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Annals of the Rheumatic Diseases Jan 2024Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several...
BACKGROUND
Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.
METHODS
Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.
RESULTS
Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.
CONCLUSIONS
In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Remission Induction; Rituximab; Practice Guidelines as Topic
PubMed: 36927642
DOI: 10.1136/ard-2022-223764 -
Journal of the American Academy of... Jun 2022Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist;... (Review)
Review
BACKGROUND
Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking.
OBJECTIVE
To evaluate the evidence of current treatment modalities for pediatric AA.
METHODS
We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available.
RESULTS
Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab.
LIMITATIONS
English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed.
CONCLUSION
Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.
Topics: Adolescent; Adrenal Cortex Hormones; Alopecia; Alopecia Areata; Autoimmune Diseases; Child; Humans; Janus Kinase Inhibitors; Prospective Studies
PubMed: 33940103
DOI: 10.1016/j.jaad.2021.04.077 -
European Journal of Neurology Jan 2023Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN.
METHODS
A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis.
RESULTS
The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin.
CONCLUSIONS
PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.
Topics: Female; Humans; Middle Aged; Male; Sjogren's Syndrome; Peripheral Nervous System Diseases; Vasculitis; Immunoglobulins, Intravenous
PubMed: 36086910
DOI: 10.1111/ene.15555 -
Travel Medicine and Infectious Disease 2022COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the... (Review)
Review
COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the literature to assess the prevalence, clinical features and outcome of autoimmune thyroid disorders triggered by COVID-19. We reviewed case reports, case series, and observational studies of autoimmune thyroiditis including Graves' disease, Hashimoto thyroiditis, and silent thyroiditis developed in COVID-19 patients by searching PubMed, SCOPUS and Web of Science and included in the systematic review. Our search yielded no prevalence study. We noted 20 reported cases: Fourteen cases of Graves' disease, 5 cases of hypothyroidism due to Hashimoto's thyroiditis and one case of postpartum thyroiditis. The majority (16/20, 80%) were middle-aged (mean age: 40 years) female patients. Autoimmune thyroiditis was diagnosed either concomitantly or 7-90 days after the COVID-19 infection. Eight out of 14 cases with Graves' disease had a known thyroid disorder and they were stable in remission. One out of 5 cases with Hashimoto's thyroiditis had known prior hypothyroidism. The majority of the patients achieved remission within 3 months. One patient with thyroid storm due to Graves' disease and one patient with myxedema coma have died. Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission. It is reasonable to routinely assess the thyroid functions both in the acute phase and during the convalescence so as not to overlook a thyroid disorder and not to delay treatment especially in patients with preexisting autoimmune thyroid diseases.
Topics: Adult; COVID-19; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Middle Aged; Thyroiditis; Thyroiditis, Autoimmune
PubMed: 35307540
DOI: 10.1016/j.tmaid.2022.102314 -
Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Annals of the Rheumatic Diseases Mar 2023To quantify global, regional and country-specific estimates of epidemiology of systemic lupus erythematosus (SLE). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To quantify global, regional and country-specific estimates of epidemiology of systemic lupus erythematosus (SLE).
METHODS
Four databases were systematically searched, and a Bayesian hierarchical linear mixed model was constructed to estimate the global, regional, and country-specific incidence and prevalence of SLE.
RESULTS
112 studies met the inclusion criteria. The global SLE incidence and newly diagnosed population were estimated to be 5.14 (1.4 to 15.13) per 100 000 person-years and 0.40 million people annually, respectively. In women, the values were 8.82 (2.4 to 25.99) per 100 000 person-years and 0.34 million people annually, while in men, the estimates were 1.53 (0.41 to 4.46) per 100 000 person-years and 0.06 million people annually, respectively. Poland, the USA and Barbados had the highest estimates of SLE incidence. Regarding prevalence, the global SLE prevalence and affected population were estimated to be 43.7 (15.87 to 108.92) per 100 000 persons and 3.41 million people, respectively. In women, the values were 78.73 (28.61 to 196.33) per 100 000 persons and 3.04 million people, while in men the estimates were 9.26 (3.36 to 22.97) per 100 000 persons and 0.36 million people, respectively. The United Arab Emirates, Barbados and Brazil had the highest SLE prevalence. In addition to regional and sex differences, age and prevalence estimation method (period or point prevalence) differences could also lead to variations in epidemiological SLE findings.
CONCLUSIONS
Epidemiological data on SLE are lacking for 79.8% of countries worldwide. The epidemiology of SLE varies substantially between different sex and age groups and is distributed unequally among geographical regions; specifically, SLE occurs more frequently in high-income countries.
Topics: Female; Humans; Male; Bayes Theorem; Incidence; Lupus Erythematosus, Systemic; Poland; Prevalence
PubMed: 36241363
DOI: 10.1136/ard-2022-223035 -
EBioMedicine Mar 2023To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing...
BACKGROUND
To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy.
METHODS
The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease outcomes in UK Biobank (N = 339,197). Identified associations were examined for replication in FinnGen (N = 260,405). We further performed tissue-specific gene expression MR, colocalization analyses, and MR with 247 blood biomarkers. A systematic review of randomized controlled trials (RCTs) on TYK2 inhibitor was performed to complement the genetic evidence.
FINDINGS
PheWAS-MR found that genetically-proxied TYK2 inhibition was associated with lower risk of a wide range of autoimmune diseases. The associations with hypothyroidism and psoriasis were confirmed in MR analysis of tissue-specific TYK2 gene expression and the associations with systemic lupus erythematosus, psoriasis, and rheumatoid arthritis were observed in colocalization analysis. There were nominal associations of genetically-proxied TYK2 inhibition with increased risk of prostate and breast cancer but not in tissue-specific expression MR or colocalization analyses. Thirty-seven blood biomarkers were associated with the TYK2 loss-of-function mutation. Evidence from RCTs confirmed the effectiveness of TYK2 inhibitors on plaque psoriasis and reported several adverse effects.
INTERPRETATION
This study supports TYK2 inhibitor as a potential treatment for psoriasis and several other autoimmune diseases. Increased pharmacovigilance is warranted in relation to the potential adverse effects.
FUNDING
None.
Topics: Male; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Autoimmune Diseases; Biomarkers; Psoriasis; Polymorphism, Single Nucleotide; TYK2 Kinase
PubMed: 36842216
DOI: 10.1016/j.ebiom.2023.104488 -
Neuroscience and Biobehavioral Reviews Mar 2018Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD)...
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD) thought to be caused by an autoimmune response to group A streptococcal infection. Based on this proposed pathophysiology, alternative treatments for acute-onset OCD have been introduced, including antibiotics and immunomodulatory interventions. However, the literature on treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking. We conducted a systematic review of articles in PubMed, Cochrane Library, and Scopus that addressed treatment for PANDAS and related disorders. Twelve research studies involving the following treatments met inclusion criteria: penicillin, azithromycin, intravenous immunoglobulin, plasma exchange, tonsillectomy, cognitive behavior therapy, NSAID and corticosteroids. In addition, 65 case reports in which patients received immunomodulatory treatments, antibiotics, and/or psychotropics were identified. We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Cognitive Behavioral Therapy; Humans; Obsessive-Compulsive Disorder; Plasma Exchange; Streptococcal Infections; Tonsillectomy
PubMed: 29309797
DOI: 10.1016/j.neubiorev.2018.01.001 -
Human Reproduction Update Jul 2019Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet abnormalities in the immune system have been suggested to explain the origin of ectopic endometrial tissues, and an association between endometriosis and autoimmune diseases has been proposed. Evaluation of current evidence investigating the association between endometriosis and autoimmune diseases from population-based studies will facilitate our understanding of the causes and consequences of endometriosis and provide a reference for better healthcare practices population-wide.
OBJECTIVE AND RATIONALE
The aim of this study was to systematically review the literature on population-based studies investigating an association between endometriosis and autoimmune diseases and to conduct a meta-analysis of combinable results to investigate the extent and robustness of evidence.
SEARCH METHODS
Four electronic databases were searched (MEDLINE, Embase, Web of Science, and CINAHL) from each database inception date until 7 April 2018. Search terms included a combination of database-specific controlled vocabulary terms and free-text terms relating to 'endometriosis' and 'autoimmune diseases'. Study inclusion criteria focused on peer-reviewed published articles that reported an association between endometriosis and autoimmune diseases, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. Quality assessment of included studies was performed based on GRADE criteria. Key information of eligible studies was abstracted into a standard form. Meta-analysis was performed for autoimmune diseases with combinable study results from at least three studies investigating an association with endometriosis. For cross-sectional studies and case-control studies, raw data from each study were documented to calculate a Mantel-Haenszel odds ratio with 95% CIs. For cohort studies, an inverse variance probability weighted model was used to pool study results to calculate a rate ratio (a hazard ratio or a standardized incidence rate) with 95% CIs.
OUTCOMES
A total of 26 published population-based cross-sectional, case-control, and cohort studies that investigated the association between endometriosis and autoimmune diseases met all eligible criteria and were included in the review. The studies quantified an association between endometriosis and several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison's disease. However, the quality of the evidence was generally poor due to the high risk of bias in the majority of the chosen study designs and statistical analyses. Only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease: SLE, SS, RA, CLD, MS, or IBD.
WIDER IMPLICATIONS
The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed. Scientists interested in research studies on endometriosis or autoimmune diseases should consider the likelihood of comorbidity when studying these two types of health conditions. Well-designed large prospective cohort studies with confounding control and mediation quantification, as well as genetic and biological studies, are needed to generate further insights into whether endometriosis is a risk factor for, or a consequence of, autoimmune diseases, and whether these two types of disorders share pathophysiological mechanisms even if they arise independently. Such insights may offer opportunities for the development of novel non-hormonal medications such as immuno-modulators or repurposing of existing immunomodulatory therapies for endometriosis.
Topics: Autoimmune Diseases; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Endometriosis; Female; Humans; Prospective Studies; Risk Factors; Sjogren's Syndrome
PubMed: 31260048
DOI: 10.1093/humupd/dmz014 -
Frontiers in Endocrinology 2021Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD.
RESULTS
The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like and were decreased in the AITD group, and harmful microbiota like was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as , , and was increased compared with the controls.
CONCLUSIONS
This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42021251557.
Topics: Case-Control Studies; Dysbiosis; Gastrointestinal Microbiome; Graves Disease; Hashimoto Disease; Humans; Risk Factors; Thyroiditis, Autoimmune
PubMed: 34867823
DOI: 10.3389/fendo.2021.774362