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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 -
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 -
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 -
Acta Dermato-venereologica Aug 2020Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa....
Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa. Drug-associated bullous pemphigoid (DABP) is a term used to describe instances of bullous pemphigoid demonstrating clinical, histological, or immunopathological features identical or similar to those of the idiopathic form of bullous pemphigoid, associated with the systemic ingestion, or topical application of particular drugs. In this study, we conducted a comprehensive search of the literature according to PRISMA guidelines and a total of 170 publications were included in the final qualitative analysis. In conclusion, 89 drugs were implicated in DABP. The strongest evidence for DABP is seen with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, penicillin and derivatives. An appreciation of the medications associated with bullous pemphigoid enables clinicians to identify potential cases of DABP earlier and cease the offending medication.
Topics: Blister; Humans; Pemphigoid, Bullous; Pharmaceutical Preparations; Pruritus; Skin
PubMed: 32176310
DOI: 10.2340/00015555-3457 -
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 -
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 -
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 -
JAMA Psychiatry Dec 2021Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of the association. It is also unclear whether the link is largely due to subsyndromal depression or holds true for clinical depression.
OBJECTIVE
To estimate the association of hypothyroidism and clinical depression in the general population.
DATA SOURCES
PubMed, PsycINFO, and Embase databases were searched from inception until May 2020 for studies on the association of hypothyroidism and clinical depression.
STUDY SELECTION
Two reviewers independently selected epidemiologic and population-based studies that provided laboratory or International Statistical Classification of Diseases and Related Health Problems diagnoses of hypothyroidism and diagnoses of depression according to operationalized criteria (eg, Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases and Related Health Problems) or cutoffs in established rating scales.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and evaluated studies based on the Newcastle-Ottawa Scale. Summary odds ratios (OR) were calculated in random-effects meta-analyses.
MAIN OUTCOMES AND MEASURES
Prespecified coprimary outcomes were the association of clinical depression with either hypothyroidism or autoimmunity.
RESULTS
Of 4350 articles screened, 25 studies were selected for meta-analysis, including 348 014 participants. Hypothyroidism and clinical depression were associated (OR, 1.30 [95% CI, 1.08-1.57]), while the OR for autoimmunity was inconclusive (1.24 [95% CI, 0.89-1.74]). Subgroup analyses revealed a stronger association with overt than with subclinical hypothyroidism, with ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28), respectively. Sensitivity analyses resulted in more conservative estimates. In a post hoc analysis, the association was confirmed in female individuals (OR, 1.48 [95% CI, 1.18-1.85]) but not in male individuals (OR, 0.71 [95% CI, 0.40-1.25]).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. Autoimmunity alone may not be the driving factor in this comorbidity.
Topics: Depressive Disorder; Female; Humans; Hypothyroidism; Male; Sex Factors
PubMed: 34524390
DOI: 10.1001/jamapsychiatry.2021.2506 -
Deutsches Arzteblatt International Jan 2023As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a...
BACKGROUND
As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19).
METHODS
The data presented here were derived from a systematic literature review.
RESULTS
PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment.
CONCLUSION
The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.
Topics: Adult; Adolescent; Child; Humans; COVID-19; SARS-CoV-2; Inflammation; Pandemics; Vaccination
PubMed: 36633452
DOI: 10.3238/arztebl.m2022.0409