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The Journal of Investigative Dermatology Apr 2024Pemphigus is a severe blistering disease caused by autoantibodies primarily against the desmosomal cadherins desmoglein (DSG)1 and DSG3 which impair desmosome integrity....
Pemphigus is a severe blistering disease caused by autoantibodies primarily against the desmosomal cadherins desmoglein (DSG)1 and DSG3 which impair desmosome integrity. Especially for the acute phase, additional treatment options allowing to reduce corticosteroids would fulfill an unmet medical need. Here, we provide evidence that epidermal growth factor receptor (EGFR) inhibition by erlotinib ameliorates pemphigus vulgaris immunoglobulin G (PV-IgG) -induced acantholysis in intact human epidermis. PV-IgG caused phosphorylation of EGFR (Y845) and SRC in human epidermis. In line with that, a phosphotyrosine kinome analysis revealed a robust response associated with EGFR and SRC family kinase signaling in response to PV-IgG but not pemphigus foliaceus autoantibodies. Erlotinib inhibited PV-IgG-induced epidermal blistering and EGFR phosphorylation, loss of desmosomes as well as ultrastructural alterations of desmosome size, plaque symmetry, keratin filament insertion and restored the desmosome midline considered as hallmark of mature desmosomes. Erlotinib enhanced both single molecule DSG3 binding frequency and strength and delayed DSG3 fluorescence recovery supporting that EGFR inhibition increases DSG3 availability and cytoskeletal anchorage. Our data indicate that EGFR is a promising target for pemphigus therapy due to its link to several signaling pathways known to be involved in pemphigus pathogenesis.
PubMed: 38642796
DOI: 10.1016/j.jid.2024.03.040 -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Pemphigus, Benign Familial; Papillomavirus Infections; Mutation; Calcium-Transporting ATPases; Male; Female; Middle Aged; Human Papillomavirus Viruses; Alphapapillomavirus
PubMed: 38637183
DOI: 10.1016/j.abd.2022.12.011 -
Cureus Mar 2024Pemphigus vulgaris is a chronic autoimmune disease of the skin caused by the production of autoantibodies targeting desmogleins 1 and 3 usually presenting in individuals...
Pemphigus vulgaris is a chronic autoimmune disease of the skin caused by the production of autoantibodies targeting desmogleins 1 and 3 usually presenting in individuals with an average age of onset of approximately 40 years. A 35-year-old obese, diabetic woman presented with fluid-filled lesions over her body for three months along with erosions and painful ulcers in her mouth and genital area for two months. Based on clinical and histopathological studies, the patient was diagnosed as a case of pemphigus vulgaris. She was started on conventional treatment with oral corticosteroids followed by pulse therapy and mycophenolate mofetil. Rituximab infusion was scheduled but could not be administered due to elevated D-dimer values. The patient underwent screening for deep vein thrombosis (DVT) and received subcutaneous enoxaparin and oral rivaroxaban. She developed severe sepsis for which she was treated with systemic antibiotics. She subsequently developed acute renal failure and underwent hemodialysis. The patient's clinical condition further deteriorated, which necessitated therapeutic plasma exchange (TPE). Collagen, colloidal silver, and silicone foam dressings were done to hasten wound healing. Two distinct approaches were employed to eliminate the pseudomembrane on the wounds. One portion was treated with hydrogen peroxide (HO), while the other was with hyaluronidase. The hyaluronidase treatment resulted in considerable improvement of the lesions. Intravenous immunoglobulin (IVIG) infusion was scheduled. However, the treatment could not be administered as the patient succumbed to death due to pulmonary thromboembolism (PTE) secondary to DVT.
PubMed: 38633948
DOI: 10.7759/cureus.56357 -
JAAD Case Reports May 2024
PubMed: 38633887
DOI: 10.1016/j.jdcr.2024.02.025 -
Clinical Case Reports Apr 2024Early intervention is imperative for potentially fatal dermatologic diseases such as pemphigus vulgaris. In rural Nepal, limited public awareness, home remedies, and...
Early intervention is imperative for potentially fatal dermatologic diseases such as pemphigus vulgaris. In rural Nepal, limited public awareness, home remedies, and delays in healthcare access lead to poor outcomes. Although biopsy confirms the diagnosis, experienced dermatologists can make an accurate clinical diagnosis when characteristic skin lesions are present.
PubMed: 38617063
DOI: 10.1002/ccr3.8754 -
International Journal of Molecular... Mar 2024Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace... (Review)
Review
Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace elements are zinc, copper, and iron. A deficiency or excess of trace elements can be associated with an increased risk of skin diseases, so increasing their supplementation or limiting intake can be helpful in dermatological treatment. In addition, determinations of their levels in various types of biological material can be useful as additional tests in dermatological treatment. This paper describes the role of these elements in skin physiology and summarizes data on zinc, copper, and iron in the course of selected, following skin diseases: , , , and . In addition, this work identifies the potential of trace elements as auxiliary tests in dermatology. According to preliminary studies, abnormal levels of zinc, copper, and iron are observed in many skin diseases and their determinations in serum or hair can be used as auxiliary and prognostic tests in the course of various dermatoses. However, since data for some conditions are conflicting, clearly defining the potential of trace elements as auxiliary tests or elements requiring restriction/supplement requires further research.
Topics: Humans; Zinc; Copper; Trace Elements; Iron; Acne Vulgaris
PubMed: 38612631
DOI: 10.3390/ijms25073823 -
BMC Infectious Diseases Apr 2024Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM...
BACKGROUND
Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM discovered in 2001, is a rapidly growing mycobacterium that exhibits multidrug resistance. Reports of infections caused by this organism, particularly tenosynovitis in the musculoskeletal system, are limited.
CASE PRESENTATION
A 71-year-old female with vesicular pemphigus, undergoing immunosuppressive therapy, presented with a progressively enlarging tumour on the dorsum of her right hand, along with erythematous papules that extended across her right forearm. The specimens of skin tissues and blood cultures revealed the presence of M. immunogenum. Magnetic resonance imaging evaluation led to the diagnosis of pyogenic extensor tenosynovitis. A multidrug regimen, comprising amikacin and clarithromycin, was initiated, followed by synovectomy. The patient underwent a course of 180 days of antimicrobial therapy and demonstrated no signs of disease recurrence one year after treatment completion.
CONCLUSION
Early diagnosis and surgical intervention are crucial to prevent the adverse prognostic implications of pyogenic extensor tenosynovitis caused by M. immunogenum. Effective management requires precise microbial identification and susceptibility testing, necessitating collaborative engagement with microbiological laboratories.
Topics: Humans; Female; Aged; Tenosynovitis; Early Diagnosis; Mycobacteriaceae; Hand; Nontuberculous Mycobacteria
PubMed: 38609847
DOI: 10.1186/s12879-024-09249-5 -
Indian Journal of Dermatology,... Mar 2024Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in...
Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in detail. Objectives To evaluate the clinical and immunological predictors associated with post-rituximab paradoxical pemphigus flare. Materials and Methods This was a prospective cohort study including adult patients with pemphigus vulgaris or foliaceus who were treated with rituximab. Patients were administered 1000 mg of intravenous rituximab on days 0 and 14 (Rheumatoid arthritis (RA) protocol), with or without oral prednisolone and/or conventional immunosuppressive agents. Baseline clinical and immunological predictors of post-rituximab pemphigus flares were assessed. Results Fifty patients (mean age 40.44 ± 12.36 years) with a mean pemphigus disease area index (PDAI) score of 27.8 ± 15.48 were administered rituximab. Post-rituximab flare occurred in 10 (20%) patients after a mean of 14.1 ± 4.33 days after the first rituximab infusion. The mean baseline PDAI score (36.4 ± 11.7 vs. 25.6 ± 15.7, P = 0.02) and serum anti-Dsg1 levels (1216.8 ± 850.1 vs. 592 ± 562.12 RU/mL, P = 0.03) were statistically significantly higher in patients experiencing a flare. Using ROC-curve analysis, a PDAI score of 328 (OR 8.3, 95% CI 1.5-44.7) was 80% sensitive and 67.5% specific in predicting post-rituximab flare, while serum anti-Dsg1 level of 31137.78 RU/ml had a sensitivity of 60% and specificity of 85%. There was no significant difference in terms of affected body surface area, type of pemphigus, starting prednisolone dose, oral immunosuppressive adjuvant, serum anti-Dsg3, serum anti-AchRM3, and peripheral CD19+ B cell population. Limitations Our study is limited by a relatively small sample size. Immunological factors were not evaluated at the time of pemphigus flare. Though these unexpected pemphigus flares are likely to be associated with rituximab infusion, the possibility of spontaneous disease exacerbation cannot be entirely excluded. Conclusions Patients with more severe pemphigus or high serum anti-Dsg1 are at risk of post-rituximab paradoxical flare, and may benefit from rituximab administration under close monitoring.
PubMed: 38595008
DOI: 10.25259/IJDVL_894_2023 -
JPMA. the Journal of the Pakistan... Mar 2024To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders.
OBJECTIVE
To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders.
METHODS
The prospective cross-sectional study was conducted at the Institute of Skin Diseases, Karachi, from December 2020 to December 2022, and comprised adult patients of either gender presenting with complaints of bullae, vesicles, pustules and crusts on the skin or mucous membrane. Diagnostic findings of each patient as obtained by clinical assessment, microscopy and direct immunofluorescence were compared. Data was analysed using SPSS 19.
RESULTS
Of the 81 patients, 41(50.6%) were males and 40(49.4%) were females. The overall median age was 35 years (interquartile range: 23 years), with 66(75%) patients aged 19-55 years. The predominant body site involved was the trunk 49(60.5%), followed by mucosa 26(32.1%). Clinical diagnosis detected 80(98.7%) cases, compared to 76(93.8%) by microscopy and 81(100%) by direct immunofluorescence.
CONCLUSION
Direct immunofluorescence was found to be the gold standard for a confirmatory diagnosis of intraepidermal immunobullous disorders, especially when clinical and histopathology findings were inconclusive.
Topics: Adult; Male; Female; Humans; Fluorescent Antibody Technique, Direct; Cross-Sectional Studies; Prospective Studies; Skin Diseases; Skin; Blister; Pemphigus
PubMed: 38591288
DOI: 10.47391/JPMA.9509 -
Heliyon Apr 2024Pemphigus is a chronic recurrent disease in dermatology. Although it is not very common, its treatment has been an increasing concern in recent years because it is... (Review)
Review
Pemphigus is a chronic recurrent disease in dermatology. Although it is not very common, its treatment has been an increasing concern in recent years because it is difficult and long-lasting. At present, there are many papers on pemphigus treatment, and to better understand the research trends and research frontiers of pemphigus treatment, it is necessary to conduct a comprehensive systematic review and analysis. We combined bibliometric and visualization methods to analyze 1365 papers published in the Web of Science database from 1992 to 2022, including basic information about countries, institutions and authors, to gain a general understanding of the treatment of pemphigus. Among them, the United States is the country with the most output, Iran's Tehran University of Medical Sciences is the institution with the most published works, and Ahmed, A. Razzaque of Tufts University is the most influential scholar. In addition, we also learned about the research hotspots and frontiers of pemphigus treatment through a series of analyses on the frequency, clustering, keywords bursts and cited literature, and we briefly reviewed the highly cited literature. We found that the current research focuses in the study of pemphigus treatment are the types, pathogenesis, and treatment of pemphigus, including glucocorticoids, immunosuppressants and many other major treatment methods. Hailey-Hailey disease, genetic susceptibility, and traditional Chinese medicine are potential research hotspots. Rituximab is a research frontier. In conclusion, we hope to provide new research ideas for promoting the development of pemphigus treatment.
PubMed: 38590872
DOI: 10.1016/j.heliyon.2024.e28462