Traumatic Insult Research Articles

Clinicopathological Correlation Of Ulceroproliferative Lesions -An Institution Based Retrospective Study

Background: Ulcero-proliferative lesions are both benign and malignant. They are versatile and can be acute or chronic, solitary or multiple, small in size or large. They occur as a result of traumatic insults, bacterial or viral infections and can also be due to post chemotherapy effects. AIM: The aim of the study is to determine the clinicopathological correlation of various ulcero-proliferative lesions of the oral cavity of north coastal region of Andhra Pradesh. OBJECTIVES: 1. To evaluate various ulcero-proliferative lesions in the oral cavity based on the demographic details.2. To correlate the demographic and histopathological features of the ulceroproliferative lesions. Materials and Methods: The study was done retrospectively in the Oral Pathology Department, of GITAM Dental College and Hospital from the archives of the past 5 years. The clinical and the histopathological features of both benign and malignant lesions are collected and are comprehensively studied. The collected data included age, gender, histopathological diagnosis were arranged in tabulated form. Results: In a total of 936 cases in the 5year archival a significant number of cases (42%) were ulceroproliferative which are further divided into benign (33%), premalignant (19%), malignant (48%). Males (51.3%) and females (48.7%) showed various ulceroproliferative lesions. Benign and premalignant lesions had a higher female predominance whereas malignant had a higher male predominance. Conclusion: Oral squamous cell carcinoma is the predominant ulcero-proliferative lesion in our study. We have also noticed a slight increase in the prevalence of both premalignant and malignant ulcero-proliferative lesions which might be due to changing lifestyle patterns in the individuals. Ulcero-proliferative lesions of the oral cavity are commonly associated with adverse habits.Further lesions can be evaluated based on the origin, either epithelial or salivary gland origin followed by a detailed follow up of the patient in prospective manner to evaluate other associated risk factors.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer’s disease pathology in the eye clinic

BackgroundAlzheimer’s disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.MethodsThe BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aβ-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments.ResultsWe aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aβ- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding.ConclusionsWe envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection.Trial registrationThe BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23–09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.

The time course of lactate and endocrine changes in dogs suffering from dog bite wounds.

The stress response after acute trauma in humans and animals has been well-recognised in the literature. However, data on temporal changes in endocrine parameters after acute trauma in previously healthy dogs are scant. To longitudinally track endocrine variables and lactate concentrations in dogs with canine bite wounds. Prospective study involving 20 dogs hospitalised after being bitten by another dog. Serum cortisol, thyroxine (total T4), thyrotropin (TSH), and lactate concentrations were measured on admission and every 8 hours after the recorded bite incident, for a 72-hour period. Median cortisol concentration was markedly elevated on admission (314.6 nmol/L; IQR 229.3-369.6) but returned to within the reference interval by 16 hours post-bite (99.5 nmol/L; IQR 48.7-225.4) and reached a nadir at 48 hours post-bite (38.5 nmol/L; IQR 32.1-115.9). Median total T4 concentration was within the reference interval on admission (20.6 nmol/L; IQR 12.7-27.9) but decreased below the reference interval by 8 hours (11.0 nmol/L; IQR 5.0-14.1) and reached a nadir 16 hours postbite (7.0 nmol/L; IQR 2.9-19.7), before gradually increasing after 64 hours to reach the reference range by 72 hours. The median TSH concentrations remained within the reference interval throughout the study period. Median lactate concentration was mildly elevated on admission (3.0 mmol/L; IQR 2.0-3.9). This study produced novel data on the temporal relationships of the hypothalamic-pituitary-adrenal and hypothalamicpituitary- thyroidal axes alterations after an acute traumatic insult in dogs.

Challenging arterial pattern of foregut and its potential impact on surgery.

Anticipating a wide range of morphological variations of arterial anatomy of foregut derivatives beyond the classical pattern, a precise understanding is pertinent to preoperative diagnosis, operative procedure and to avoid potentially devastating post-operative outcome during various traumatic and non-traumatic vascular insult of foregut. The study aimed to revisit the morphological details and update unusual configurations of arteries of foregut to establish clinico-anatomical correlations. This study described the detailed branching pattern of coeliac trunk (CT) as principal artery of foregut with source & course of hepatic, gastric, duodenal and pancreatic branches in 58 cadaveric dissections. Based on morphology, different types and subtypes were made. The descriptions were explained using figures and pertinent tables. Among classical branches of CT, splenic artery was found as most stable whereas other two branches were found to be most variable with missing common hepatic artery in 11 cases. In addition to classical trifurcation (65.52%), different types of bifurcation (12.07%) and tetrafurcations (22.41%) of CT were observed. Regarding variations of hepatic arteries (27.59%), both non-classical origin and accessory hepatic branches were found. In case of gastric branches, more variant origins were seen with right gastric (50%) as compared to left gastric artery (34.48%). Other morphological variations included non-classical origin of gastro-duodenal artery (18.96%) along with presence of accessory pancreatic (17.13%) and duodenal arteries (6.38%). Awareness of anatomical variations regarding circulatory dynamics of foregut is worth knowing in order to facilitate successful planning of surgery involving upper abdominal organs with least complications.

Causes of Admission, Mortality and Pathological Findings in European Hedgehogs: Reports from Two University Centers in Italy and Switzerland.

European hedgehogs (Erinaceus europaeus) are nocturnal insectivores frequently found in urban areas. In the last decades, their population has declined in various European countries and human activities have emerged as significant contributors to this trend. While the literature has mainly focused on trauma as the major cause of mortality, few authors have considered pathological findings. The present study is based on the results of full post-mortem examinations performed on 162 European hedgehogs in Italy and 109 in Switzerland. Unlike in previous studies, the main cause of mortality was infectious diseases (60.5%), followed by traumatic insults (27.7%). The lungs were the main organ affected, showing mostly lymphoplasmacytic (45.9%), granulomatous (18.1%) or suppurative (8.2%) pneumonia. Nematodes were detected in 57.2% of all lungs and were significantly associated with pneumonia (p-value < 0.001). To our knowledge, this is the first study to report infectious diseases as the main cause of hedgehog death, emphasizing the need for wildlife rescue centers to adopt appropriate diagnostic and therapeutic measures. Further research is necessary to determine the broad range of infectious agents that affect this species and elucidate their interplay with the host. Finally, citizen sensitization should be implemented to promote responsible behaviors that could reduce human-related traumatic events.

Multiple Sclerosis and Other Acquired Demyelinating Diseases of the Central Nervous System.

Acquired demyelinating diseases of the central nervous system (CNS) comprise inflammatory conditions, including multiple sclerosis (MS) and related diseases, as well as noninflammatory conditions caused by toxic, metabolic, infectious, traumatic, and neurodegenerative insults. Here, we review the spectrum of diseases producing acquired CNS demyelination before focusing on the prototypical example of MS, exploring the pathologic mechanisms leading to myelin injury in relapsing and progressive MS and summarizing the mechanisms and modulators of remyelination. We highlight the complex interplay between the immune system, oligodendrocytes and oligodendrocyte progenitor cells (OPCs), and other CNS glia cells such as microglia and astrocytes in the pathogenesis and clinical course of MS. Finally, we review emerging therapeutic strategies that exploit our growing understanding of disease mechanisms to limit progression and promote remyelination.

Neuroprotective gap-junction-mediated bystander transformations in the adult zebrafish spinal cord after injury

The adult zebrafish spinal cord displays an impressive innate ability to regenerate after traumatic insults, yet the underlying adaptive cellular mechanisms remain elusive. Here, we show that while the cellular and tissue responses after injury are largely conserved among vertebrates, the large-size fast spinal zebrafish motoneurons are remarkably resilient by remaining viable and functional. We also reveal the dynamic changes in motoneuron glutamatergic input, excitability, and calcium signaling, and we underscore the critical role of calretinin (CR) in binding and buffering the intracellular calcium after injury. Importantly, we demonstrate the presence and the dynamics of a neuron-to-neuron bystander neuroprotective biochemical cooperation mediated through gap junction channels. Our findings support a model in which the intimate and dynamic interplay between glutamate signaling, calcium buffering, gap junction channels, and intercellular cooperation upholds cell survival and promotes the initiation of regeneration.

Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.

Heterotopic ossification (HO) is a debilitating pathology where ectopic bone develops in areas of soft tissue. HO can develop as a consequence of traumatic insult or as a result of dysregulated osteogenic signaling, as in the case of the orphan disease fibrodysplasia ossificans progressiva (FOP). Traumatic HO (tHO) formation is mediated by the complex interplay of signaling between progenitor, inflammatory, and nerve cells, among others, making it a challenging process to understand. Research into the pathogenesis of genetically mediated HO (gHO) in FOP has established a pathway involving uninhibited activin-like kinase 2 receptor (ALK2) signaling that leads to downstream osteogenesis. Current methods of diagnosis and treatment lag behind pre-mature HO detection and progressive HO accumulation, resulting in irreversible decreases in range of motion and chronic pain for patients. As such, it is necessary to draw on advancements made in the study of tHO and gHO to better diagnose, comprehend, prevent, and treat both.

Determination of Tight Junction Integrity in Brain Endothelial Cells Based on Tight Junction Protein Expression.

Blood-brain barrier (BBB) dysfunction and hyperpermeability that occurs following traumatic and ischemic insults lead to various downstream ill effects such as cerebral edema and elevation of intracranial pressure. The inter-endothelial tight junctions that consist of tight junction proteins are critical regulators of BBB dysfunctions and hyperpermeability. The major tight junction-associated proteins of the BBB are occludin, claudins, and junctional adhesion molecules that are intracellularly linked to the adaptor protein zonula occludens-1 (ZO-1). Quantitative measurement of tight junction-associated proteins provides valuable insight into barrier integrity and mechanisms that regulate microvascular hyperpermeability. Western blot analysis is a commonly used method to separate and identify proteins in a mixture using gel electrophoresis. Understanding the changes in the expression of one or more of these proteins is critical to evaluating barrier integrity and permeability in health and disease. Furthermore, studying them will provide insight into the associated downstream signaling pathways and evaluation of therapeutic approaches for regulating BBB permeability. Herein, we have described the protocol for immunoblot analysis of ZO-1 as an indicator of tight junction integrity in brain microvascular endothelial cells.

Epidural Steroid Injection Prior to Spinal Surgery: A Step-Wise and Wise Approach.

An epidural steroid injection (ESI) is used to treat a number of morbid central nervous system pathologies and is considered a reasonably safe procedure. This study aimed to determine the relative infection risk after spinal surgery by comparing outcomes in spinal surgery patients who received an ESI shortly prior to the surgery against those who did not receive an ESI shortly prior to the surgery. The present study is a retrospective cohort study using a multi-institutional healthcare database, TriNetX, to collect data on patients who received spinal surgery with and without having had ESIs six months before surgery. Two cohorts were generated: Cohort 1 included patients who had received an ESI in the six months prior to spinal surgery, and cohort 2 included patients who did not have an ESI in the six months prior to spinal surgery. The patients in cohort 2 had propensity scores matched 1:1 to those in cohort 1 using common baseline demographics, comorbidities and spinal procedure indications. The spinal procedures and surgeries considered for the analysis includedopen procedures for any purpose, including exploration, decompression, resection, revision or biopsy. Multiple outcomes were compared across these two cohorts in the three months following the spinal procedure/surgery, including the occurrence of death, surgical site infection, epidural and/or spinal abscess, and dural tear. An ESI in the six months prior to spinal surgery was associated with a significant decrease in the likelihood epidural/spinal abscess in the three months after surgery.There was no change in mortality, wound infection or identification of dural tear in the three months after spinal surgeryfor those who received an ESI six months before spinal surgery. This data suggests that epidural steroid injections' anti-inflammatory effects provide benefits before surgery beyond symptomatic relief. Given that the degeneration of spinal pathologies is typically advanced rather than corrected by the body's inflammatory response, it is likely that preventing hyperactivation of the body's immune system in the months preceding surgical intervention, a traumatic insult, is protective compared to no intervention and, importantly, without major adverse effects.

A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration.

The degeneration of axons and their terminals occurs following traumatic, toxic, or genetically-induced insults. Common molecular mechanisms unite these disparate triggers to execute a conserved nerve degeneration cascade. In this review, we will discuss how models of peripheral nerve injury and neuropathy in Drosophila have led the way in advancing molecular understanding of axon degeneration and nerve injury pathways. Both neuron-intrinsic as well as glial responses to injury will be highlighted. Finally, we will offer perspective on what additional questions should be answered to advance these discoveries toward clinical interventions for patients with neuropathy.

Destabilization of the medial meniscus to induce post-traumatic osteoarthritis in domestic pigs

IntroductionPost-traumatic osteoarthritis (PTOA) develops following traumatic articular insult. One model system used to study the progression and treatment of PTOA is the destabilization of the medial meniscus (DMM) as first described by Glasson et al performed in mini-pigs. Miniature pigs are less available, more expensive, and have synovial fluid sampling limitations, limiting the availability of osteoarthritis biomarkers compared to domestic pigs. ObjectivesThe following technical note details stepwise procedures and animal welfare strategies for the use of Yorkshire pigs as a large animal PTOA model. MethodsThe following technical note details stepwise procedures to perform peroperative saphenous nerve block, DMM, and subsequent postoperative management in Yorkshire pigs as a large animal PTOA model. ResultsAt 4 weeks post-operatively, all pigs develop mild-moderate PTOA based on postmortem joint dissections. ConclusionsThis technical note provides further details on the arthrotomy approach to destabilize the medial meniscus of domestic pigs as a model of PTOA.

The Impact of COVID-19 Infection on Concurrent Traumatic Insults: An Analysis from the West Virginia Trauma System

Introduction With the onset of the COVID-19 pandemic, elective surgeries were decreased and associated with worsened outcomes. Trauma outcomes have been varied, and rural traumas have not been solely analyzed. This study investigated outcomes related to COVID-19 infection at a rural Level I trauma center in West Virginia (WV). Methods A retrospective analysis of trauma outcomes of patients aged 18 years and older from March 30, 2020, until December 21, 2021, presenting to a Level I trauma center in WV was conducted. Data was collected from the John Michael Moore Trauma Center trauma registry. Mortality, complications, injury characteristics, comorbidities, and demographics were examined. Results Out of 2,118 patients tested for the novel coronavirus, 61 (1.7%) were positive (COV+). There was no significant increase in mortality regarding COVID-19 infection. COV+ patients had an increased length of stay (median 5.2 vs. 3.6, p=0.015) and intubation rates (21.3% vs. 12.5%, p=0.070), but fewer days on a ventilator (median, 2 vs. 3, p=0.012). COV+ patients were more likely to be discharged to rehabilitation centers, skilled nursing facilities, or long-term acute care hospitals (44.3% vs. 34.5%), and less often routine or home measures (42.6% vs. 58.7%) (p=0.015). Conclusion This single retrospective study found increased rates of length of stay and intubation rates with no increased rates of mortality or complications in COV+ trauma patients compared to non-COV+ trauma patients. Further research is needed to validate and characterize the impact of COVID-19 for the entirety of the state.

ID: 209649 Peripheral Nerve Stimulation: A New Horizon for Traumatic Brachial Plexus Injury

A traumatic insult to the brachial plexus can result in a wide range of symptoms including numbness, pain, paresthesia, and weakness. [1] While surgical intervention has historically been the standard of care and can undoubtedly improve symptoms, it is not without risk. [2] The use of temporary percutaneous peripheral nerve stimulation (PNS) (SPRINT® PNS system, SPR Therapeutics) has emerged as a minimally invasive potential alternative to surgical intervention. We present a case of ballistic trauma to the brachial plexus with multilevel plexal involvement treated with a SPRINT® PNS system.

Mechanisms of Mitochondrial Oxidative Stress in Brain Injury: From Pathophysiology to Therapeutics.

Mitochondrial oxidative stress has been implicated in various forms of brain injury, both traumatic and non-traumatic. Due to its oxidative demand, the brain is intimately dependent on its mitochondrial functioning. However, there remains appreciable heterogeneity in the development of these injuries regarding ROS and their effect on the sequelae. These include traumatic insults such as TBIs and intracranial hemorrhaging secondary to this. In a different vein, such injuries may be attributed to other etiologies such as infection, neoplasm, or spontaneous hemorrhage (strokes, aneurysms). Clinically, the manner of treatment may also be adjusted in relation to each injury and its unique progression in the context of ROS. In the current review, then, the authors highlight the role of mitochondrial ROS in various forms of brain injury, emphasizing both the collective and unique elements of each form. Lastly, these narratives are met with the current therapeutic landscape and the role of emerging therapies in treating reactive oxygen species in brain injuries.

Poly ADP-Ribose Polymerase-1 inhibition by 3-aminobenzamide recuperates HEI-OC1 auditory hair cells from blast overpressure-induced cell death.

Introduction: Poly ADP-Ribose Polymerase-1 (PARP1), a DNA repair enzyme is implicated as a key molecule in the pathogenesis of several neurodegenerative disorders. Traumatic insults inducing oxidative stress results in its over-activation causing inflammation and cell death (Parthanatos). As PARP1 inhibition is known to reduce oxidative stress, we hypothesized that PARP1 inhibition by a known inhibitor 3-aminobenzamide (3AB) might recuperate the damage in an in vitro model of blast injury using HEI-OC1 cells (mouse auditory hair cells). Methods: Here, we evaluated the protective effect of 3AB on HEI-OC1 cells following single and repetitive blast overpressures (BOPs). Results: We found that inhibition of PARP1 b 3AB inhibits the PARP1 enzyme and its action of a post-translational modification i.e. formation of Poly ADP-Ribose Polymers which leads to massive ATP depletion. PARP inhibition (3AB treatment) reduced the oxidative stress (4HNE, a marker of lipid peroxidation, and 8OHdG, a marker of oxidative DNA damage) in cells exposed to single/repetitive BOPS through up-regulation of Nrf2, a transcriptional regulator of antioxidant defense and the GCLC, a rate limiting enzyme in the synthesis of glutathione. Discussion: Overall, we found that PARP inhibition by 3AB helps to maintain the viability of BOP-exposed auditory hair cells by recuperating the ATP pool from both mitochondrial and glycolytic sources.

Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis.

The teeth are vertebrate-specific, highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability for self-repair, the teeth can often be impaired by traumatic, inflammatory, and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and in particular an evolving framework of developmental engineering has pioneered functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have achieved functionally robust and physiologically relevant tooth regeneration after implantation in animals and in humans. The discussion of this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.

Biomechanics of Traumatic Head and Neck Injuries on Women: A State-of-the-Art Review and Future Directions.

The biomechanics of traumatic injuries of the human body as a consequence of road crashes, falling, contact sports, and military environments have been studied for decades. In particular, traumatic brain injury (TBI), the so-called "silent epidemic", is the traumatic insult responsible for the greatest percentage of death and disability, justifying the relevance of this research topic. Despite its great importance, only recently have research groups started to seriously consider the sex differences regarding the morphology and physiology of women, which differs from men and may result in a specific outcome for a given traumatic event. This work aims to provide a summary of the contributions given in this field so far, from clinical reports to numerical models, covering not only the direct injuries from inertial loading scenarios but also the role sex plays in the conditions that precede an accident, and post-traumatic events, with an emphasis on neuroendocrine dysfunctions and chronic traumatic encephalopathy. A review on finite element head models and finite element neck models for the study of specific traumatic events is also performed, discussing whether sex was a factor in validating them. Based on the information collected, improvement perspectives and future directions are discussed.

Effects of glutamine and arginine combination on pro- and anti-inflammatory cytokines.

Cytokines were beneficial for diagnosis and treatment, which in clinical situations introduced from the perspective of pro and anti-inflammatory effects. An inflammatory response is commonly associated with various severe traumatic insults that consequently recruit the immune cells into the target organs and causing systemic inflammatory response that can lead to sepsis. Immune-modulating nutrients, such as glutamine and arginine, are known as pathophysiological modulate in inflammation. The aim of this study was to evaluate the effect of oral gavage supplementation with a combination of glutamine and arginine on inflammatory cytokines in intestinal mucosa, specifically jejunum. Sixteen Rattus norvegicus rats (average weight 150-200 g) were randomly divided into two groups: groups A and B, both intraperitoneal injected by 2 ml NaCl 0.9%. Group A orally supplemented with 1 ml dextrose 5% daily, meanwhile, group B orally supplemented with 1 ml combination of glutamine and arginine (contains 250 mg/kg glutamine and 250 mg/kg arginine) daily. The experiment lasted for 3 days. We compared the pro and anti-inflammatory cytokines (IL-10, NF-κB, TNF-α, IL-8, and MMP-8) between the two groups by the Mann-Whitney test. More IL-10, TNF-α, and IL-8 cytokine-produced cells found in group A. Group B produced significantly lower TNF-α (p = 0.009) and IL-8 (p = 0.003). The number of NF-κB and MMP-8 were slightly higher in group B. Giving a combination of glutamine and arginine as nutrition supplementation has beneficial effects in decreasing almost half of the cells that produce TNF-α and IL-8. Further studies must be carried out to support a standard guideline for this recommendation.

Erosive Pustular Dermatosis: Delving into Etiopathogenesis and Management.

Erosive pustular dermatosis (EPD) is a chronic inflammatory skin disorder that usually affects mature individuals. It predominantly affects the scalp and can lead to scarring alopecia. Risk factors include actinic damage and androgenetic alopecia. A traumatic insult to the skin is considered a vital trigger of the condition. EPD is a diagnosis of exclusion; thus, several neoplastic, infectious, vesiculobullous, and inflammatory conditions should be ruled out. Biopsy and clinicopathologic correlation are required to differentiate between EPD and these entities. A dysregulated, chronic immune response is considered central to the etiopathogenesis of EPD. We performed an evidence-based systematic review of the management options. There were predominantly studies with level IV and V evidence and only two with level III. Despite the responsiveness of EPD to potent topical steroids, such as clobetasol propionate, recurrence occurs after treatment withdrawal. With the available data, tacrolimus 0.1%, curettage-assisted aminolevulinic acid-photodynamic therapy, and systemic retinoids can be considered second-line options for EPD with a role in maintenance regimens. However, controlled data and more powerful studies are needed to make solid recommendations.