Efficacy and safety of intravenous immunoglobulins for the treatment of viral encephalitis: a systematic literature review
Journal of neurology. 2021
BACKGROUND For most viral encephalitides, therapy is merely supportive. Intravenous immunoglobulins (IVIG) have been used as a prophylactic and therapeutic approach. We conduct a systematic review on the safety and efficacy of IVIG in viral encephalitis. METHODS We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with viral encephalitis treated with IVIG as of May 31, 2019. The main outcomes assessed were therapeutic efficacy and safety. For an increased homogeneity of the population, atypical viral infections were excluded, as were reports on prophylactic IVIG use, intrathecal application of immunoglobulins, or use of antibody-enriched IVIG-preparations. Data were extracted from published studies. Descriptive statistics were used. RESULTS We included a total of 44 studies (39 case reports). The case reports cover a total of 53 patients. Our search retrieved two prospective and three retrospective studies. These show heterogeneous results as to the efficacy of IVIG therapy. Only one study reports a significant association between IVIG-use and death (odds ratio 0.032; 95% confidence interval 0.0033-0.3024; p = 0.0027). None of the studies report significant differences in the number of serious adverse events. CONCLUSION Data on the efficacy of IVIG-therapy is heterogeneous. While it seems generally safe, evident superiority compared to supportive treatment has not been demonstrated so far. Future trials should also investigate the optimal dosing and timing of IVIG and their benefit in the immunosuppressed.
A review of severe thrombocytopenia in Zika patients - Pathophysiology, treatment and outcome
Travel medicine and infectious disease. 2021;45:102231
BACKGROUND During the 2015 Zika virus infection (ZVI) epidemic swiping through the Americas, few cases of ZVI with severe, potentially life-threatening thrombocytopenia were reported. Platelet transfusion, corticosteroids and intravenous immunoglobulins (IVIG) were in most cases applied as therapeutic options, predominantly with success. We present a comprehensive overview concerning the pathophysiology, treatment strategies and outcomes of patients with ZVI and severe thrombocytopenia (platelet count <50 × 10(9)/L). METHOD A literature search was performed. RESULTS Eleven case reports and case series with a total of 28 patients met the inclusion criteria; including five cases with lethal outcome. Therapeutic strategies, including platelet transfusion, administration of steroids and/or IVIG were described in 24 cases. CONCLUSIONS Severe thrombocytopenia is a rare, but potentially life-threatening complication of ZVI. The principal pathophysiological mechanism appears to immune-induced thrombocytopenia. Due to a paucity of cases, the optimal treatment strategy remains to be elucidated.
Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis
Frontiers in pediatrics. 2021;9:697938
Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies. Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts. Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures. Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.
The Effectiveness of Different Doses of Intravenous Immunoglobulin on Severe Hand, Foot and Mouth Disease: A Meta-Analysis
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2019
OBJECTIVE To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of Intravenous Immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. METHODS A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until 30 June 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs, We used random effects models (or fixed effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. RESULTS From a total of 420 entries identified via searches, 8 RCTs involving 1450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1g/kg per day) had shorter fever clearance time (p < 0.05), shorter rash regression (p < 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). CONCLUSION The high-dose group has a better prognosis, however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.
Treatment of Sydenham's chorea: a review of the current evidence
Tremor and Other Hyperkinetic Movements (New York, N.y.). 2017;7:456.
BACKGROUND Sydenham's chorea (SC), the neurologic manifestation of rheumatic fever, remains the most prevalent form of chorea in children. Suggested treatments of chorea in SC include prophylactic penicillin, symptomatic (antipsychotic and anticonvulsant) medications, and immunomodulatory therapy (steroids, intravenous immunoglobulin (IVIG), and plasma exchange). In this manuscript, we undertook a systematic review of the published literature to examine the data supporting these therapeutic recommendations. METHODS A search of PubMed, Embase, Psychinfo, and clinicaltrials.gov was conducted for publications pertaining to the treatment of SC/rheumatic chorea from 1956 to 2016. RESULTS Penicillin prophylaxis appears to reduce the likelihood of further cardiac complications and the recurrence rate of chorea. Data on symptomatic therapy for chorea are limited to individual case reports or series and rare comparison studies. The efficacy of steroid use is supported by a single placebo-controlled study and several case series. Information on other immunomodulatory therapies such as IVIG and plasmapheresis are limited to a small number of reports and a single comparison study. DISCUSSION Treatment decisions in SC are currently based on the treating physician's clinical experience, the desire to avoid side effects, and the existence of only limited scientific evidence. Based on a review of the available literature, chorea often improves with symptomatic therapy and immunotherapy tends to be reserved for those who fail to respond. Steroids are beneficial; however, data using IVIG and plasmapheresis are very limited. Larger, well-controlled studies, using standardized assessment scales, are required if therapeutic decisions for SC are to be based on meaningful information.
Intravenous immunoglobulin for the treatment of childhood encephalitis
The Cochrane Database of Systematic Reviews. 2017;((10)):CD011367.
BACKGROUND Encephalitis is a syndrome of neurological dysfunction due to inflammation of the brain parenchyma, caused by an infection or an exaggerated host immune response, or both. Attenuation of brain inflammation through modulation of the immune response could improve patient outcomes. Biological agents such as immunoglobulin that have both anti-inflammatory and immunomodulatory properties may therefore be useful as adjunctive therapies for people with encephalitis. OBJECTIVES To assess the efficacy and safety of intravenous immunoglobulin (IVIG) as add-on treatment for children with encephalitis. SEARCH METHODS The Cochrane Multiple Sclerosis and Rare Diseases of the CNS group's Information Specialist searched the following databases up to 30 September 2016: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and the WHO ICTRP Search Portal. In addition, two review authors searched Science Citation Index Expanded (SCI-EXPANDED) & Conference Proceedings Citation Index - Science (CPCI-S) (Web of Science Core Collection, Thomson Reuters) (1945 to January 2016), Global Health Library (Virtual Health Library), and Database of Abstracts of Reviews of Effects (DARE). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing IVIG in addition to standard care versus standard care alone or placebo. DATA COLLECTION AND ANALYSIS Two review authors independently selected articles for inclusion, extracted relevant data, and assessed quality of trials. We resolved disagreements by discussion among the review authors. Where possible, we contacted authors of included studies for additional information. We presented results as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). MAIN RESULTS The search identified three RCTs with 138 participants. All three trials included only children with viral encephalitis, one of these included only children with Japanese encephalitis, a specific form of viral encephalitis. Only the trial of Japanese encephalitis (22 children) contributed to the primary outcome of this review and follow-up in that study was for three to six months after hospital discharge. There was no follow-up of participants in the other two studies. We identified one ongoing trial.For the primary outcomes, the results showed no significant difference between IVIG and placebo when used in the treatment of children with Japanese encephalitis: significant disability (RR 0.75, 95% CI 0.22 to 2.60; P = 0.65) and serious adverse events (RR 1.00, 95% CI 0.07 to 14.05; P = 1.00).For the secondary outcomes, the study of Japanese encephalitis showed no significant difference between IVIG and placebo when assessing significant disability at hospital discharge (RR 1.00, 95% CI 0.60 to 1.67). There was no significant difference (P = 0.53) in Glasgow Coma Score at discharge between IVIG (median score 14; range 3 to 15) and placebo (median 14 score; range 7 to 15) in the Japanese encephalitis study. The median length of hospital stay in the Japanese encephalitis study was similar for IVIG-treated (median 13 days; range 9 to 21) and placebo-treated (median 12 days; range 6 to 18) children (P = 0.59).Pooled analysis of the results of the other two studies resulted in a significantly lower mean length of hospital stay (MD -4.54 days, 95% CI -7.47 to -1.61; P = 0.002), time to resolution of fever (MD -0.97 days, 95% CI -1.25 to -0.69; P < 0.00001), time to stop spasms (MD -1.49 days, 95% CI -1.97 to -1.01; P < 0.00001), time to regain consciousness (MD -1.10 days, 95% CI -1.48 to -0.72; P < 0.00001), and time to resolution of neuropathic symptoms (MD -3.20 days, 95% CI -3.34 to -3.06; P < 0.00001) in favour of IVIG when compared with standard care.None of the included studies reported other outcomes of interest in this review including need for invasive ventilation, duration of invasive ventilation, cognitive impairment, poor adaptive functioning, quality of life, number of seizures, and new diagnosis of epilepsy.The quality of evidence was very low for all outcomes of this review. AUTHORS' CONC
A systematic review of the therapy for Mycoplasma pneumoniae infections in children
Zhonghua Er Ke Za Zhi. Chinese Journal of Pediatrics. 2016;54((2)):111-8.
OBJECTIVE To evaluate the therapeutic effects of antibacterial agents, glucocorticoid and intravenous immunoglobulin (IVIG) in treating Mycoplasma pneumoniae(MP) infections. METHOD The literature was screened by the inclusion and exclusion criteria after searching at Cochrane Library, Pubmed, Wanfang, CNKI, and Weipu databases. According to JADAD evaluation system, the relevant information in each included report from the literature was evaluated. The evidence-based analysis was performed for the therapeutic effects of macrolides, glucocorticoid, and IVIG in treating MP infections. Meta-analysis was conducted on the suitable literature by RevMan 5.3 software supplied by Cochrane collaboration. Descriptive analysis was conducted on the literature unsuitable for meta-analysis. RESULT (1) Seven foreign RCT reports and 7 domestic RCT reports were included in the analysis of the therapeutic effect of macrolides. There was a high heterogeneity among the 7 foreign reports. Five of these reports showed no significant difference in clinical effects between macrolides and non-macrolide antibacterial agents. The forest plot analysis of antipyretic timing and cough duration in the domestic literature with complete indicators suggested that for azithromycin sequential therapy vs. erythromycin intravenous therapy, the mean difference of antipyretic timing was-1.10 (95%CI: -1.60,-0.60) and the mean difference of cough duration was-1.56 (95%CI: -2.10,-1.03). (2) Three foreign RCT reports and 5 domestic RCT were included in the analysis of glucocorticoid therapy. The JADAD scores of all the reports were 1. The basic therapy drug was macrolides. The results of sub-group analysis suggested that for the patients who used glucocorticoid early vs. the patients who used non-glucocorticoid therapy, the mean difference of antipyretic time was-1.77(95%CI: -2.44,-1.10) and the mean difference of cough duration was-2.47 (95%CI: -2.86,-2.08); for the patients treated with glucocorticoid at 10 days after onset of diseases vs. the patients received non-glucocorticoid therapy, the mean difference of antipyretic time was-3.41 (95%CI: -4.10,-2.73) and the mean difference of cough duration was-2.25 (95%CI: -4.38,-0.12). (3) Regarding IVIG, all the included reports were case study or case report. Most of the literature focused on severe Mycoplasma pneumoniae infection and those with extrapulmonary complications. The limited results suggested a trend of the shortening of disease process and improvement of clinical symptoms by IVIG. CONCLUSION There was no exact evidence of the therapeutic effects of antibacterial agents in Mycoplasma pneumoniae infections. A trend of better therapeutic effect was inferred in macrolide antibiotics, especially azithromycin. The improvement of clinical symptoms was suggested with the usage of glucocorticoid as adjuvant therapy. IVIG as an adjuvant therapy is at an exploration stage.
PANDAS: a systematic review of treatment options
International Journal of Pediatric Otorhinolaryngology. 2016;89:149-53.
INTRODUCTION Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) is a rare but important condition for pediatric otolaryngologists to recognize. Several treatment options exist including tonsillectomy, antibiotic treatment/prophylaxis, intravenous immunoglobulin (IVIG), and psychiatric medications/therapy. METHODS A systematic review of the PubMed, EMBASE, and Scopus databases was performed searching for articles that focused exclusively on the aforementioned treatment modalities in the PANDAS population. Review articles, single patient case reports, and studies examining the natural history or diagnostic strategies were excluded. RESULTS Five articles regarding tonsillectomy treatments with level of evidence (LOE) 4 were found but no clear benefit could be determined. Three articles were selected involving the use of antibiotic therapy. One prospective study and one double-blind randomized control trial (DB RCT) supported the use of antibiotics but a separate DB RCT showed no benefit. Two selected articles described the use of IVIG one unblinded RCT and one retrospective study. One prospective study on cognitive-behavioral therapy (CBT) showed benefit in PANDAS. CONCLUSION There is a paucity of high-level studies regarding this rare disorder and no hard treatment recommendations can be made. Tonsillectomy should only be performed in those who are surgical candidates based on current published guidelines. Antibiotics are an option but provide uncertain benefit. CBT remains a low-risk option. Studies support the use of IVIG, however more investigation is needed prior to widespread adoption of this treatment given its potential risks.
Intravenous immunoglobulin in acute Sydenham's chorea: a systematic review
Journal of Paediatrics & Child Health. 2015;51((12)):1235-8.
Sydenham's chorea (SC) is a major manifestation seen in 25% of patients with acute rheumatic fever. SC is the prototypic autoimmune neurological disorder, which has a less appreciated associated risk of psychiatric morbidity. We undertook a systematic review to examine whether the use of intravenous immunoglobulin affects clinical recovery and morbidity. Copyright © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis
BMC Neurology. 15:39, 2015.. 2015;15:39.
BACKGROUND Postpolio syndrome (PPS) is characterized by progressive disabilities that develop decades after prior paralytic poliomyelitis. Because chronic inflammation may be the process underlying the development of PPS, immunomodulatory management, such as intravenous immunoglobulin (IVIg) administration, may be beneficial. METHODS We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of IVIg in managing PPS. Electronic databases, including PubMed, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials, were searched for articles on PPS published before December 2014. The primary outcomes were pain severity, fatigue scores, and muscle strength. The secondary outcomes were physical performance, quality of life (QoL), and cytokine expression levels. RESULTS We identified 3 RCTs involving 241 patients and 5 prospective studies involving 267 patients. The meta-analysis of pain severity (weighted mean difference [WMD]=-1.02, 95% confidence interval [CI]=-2.51 to 0.47), fatigue scores (WMD=0.28, 95% CI -0.56 to 1.12), and muscle strength revealed no significant differences between the IVIg and the placebo group. Regarding QoL, the RCTs yielded controversial outcomes, with improvement in only certain domains of the Short Form 36 (SF-36). Moreover, one prospective study reported significant improvement on SF-36, particularly in patients aged younger than 65 years, those with paresis of the lower limbs, and high pain intensity. CONCLUSION The present review indicated that IVIg is unlikely to produce significant improvements in pain, fatigue, or muscle strength. Thus, routinely administering IVIg to patients with PPS is not recommended based on RCTs. However, a potential effect in younger patients with lower limbs weakness and intense pain requires confirmation from further well-structured trials.