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American Journal of Clinical Dermatology Nov 2023Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases present in patients with AA. However, some studies have conflicting results, and analyses conducting a comprehensive approach are lacking.
OBJECTIVE
The aim of our study was to provide an updated systematic review and meta-analysis of medical comorbidities associated with AA.
METHODS
We searched PubMed, Embase, and Web of Science for case-control, cross-sectional, and cohort studies investigating medical comorbidities in AA published from inception through 1 February 2023.
RESULTS
We screened 3428 abstracts and titles and reviewed 345 full text articles for eligibility. Ultimately, 102 studies were analyzed, comprising 680,823 patients with AA and 72,011,041 healthy controls. Almost all included studies (100 of 102 studies) were of satisfactory to high quality (Newcastle-Ottawa scale score ≥ 4). Among patients with AA, comorbidities with the highest odds ratios (OR) compared with healthy controls and data available from more than one study included vitamin D deficiency (OR 10.13, 95% CI 4.24-24.20), systemic lupus erythematous (OR 5.53, 95% CI 3.31-9.23), vitiligo (OR 5.30, 95% CI 1.86-15.10), metabolic syndrome (OR 5.03, 95% CI 4.18-6.06), and Hashimoto's thyroiditis (OR 4.31, 95% CI 2.51-7.40). AA may be a protective factor for certain disorders, for which the AA group had lower odds compared with healthy controls, such as irritable bowel syndrome (OR 0.38, 95% CI 0.14-0.99) and colorectal cancer (OR 0.61, 95% CI 0.42-0.89).
CONCLUSION
These findings corroborate and contextualize the risks across comorbidities for patients with AA. Further work should be done to identify the underlying pathophysiology and understand appropriate screening criteria.
Topics: Humans; Alopecia Areata; Cross-Sectional Studies; Comorbidity; Autoimmune Diseases
PubMed: 37464249
DOI: 10.1007/s40257-023-00805-4 -
Brain, Behavior, and Immunity Oct 2023Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses.
OBJECTIVES
To systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD.
METHODS
Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.
RESULTS
The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p = 0.027).
CONCLUSION
In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity.
Topics: Humans; Bipolar Disorder; Lipid Peroxidation; Depression; Antioxidants; Depressive Disorder, Major; Aldehydes; Biomarkers; Cholesterol; Lipids
PubMed: 37557967
DOI: 10.1016/j.bbi.2023.08.007 -
BMJ Open Respiratory Research Nov 2023Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been linked with ILD presentation and adverse outcomes, the association of anti-Ro52 antibody with ILD is less studied. Hence, we investigated this association in various autoimmune diseases in the current study.
DESIGN
We designed a systematic review and meta-analysis and did a comprehensive search from inception until 2 January 2023.
DATA SOURCES
A systematic search was conducted in four electronic databases: PubMed, Web of Science, Scopus and Embase.
ELIGIBILITY CRITERIA
Observational studies that reported ILD diagnosis (outcome) and anti-Ro antibody (exposure) status in any autoimmune conditions (population) were included. The association between rapidly progressive ILD (RP-ILD) and anti-Ro52 was studied in idiopathic inflammatory myopathies (IIM).
DATA EXTRACTION AND SYNTHESIS
Collected data included study characteristics and ORs with 95% CIs. Quality assessment was performed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. Random effects meta-analysis was used to pool the effect estimates.
RESULTS
A total of 2353 studies were identified, from which 59 articles met the eligibility criteria. Anti-Ro52/SSA positivity was associated with ILD in all autoimmune disease subgroups: IIM (OR=3.08; 95% CI: 2.18 to 4.35; p value<0.001; I=49%), systemic lupus (OR=2.43; 95% CI: 1.02 to 5.79; p=0.046; I=71%), Sjogren (OR=1.77; 95% CI: 1.09 to 2.87; p=0.021; I=73%), systemic sclerosis (OR=1.71; 95% CI: 1.04 to 2.83; p=0.036; I=43%), mixed connective tissue disease (OR=3.34; 95% CI: 1.82 to 6.13; p<0.001; I=0%). Additionally, anti-Ro52-positive myopathy patients were more likely to have simultaneous RP-ILD (OR=2.69; 95% CI:1.50 to 4.83; p<0.001; I=71%).
CONCLUSION
Anti-Ro52/SSA positivity is associated with a higher frequency of ILD diagnosis in various autoimmune diseases. Anti-Ro52/SSA is also linked with a more severe lung involvement (RP-ILD). Future studies can investigate the benefits of screening for anti-Ro52 and its association with ILD development.
PROSPERO REGISTRATION NUMBER
CRD42022381447.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Autoimmune Diseases; Lung Diseases, Interstitial; Scleroderma, Systemic; Myositis
PubMed: 38030264
DOI: 10.1136/bmjresp-2023-002076 -
Journal of Clinical Neuromuscular... Dec 2023Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle...
OBJECTIVES
Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies.
RESULTS
We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases).
CONCLUSIONS
IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Topics: Male; Middle Aged; Humans; Female; Isaacs Syndrome; Thymoma; Anticonvulsants; Thymus Neoplasms; Autoantibodies; Potassium Channels, Voltage-Gated; Carbamazepine; Receptors, Cholinergic; Steroids; Recurrence
PubMed: 37962197
DOI: 10.1097/CND.0000000000000460 -
Cureus Jul 2023Autoimmune diseases manifest in genetically predisposed individuals exposed to certain triggers that aggravate immune dysfunction and result in an exacerbated immune... (Review)
Review
Autoimmune diseases manifest in genetically predisposed individuals exposed to certain triggers that aggravate immune dysfunction and result in an exacerbated immune response in the form of hyperactivity to both the humoral and cell-mediated response. The devastating reality apart from the severity of the disease is that multiple immune diseases could co-occur, increasing the patient's physical, psychological, and financial burden. Autoimmune diseases are utterly deranging. One of the dreadful autoimmune diseases is systemic lupus erythematosus (SLE). SLE is a rheumatological disease that affects multiple systems, and there are no predictors to know which system will be affected in the future. It could affect the mucocutaneous system. It could also present with hematological, rheumatological, neuronal, renal, pulmonary, and cardiac manifestations. SLE is prevalent in females, predominantly in the childbearing age group. The pharmacological therapy and bombarding pathophysiology of the disease lead to obstetrical and gynecological complications such as infertility, abortion, miscarriage, and stillbirth. Over the past decade, the autoimmune disease comorbidity increased eminently. One of the common associations is rheumatological diseases (like rheumatoid arthritis, Sjogren syndrome, and SLE) with gynecological diseases (e.g., endometriosis and uterine fibroids). SLE and endometriosis have strong associations, and the prevalence of each condition is relatively high among the female population. is a chronic disease triggered by inflammation, hormonal milieu, and other predisposing factors that lead to the fibrous tissue that lines the uterus (endometrial tissue) to be implanted at sites other than the uterus, commonly in the peritoneum and mesentery. The pathogenesis of this association remains unexplained. The approved theory is that their immune dysfunction is summarized by the elevated humoral and cell-mediated response, which leads to an attack to the epithelium, mesothelium, and Serosa and leads to fibrous tissue deposition in different sites other than the uterus. Statistical evaluations have shown a remarkable association between autoimmune diseases and both gynecological and nongynecological diseases.
PubMed: 37621818
DOI: 10.7759/cureus.42362 -
Autoimmunity Reviews Dec 2023Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence regarding their efficacy and safety in systemic and cutaneous lupus erythematosus.
METHODS
We searched for systemic and cutaneous lupus erythematosus patients who were treated with JAK inhibitors in PubMed, Embase, Web of Science, and the Cochrane Library until February 28, 2023. The quality of clinical trials was assessed using the Cochrane risk-of-bias tool. Meta-analysis was conducted when at least three studies had comparable measures of outcome. If meta-analysis was not feasible, a descriptive review was carried out.
RESULTS
We included 30 studies, consisting of 10 randomized controlled trials and 20 case series or reports, with a total of 2,460 patients. JAK inhibitors were found to be more effective than placebo in systemic lupus erythematosus (SLE) based on the percentage of achieving SLE Responder Index (SRI)-4 response (RR = 1.18; 95% CI 1.07 to 1.31; p = 0.001), British Isles Lupus Assessment Group -based Composite Lupus Assessment (BICLA) response (RR = 1.16; 95% CI 1.02 to 1.31; p = 0.02), Lupus Low Disease Activity State (LLDAS) (RR = 1.28; 95% CI 1.07 to 1.54; p = 0.008), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) remission of arthritis or rash (RR = 1.09; 95% CI 1.00 to 1.18; p = 0.04), particularly in treating musculoskeletal and mucocutaneous involvement. However, the effect of JAK inhibitors on cutaneous lupus erythematosus was uncertain. JAK inhibitors and placebo had a similar incidence of adverse events (RR = 1.01; 95% CI 0.97 to 1.04; p = 0.65).
CONCLUSION
JAK inhibitors could be a potential treatment option for systemic and cutaneous lupus erythematosus, particularly in treating cutaneous and musculoskeletal lesions of SLE. JAK inhibitors had a safe profile.
Topics: Humans; Janus Kinase Inhibitors; Lupus Erythematosus, Systemic; Arthritis; Lupus Erythematosus, Cutaneous; Skin; Treatment Outcome
PubMed: 37678618
DOI: 10.1016/j.autrev.2023.103440 -
Autoimmunity Reviews Feb 2024Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship with non-infectious uveitis (NIU), an inflammatory ocular disorder, remains inconclusive.
METHODS
A systematic search was conducted in three databases from database inception until May 8, 2023, to investigate the potential relationship between vitamin D deficiency and NIU. We included observational studies reporting the measurement of vitamin D levels in patients with NIU and healthy controls without restriction of language or date of publication. Three pairs of authors independently screened the title and abstracts for potential eligibility and then in full text. A third author resolved disagreements. Three pairs of independent reviewers abstracted the data from the fully reviewed records and evaluated the risk of bias. We followed The MOOSE and PRISMA guidelines. Random effects meta-analyses were used for primary analysis. Studies not included in the meta-analysis were summarized descriptively. This review was registered in PROSPERO: CRD42022308105.
FINDINGS
Of 933 records screened, 11 studies were included, and five were meta-analyzed, encompassing 354 cases and 5728 controls (mean participant age ranging from 7.1 to 58.9 years). Patients with vitamin D deficiency exhibited an Odds Ratio of 2.04 (95% CI = 1.55-2.68, P < 0.00001) for developing NIU compared to controls. Overall, potential sources of bias were low across most studies.
INTERPRETATION
Our findings suggest that vitamin D may play an essential role in the pathophysiology of NIU. While the included studies demonstrated generally low potential bias, additional rigorous prospective studies are necessary to confirm these findings and further elucidate the underlying mechanisms involved. Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing NIU if substantiated. Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for NIU.
Topics: Humans; Uveitis; Vitamin D; Vitamin D Deficiency
PubMed: 38052262
DOI: 10.1016/j.autrev.2023.103497 -
Viruses Jul 2023It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as... (Review)
Review
It is known that SARS-CoV-2 infection can result in gastrointestinal symptoms. For some, these symptoms may persist beyond acute infection, in what is known as 'post-COVID syndrome'. We conducted a systematic review to examine the prevalence of persistent gastrointestinal symptoms and the incidence of new gastrointestinal illnesses following acute SARS-CoV-2 infection. We searched the scientific literature using MedLine, SCOPUS, Europe PubMed Central and medRxiv from December 2019 to July 2023. Two reviewers independently identified 45 eligible articles, which followed participants for various gastrointestinal outcomes after acute SARS-CoV-2 infection. The study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tools. The weighted pooled prevalence for persistent gastrointestinal symptoms of any nature and duration was 10.8% compared with 4.9% in healthy controls. For seven studies at low risk of methodological bias, the symptom prevalence ranged from 0.2% to 24.1%, with a median follow-up time of 18 weeks. We also identified a higher risk for future illnesses such as irritable bowel syndrome, dyspepsia, hepatic and biliary disease, liver disease and autoimmune-mediated illnesses such as inflammatory bowel disease and coeliac disease in historically SARS-CoV-2-exposed individuals. Our review has shown that, from a limited pool of mostly low-quality studies, previous SARS-CoV-2 exposure may be associated with ongoing gastrointestinal symptoms and the development of functional gastrointestinal illness. Furthermore, we show the need for high-quality research to better understand the SARS-CoV-2 association with gastrointestinal illness, particularly as population exposure to enteric infections returns to pre-COVID-19-restriction levels.
Topics: Humans; Incidence; COVID-19; Prevalence; SARS-CoV-2; Inflammatory Bowel Diseases
PubMed: 37631968
DOI: 10.3390/v15081625 -
Neurogastroenterology and Motility Sep 2023Dermatomyositis (DM) is a rare autoimmune disease characterized by distinctive skin rash, muscle inflammation with symmetrical and progressive muscle weakness, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dermatomyositis (DM) is a rare autoimmune disease characterized by distinctive skin rash, muscle inflammation with symmetrical and progressive muscle weakness, and elevated serum levels of muscle-associated enzymes. DM may affect skeletal muscles involved in swallowing, leading to dysphagia, which can negatively impact individual's physical and psychosocial well-being. Despite this, dysphagia in patients with DM remains poorly understood. This systematic review and meta-analysis aimed to evaluate the prevalence and clinical features of dysphagia in patients with DM and juvenile DM (JDM).
METHODS
Four electronic databases were systematically searched until September 2022. Studies with patients with DM or JDM and dysphagia were included. The pooled prevalence of all included studies was calculated, and the clinical characteristics of dysphagia were qualitatively analyzed.
KEY RESULTS
Thirty-nine studies with 3335 patients were included. The overall pooled prevalence of dysphagia was 32.3% (95% CI: 0.270, 0.373) in patients with DM and 37.7% (95% CI: -0.031, 0.785) in patients with JDM. Subgroup analyses revealed that Sweden had the highest prevalence (66.7% [95% CI: 0.289, 1.044]), whereas Tunisia had the lowest prevalence (14.3% [95% CI: -0.040, 0.326]). Moreover, South America had the highest prevalence (47.0% [95% CI: 0.401, 0.538]), whereas Africa had the lowest prevalence (14.3% [95% CI: -0.040, 0.326]). Dysphagia in patients with DM and JDM was characterized by both oropharyngeal and esophageal dysfunctions, with predominant difficulties in motility.
CONCLUSIONS & INFERENCES
Our findings showed that dysphagia affects one in three patients with DM or JDM. However, the documentation on the diagnosis and management of dysphagia in the literature is inadequate. Our results highlighted the need to use both clinical and instrumental assessments to evaluate swallowing function in this population.
Topics: Humans; Deglutition Disorders; Dermatomyositis; Prevalence; Esophageal Diseases; Deglutition
PubMed: 37010885
DOI: 10.1111/nmo.14572 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983