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Neurological Sciences : Official... Feb 2024Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are... (Review)
Review
BACKGROUND
Tics and stereotypies are childhood-onset repetitive behaviours that can pose significant diagnostic challenges in clinical practice. Both tics and stereotypies are characterised by a complex co-morbidity profile, however little is known about the co-occurrence of these hyperkinetic disorders in the same patient population.
OBJECTIVE
This review aimed to assess the relationship between tics and stereotypies when these conditions present in co-morbidity.
METHODS
We conducted a systematic literature review of original studies on co-morbid tics and stereotypies, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Our literature search identified six studies of suitable sample size (n ≥ 40) presenting data on the association between tics and stereotypies in otherwise typically developing patients. A considerable proportion (23%) of patients diagnosed with stereotypic movement disorder present with co-morbid tics (range 18-43%). Likewise, the prevalence of primary stereotypies is increased in patients with tic disorders such as Tourette syndrome (8%, range 6-12%).
DISCUSSION
Tics and stereotypies can often develop in co-morbidity. The association of tics and stereotypies in the same patient has practical implications, in consideration of the different treatment approaches. Future research should focus on the assessment and management of both conditions, particularly in special populations (e.g. patients with pervasive developmental disorders).
Topics: Child; Humans; Comorbidity; Stereotypic Movement Disorder; Tic Disorders; Tics; Tourette Syndrome
PubMed: 37775616
DOI: 10.1007/s10072-023-07095-y -
JMIR Dermatology Sep 2023Psychogenic purpura is an idiopathic psychodermatologic condition of recurrent, painful purpura precipitated by psychological stress, predominantly affecting young... (Review)
Review
BACKGROUND
Psychogenic purpura is an idiopathic psychodermatologic condition of recurrent, painful purpura precipitated by psychological stress, predominantly affecting young females. Little consensus exists on the diagnostic guidelines for this rare condition, often resulting in costly, unnecessary, and stressful investigations as well as prolonged hospital admissions.
OBJECTIVE
With this first up-to-date systematic review of 134 cases of psychogenic purpura in over a decade, we aim to thoroughly investigate the diagnostic strategy and treatment regimens used in the last decade. With a sooner diagnosis, patient stress and nosocomial ecchymoses can be minimized, and treatment can be expedited.
METHODS
We conducted a literature review of 4 databases (PubMed, Ovid Embase, Ovid MEDLINE, and Web of Science) on October 5, 2022 that yielded 46 full-text articles, which were reviewed and extracted by 2 independent reviewers.
RESULTS
We analyzed a total of 134 cases, consisting largely of females (125/134, 93.3%) with purpura on the upper (103/134, 76.9%) or lower limbs (112/134, 83.6%). Apart from a paresthesia prodrome, patients commonly experienced headaches, malaise, and arthralgia or myalgia. Approximately 70% (95/134) of patients reported a physiological or psychological stressor or psychiatric diagnosis before the development of the purpura. Laboratory testing almost always revealed unremarkable results. The intradermal washed autoerythrocyte sensitization test was positive in 98% (42/43) of cases. Histopathology biopsy findings commonly revealed dermal erythrodiapedesis or hemorrhage (n=34) and perivascular inflammatory infiltrates (n=17). Approximately 42% (56/134) of patients received a novel psychiatric diagnosis, with depression being the most common (40/72, 56%). In both patients with and those without a novel psychiatric diagnosis, observation, counseling, treatment with antidepressants (ie, selective serotonin reuptake inhibitors), and psychotherapy (ie, cognitive behavioral therapy) prevailed in the resolution of the purpura.
CONCLUSIONS
Due to the unclear etiology and infrequent presentation of this condition, it remains a diagnosis of exclusion based on clinical suspicion evaluating the presence of stressors or psychiatric comorbidities and exclusion of systemic conditions. Clinical confirmation can be sought through a positive autoerythrocyte sedimentation test, characteristic histopathology findings, and remission of purpura after psychiatric treatment.
PubMed: 37703091
DOI: 10.2196/48153 -
Frontiers in Immunology 2023Galactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Galactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment options. This updated systematic review aimed to determine the diagnostic and prognostic value of Gd-IgA1 assessment in biological fluids in patients with IgAN.
METHODS
PRISMA guidelines were followed in this review. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Information/China Science and Technology Journal Database, and WANFANG for studies published between database inception and January 31, 2023. Eligible studies that evaluated aberrant IgA1 glycosylation in IgAN patients relative to controls were identified, and random effects meta-analyses were used to compare Gd-IgA1 levels in different groups. The quality of the evidence was assessed using the Newcastle-Ottawa Scale. This study was registered on PROSPERO (CRD42022375246).
FINDINGS
Of the 2727 records identified, 50 were eligible and had available data. The mean Newcastle-Ottawa Scale score was 7.1 (range, 6-8). Data synthesis suggested that IgAN patients had higher levels of blood and/or urine Gd-IgA1 compared with healthy controls (standard mean difference [SMD]=1.43, 95% confidence interval [CI]=1.19-1.68, P<0.00001), IgA vasculitis patients (SMD=0.58, 95% CI=0.22-0.94, P=0.002), and other kidney disease patients (SMD=1.06, 95% CI=0.79-1.33, P<0.00001). Moreover, patients with IgAN had similar levels of serum Gd-IgA1 compared to first-degree relatives (SMD=0.38, 95% CI= -0.04-0.81, P=0.08) and IgA vasculitis with nephritis patients (SMD=0.12, 95% CI= -0.04-0.29, P=0.14). In addition, ten studies demonstrated significant differences in serum Gd-IgA1 levels in patients with mild and severe IgAN (SMD= -0.37, 95% CI= -0.64--0.09, P=0.009).
CONCLUSIONS
High serum and urine Gd-IgA1 levels suggest a diagnosis of IgAN and a poor prognosis for patients with this immunological disorder. Future studies should use more reliable and reproducible methods to determine Gd-IgA1 levels.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375246, identifier CRD42022375246.
Topics: Humans; Glomerulonephritis, IGA; Prognosis; IgA Vasculitis; Immunoglobulin A
PubMed: 37671165
DOI: 10.3389/fimmu.2023.1209394 -
Journal of Clinical Medicine Aug 2023Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO)... (Review)
Review
Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO) measures (PROMs) that are validated for other diseases. However, the validity evidence to support the use of existing PROMs in patients with TTP is unknown. In a systematic review of the literature, including studies of adults and children with TTP, we assessed the validity evidence for use of PROMs in clinical research and clinical practice, characterized HRQoL, described the integration of PROMs in clinical practice and evaluated PRO scores for patients with TTP compared with reference populations. From an initial 4518 studies, we identified 14 studies using 16 PROMs to assess general HRQoL domains in patients in remission. No identified studies assessed the validity of PROMs for the context of use of TTP and no studies described PROM integration into TTP clinical practice or evaluated PROMs that were specific for patients with TTP. Moreover, PRO scores were worse in patients with TTP compared with reference populations and other chronic conditions. We conclude that, in patients with TTP, PROMs pick up on important patient experiences not captured by clinical outcomes at present. There is, therefore, a need for studies that assess the validity of existing PROMs in patients with TTP to determine if TTP-specific PROMs specific to patients with TTP should be developed.
PubMed: 37568558
DOI: 10.3390/jcm12155155 -
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 -
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 -
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 -
Annals of Hematology Apr 2023There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®),...
There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Consensus; COVID-19; Thrombocytopenia; Thrombopoietin; Receptors, Fc; Benzoates; Hydrazines; Recombinant Fusion Proteins
PubMed: 36826482
DOI: 10.1007/s00277-023-05114-8 -
Journal of Xenobiotics Jan 2023Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and... (Review)
Review
Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.
PubMed: 36810430
DOI: 10.3390/jox13010005