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Vaccines Sep 2022With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have... (Review)
Review
With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization.
PubMed: 36146522
DOI: 10.3390/vaccines10091444 -
Journal of Autoimmunity Oct 2022Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena.... (Review)
Review
Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with autoimmune phenomena. However, the interplay between COVID-19 or vaccination against SARS-CoV-2 and Berger glomerulonephritis or Henoch-Schönlein vasculitis, two diseases mediated by immunoglobulin A, has never been comprehensively investigated. Therefore, we carried out a systematic review of the literature on this topic. Following databases were used: Google Scholar, Excerpta Medica and the United States National Library of Medicine. Eighty-seven patients with immunoglobulin A-mediated diseases associated with SARS-CoV-2 infection or vaccination against coronavirus were sorted out (53% males, 47% females; 34 17-51 years of age, median and interquartile range): 47 cases of Berger glomerulonephritis and 40 of Henoch-Schönlein vasculitis. Approximately 50% (N = 24) of Berger glomerulonephritis and 10% (N = 4) of Henoch-Schönlein vasculitis patients presented with a pre-existing history of immunoglobulin A-mediated disease. Almost all cases of Berger glomerulonephritis were vaccine-associated (N = 44; 94%), while most cases of Henoch-Schönlein vasculitis were infection-associated (N = 23; 57%). Among vaccine-associated immunoglobulin A diseases, about 90% were associated to mRNA-based vaccines. Our analysis supports the hypothesis that COVID-19 and vaccination against SARS-CoV-2 may trigger or exacerbate an immunoglobulin A-mediated diseases.
Topics: Humans; Male; Female; Immunoglobulin A; COVID-19; SARS-CoV-2; IgA Vasculitis; Glomerulonephritis; Vaccination
PubMed: 36108473
DOI: 10.1016/j.jaut.2022.102899 -
Blood Advances May 2023Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to... (Meta-Analysis)
Meta-Analysis
Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Standard of Care; Neoplasm Recurrence, Local; Hemorrhage; Purpura, Thrombocytopenic, Idiopathic
PubMed: 36053773
DOI: 10.1182/bloodadvances.2022008443 -
Children (Basel, Switzerland) Jul 2022The external genitalia are notoriously implicated in every fifth male with Henoch−Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized.... (Review)
Review
The external genitalia are notoriously implicated in every fifth male with Henoch−Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized. To characterize the involvement of the external male genitalia in this vasculitis, we performed a systematic review of the literature. For the final analysis, we selected 85 reports published between 1972 and 2022, which reported on 114 Henoch−Schönlein cases (≤ 18 years, N = 104) with a penile (N = 18), a scrotal (N = 77), or both a penile and a scrotal (N = 19) involvement. The genital involvement mostly appeared concurrently with or after the cutaneous features of Henoch−Schönlein syndrome, while it preceded the presentation of Henoch−Schönlein syndrome in 10 cases. Patients with penile involvement (N = 37) presented with swelling (N = 26), erythema (N = 23), and purpuric rash (N = 15). Most patients were otherwise asymptomatic except for transient micturition disorders (N = 2) or priapism (N = 2). Patients with scrotal involvement (N = 96) presented with pain (N = 85), swelling (N = 79), erythema (N = 42), or scrotal purpura (N = 22). The following scrotal structures were often involved: scrotal skin (N = 83), epididymis (N = 49), and testes (N = 39). An ischemic testicular damage was noted in nine patients (four with torsion and five without). The scrotal skin involvement was mostly bilateral, while that of the epididymis and testis were mostly (p < 0.0001) unilateral (with a significant predilection for the left side). In conclusion, this analysis allows for better categorization of the involvement of external male genitalia in Henoch−Schönlein vasculitis. Scrotal involvement can result from skin inflammation, epididymitis, orchitis, or testicular ischemia.
PubMed: 36010045
DOI: 10.3390/children9081154 -
Hematology Reports Aug 2022The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic... (Review)
Review
INTRODUCTION
The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic microangiopathies. Our review with a brief case presentation highlights the increasing recognition of TTP in COVID-19 and describes its salient characteristics.
METHODS
We screened the available literature in PubMed, EMBASE, and Cochrane databases from inception until April 2022 of articles mentioning COVID-19-associated TTP in English language.
RESULTS
From 404 records, we included 8 articles mentioning data of 11 patients in our review. TTP was predominantly reported in females (72%) with a mean age of 48.2 years (SD 15.1). Dyspnea was the most common symptom in one third of patients (36.6%). Neurological symptoms were reported in 27.3% of cases. The time to diagnosis of TTP was 10 days (SD 5.8) from onset of COVID-19. All 11 cases underwent plasma exchange (PLEX), with a mean of 12 sessions per patient, whereas 6 cases received Rituximab (54.5%), and 3 received Caplacizumab (27.3%). One patient died from the illness.
CONCLUSION
This review of available literature highlights the atypical and refractory nature of COVID-19-associated TTP. It required longer sessions of PLEX, with half of the patients receiving at least one immunosuppressant.
PubMed: 35997402
DOI: 10.3390/hematolrep14030035 -
Annals of Translational Medicine Jun 2022We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially...
Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials.
BACKGROUND
We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially fatal disorder characterized by systemic microvascular thrombosis.
METHODS
Randomized controlled trials (RCTs) were conducted from PubMed, Embase, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases. RCTs of caplacizumab treatment for TPP were mainly included. Data from eligible studies were extracted and analyzed using relative effect sizes versus placebo use. The Cochrane bias assessment tool was used to assess the risk of bias of included studies, and the assessment results were presented graphically in Revman5.3.
RESULTS
Four RCTs with a total of 416 patients were included, all of which were of high quality. Caplacizumab was associated with improvements in platelet counts normalization time [weighted mean difference (WMD) -1.18, 95% confidence interval (CI): -2.55 to 0.19, I=69.9%, P=0.036], plasma exchange (PE) time (WMD -2.97, 95% CI: -4.44 to -1.50, I=8.2%, P=0.163) and hospital stay (WMD -2.88, 95% CI: -4.56 to -1.21, I=48.7%, P=0.036). In addition, the occurrence of adverse events was also investigated. The difference in mortality between the two groups was not statistically significant [relative risk (RR) 0.56, 95% CI: 0.18 to 1.72, I=22.7%, P=0.275], relapse (RR 0.68, 95% CI: 0.13 to 3.49, I=78.3%, P=0.01), or major thrombotic events (RR 1.01, 95% CI: 0.65 to 1.57, I=43.4%, P=0.151).
CONCLUSIONS
Caplacizumab shortens the platelet normalization time, PE time, and hospital stay in patients with TTP, and did not significantly increase the risk of adverse events. These results indicate that caplacizumab treatment provides significant benefits to patients with TTP. Even though this is evidence from RCTs, few original studies were included, so more multicenter RCTs are required.
PubMed: 35845542
DOI: 10.21037/atm-22-2847 -
Journal of Clinical Apheresis Oct 2022The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma...
OBJECTIVE
The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP).
METHODS
We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data.
RESULTS
We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin.
CONCLUSION
Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.
Topics: Albumins; Humans; Outcome Assessment, Health Care; Plasma Exchange; Prospective Studies; Purpura, Thrombotic Thrombocytopenic
PubMed: 35726507
DOI: 10.1002/jca.21996 -
Journal of Emergency Nursing Jul 2022Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19....
INTRODUCTION
Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19. COVID-19 has not been formally established in literature as a trigger for immunoglobulin A vasculitis. However, a main pathogenetic mechanism of COVID-19 is vascular damage, which makes it likely that vasculitis associated with COVID-19 (ie, COVID-19-mediated immunoglobulin A vasculitis) could be biologically plausible, with serious implications, especially for adults. The purpose of this review is to assist emergency nurses in gaining knowledge on the pathophysiology, symptoms, and treatment of COVID-19-mediated immunoglobulin A vasculitis.
METHODS
A systematic search for case reports of COVID-19-associated immunoglobulin A vasculitis was conducted in the PubMed and Scopus electronic databases. The search terms used were COVID-19, coronavirus 2019, SARS COVID-19, and IgA vasculitis, case reports. The following were the inclusion criteria: publication dates between December 1, 2019, and December 1, 2021; full-text article, clinical case studies, and letters to the editor available electronically in English. The following were exclusion criteria: a summary of reports and newspaper publications.
RESULTS
Only 13 clinical cases met the inclusion criteria. The median age of patients described in the case reports were 38.1 years. Of them, 3 children were less than 5 years old. Twelve patients were male. In 7 of 13 cases of immunoglobulin A vasculitis, renal involvement was found.
DISCUSSION
The analysis of published clinical cases showed that COVID-19-associated immunoglobulin A vasculitis affected mostly adults and was characterized by a more severe course because of renal involvement. COVID-19 may be a possible trigger for immunoglobulin A-related disorders. More research is needed to better understand the relationship between immunoglobulin A vasculitis and COVID-19.
Topics: Adult; COVID-19; Child; Child, Preschool; Female; Humans; IgA Vasculitis; Immunoglobulin A; Male; Vasculitis
PubMed: 35691763
DOI: 10.1016/j.jen.2022.05.002 -
Scientific Reports Jun 2022Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic... (Meta-Analysis)
Meta-Analysis
Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.
Topics: Autoantibodies; Autoimmunity; Gene Frequency; HLA-DRB1 Chains; Humans; Immunoglobulin G; Pemphigus
PubMed: 35654912
DOI: 10.1038/s41598-022-13042-2 -
Oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19): A systematic review.PloS One 2022We reviewed the prevalence, the likely aetiopathogenesis, and the management of oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19), caused by...
We reviewed the prevalence, the likely aetiopathogenesis, and the management of oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). English language manuscripts searched using standard databases yielded 26 articles that met the inclusion criteria. In total, 169 cases (75 females; 94 males) from 15 countries with a spectrum of COVID-19 severities were reviewed. Gustatory perturbations were prevalent in over 70%. Mucocutaneous manifestations were reported predominantly on the tongue, palate, buccal mucosa, gingivae, and lips and included ulcers, blisters, erosions, papillary hyperplasia, macules, glossitis, and mucositis. Ulcerative lesions, present in over 50 percent, were the most common oral manifestation. Lesions resembling candidal infections, with burning mouth, were prevalent in 19%. Petechiae and angina bullosa were generally seen, subsequent to COVID-19 therapies, in 11%. Ulcerated, necrotic gingivae were documented in severely ill with poor oral hygiene. These manifestations, present across the COVID-19 disease spectrum, were commonly associated with the immunosuppressed state and/ or the concurrent antimicrobial/steroidal therapies. In summary, a wide variety of orofacial mucocutaneous lesions manifest in COVID-19. They are likely to be secondary to the disease-associated immune impairment and/or pharmaco-therapy rather than a direct result of SARS-CoV-2 infection per se.
Topics: COVID-19; Female; Humans; Male; SARS-CoV-2
PubMed: 35648785
DOI: 10.1371/journal.pone.0265531