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Internal and Emergency Medicine Jan 2024Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small-vessel vasculitis (IgAV) that typically presents with a variable tetrad of symptoms. HSP if often...
BACKGROUND
Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small-vessel vasculitis (IgAV) that typically presents with a variable tetrad of symptoms. HSP if often preceded by respiratory tract infections, vaccinations, drugs or malignancies. During the recent COVID-19 pandemic multiples cases of HSP have been described after both infection and vaccination for SARS-CoV2. This study aims to perform a systematic review of literature and describe an additional complicated case of de-novo HSP appeared after the administration of the third dose of a mRNA-SARS-CoV2 vaccination.
METHODS
Electronic bibliographic research was performed to identify all the original reports describing cases of de-novo HSP or IgAV appeared after respiratory infection or vaccine administration for SARS-CoV2. We included all case series or case reports of patients who respected our inclusion and exclusion criteria.
RESULTS
Thirty-eight publications met our pre-defined inclusion criteria, for an overall number of 44 patients. All patients presented with palpable purpura variable associated with arthralgia, abdominal pain or renal involvement. Increased levels of inflammation markers, mild leukocytosis and elevated D-dimer were the most common laboratory findings. Up to 50% of patients presented proteinuria and/or hematuria. Almost all skin biopsies showed leukocytoclastic vasculitis, with IgA deposits at direct immunofluorescence in more than 50% of cases.
CONCLUSIONS
Our results suggest that the immune response elicited by SARS-CoV2 vaccine or infection could play a role in the development of HSP. Current research suggests a possible role of IgA in immune hyperactivation, highlighted by early seroconversion to IgA found in some COVID-19 patients who develop IgA vasculitis.
Topics: Humans; COVID-19; IgA Vasculitis; Immunoglobulin A; Pandemics; RNA, Viral; SARS-CoV-2; Vaccines
PubMed: 37500944
DOI: 10.1007/s11739-023-03366-w -
International Journal of Technology... Jul 2023Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematological disease whose clinical management includes caplacizumab along with plasma exchange and...
Effectiveness and safety of caplacizumab in acquired thrombotic thrombocytopenic purpura: health technology assessment and classification according to the methodology established in Colombia.
OBJECTIVES
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare hematological disease whose clinical management includes caplacizumab along with plasma exchange and immunosuppression, according to international guidelines. Caplacizumab has been available in Colombia since 2022. This study seeks to determine the therapeutic classification of caplacizumab according to the methodology of the Instituto de Evaluación Tecnológica en Salud.
METHODS
The classification was carried out through a deliberative process following the modified Delphi technique, with a panel of experts, made up of four hemato-oncologists, a pharmaceutical chemist, and a patient. The results of effectiveness and safety obtained through a systematic review, therapeutic thresholds (clinical significance), and degree of acceptability (willingness to use the technology) were used for the classification.
RESULTS
Fourteen effectiveness and safety outcomes were submitted for the classification process. Caplacizumab showed clinical significance for some effectiveness outcomes, was not considered inferior in terms of safety, and displayed acceptability of use. Through consensus, the panel determined that caplacizumab plus the standard regimen is superior to the standard regimen in terms of treatment response and composite outcome, and no different for the other effectiveness and safety outcomes. Likewise, in overall terms, the panel determined that caplacizumab together with the standard regimen is superior to the standard regimen.
CONCLUSION
Treatment with caplacizumab together with the standard regimen was considered superior to the standard regimen for the treatment of patients with aTTP, as it showed clinically significant benefits in critical outcomes for decision making, and a safety profile no different to its comparator.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Technology Assessment, Biomedical; Colombia
PubMed: 37476982
DOI: 10.1017/S0266462323000442 -
Journal of Ethnopharmacology Dec 2023Spatholobi caulis (SC), the dried vine stem of Spatholobus suberectus Dunn, is known as Ji Xue Teng in China, and has long been used as traditional Chinese medicine... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Spatholobi caulis (SC), the dried vine stem of Spatholobus suberectus Dunn, is known as Ji Xue Teng in China, and has long been used as traditional Chinese medicine (TCM) to treat anaemia, menstrual abnormalities, rheumatoid arthritis, purpura, etc. AIM OF THE REVIEW: The aim of this review is to provide a systematic and updated summary of the traditional uses, chemical constituents, biological activities and clinical applications of SC. In addition, several suggestions for future research on SC are also proposed.
MATERIALS AND METHODS
Extensive information and data on SC were obtained from electronic databases (ScienceDirect, Web of Science, PubMed, CNKI, Baidu Scholar, Google Scholar, ResearchGate, SpringerLink and Wiley Online). Additional information was collected from Ph.D. and MSc dissertations, published books, and classic material medica.
RESULTS
To date, phytochemical studies have revealed that approximately 243 chemical ingredients have been isolated from SC and identified, including flavonoids, glycosides, phenolic acids, phenylpropanoids, volatile oils, sesquiterpenoids and other compounds. Many studies have indicated that extracts and pure constituents from SC possess a wide spectrum of in vitro and in vivo pharmacological effects, such as anti-tumour, haematopoietic, anti-inflammatory, antidiabetic, antioxidant, antiviral and antibacterial effects, as well as other activities. SC could be applied to the treatment of leukopenia, aplastic anemic, endometriosis, etc. according to the clinical reports. The traditional efficacies of SC is due to the biological functions of its chemical compounds, especially flavonoids. However, research investigating the toxicological effects of SC is relatively limited.
CONCLUSIONS
SC is widely used in TCM formulae and its some traditional efficacies has been confirmed by extensive recent pharmacological and clinical studies. Most the biological activities of the SC may be attributed to flavonoids. However, in-depth studies on the molecular mechanisms of the effective ingredients and extracts of SC are limited. Further systematic studies focusing on pharmacokinetics, toxicology and quality control are needed to ensure the effective and safe application of SC.
Topics: Ethnopharmacology; Medicine, Chinese Traditional; Phytotherapy; Drugs, Chinese Herbal; Phytochemicals; Flavonoids; Plant Extracts
PubMed: 37393029
DOI: 10.1016/j.jep.2023.116854 -
Journal of Clinical Medicine Jun 2023Eltrombopag is an agonist that binds to the membrane-bound domain of the thrombopoietin receptor used in immune thrombocytopenic purpura (ITP). We conducted a... (Review)
Review
Eltrombopag is an agonist that binds to the membrane-bound domain of the thrombopoietin receptor used in immune thrombocytopenic purpura (ITP). We conducted a meta-analysis of randomized controlled trials to assess the efficacy and safety of eltrombopag in adults and children with refractory ITP. Adults who received eltrombopag had a significantly better platelet response (relative risk [RR], 3.65; 95% confidence interval [CI], 2.39-5.55), but there were no differences in the incidence of bleeding (RR, 0.8; 95% CI, 0.52-1.22) and adverse effects (RR, 0.99; 95% CI, 0.55-1.78) compared with the placebo. In children, there was no difference between eltrombopag and placebo for a platelet response >50,000/mm (RR, 3.93; 95% CI, 0.56-27.79) and the number of adverse events (RR, 0.99; 95% CI, 0.25-1.49); however, a lower incidence of bleeding was observed (RR, 0.47; 95% CI, 0.27-0.83). Treatment with eltrombopag protected adults and children from severe disease and death.
PubMed: 37373566
DOI: 10.3390/jcm12123872 -
Annals of Hematology Jul 2023All-trans retinoic acid (ATRA) application is a novel treatment approach for primary immune thrombocytopenia (ITP). This study aimed to evaluate the efficacy and safety... (Meta-Analysis)
Meta-Analysis
All-trans retinoic acid (ATRA) application is a novel treatment approach for primary immune thrombocytopenia (ITP). This study aimed to evaluate the efficacy and safety of ATRA in the treatment of ITP. The databases of PubMed (MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Internet were searched on August 5, 2022, to find randomized controlled trials (RCTs) and observational studies. Five observational studies and four RCTs from China were included, and 760 Chinese patients were analyzed. In the five observational studies, the pooled overall response rate (ORR) and complete response rate (CRR) were 59.5% (95% confidence interval [CI], 52.4-66.4%) and 20.6% (95% CI, 14.3-27.6%), respectively. In the selected four RCTs, the pooled odds ratios for sustained response rate, ORR, and CRR were 3.00 (95% CI, 1.97-4.57; P < 0.01), 3.21 (95% CI, 2.15-4.78; P < 0.01), and 2.12 (95% CI, 1.17-3.86; P = 0.01), respectively. ATRA was associated with a reduction in relapse rate and salvage treatment rate (odds ratio, 0.30; 95% CI, 0.18-0.50; P < 0.01; 0.36; 95% CI, 0.23-0.56; P < 0.01, respectively). The pooled odds ratios for grade 1-2 dry skin, headache (or dizziness), and rash acneiform were 49.99 (95% CI, 16.05-155.67; P < 0.01), 1.75 (95% CI, 0.98-3.12; P = 0.06), and 0.37 (95% CI, 0.10-1.34; P = 0.13), respectively. This study suggests that ATRA may significantly improve the initial and long-term response of patients with ITP.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Tretinoin; Chronic Disease; Remission Induction; China
PubMed: 37166528
DOI: 10.1007/s00277-023-05263-w -
Expert Review of Hematology May 2023Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in iTTP. However, the effect on different populations remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of caplacizumab for treating iTTP.
MATERIALS AND METHODS
We searched PubMed, Embase, and the Cochrane Library for studies until 24 March 2023. Participants were hospitalized patients with iTTP. Interventions included caplacizumab versus placebo or standard of care (SOC). Outcomes assessed included all-cause mortality, exacerbation, relapse, refractory, time-to-platelet-count-recovery, length of TPE and hospital stay, bleeding, and thrombosis.
RESULTS
A total of 1119 patients from eight studies were subjected to meta-analysis. The results of the meta-analysis showed that iTTP patients treated with caplacizumab achieved a reduction in mortality (RR 0.38, 95% CI: 0.19-0.75), exacerbation (RR 0.29, 95% CI: 0.14-0.61) and refractory (RR 0.50, 95% CI: 0.31-0.81). Besides, adding caplacizumab to SOC was associated with a shorten time-to-platelet-count-recovery (MD - 2.31, 95% CI: -3.86 to -0.77) and length of TPE (MD - 4.61, 95% CI: -6.20 to -3.02). In terms of safety, the bleeding rate was higher in the caplacizumab group (RR 1.57, 95% CI: 1.21-2.02), while there was no significant difference in hospital stay and thrombosis between the two groups.
CONCLUSIONS
Caplacizumab is an effective treatment for patients with iTTP, especially in reducing all-cause mortality, exacerbations, refractoriness, and the time-to-platelet-count-recovery. Although the risk of bleeding may be increased, it is generally modest and manageable.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Hemorrhage; Single-Domain Antibodies; Plasma Exchange
PubMed: 37045600
DOI: 10.1080/17474086.2023.2202850 -
Expert Opinion on Pharmacotherapy Apr 2023In this paper, we systematically review the efficacy and safety of thrombopoietin receptor agonists (TPORAs) for treatment of persistent and chronic immune... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
In this paper, we systematically review the efficacy and safety of thrombopoietin receptor agonists (TPORAs) for treatment of persistent and chronic immune thrombocytopenia (ITP) in children and adults.
METHODS
We searched PubMed, MEDLINE, ScienceDirect, Scopus, EMbase and the Cochrane Library to collect randomized controlled trials (RCTs) of TPO-RAs which including avatrombopag hetrombopag eltrombopag and romiplostim treated persistent and chronic ITP from their earliest records to February 2022.
RESULTS
We included 15 RCTs with a total of 1563 patients. There were ten trials of adults and five trials of children. The results of meta-analysis showed that in adult patients, patients treated with TPO-RAs had longer duration of platelet response, higher platelet response rate, lower use of rescue therapy, and lower incidence of bleeding events, and similar incidence of adverse events compared with placebo. Except for the incidence of any bleeding, the results in children were consistent with those in adults. The network meta-analysis of data on overall platelet response rates in adults showed that avatrombopag was more effective than eltrombopag and hetrombopag.
CONCLUSIONS
TPO-RAs has better efficacy and higher safety in the treatment of ITP. And the overall response rate of avatrombopag in adults was higher than that in eltrombopag and hetrombopag.
Topics: Humans; Adult; Child; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Hydrazines; Benzoates; Hemorrhage; Recombinant Fusion Proteins
PubMed: 37010022
DOI: 10.1080/14656566.2023.2198089 -
Transfusion and Apheresis Science :... Jun 2023Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE.
METHOD
The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients' data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis.
RESULTS
A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group.
CONCLUSION
Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Prospective Studies; Treatment Outcome; Plasma Exchange
PubMed: 36878741
DOI: 10.1016/j.transci.2023.103661 -
The Cochrane Database of Systematic... Feb 2023IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel... (Review)
Review
BACKGROUND
IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for (1) the prevention of severe kidney disease in people with IgAV with or without kidney involvement at onset, (2) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in IgAV, and (3) the prevention of recurrent episodes of IgAV-associated kidney disease.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 2 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in IgAV compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, assessed the risk of bias and extracted data from each study. Statistical analyses were performed using the random-effects model, and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Twenty studies (1963 enrolled participants) were identified; one three-arm study has been assessed as two studies. Nine studies were at low risk of bias for sequence generation (selection bias), and nine studies were at low risk of bias for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and outcome assessment (detection bias) was at low risk of bias in four and seven studies, respectively. Nine studies reported complete outcome data (attrition bias), while 10 studies reported expected outcomes, so were at low risk of reporting bias. Five studies were at low risk of other bias. Eleven studies evaluated therapy to prevent persistent kidney disease in IgAV with or without kidney involvement at presentation. There was probably no difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32) or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of IgAV compared with placebo or supportive treatment (moderate certainty evidence). There may be no differences in the risk of any persistent kidney disease with antiplatelet therapy (three studies) or heparin (two studies) in children with or without any kidney disease at study entry, although heparin may reduce the risk of proteinuria by three months compared with placebo or no specific treatment (2 studies, 317 children: RR 0.47, 95% CI 0.31 to 0.73). One study comparing montelukast with placebo found no differences in outcomes as assessed by severity scale scores. Nine studies examined the treatment of severe IgAV-associated kidney disease. In two studies (one involving 56 children and the other involving 54 adults), there may be no differences in efficacy outcomes or adverse effects with cyclophosphamide compared with placebo or supportive treatment. In two studies, there may be no differences in the numbers achieving remission of proteinuria with intravenous (IV) cyclophosphamide compared with mycophenolate mofetil (MMF) (65 children evaluated) or tacrolimus (142 children evaluated). In three small studies comparing cyclosporin with methylprednisolone (15 children), MMF with azathioprine (26 children), or MMF with leflunomide (19 children), it is unclear whether the treatment had any effect on the numbers in remission or the degree of proteinuria between treatment groups because of small numbers of included participants. In one study comparing plasmapheresis, cyclophosphamide and methylprednisolone with cyclophosphamide and methylprednisolone, there may be no difference in the numbers achieving remission. One study compared fosinopril with no specific therapy and reported fosinopril reduced the number of participants with proteinuria. No studies were identified that evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of IgAV.
AUTHORS' CONCLUSIONS
There are no substantial changes in conclusions from this update compared with the initial review or the previous update despite the addition of five studies. From generally low to moderate certainty evidence, we found that there may be little or no benefit in the use of corticosteroids or antiplatelet agents to prevent persistent kidney disease in children with IgAV in participants with no or minimal kidney involvement at presentation. We did not find any studies which evaluated corticosteroids in children presenting with IgAV and nephritic and/or nephrotic syndrome, although corticosteroids are recommended in such children in guidelines. Though heparin may be effective in reducing proteinuria, this potentially dangerous therapy is not justified to prevent serious kidney disease when few children with IgAV develop severe kidney disease. There may be no benefit of cyclophosphamide compared with no specific treatment or corticosteroids. While there may be no benefit in the efficacy of MMF or tacrolimus compared with IV cyclophosphamide in children or adults with IgAV and severe kidney disease, adverse effects, particularly infections, may be lower in MMF or tacrolimus-treated children. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin, MMF or leflunomide have any role in the treatment of children with IgAV and severe kidney disease. We did not identify any studies which evaluated corticosteroids.
Topics: Adult; Child; Humans; Fosinopril; IgA Vasculitis; Kidney Diseases; Leflunomide; Proteinuria; Tacrolimus; Vasculitis
PubMed: 36853224
DOI: 10.1002/14651858.CD005128.pub4 -
International Journal of Molecular... Feb 2023Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor...
Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% ( = 27/64) achieved remission; 20.3% ( = 13/64) achieved complete remission (CR) and 18.7% ( = 12/64) partial remission (PR). 60.9% ( = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% ( = 26/38) achieved CR and 7.8% achieved ( = 3/38) PR. 23.6% ( = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% ( = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.
Topics: Adult; Female; Humans; Male; Glomerulonephritis, IGA; IgA Vasculitis; Kidney Failure, Chronic; Plasma Exchange
PubMed: 36835388
DOI: 10.3390/ijms24043977