-
BioRxiv : the Preprint Server For... May 2024Binding of autoantibodies to keratinocyte surface antigens, primarily desmoglein 3 (Dsg3) of the desmosomal complex, leads to the dissociation of cell-cell adhesion in...
Binding of autoantibodies to keratinocyte surface antigens, primarily desmoglein 3 (Dsg3) of the desmosomal complex, leads to the dissociation of cell-cell adhesion in the blistering disorder pemphigus vulgaris (PV). After the initial disassembly of desmosomes, cell-cell adhesions actively remodel in association with the cytoskeleton and focal adhesions. Growing evidence highlights the role of adhesion mechanics and mechanotransduction at cell-cell adhesions in this remodeling process, as their active participation may direct autoimmune pathogenicity. However, a large part of the biophysical transformations after antibody binding remains underexplored. Specifically, it is unclear how tension in desmosomes and cell-cell adhesions changes in response to antibodies, and how the altered tensional states translate to cellular responses. Here, we showed a tension loss at Dsg3 using fluorescence resonance energy transfer (FRET)-based tension sensors, a tension loss at the entire cell-cell adhesion, and a potentially compensatory increase in junctional traction force at cell-extracellular matrix adhesions after PV antibody binding. Further, our data indicate that this tension loss is mediated by the inhibition of RhoA at cell-cell contacts, and the extent of RhoA inhibition may be crucial in determining the severity of pathogenicity among different PV antibodies. More importantly, this tension loss can be partially restored by altering actomyosin based cell contractility. Collectively, these findings provide previously unattainable details in our understanding of the mechanisms that govern cell-cell interactions under physiological and autoimmune conditions, which may open the window to entirely new therapeutics aimed at restoring physiological balance to tension dynamics that regulates the maintenance of cell-cell adhesion.
PubMed: 38766211
DOI: 10.1101/2024.05.03.592394 -
Clinical and Experimental Medicine May 2024The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology.
OBJECTIVE
To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors.
METHODS
Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies.
RESULTS
A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%.
CONCLUSION
These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.
Topics: Pemphigus; Humans; Prevalence; Incidence; Neoplasms; Europe; North America; Asia
PubMed: 38758217
DOI: 10.1007/s10238-024-01354-8 -
Cureus May 2024Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich...
Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich variant of hyaline vascular Castleman disease in Saudi Arabia. A 24-year-old Saudi female known to have acetylcholine receptor antibody-positive myasthenia gravis (MG) presented with shortness of breath, oral thrush, and an acute myasthenia gravis exacerbation, necessitating intensive care unit (ICU) admission. During her hospitalization, she was found to have a large pelvic mass. The mass was surgically excised. The diagnosis of stroma-rich hyaline vascular Castleman disease was rendered after histopathological examination. The patient's symptoms improved after the surgery. This case underscores the importance of considering Castleman disease in complex clinical presentations, especially in the context of autoimmune and paraneoplastic diseases. Recognition and timely intervention are crucial for patient management. Additionally, the report adds to the global literature on Castleman disease, emphasizing the need for further research into its clinical manifestations and associations.
PubMed: 38756713
DOI: 10.7759/cureus.60435 -
International Journal of Women's... Jun 2024
PubMed: 38756624
DOI: 10.1097/JW9.0000000000000153 -
Clinical Case Reports May 2024Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion affecting the skin and mucous membranes,...
Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion affecting the skin and mucous membranes, predominantly affects females in their fifth and sixth decades of life. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. PV should always be considered in the differential diagnosis of oral ulcerative and vesiculobullous lesions in both children and adolescents.
PubMed: 38756617
DOI: 10.1002/ccr3.8954 -
Cureus Apr 2024Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both... (Review)
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.
PubMed: 38752055
DOI: 10.7759/cureus.58288 -
Cureus Apr 2024Pemphigus herpetiformis (PH) is a rare autoimmune blistering disorder that typically presents in adults. However, its occurrence in paediatric patients, especially in...
Pemphigus herpetiformis (PH) is a rare autoimmune blistering disorder that typically presents in adults. However, its occurrence in paediatric patients, especially in very young children, is exceedingly rare. It presents with clinical features resembling dermatitis herpetiformis (DH) and immunologic characteristics similar to pemphigus, belonging to the group of intraepidermal autoimmune bullous diseases. We present the case of a three-year-old female with a history of annular and vesicular lesions on both forearms and legs. A skin biopsy revealed epidermal acanthosis, marked spongiosis, numerous intra-epidermal blisters, and exocytosis of eosinophils and neutrophils. A superficial perivascular lymphocytic infiltrate, accompanied by eosinophils and neutrophils, was also observed in the dermis. The diagnosis was also supported by direct and indirect immunofluorescence. The patient was treated with clobetasol ointment and dapsone, which showed significant improvement in the skin lesions. This case underscores the importance of considering PH in the differential diagnosis of vesicobullous diseases in children and the need for further research to elucidate its pathogenesis and optimal management.
PubMed: 38752034
DOI: 10.7759/cureus.58286 -
Clinical Case Reports May 2024IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease...
KEY CLINICAL MESSAGE
IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease may not respond to the aforementioned medications. Our study highlights the role of TNFa inhibitor as an alternative modality in the treatment of recalcitrant IgA pemphigus.
ABSTRACT
IgA pemphigus is a rare autoimmune blistering disease characterized by a pruritic, annular, vesiculopustular eruption. In IgA pemphigus, there are IgA autoantibodies targeting the keratinocyte cell surface adhesion molecules, causing cell-to-cell dehiscence and a flaccid vesiculopustular eruption, mainly in the axilla and groin. Dapsone, despite being the drug of choice for treating IgA pemphigus, is not effective in clearing lesions in a minority of patients and such rare cases of recalcitrant IgA pemphigus need alternative modalities of treatment. Here, we report the successful treatment of a 50-year-old male patient with an adalimumab injection who had a poor response to dapsone.
PubMed: 38751960
DOI: 10.1002/ccr3.8807 -
Journal of Medicine and Life Jan 2024Pemphigus vulgaris (PV) is a potentially fatal autoimmune disease characterized by blistering of the skin, mucous membranes, and oral cavity. Genetics are implicated in...
Pemphigus vulgaris (PV) is a potentially fatal autoimmune disease characterized by blistering of the skin, mucous membranes, and oral cavity. Genetics are implicated in its etiology, with the gene identified as a potential risk factor for pemphigus in certain populations, suggesting its role as a novel molecular target for therapeutic intervention. This study aimed to detect single nucleotide polymorphisms (SNPs) rs17315309 A/G and rs2304365 C/G in the gene among Iraqi/Arabic patients with PV. A total of 90 Iraqi subjects participated in this study, including 45 patients diagnosed with PV and 45 healthy controls. SNP analysis was performed using High-Resolution Melt Analysis (HRMA) with Eva Green I Dye. For SNP rs17315309 A/G, the distribution of heterozygous genotypes showed highly significant differences between the patient and healthy groups ( = 0.005), with the mutant G-allele being significantly more prevalent in patients than in the healthy group ( = 0.001). In contrast, for SNP rs2304365 C/G, the distribution of heterozygous and mutant genotypes did not differ significantly between patients and healthy individuals ( = 0.8 and = 0.3, respectively), with the mutant G-allele also showing no significant difference ( = 0.4). Our data indicate a significant association between PV and the rs17315309 A/G SNP in the gene among the Iraqi population of Arabic origin. However, no association was found between patients with PV and the rs2304365 C/G SNP in the same gene.
Topics: Humans; Pemphigus; Iraq; Polymorphism, Single Nucleotide; Male; Female; Adult; Case-Control Studies; Genetic Predisposition to Disease; Middle Aged; Genotype
PubMed: 38737652
DOI: 10.25122/jml-2023-0227 -
Molecular Biology Reports May 2024Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific...
BACKGROUND
Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses.
METHODS AND RESULTS
We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls.
CONCLUSIONS
We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.
Topics: Dermatitis, Atopic; Animals; Dogs; MicroRNAs; Cyclic Nucleotide Phosphodiesterases, Type 4; Biomarkers; Dog Diseases; Male; Leukocytes, Mononuclear; Female
PubMed: 38734860
DOI: 10.1007/s11033-024-09605-3