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Dermatologic Therapy Mar 2021
Meta-Analysis
Topics: Arthritis, Rheumatoid; Humans; Pemphigus; Skin
PubMed: 33528863
DOI: 10.1111/dth.14845 -
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 -
Annals of Palliative Medicine Jan 2021At the end of the last century, genome-wide association studies revealed a significant genetic association between bipolar disorder and autoimmune diseases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
At the end of the last century, genome-wide association studies revealed a significant genetic association between bipolar disorder and autoimmune diseases. Subsequently, the theory of immune pathogenesis of bipolar disorder gradually formed, and the research on autoimmune diseases and bipolar comorbidities began to extend to other diseases, but their correlation is still controversial. To explore the differences in the prevalence of bipolar disorder in patients with autoimmune disease and normal healthy people through meta-analysis, and to examine the relationship between bipolar disorder and autoimmune disease by reviewing the relevant literature.
METHODS
The Cochrane, PubMed, and Embase databases were searched by computer from the date of inception of the database to July 2020. The main topics of the search were based on common autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, pemphigus, and Sjogren's syndrome. The databases were comprehensively searched for controlled studies regarding the prevalence of bipolar disorder in patients with autoimmune diseases. Review Manager 5.3 software was used for meta-analysis.
RESULTS
In total, 10 cohort and case control studies were included. From these, 16 control groups were extracted based on nine autoimmune diseases. The meta-analysis demonstrated that the incidence of bipolar disorder was significantly increased in patients with autoimmune disease compared to patients without autoimmune disease, [mean difference (MD) =1.54, 95% confidence interval (CI): 1.28-1.86, P<0.00001]. Also, in the meta-analysis based on five cross-sectional analyses (in which a total of five control groups were extracted based on five autoimmune diseases), the high comorbidity rate of autoimmune diseases and bipolar disorder was verified (MD =2.23, 95% CI: 1.62-3.07, P<0.00001).
CONCLUSIONS
The prevalence of bipolar disorder is markedly higher in patients with autoimmune disease. Yet, more basic research is needed to verify the special significance of immune mechanisms in bipolar disorder.
Topics: Autoimmune Diseases; Bipolar Disorder; Cross-Sectional Studies; Genome-Wide Association Study; Humans; Prevalence
PubMed: 33440965
DOI: 10.21037/apm-20-2293 -
International Immunopharmacology Mar 2021Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some...
Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some specific types of drugs, have been found to be involved in the induction of pemphigus. Here, we have designed a systematic review by searching PubMed/Medline and Embase databases to find the drugs, involved in pemphigus induction and exacerbation (updated on 19 August 2019). From 1856 initially found articles, 134 studies (198 patients; 170 patients in the drug-induced patients and 28 in exacerbation group) have been included. Regarding drug-induced cases, the mean age was 57.19 ± 16.9-year-old (ranged 8-105), and patients had developed pemphigus within a mean of 154.27 days. Pemphigus vulgaris (38.9%), pemphigus foliaceus (33.5%), and paraneoplastic pemphigus (3.6%) were the most common subtypes. Furthermore, penicillamine (33.1%), captopril (7.7%), and bucillamine (6.5%) were the most reported drugs related to pemphigus induction; penicillamine was associated with the most persistent disease. Regardless of disease subtype, cutaneous, mucocutaneous, and mucosal involvements were reported in 68.6%, 30.1%, and 1.3% of patients, respectively. In total, the IgG deposition in the pathological studies, being positive for autoreactive antibodies in the serum against desmoglein 3 (Dsg3), and desmoglein 1 (Dsg1), were reported in 93%, 34.9%, and 72.7% of reported patients, respectively. Regarding the management of such patients, in 75% of healed cases, treatment (mainly transient systemic and topical corticosteroids and/or azathioprine) was needed besides stopping the probable pemphigus-inducing culprit drug, while drug cessation was enough to control the disease in 25%. As the outcomes, the lesions in 129 of 147 (87.8%) patients had been healed, while in 18 (12.2%), no healing was reported; fifteen out of 18 had died. In conclusion, some specific groups of treatments can induce pemphigus, including penicillamine, captopril, and bucillamine; despite the similar clinical and pathological manifestations to classical pemphigus, most of the cases are less severe and have a better prognosis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antirheumatic Agents; Captopril; Cysteine; Drug-Related Side Effects and Adverse Reactions; Humans; Pemphigus; Penicillamine
PubMed: 33418246
DOI: 10.1016/j.intimp.2020.107299 -
International Journal of Dermatology Jan 2021
Meta-Analysis
Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Pemphigus
PubMed: 33070309
DOI: 10.1111/ijd.15238 -
The American Journal of Dermatopathology Oct 2021Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue has been proposed as a potential tool in the diagnosis of autoimmune bullous diseases (AIBDs) in... (Meta-Analysis)
Meta-Analysis
Immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tissue has been proposed as a potential tool in the diagnosis of autoimmune bullous diseases (AIBDs) in lieu of standard direct immunofluorescence (DIF) microscopy. To comprehensively determine the diagnostic accuracy of immunoglobulin and complement IHC for diagnosis of AIBDs, we conducted a systematic review and multivariate Bayesian model-based meta-analysis of the literature. Quality and heterogeneity assessment of studies was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist and the I2 index, respectively. Electronic searches using PubMed from April 1964 to July 2020 identified 14 articles meeting predetermined inclusion and exclusion criteria. Median sensitivities with 95% credible intervals in pemphigus and pemphigoid were 0.24 (0.01-0.89) and 0.22 (0.02-0.77) with immunoglobulin G (IgG), 0.77 (0.39-0.95) and 0.25 (0.02-0.85) with IgG4, 0.11 (0.02-0.32) and 0.86 (0.56-0.98) with C3d, and 0.84 (0.56-0.97) and 0.75 (0.37-0.94) with C4d, respectively. Specificities were 1.00 (0.00-1.00) with IgG, 0.98 (0.89-1.00) with IgG4, 0.99 (0.97-1.00) with C3d, and 0.99 (0.97-1.00) with C4d. The risk of bias and heterogeneity among studies was a serious problem, decreasing the level of evidence. Our work suggests that, in selected cases, paraffin-based IHC may be a helpful procedure to screen for AIBDs, especially when specialized laboratories and/or biopsy specimens for DIF do not exist. Nevertheless, more studies with a refined quality design are needed to explore the true usefulness of this diagnostic method in AIBDs.
Topics: Autoimmune Diseases; Complement C3d; Complement C4b; Dermatitis Herpetiformis; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunohistochemistry; Paraffin Embedding; Pemphigoid, Bullous; Pemphigus; Peptide Fragments; Skin Diseases, Vesiculobullous
PubMed: 33055534
DOI: 10.1097/DAD.0000000000001817 -
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 -
Journal of the American Academy of... Jul 2021Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials.
OBJECTIVE
To determine the best first-line steroid-sparing adjuvants for pemphigus treatment.
METHODS
Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose.
RESULTS
Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, -11,830.5 mg (95% CI, -14,089.48 to -9571.52), -3032.48 mg (-4700.74 to -1364.22), and -2469.54 mg (-4128.42 to -810.66), respectively.
LIMITATIONS
The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons.
CONCLUSION
Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.
Topics: Azathioprine; Cyclophosphamide; Cyclosporine; Drug Therapy, Combination; Humans; Immunologic Factors; Mycophenolic Acid; Network Meta-Analysis; Pemphigus; Randomized Controlled Trials as Topic; Recurrence; Rituximab; Steroids
PubMed: 32798583
DOI: 10.1016/j.jaad.2020.08.028 -
Dermatologic Therapy Nov 2020COVID-19 had a great impact on medical approaches among dermatologist. This systematic review focuses on all skin problems related to COVID-19, including primary and...
COVID-19 had a great impact on medical approaches among dermatologist. This systematic review focuses on all skin problems related to COVID-19, including primary and secondary COVID-related cutaneous presentations and the experts recommendations about dermatological managements especially immunomodulators usage issues. Search was performed on PubMed, Scopus, Embase and ScienceDirect. Other additional resources were searched included Cochrane, WHO, Medscape and coronavirus dermatology resource of Nottingham university. The search completed on May 3, 2020. Three hundred seventy-seven articles assigned to the inclusion and exclusion groups. Eighty-nine articles entered the review. Primary mucocutaneous and appendageal presentations could be the initial or evolving signs of COVID-19. It could be manifest most commonly as a maculopapular exanthamatous or morbiliform eruption, generalized urticaria or pseudo chilblains recognized as "COVID toes" (pernio-like acral lesions or vasculopathic rashes). During pandemic, Non-infected non-at risk patients with immune-medicated dermatologic disorders under treatment with immunosuppressive immunomodulators do not need to alter their regimen or discontinue their therapies. At-risk o suspected patients may need dose reduction, interval increase or temporary drug discontinuation (at least 2 weeks). Patients with an active COVID-19 infection should hold the biologic or non-biologic immunosuppressives until the complete recovery occur (at least 4 weeks).
Topics: COVID-19; Chilblains; Humans; Immunosuppressive Agents; Skin Diseases; Skin Diseases, Viral
PubMed: 32639077
DOI: 10.1111/dth.13986 -
Dermatologic Therapy Nov 2020In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection),... (Review)
Review
In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection), and the most proper management strategies include both issues that are what this systematic review targets. Databases of PubMed, Scopus, Google Scholar, Medscape, and Centre of Evidence-Based Dermatology, coronavirus dermatology resource of Nottingham University searched completely up to May 15, 2020, and initial 237 articles were selected to further review and finally 9 articles (including 12 patients) entered to this study. From 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only 1 patient required Intensive Care Unit admission, the others have been treated for mild-moderate symptoms with conventional therapies. The biologic or immunosuppressive/immunomodulator agents have been ceased during the course of disease. The course of coronovirus diseases 2019 (COVID-19) and its management was as similar as normal populations. Their underlying dermatologic disease were exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. Exacerbation of patients underlying dermatologic disease was mild to moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence and disturbing cytokine storms in these patients.
Topics: Aged; Biological Products; COVID-19; Chronic Disease; Dermatologic Agents; Disease Progression; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Recurrence; Risk Assessment; Risk Factors; Skin Diseases; Treatment Outcome
PubMed: 32558193
DOI: 10.1111/dth.13867