within normal limits for most patients. CONCLUSIONS:Nutritional, hematologic, and inflammatory abnormalities are common and often present, even in infancy, among patients with RDEB. These findings underscore the need for standardized, age-specific laboratory monitoring protocols beginning in early childhood. Early recognition of and intervention for abnormalities may improve long-term outcomes in this medically complex population.
Dystrophic epidermolysis bullosa (DEB) and junctional EB (JEB) are severe, bullous genodermatoses induced by mutations of genes encoding structural skin proteins that disrupt epidermal adhesion. Until recently, treatment was limited to symptomatic care. Since 2022, three therapies - birch triterpenes gel (Filsuvez), beremagene geperpavec-svdt (B-VEC, Vyjuvek), and prademagene zamikeracel (pz-cel, Zevaskyn) - have received regulatory approval, representing the first specific interventions for epidermolysis bullosa. Herein, we provide an overview on their mechanisms of action, efficacy, safety, and clinical implications.
Epidermolysis bullosa (EB) is a chronic blistering skin disease with a propensity for bacterial colonization, critical colonization and/or infection, namely with Staphylococcus aureus and Pseudomonas aeruginosa. While P. aeruginosa cutaneous and systemic infection are associated with significant morbidity in the EB population, critical colonization poses its own risks, given its impairment of wound healing and the hypothesized association of flagellated bacteria with wound-induced skin cancer. There is a paucity of published literature describing topical management of P. aeruginosa colonization/critical colonization in patients with EB. The purpose of this review is to describe current and emerging treatment modalities for the topical management of P. aeruginosa colonization/critical colonization in patients with EB, extrapolating from current evidence-based practices in other skin conditions that may be relevant to patients with EB.
Epidermolysis bullosa simplex-severe (EBS-severe) caused by KRT5 p.Glu477Lys is a rare and particularly severe subtype associated with high neonatal morbidity and mortality. We report an infant who during the neonatal period required prolonged multidisciplinary intensive care for the management of several complications, including extensive wounds with blood loss leading to secondary anemia, failure to thrive with gastroesophageal reflux, respiratory distress with stridor and a necrotizing soft tissue infection, ultimately requiring surgical debridement and grafting. Pain control proved inadequate despite continuous morphine infusion, leading to initiation of methadone, which provided effective and stable analgesia. This case underscores the severe multisystem morbidity of KRT5 p.Glu477Lys-associated GS-EBS and underscores the role of methadone in effective pain management in critically affected EB neonates.
Epidermolysis bullosa (EB) is a heterogeneous group of rare genodermatoses marked by skin fragility and bullae formation induced by minor trauma. Pathologic variants in at least 21 genes are associated with EB, grouped into four major subtypes based predominantly on the plane of cleavage within the skin. EB simplex is characterized by epidermal bullae formation and is due to gene mutations that affect epidermal proteins, most commonly keratin filaments. Junctional EB is due to gene mutations affecting proteins in the basement membrane zone, causing a split within the lamina lucida of the dermal-epidermal junction. Dystrophic EB is characterized by subepidermal bullae formation and is due to mutations in the gene encoding type VII collagen, which makes up the anchoring fibrils in the papillary dermis. Kindler EB is the rarest subtype and may be associated with cleavage at various levels within the skin due to a mutation in the FERMT1 gene causing defects in kindlin-1, a protein associated with integrins and focal adhesions. Because EB is such a heterogeneous disease, an understanding of genotype-phenotype correlations is necessary to help guide management. Traditionally, the first step in diagnosis was inducing a blister that was biopsied for immunofluorescence mapping. Currently, the gold standard for diagnosis is a blood sample or buccal swab for extraction of genomic DNA via next-generation sequencing, which can identify the exact causative gene. A diagnosis of EB is life altering for patients and families alike. A firm understanding of EB classification and initial diagnostic workup can help dermatologists feel empowered to support and counsel families.
Severe junctional epidermolysis bullosa (JEB) is a rare, incurable, autosomal recessive blistering disorder with a uniformly poor prognosis. We present the case of a female infant diagnosed shortly after birth with genetically confirmed severe JEB, whose family prioritized comfort-focused care and memory-making over life-prolonging interventions. Her interdisciplinary care centered on symptom relief, bonding, and alignment with family values. This case underscores the importance of early diagnosis and values-based decision-making in managing rare, life-limiting conditions like severe JEB.
Epidermolysis bullosa (EB) is a group of rare, fragile skin disorders that poses unique challenges. To support clinicians who lack familiarity with caring for patients with EB, we utilized a tool called an "OurPractice Advisory" (OPA) within Epic, our institution's electronic health record (EHR) platform. The OPA displays crucial resources for providers to assist with the management of patients with EB during an emergency department visit and/or hospitalization. The OPA includes practical guidance regarding wound care, supply procurement, consult recommendations, and complication prevention strategies. By leveraging an existing EHR tool, this initiative aims to provide immediate assistance to providers, enhance patient outcomes, and serve as a model for managing various complex conditions.
Pruritus and pain are pervasive, often debilitating symptoms in epidermolysis bullosa (EB), arising from complex immune, neural, and barrier dysfunction. Pruritus, especially in dystrophic and junctional EB subtypes, results from Th2/Th17-mediated inflammation, neuropeptide signaling, and neuropathic changes. Management includes antihistamines, topical agents, gabapentinoids, and emerging systemic therapies, such as dupilumab, JAK inhibitors, and neurokinin-1 inhibitors. Pain in EB is multifactorial, combining nociceptive and neuropathic mechanisms due to chronic wound, fibrosis, and nerve sensitization, requiring multimodal treatment strategies, including psychosocial therapies, analgesics, neuropathic agents, anti-inflammatory medications, and opioids. This review summarizes practical approaches to managing EB-associated pruritus and pain in the context of advancing insights into underlying pathophysiologic pathways.
Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive genodermatosis characterized by palmoplantar hyperkeratosis and severe periodontitis, leading to premature loss of both primary and permanent teeth, and treatment responses are often unsatisfactory. We report a 20-year-old female patient with PLS who presented with extensive palmoplantar hyperkeratosis and widespread psoriasiform plaques refractory to multiple conventional therapies. Treatment with ustekinumab resulted in marked clinical improvement by the sixth month after three subcutaneous injections. The patient has remained in sustained clinical remission during 6 years of continuous therapy, with only mild and intermittent recurrent plaques on the knees, suggesting that biologic therapy may represent a sustainable option in selected cases of PLS.
BACKGROUND AND OBJECTIVES:This study aimed to characterize the clinical spectrum, diagnostic delay, treatment patterns, and outcomes of pediatric mycosis fungoides (MF) and to identify predictors of early response. METHODS:This national multicenter retrospective study included patients diagnosed with histopathologically confirmed MF before 18 years of age. Demographic, clinical, histopathologic, immunophenotypic, staging, treatment, and follow-up data were collected. Early response at 3-6 months (partial/complete response) was analyzed using logistic regression. RESULTS:A total of 133 patients were included; 60.9% (81/133) were male. Median age at diagnosis was 13 years (IQR, 9-15) and median diagnostic delay was 18 months (IQR, 8-48). Classic morphology was recorded in 78.2% (104/133), and hypopigmented MF in 36.1% (48/133); overlapping morphologies were documented in 42.1% (56/133). Stage IA disease was present in 59.4% (79/133). Phototherapy was used in 60.9% (81/133). Early response occurred in 91.0% (121/133). BSA < 10% was independently associated with higher odds of early response (aOR 8.42, 95% CI 1.71-41.54; p = 0.009), whereas older age at diagnosis predicted lower odds (aOR 0.81 per year, 95% CI 0.67-0.98; p = 0.029). Relapse occurred in 28.5% (37/130) within median follow-up of 22 months (median time to relapse of 8 months); 67.6% (25/37) relapsed within 12 months. CONCLUSION:In this cohort, pediatric MF presented at an early stage. Despite favorable early responses, relapse occurred in nearly one third, often within the first year, supporting long-term surveillance. Higher BSA involvement and older age at diagnosis were associated with reduced early response.
A 7-year-old boy presented with a 3-year history of a slow-growing superficial cutaneous nodule adjacent to the right acromion, with subsequent development of a second subcutaneous mass near the right scapula. Biopsy of the primary lesion revealed a rare non-neural granular cell tumor (NNGCT) lacking S100 expression, distinguishing it from classic granular cell tumors (GCT), and molecular profiling identified a DCTN1::ALK fusion alongside an ATP6AP2 frameshift mutation, the latter reported predominantly in GCT. To our knowledge, this is the first documented NNGCT harboring both alterations, suggesting potential biologic overlap between NNGCT and GCT while expanding the current framework of granular cell tumor classification. This case also highlights the reported potential for recurrence and multifocal disease or regional spread in NNGCT, supporting complete surgical excision with long-term follow-up.
Acral injections for conditions such as palmoplantar hyperhidrosis are associated with significant procedural pain, frequently limiting their use in pediatric populations. While nerve blocks, cryoanalgesia, and topical anesthetics can mitigate discomfort during palmar injections, each has practical limitations. This report describes a multimodal technique combining cryoanalgesia, pressure, and vibration using a handheld massager that substantially reduces injection-related pain and patient distress.
We present a case where the combination of severe hydrops fetalis, lymphangiectasia, and skin desquamation created a clinical picture that masqueraded as epidermolysis bullosa (EB). A neonate presented at birth with severe hydrops fetalis and extensive skin sloughing. Skin biopsy findings were consistent with EB; however, the clinical course and genetic testing were inconsistent with this diagnosis, and the postmortem examination revealed the underlying cause to be severe congenital diffuse lymphangiectasia. It is important for clinicians to consider edema bulla and tissue hypoxia as a cause of skin blistering and sloughing in the setting of hydrops fetalis.
The neonatal period represents a critical window for skin barrier maturation, microbial colonization, and immune development. As such, early-life exposures may exert lasting effects on dermatologic and systemic health. A common early-life exposure is blue light phototherapy (BLP), a life-saving treatment for neonatal hyperbilirubinemia. Although BLP is traditionally regarded as a localized, superficial intervention, emerging evidence suggests that it is a biologically active exposure that directly interacts with developing skin, thereby influencing barrier integrity, the developing microbiome, and immune signaling. As an active immune organ, neonatal skin has been proposed to engage in dynamic crosstalk with the nervous, gut, and endocrine systems. Therefore, BLP may act systemically by modulating these interconnections. These effects raise concerns about the potential long-term impact of BLP during this critical developmental period. The development of immune-mediated conditions, such as atopic dermatitis (AD), is of particular interest as they are hypothesized to engage in these cross-system networks. This review examines the multifactorial relationship between BLP and neonatal skin development, highlighting BLP as an active exposure that may interact with developing skin, microbiome, and immune system, while emphasizing the need for longitudinal studies to clarify long-term clinical implications.
Epidermolysis bullosa simplex (EBS) is an inherited mechanobullous disorder with limited systemic treatment options. Emerging evidence suggests that inflammatory pathways and pruritus may significantly contribute to disease severity, creating the possibility for therapeutic targets. This report describes a premature infant with EBS, severe (EBS-sev) and failure to thrive, who was treated with dupilumab at 5 months and 12 days of age. Treatment resulted in sustained improvement in skin integrity and clinical stability, suggesting that dupilumab may be considered as a potential therapeutic option for future cases of EBS.
Vaccination-induced granuloma is a common clinical diagnosis, but few reports have described the diagnostic utility of comprehensive pathological and microbiological examinations. This report details a case of DTaP-IPV vaccination-induced granuloma where the use of multi-virus/microbial real-time polymerase chain reaction (PCR) enabled a definitive molecular diagnosis. This advanced testing method confirmed the presence in the excised tissue of Bordetella pertussis and poliovirus genes from the vaccine components, a novel finding for this type of lesion. In cases requiring a definitive diagnosis, especially those where malignancy is a differential, surgical excision followed by multiplex PCR testing is a reliable option.
