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Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
Journal of Stomatology, Oral and... Oct 2022This systematic review aimed to evaluate complications and survival rates of dental implants placed in patients suffering from autoimmune diseases.
PURPOSE
This systematic review aimed to evaluate complications and survival rates of dental implants placed in patients suffering from autoimmune diseases.
MATERIALS AND METHODS
A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review guidelines (PRISMA), using Google scholar and PubMed electronic databases with a stop date of September 2021. The eligibility criteria included all full text human studies in the English language literature reporting on patients with autoimmune diseases treated with dental implants.
RESULTS
Fifty-five studies reporting on nine distinct autoimmune diseases were analyzed: 17 on Sjögren's syndrome (SS), 11 on oral lichen planus (OLP), 8 on Type 1 diabetes, 6 on rheumatoid arthritis (RA), 4 on systemic scleroderma (SSc), 3 on Crohn's disease (CD), 3 on systemic lupus erythematosus (SLE), 2 on mucous membrane pemphigoid (MMB) and 1 on pemphigus vulgaris (PV). Despite the heterogeneity and methodological limitations of most of the studies, results showed that dental implant survival rates were comparable to those reported in the general population. However, patients with secondary SS or erosive OLP were more susceptible to developing peri-mucositis and increased marginal bone loss.
CONCLUSION
This review suggested that dental implants may be considered as a safe and viable therapeutic option in the management of edentulous patients suffering from autoimmune diseases. Nevertheless, scrupulous maintenance of oral hygiene and long-term follow-up emerge as being the common determinants for uneventful dental implant treatment.
Topics: Dental Implants; Humans; Lichen Planus, Oral; Sjogren's Syndrome
PubMed: 35033725
DOI: 10.1016/j.jormas.2022.01.005 -
Autoimmunity Reviews Mar 2021Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune... (Review)
Review
Regulatory T cells (Tregs) are a subset of T cells responsible for the regulation of immune responses, thereby maintaining immune homeostasis and providing immune tolerance to both self and non-self-antigens. An increasing number of studies revealed Treg numbers and functions in a variety of autoimmune diseases. Treg deficiency can cause the development of several autoimmune skin diseases including vitiligo, alopecia areata, pemphigoid and pemphigus, psoriasis, and systemic sclerosis. Many clinical trials have been performed for autoimmune conditions using polyclonal Tregs, but efficiency can be significantly improved using antigen-specific Tregs engineered using T cell receptor (TCR) or chimeric antigen receptor (CAR) constructs. In this review, we systematically reviewed altered frequencies, impaired functions, and phenotypic features of Tregs in autoimmune skin conditions. We also summarized new advances in TCR and CAR based antigen-specific Tregs tested both in animal models and in clinics. The advantages and limitations of each approach were carefully discussed emphasizing possible clinical relevance to patients with autoimmune skin diseases. Moreover, we have reviewed potential approaches for engineering antigen-specific Tregs, and strategies for overcoming possible hurdles in clinical applications. Thereby, antigen-specific Tregs can be infused using autologous adoptive cell transfer to restore Treg numbers and to provide local immune tolerance for autoimmune skin disorders.
Topics: Animals; Autoimmune Diseases; Humans; Immune Tolerance; Receptors, Antigen, T-Cell; Skin Diseases; T-Lymphocytes, Regulatory
PubMed: 33476816
DOI: 10.1016/j.autrev.2021.102761 -
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 -
Dermatology Online Journal Aug 2020Pemphigus has been associated with other autoimmune and autoinflammatory disorders. Specifically, some case reports in the literature document coexistence of pemphigus... (Meta-Analysis)
Meta-Analysis
Pemphigus has been associated with other autoimmune and autoinflammatory disorders. Specifically, some case reports in the literature document coexistence of pemphigus with psoriasis, but this association is lacking larger scale investigation. With this in mind, we conducted a systematic review and meta-analysis to evaluate the association between pemphigus and psoriasis. In doing so, we found an association between the two conditions. Pemphigus was more common in patients with psoriasis than in controls (OR 2.64, 95% CI 1.24-5.59, P=0.01), with heterogeneity (I2=94%). We go on to propose pathophysiologic mechanisms and its relevance for diagnostic and management considerations.
Topics: Humans; Pemphigus; Psoriasis
PubMed: 32941727
DOI: No ID Found -
Frontiers in Immunology 2023Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with...
BACKGROUND
Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF.
MATERIALS AND METHODS
A search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg.
RESULTS
Most patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively.
DISCUSSION
In pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life.
Topics: Humans; Pemphigus; Immunoglobulins, Intravenous; Quality of Life; Immunosuppressive Agents; Rituximab; Recurrence; Biological Products
PubMed: 37901249
DOI: 10.3389/fimmu.2023.1267668 -
Cureus Sep 2023Artificial intelligence (AI) has been cited as being helpful in the diagnosis of diseases, the prediction of prognoses, and the development of patient-specific... (Review)
Review
Artificial intelligence (AI) has been cited as being helpful in the diagnosis of diseases, the prediction of prognoses, and the development of patient-specific therapeutic strategies. AI can help dentists, in particular, when they need to make important judgments quickly. It can eliminate human mistakes in making decisions, resulting in superior and consistent medical treatment while lowering the workload on dentists. The existing studies relevant to the study and application of AI in the diagnosis of various forms of mouth ulcers are reviewed in this work. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed in the preparation of the review. There were no rule violations, with the significant exception of the use of a better search method that led to more accurate findings. Using search terms mainly such as AI, oral health, oral ulcers, oral herpes simplex, oral lichen planus, pemphigus vulgaris, recurrent aphthous ulcer (RAU), oral cancer, premalignant and malignant disorders, etc., a comprehensive search was carried out in the reliable sources of literature, namely PubMed, Scopus, Embase, Web of Science, Ovid, Global Health, and PsycINFO. For all papers, exhaustive searches were done using inclusion criteria as well as exclusion criteria between June 28, 2018, and June 28, 2023. An AI framework for the automatic categorization of oral ulcers from oral clinical photographs was developed by the authors, and it performed satisfactorily. The newly designed AI model works better than the current convolutional neural network image categorization techniques and shows a fair level of precision in the classification of oral ulcers. However, despite being useful for identifying oral ulcers, the suggested technique needs a broader set of data for validation and training purposes before being used in clinical settings. Automated OCSCC identification using a deep learning-based technique is a quick, harmless, affordable, and practical approach to evaluating the effectiveness of cancer treatment. The categorization and identification of RAU lesions through the use of non-intrusive oral pictures using the previously developed ResNet50 and YOLOV algorithms demonstrated better accuracy as well as adequate potential for the future, which could be helpful in clinical practice. Moreover, the most reliable projections for the likelihood of the presence or absence of RAU were made by the optimized neural network. The authors also discovered variables associated with RAU that might be used as input information to build artificial neural networks that anticipate RAU.
PubMed: 37842407
DOI: 10.7759/cureus.45187 -
Frontiers in Immunology 2021The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may...
The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may be associated with these antibodies. In this review we analyze clinicopathological, immunologic and outcome features of anti-Dsc autoimmune blistering diseases patients, to improve their diagnosis and management. We conducted a systematic search of PubMed and Embase (1990-present) for studies reporting cases of autoimmune blistering diseases with anti-Dsc antibodies. We classified the selected patients as patients with exclusively anti-Dsc autoantibodies, and patients with anti-Dsc and other autoantibodies. Of 93 cases with anti-Dsc autoantibodies included, 38 (41%) had exclusively these antibodies. Only 18% of patients presented with the typical clinicopathological phenotype of pemphigus vulgaris or pemphigus foliaceous. Mucosal involvement was seen in approximately half of the patients. Up to 18% of cases were associated with neoplasms. Acantholysis was described in 54% of cases with histopathological information. Treatments and outcomes vary in the different clinical phenotypes. The presence of anti-Dsc antibodies must be suspected mainly in those patients with either atypical pemphigus, in special with clinical pustules, or in cases showing intraepithelial or dermal neutrophilic/eosinophilic infiltrate on histological examination and dual pattern by direct immunofluorescence examination.
Topics: Acantholysis; Animals; Autoantibodies; Autoimmunity; Desmocollins; Desmogleins; Eosinophils; Humans; Neutrophils; Pemphigus; Phenotype; Skin
PubMed: 34567003
DOI: 10.3389/fimmu.2021.740820 -
International Journal of Environmental... May 2023(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic... (Review)
Review
(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed.
Topics: Child; Humans; Aged; Saliva; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Autoantibodies; Arthritis, Rheumatoid
PubMed: 37239511
DOI: 10.3390/ijerph20105782 -
JAAD International Dec 2022Systemic glucocorticoids are first-line treatment options for autoimmune blistering diseases; however, their long-term use is associated with significant toxicities. (Review)
Review
BACKGROUND
Systemic glucocorticoids are first-line treatment options for autoimmune blistering diseases; however, their long-term use is associated with significant toxicities.
OBJECTIVE
To evaluate the side effects of steroid-sparing agents and compare them with those of steroids.
METHODS
We searched Cochrane Reviews, Embase, MEDLINE, and Scopus between October 1978 and May 2020 using the keywords "bullous pemphigoid," "pemphigus," "autoimmune blistering diseases," and "side effects." A total of 31 randomized controlled trials and retrospective case series were critically appraised.
RESULTS
This review includes a total of 1685 patients with autoimmune blistering diseases, of whom 781 had bullous pemphigoid and 904 had either pemphigus vulgaris or pemphigus foliaceous.
LIMITATIONS
A major limitation is that because adjuvants are generally used in combination with steroids, only 12 of the studies reviewed included a "steroid-only" arm to allow for a direct comparison of side effects. Additionally, there is inadequate literature and lack of standardized grade reporting of specific side effects of each steroid-sparing agent.
CONCLUSION
In the future, researchers should consider implementing the Common Terminology Criteria for Adverse Events, version 5.0, for reporting of all side effects to allow for consistency and standardization. It would be useful to have an index similar to the Glucocorticoid Toxicity Index to quantify these side effects.
PubMed: 36089938
DOI: 10.1016/j.jdin.2022.07.005