Blistering Disorder Research Articles

Characterization of Disparities, Diagnoses and Treatment Outcomes with Pemphigus Vulgaris

Pemphigus vulgaris (PV) and foliaceus (PF) are classified as rare autoimmune blistering disorders in which IgG antibodies destroy desmosome proteins desmoglein 1 and desmoglein 3 within the stratum spinosum of the epithelial layer of the skin. These disorders once used to be a fatal condition, but the advent of steroids and immunosuppressants has made these diseases manageable. Such treatments, however, only alleviate symptoms and have not been viable in allowing patients to achieve prolonged steroid-free remission. In 2018, the US Food and Drug Administration (FDA) approved the anti-CD20 monoclonal antibody rituximab as the first-line treatment for moderate to severe cases of pemphigus. While rituximab has been generally successful in treating this disease and has led to prolonged steroid-free remission in many patients, treatment disparities and differences in patient outcomes due to social determinants of health have not yet been studied in the context of PV and PF. Such studies have already been conducted with more common dermatological disorders such as hidradenitis suppurativa (HS), which show significant evidence of outcome disparities due to social factors such as race, ethnicity and socioeconomic status. However, such studies have yet to be conducted with pemphigus likely because of how rare the disease is and because the current first-line treatment was FDA approved recently in 2018. The aim of this study is to conduct a retrospective multivariable analysis of 100 patients with pemphigus from UT Southwestern Medical Center and Parkland County Hopital to determine which social factors are the most responsible for any discovered pemphigus treatment outcome disparities. The impacts of this study are far-reaching as any discovered disparities can alert dermatologists to place a special emphasis to address any social factors that may play a role in leading to treatment outcome differences for patients with pemphigus.

Evaluating the Current Landscape of Epidermolysis Bullosa Treatments: A Systematic Review

Introduction: Epidermolysis bullosa (EB) encompasses a group of rare blistering disorders that affect both the skin and mucous membranes. There is currently no cure for EB, and only supportive treatment is available to manage symptoms of pruritus and wounds. This paper analyzes the current treatment modalities of epidermolysis bullosa and provides a comprehensive review. Methods: A comprehensive literature search was conducted in PubMed using relevant keywords and MeSH terms. Inclusion criteria included manuscripts published in the English language and must include a control group. Two independent reviewers will assess study eligibility based on predetermined criteria. Data extraction will cover study characteristics, participant demographics, treatment outcomes, and relevant findings. Results: 21 articles were identified which examined the effects of various interventions for the treatment of epidermolysis bullosa. Gene therapy studies demonstrated promising results, specifically those transducing the COL7A1 gene into patients showed significant wound healing. Topical therapies with bermagene geperpavec, diacerin, and b-vec showed promising results, while oleogel S-10 and SD-101 had mixed results. Oral therapies, including those with tetracycline, mycophenolate mofetil, serlopitant, and ECG showed limited results in improving patient outcomes. Conclusion: The current literature shows a wide range of investigated therapies for the treatment and management of epidermolysis bullosa. Treatment modalities identified in this literature review were categorized into gene, oral, or topical therapies. While gene therapy stood out as an effective intervention in improving wound healing and patient reported outcomes, challenges were persistent amongst studies including small sample sizes and limited follow-up, warranting cautious optimism.

Novel readthrough agent suppresses nonsense mutations and restores functional type VII collagen and laminin 332 in epidermolysis bullosa

Recessive Dystrophic Epidermolysis Bullosa (RDEB) and Junctional Epidermolysis Bullosa (JEB) are lethal blistering skin disorders resulting from mutations in genes coding for type VII collagen (COL7A1) and laminin 332 (LAMA3, LAMB3, or LAMC2), respectively. In RDEB, 25% of patients harbor nonsense mutations causing premature termination codons (PTCs). In JEB, a majority of mutations in LAMB3 are nonsense mutations (80%). ELX-02, an aminoglycoside analog, has demonstrated superior PTC readthrough activity and lower toxicity compared to gentamicin in various genetic disorders. This study investigated ELX-02's ability to suppress PTCs and promote the expression of C7 and laminin 332 in primary RDEB keratinocytes/fibroblasts and primary JEB keratinocytes harboring nonsense mutations. ELX-02 induced a dose-dependent production of C7 or laminin β3 that surpassed the results achieved with gentamicin. ELX-02 reversed RDEB and JEB cellular hypermotility and improved poor cell-substratum adhesion in JEB cells. Importantly, ELX-02-induced C7 and laminin 332 localized to the dermal-epidermal junction. This is the first study demonstrating that ELX-02 can induce PTC readthrough and restore functional C7 and laminin 332 in RDEB and JEB caused by nonsense mutations. Therefore, ELX-02 may offer a novel and safe therapy for RDEB, JEB, and other inherited skin diseases caused by nonsense mutations.

Human leukocyte antigen class II (DRB1 and DQB1) alleles frequencies in patients with bullous pemphigoid, Stevens–Johnson syndrome and toxic epidermal necrolysis in Russian population

BACKGROUND: Bullous pemphigoid is known to be an autoimmune, life-threatening blistering skin disorder characterized by subepidermal blister formation. In bullous pemphigoid activation of B-cell immunity depends on the interaction between T-cell receptors and classic HLA II molecules. Similar interrelation has been revealed in a vast variety of studies on severe allergic reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. It was also suggested that Stevens-Johnson syndrome and toxic epidermal necrolysis might be associated both with HLA I and II classes. AIM: To assess the prevalence of HLA-DRB1 and DQB1 alleles at a low and high-resolution levels in patients with bullous pemphigoid and Stevens-Johnson syndrome / toxic epidermal necrolysis. MATERIALS AND METHODS: 29 Bullous pemphigoid, 14 Stevens-Johnson syndrome / toxic epidermal necrolysis patients and 92 health volunteers were included in the study. HLA-DRB1 and DQB1 alleles were assessed by polymerase chain reaction using specific primers. RESULTS: At a low-resolution level, HLA-DRB1*4 (p 0.02) and DRB1*14 (p 0.0015) alleles were statistically significantly revealed in bullous pemphigoid patients compared to health controls. Additionally, at the high-resolution level the predisposing to bullous pemphigoid HLA-DRB1*04:02 allele was also identified (p 0.01). At the low-resolution level of HLA-DQB1 typing we displayed protective and predisposing to bullous pemphigoid alleles HLA-DQB1*1 (p 0.01) and HLA-DQB1*2 (p 0.039) respectively. At the low-resolution level of HLA-DQB1 typing, the chances to obtain DQB1*03:02 allele were 3.71 times higher compared to healthy volunteers (p 0.01). In patients with Stevens-Johnson syndrome / toxic epidermal necrolysis, HLA-DRB1*4 allele was shown to be predisposing (p 0.03). For all other types of HLA alleles (DRB1 and DQB1) at the high-resolution level no any statistically significant results have been observed in these patients. CONCLUSION: We identified HLA-DRB1*4, DRB1*14, DRB1*04:02 alleles predisposing to the development of bullous pemphigoid, with the HLA-DQB1*1 allele being protective for the development of bullous pemphigoid and HLA-DRB1*4 allele predisposing to the development of severe drug reactions of Stevens-Johnson syndrome / toxic epidermal necrolysis. No any protective alleles in Stevens-Johnson syndrome / toxic epidermal necrolysis patients were detected.

Blistering Disorders of the Foot.

Multiple pathophysiologic and biomolecular processes lead to bullae, including disruption of adhesion molecules, accumulation of cell injury, and traumatic injury. Blistering disorders of the foot can cause symptoms such as pruritus, pain, and drainage and significantly impact quality of life. Microbiologic and histopathologic examination of tissue specimens should be considered for concerns regarding atypical etiology.This retrospective case series describes patients seen in a community hospital outpatient wound center in southeastern Wisconsin between January 2021 and June 2023 for atypical blistering disorders of the foot. The cases herein describe the history, clinical presentation, and treatment of three atypical blistering disorders of the foot. An 86-year-old man presented complaining of intensely pruritic blistering lesions to both feet. Histopathologic findings indicated eosinophilic infiltrate, and the patient was treated for an eosinophilic drug reaction. A 65-year-old man presented complaining of multiple painful blisters to the plantar aspect of both feet. Histopathologic examination of unroofed blister indicated bullous tinea. Finally, a 44-year-old man with long-standing type 1 diabetes presented complaining of a several-week history of a single blister to his anterior right foot of unknown etiology. The patient was diagnosed with bullosis diabeticorum.Blistering disorders of the foot are diagnostic challenges; diagnostic clarity is assisted by thorough history, clinical presentation, treatment response, microbial analysis, and histopathologic findings.

Hailey-Hailey Disease: Case Series and Review of Systemic Medications.

Hailey-Hailey disease (HHD) is a rare inherited blistering skin disorder characterized by a chronic relapsing course. While it does not pose a serious threat to the patient's health, the quality of life can change. Unfortunately, there is currently no standard treatment for this condition. In this observational retrospective cohort study, our aim was to discover the demographic characteristics and treatment strategies for managing HHD. In this retrospective cohort study, we documented the demographic, clinical, and histopathological characteristics beside various treatment employed options of patients diagnosed with HHD at Razi Hospital over the past 14 years. A total of 32 patients with HHD were enrolled in the study (15 male and 17 female). The mean age of patients was 50.41 ± 13.15 (22-77) years. The average age of disease onset was 37.31 ± 11.88 (15-60) years. Among the participants, 16 individuals (50%) affirm a positive family history of some kind of pemphigoid blisters. The most common site of disease activity was the inguinal area, observed in 14 patients (33.33%). Histopathological examination discovered the existence of suprabasal acantholysis in all of the specimens. Worthily, direct immunofluorescence analysis showed negative results in all skin biopsies. All patients received topical steroids and either topical or systemic antimicrobial agents. In cases of flares, systemic steroids were the most popular and favorable treatment choice during flares. Indeed, Hailey-Hailey disease, characterized by its chronic inflammatory and rare nature with a relapsing and remitting course, poses a significant challenge for dermatologists. The treatment of HHD has been less than satisfactory and it often presents a challenge and could be misdiagnosed. Among the available treatment options, topical steroids and antimicrobial agents are the most administered therapies.

Pemphigoid diseases in patients with end-stage kidney diseases: pathogenesis and treatment.

Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.

Case series of cutaneous myiasis in neglected cases of autoimmune bullous disorders.

Myiasis is an infestation of the tissues and organs of living vertebrates and humans by fly larvae, usually those belonging to the Calliphoridae family. The larvae feed on the host's necrotic or living tissue. Preexisting dermatological conditions and poor hygiene have been described as predisposing factors for myiasis, and it is especially common among neglected, dependent patients. Based on our literature search, we could find only a few case reports reported on cutaneous myiasis in autoimmune bullous disorders. It is especially more common in the South Indian Tamil Nadu population due to the false belief that autoimmune blistering disorders like pemphigus and bullous pemphigoid are considered chicken pox and treated with neem and turmeric preparation with poor hygiene. Herein we report a series of eight autoimmune blistering disorders with cutaneous myiasis.

Clinical and demographic characteristics of mucous membrane pemphigoid in India: A retrospective analysis.

Background Mucous membrane pemphigoid (MMP) is a rare subepidermal autoimmune blistering disorder. The clinical and demographic parameters of this disease in Indian patients have not yet been elucidated in detail. Objective We aimed to study the clinical and demographic characteristics, disease course, and treatment aspects of MMP patients. Methods The data for this study were obtained by reviewing the case record forms of patients registered in the Autoimmune Bullous Disease (AIBD) Clinic of the Department of Dermatology, Venereology & Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, a tertiary care centre in India. The diagnosis of MMP was established on the basis of clinical and immune-histopathological features which are consistent with standard diagnostic criteria for the disease. Results A total of 52 patients with MMP registered in the AIBD clinic were included. The mean age at disease onset was 50 years and the average age at presentation was 56 years. Females outnumbered males in the study with a ratio of 1.36:1. The oral and ocular mucosae were the most commonly affected sites (82.6% and 63.4% respectively). Visual difficulty was reported by half the patients (26 of 52 patients). IgG, C3, and IgA deposits were detected on direct immunofluorescence (DIF) in 29, 21, and 11 patients, respectively. Serologic analysis was performed in only 7 of the patients and of these, just 1 exhibited a positive result on multivariant ELISA and epidermal pattern of binding on salt split skin indirect immunofluorescence. Most patients were treated with prednisolone (44 of 52). Steroid-sparing adjuvants were used in combination including cyclophosphamide, azathioprine, methotrexate, dapsone, and colchicine. Rituximab was administered in 7 patients with severe or refractory disease. Limitations This is a retrospective analysis of data available from a clinic registry. In patients with negative direct immunofluorescence on biopsy, the diagnosis was based on clinico-pathologic consensus. Conclusion MMP is not as uncommon in India as the paucity of reports suggest. Visual complications are frequent in Indian MMP patients. A high index of suspicion is required for early diagnosis and appropriate treatment to prevent ocular complications.

Exploring the Potential Advantages of Traditional Therapies in Autoimmune Blistering Illnesses: A Comprehensive Review and Analysis, Research

Autoimmune blistering diseases, such as Linear IgA Bullous Dermatosis (LABD) and Chronic Bullous Disease of Childhood (CBDC), provide considerable therapeutic treatment issues. Samana Aushadhis are regularly prescribed by Ayurvedic practitioners as part of therapy regimens for dermatological diseases including LABD and CBDC. Although anecdotal data and clinical observations point to the potential usefulness of traditional medicines in promoting long-term remission and alleviating symptoms, the precise mechanisms by which they exert their therapeutic benefits in LABD/CBD remain incompletely known in contemporary science. The potential advantages of traditional therapies in autoimmune blistering illnesses are being investigated through clinical trials, observational research, and mechanistic investigations. The therapeutic potential of these herbal remedies in LABD and CBDC is being investigated through clinical trials, observational research, and mechanistic investigations. Clinical trials, observational studies, and mechanistic investigations are being conducted in an effort to better understand the therapeutic potential of conventional medications in autoimmune blistering disorders. The effectiveness of these herbal treatments in causing remission and easing symptoms in LABD and CBDC is being closely examined. Overall, while traditional therapies hold promise in the management of autoimmune blistering diseases like LABD and CBDC, more research is necessary to fully understand their mechanisms of action and therapeutic potential. Through rigorous scientific inquiry, the integration of traditional and contemporary medicine may offer new avenues for managing these difficult conditions. Clinical trials, observational research, and mechanistic investigations are all contributing to the exploration of the therapeutic potential of these herbal remedies in LABD and CBDC.

Mild cognitive impairment in pemphigus.

Pemphigus is a group of autoimmune blistering disorders that have been associated with dementia in previous studies. Mild cognitive impairment (MCI) can be the first stage of progression into dementia. The objective of the present study was to evaluate the frequency of MCI in pemphigus patients compared to a control group. This case-control study included 80 patients with pemphigus referred to the dermatology clinics of Shohadaye Tajrish and Loghman Hakim hospitals, Tehran, Iran, in 2021. A group of 80 individuals without pemphigus who visited the same clinics for cosmetic consultation or interventions were regarded as controls. Age, sex, marital status, and education were recorded for all participants. Disease duration, medications, and severity were noted for pemphigus patients. The Persian version of the Montreal Cognitive Assessment (MoCA) test was used to assess cognitive function. MCI was significantly more frequent in pemphigus patients than in controls (55% vs. 37.5%, P = 0.026). Furthermore, the total MoCA score was significantly lower in pemphigus patients compared to controls (23.98 ± 3.77 vs. 25.21 ± 3.45, P = 0.032); however, among MoCA's different domains, only the executive functions score was significantly lower in pemphigus patients (P = 0.010). After adjustment, multivariable logistic regression analysis revealed that every 1-year higher education in patients decreased the odds of MCI by 52% (adjusted odds ratio = 0.483, 95% confidence interval 0.326; 0.715, P < 0.001). The frequency of MCI was found to be significantly higher, and overall scores of the MoCA test, as well as its executive function domain, were significantly lower among pemphigus patients in this study compared to the control group. Additionally, a higher level of education was associated with decreased odds of MCI in pemphigus patients. Identifying pemphigus patients with MCI through the use of the MoCA test can facilitate early intervention, enabling them to seek help and support.

Childhood Bullous Pemphigoid with Atypical Immunopathology: A Case Series

Bullous pemphigoid (BP) is a rare autoimmune blistering disorder primarily affecting older adults, with limited occurrences in children. BP in children typically manifests as large, tense blisters on the skin, often on flexural areas. It also more often affects the oromucosal areas and the face in children than in adults. Diagnosis involves histopathological examination revealing eosinophilic spongiosis or subepidermal split, immunofluorescence tests highlighting immunoglobulin G (IgG) and C3 depositions, and immunological assays detecting BP180 and BP230 IgG autoantibodies. This report presents two cases of childhood BP (CBP) with atypical immunopathological findings. Clinically, the two cases had generalized plaques and bullae, including the face. The first case exhibited the characteristic linear deposits of IgG and C3 on the basement membrane through direct immunofluorescence (DIF) and revealed negative anti-BP180 antibodies on enzyme-linked immunosorbent assay (ELISA). In contrast, the second case showed negative DIF results, despite clinical suspicion, but had positive anti-BP180 IgG antibodies on ELISA. It is, therefore, crucial to consider the complete clinical presentation of the patient, in conjunction with the histological findings and immunopathologic assessments to diagnose CBP.

A Comprehensive Review on the Efficacy of Anti-CD20 Therapies in Pemphigus Treatment.

Pemphigus, an autoimmune blistering disorder, poses significant therapeutic challenges due to dysregulated B cells and the involvement of CD20. This review assesses the efficacy of anti-CD20 therapies, including rituximab, ofatumumab, ocrelizumab, and obinutuzumab, in pemphigus treatment. Mechanisms of action, clinical studies, and safety profiles were analyzed, revealing diverse impacts on disease severity. B cell depletion emerged as a pivotal factor, disrupting the autoimmune process and reducing pathogenic antibodies. Varied efficacy and safety profiles among agents underscore the need for personalized treatment strategies guided by biomarkers. Challenges such as resistance and long-term safety concerns necessitate continued research and vigilance. In clinical practice, insights from this review inform nuanced, tailored approaches for improved pemphigus management. The dynamic landscape of emerging therapies and personalized medicine emphasizes the need for ongoing research and strategic clinical decision-making. This review is a foundation for future investigations, providing insights for clinicians and researchers in optimizing pemphigus treatment.

Rituximab in Childhood and Juvenile Pemphigus Vulgaris: A Systematic Review.

Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.

Immunopathogenesis and Therapeutic Insights into Cicatricial Pemphigoid: A Comprehensive Review

Cicatricial Pemphigoid (CP), also known as mucous membrane pemphigoid, is a rare autoimmune blistering disorder characterized by subepithelial blistering and scarring of mucous membranes. The hallmark of CP is the formation of autoantibodies against structural proteins within the basement membrane zone, leading to an array of clinical manifestations affecting oral, ocular, and other mucosal surfaces. This review aims to elucidate the complex immunopathogenic mechanisms underlying CP, exploring the role of autoantigens such as BP180 and BP230, as well as the involvement of inflammatory mediators and immune cells. Additionally, the article provides a comprehensive overview of current diagnostic modalities and therapeutic approaches, ranging from systemic corticosteroids to novel immunomodulatory agents and biological therapies. The challenges in managing CP, including potential side effects of immunosuppressive treatments, are discussed alongside emerging strategies to enhance treatment efficacy and minimize adverse effects. A deeper understanding of the molecular pathways involved in CP pathogenesis is crucial for the development of targeted therapies, fostering improved patient outcomes and quality of life

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study

BackgroundAutoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. ObjectiveTo examine if ABDs elevate the risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. MethodsA population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996–2021 (n=3,322) was compared with an age and sex-matched comparison cohort from the general population (n=33,195). ResultsCompared with the general population, patients with ABDs had higher one-year risks of ASCVD (3.4% vs. 1.6%), heart failure (1.9% vs. 0.7%), arrhythmia (3.8% vs. 1.3%), venous thromboembolism (1.9% vs. 0.3%), and cardiovascular death (3.3% vs. 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABD with the outcomes during the entire follow-up were 1.24 (1.09–1.40) for ASCVD, 1.48 (1.24–1.77) for heart failure, 1.16 (1.02–1.32) for arrhythmia, 1.87 (1.50–2.34) for VTE, and 2.01 (1.76–2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LimitationsOur findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. ConclusionPatients with ABDs had an elevated cardiovascular risk compared with age and sex-matched controls.

Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA.

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL-6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL-6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL-6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll-like receptor (TLR) ligands, pathogen-associated and damage-associated molecular pattern molecules. Invitro, TLR ligands induced IL-6 expression via NF-κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL-6 via TLR1/2 and NF-κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR-mediated persistent skin inflammation might increase the risk of IL-6-related systemic complications, including RDEB.

Linear IgA bullous dermatosis of childhood: Retrospective single-center cohort.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder impacting children and adults. In this single-center retrospective chart review of pediatric patients with LABD at a large tertiary referral center, we report the unifying and unique clinical features of 10 pediatric patients. Patients typically presented with the "cluster of jewels" sign (n = 6; 60%), mucous membrane involvement (n = 5; 50%) and had a mean disease duration of 38 months; six patients (60%) required inpatient admission for management of their skin disease, including all five patients who had mucous membrane involvement. Our findings suggest that pediatric LABD may be a disease with high morbidity and may be associated with severe complications when mucous membranes are involved.

Intravenous gentamicin therapy induces functional type VII collagen in patients with recessive dystrophic epidermolysis bullosa: an open-label clinical trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable widespread blistering skin disorder caused by mutations in the gene encoding for type VII collagen (C7), the major component of anchoring fibrils. To evaluate the efficacy and safety of intravenous (IV) gentamicin readthrough therapy in patients with RDEB harbouring nonsense mutations. The primary outcomes were increased expression of C7 in patients' skin and safety assessments (ototoxicity, nephrotoxicity, autoimmune response); secondary outcomes included measuring wound healing in target wounds and assessment by a validated Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) scoring system. An open-label pilot trial to assess two different IV gentamicin regimens between August 2018 and March 2020 with follow-up through to 180 days post-treatment was carried out. Three patients with RDEB with confirmed nonsense mutations in COL7A1 in either one or two alleles and decreased baseline expression of C7 at the dermal-epidermal junction (DEJ) of their skin participated in the study. Three patients received gentamicin 7.5 mg kg-1 daily for 14 days and two of the three patients further received 7.5 mg kg-1 IV gentamicin twice weekly for 12 weeks. Patients who had pre-existing auditory or renal impairment, were currently using ototoxic or nephrotoxic medications, or had allergies to aminoglycosides or sulfate compounds were excluded. After gentamicin treatment, skin biopsies from all three patients (age range 18-28 years) exhibited increased C7 in their DEJ. With both regimens, the new C7 persisted for at least 6 months post-treatment. At 1 and 3 months post-treatment, 100% of the monitored wounds exhibited > 85% closure. Both IV gentamicin infusion regimens decreased EBDASI total activity scores. Of the patients assessed with the EBDASI, all exhibited decreased total activity scores 3 months post-treatment. All three patients completed the study; no adverse effects or anti-C7 antibodies were detected. IV gentamicin induced the readthrough of nonsense mutations in patients with RDEB and restored functional C7 in their skin, enhanced wound healing and improved clinical parameters. IV gentamicin may be a safe, efficacious, low-cost and readily available treatment for this population of patients with RDEB.

Increased healthcare burden and comorbidity risks of pediatric patients with dystrophic epidermolysis bullosa: Analysis of Nationwide Emergency Department Sample 2015-2019.

Dystrophic epidermolysis bullosa (DEB) describes a rare genetic blistering disorder characterized by fragile skin. This study aimed to classify the frequency, demographics, cost, and comorbidities associated with emergency department (ED) visits due to DEB. The Nationwide Emergency Department Sample (NEDS) was analyzed for pediatric (age <18) ED visits from 2015 to 2019. DEB was identified with ICD-10-CM code Q81.2. Weighted frequency, prevalence, and 95% confidence intervals (CIs) of comorbidities were determined among ED visits with and without a DEB diagnosis. From 2015 to 2019, 53 (weighted 242) cases of DEB among 27,223,220 pediatric ED visits were captured. Patients with DEB were more likely to visit the ED in summer compared with those without a diagnosis of DEB (35.7% vs. 21.4%, P < .05). More than half of patients with DEB were admitted to the hospital (56.2%, 95% CI: 39.3-72.5, P < .001) versus only 3.4% (95% CI: 3.1-3.7) of other patients. For ED visits with a secondary DEB diagnosis, the top three primary diagnoses were fever, constipation, and bone marrow transplant aftercare. Patients with DEB had higher rates of hypertension, cellulitis, sepsis, acute and chronic kidney injury, esophageal obstruction, gastroesophageal reflux disease, cardiomyopathy, and anxiety, compared to patients without DEB (all P < .001). DEB is a complex blistering disorder with multisystemic manifestations. Patients with DEB have significantly higher admission rates and commonly present with infectious or gastrointestinal complications. Understanding the features of ED visits due to DEB can better prepare healthcare teams and improve patient outcomes.