Benefit Of Intravenous Immunoglobulin Research Articles

Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis.

The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI -2.56, 3.31) and ICU (MD 0.36; 95% CI -0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.

Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis

BackgroundThe benefit of IVIG (Intravenous Immunoglobulin) therapy for COVID-19 remains controversial. We performed a meta-analysis to investigate the efficacy of IVIG treatment in patients with COVID-19. MethodsWe searched articles from Web of Science, PubMed, Embase, the Cochrane Library, MedRxiv between 1 January 2020 and February 17, 2021. We selected randomized clinical trials and observational studies with a control group to assess the efficiency of IVIG in treating patients with COVID-19. Subjects were divided into ‘non-severe’, ‘severe’ and ‘critical’ three subgroups based on the information of the study and the World Health Organization (WHO) definition of severity. We pooled the data of mortality and other outcomes using either a fixed-effect model or a random-effects model. ResultsOur meta-analysis retrieved 4 clinical trials and 3 cohort studies including 825 hospitalized patients. The severity of COVID-19 is associated with the efficiency of IVIG. In critical subgroup, IVIG could reduce the mortality compared with the control group [RR = 0.57 (0.42–0.79, I2 = 025%). But there was no significant difference in the severe or non-severe subgroups. ConclusionIVIG has demonstrated clinical efficacy on critical ill patients with COVID-19. There may be a relationship between the efficacy of IVIG and the COVID-19 disease severity. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from IVIG are warranted in the future.

P157 Potential benefit of intravenous immunoglobulin in connective tissue disease associated interstitial lung diseases

Abstract Background/Aims Intravenous immunoglobulin (IVIg) confers significant benefit in range of connective tissue diseases (CTD) including inflammatory myopathy (IM) of which interstitial lung diseases (ILD) are a major complication. This study aimed to assess the efficacy of IVIg on pulmonary involvement in refractory active CTD including systemic sclerosis (SSc). Methods All patients with CTD-ILD confirmed on HRCT either with IM or SSc overlap myositis who did not achieve satisfactory clinical response to standard immunosuppressive agents and subsequently received regular IVIg infusions for IM were retrospectively identified. Serial lung function tests and immunosuppressive treatment regimen 9-12 months prior and 9-12 months after repeat courses of IVIg were recorded. Progressive ILD was considered when, despite immunosuppressive treatment, a relative FVC decline≥10% and/or relative DLco decline ≥15% were identified during the 9-12 months preceding IVIg treatment. The significance of median DLco and FVC percentage relative change to IVIg treatment was assessed by Wilcoxon signed-rank test. Results 22 patients (mean age 50.5±13.1 years old) with IM-ILD treated with IVIg were identified. ILD occurred in association with IM in 10 patients, overlap SSc myositis in another 11 patients, while one had mixed connective tissue disease with myositis. Lung function results were available for 19/22 (86%). Eight patients (42.1%) were found to have progressive ILD(four with IM and four with overlap SSc-myositis). The median change in FVC% predicted and DLco% predicted in the 9-12 months before and after IVIg treatment is presented in Table 1. There was a significant difference in the DLco% predicted rate of relative change before and after IVIg treatment (p = 0.035) for the overall cohort. However, no differences in lung function were observed in the rate of relative change between patients with IM and patients with SSc myositis overlap. Significant improvement in DLco% predicted values was identified in the subgroup analysis of patients with progressive ILD(p = 0.012). P157 Table 1:The median change in FVC and DLco% predicted values prior and after the IVIg treatmentPatients with myositis related ILD9-12 months before IVIg treatment (relative change)9-12 months after IVIg treatment (relative change)p-valueAll (n = 19)FVC % predicted-3.8 (-54.4 - 14.6)2.1 (-33 - 33.7)0.145DLco % predicted-9.2 (-60.7 - 9.2)-2.3 (-26 - 41.9)0.035PM/DM (n = 10)FVC % predicted-1.8 (-20.2 - 14.6)0.8 (-33 - 30.9)0.401DLco % predicted-9.6 (-60.7 - 9.2)-2.4 (-26 - 41.9)0.093SSc-PM/DM overlap (n = 11)FVC % predicted-6 (-54.4 - 10.6)3.4 (-19.9 - 33.7)0.139DLco % predicted-10.8 (-47.1 - 2.5)4.2 (-22.7 - 16.8)0.173Progressive ILD (n = 8)FVC % predicted-14.5 (-54.4 - 14.6)5.7 (-11.9 - 33.7)0.123DLco % predicted-25.3 (-60.6 - -14.1)12 (-2.3 - 41.9)0.012 Conclusion IVIg may be an effective rescue therapy in the prevention of further lung function decline in refractory myositis and SSc overlap in particular in subgroups with progressive ILD. Future studies to determine its role in CTD-ILD are warranted. Disclosure V. Kouranos: None. L.V. Host: None. C. Campochiaro: None. A. Wells: None. C.P. Denton: None. V.H. Ong: None. E. Renzoni: None.

LIVEdoid vasculopathy – benefit of intravenous immunoglobulin in a refractory case

Livedoid vasculopathy is a rare vascular disease which typically manifests as recurrent ulcerative lesions on the lower extremities. It is classified as a vasculopathy, not a true vasculitis, and defined as a vasooclusive syndrome, caused by non-inflammatory thrombosis of the upper and mid-dermal venulae. Main disorders associated with LV include thrombophilias, autoimmune diseases and neoplasia. A triad of clinical features is present in most patients and consist of livedo racemosa (less frequently livedo reticularis), ulcerations and atrophie blanche. Management generally relies on antiplatelet drugs, anticoagulants, vasodilators and fibrinolytic therapy. Some benefit has been observed with intravenous immunoglobulin, colchicine, hyperbaric oxygen, while glucocorticoids are efficient to a lesser extent. This case report highlights a refractory clinical form with no identifiable predisposing condition, which proved responsive only to intravenous immunoglobulin.

Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.

AimsPrevious uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)‐related dilated cardiomyopathy (DCM). This randomized, double‐blind, placebo‐controlled, single‐centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.Methods and resultsFifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6‐min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end‐diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (−7;5) vs. placebo −2 (−6;6), P = 0.904] and LVEDV (IVIg −16 ± 49 mL/m2 vs. placebo −29 ± 40 mL/m2; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.ConclusionIntravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.

The Prosid Study: Evaluating Efficacy and Safety of Intravenous Immunoglobulin (IVIG) 10% in Primary Infection Prophylaxis in Patients with Chronic Lymphocytic Leukemia- Study Design

The Prosid Study: Evaluating Efficacy and Safety of Intravenous Immunoglobulin (IVIG) 10% in Primary Infection Prophylaxis in Patients with Chronic Lymphocytic Leukemia- Study Design

Corticosteroid-sparing benefit of intravenous immunoglobulin in systemic sclerosis-associated myopathy: A comparative study in 52 patients.

Little is known about systemic sclerosis (SSc)-associated myopathy (SScAM) treatment. Herein we evaluated the use of intravenous immunoglobulin (IVIg) in SScAM. We conducted a retrospective study of patients with SScAM in the Internal medicine department of Cochin University Hospital between 1993 and 2017. Fifty-two patients were included comprising 18 (34.6%) with limited SSc and 34 (65.4%) with diffuse SSc. SScAM occurred at a median [interquartile range (IQR)] time of 1 month [0-15] after SSc diagnosis. Thirty-four patients (65.4%) had muscle weakness, 28 (53.8%) had myalgia and 24 (46.2%) had dysphagia. Fifty patients (96.2%) had increased creatine kinase, 22/26 (84.6%) had myopathic electromyography, 10/12 (83.3%) had a high intensity signal of girdle muscles on MRI and 49/50 (98%) had abnormal muscle biopsy. Eighteen (34.6%) patients received IVIg. Severe adverse events occurred in 3/18 (16.7%) patients. When compared to patients who did not receive IVIg, patients who received IVIg had a significantly higher maximal corticosteroid (CS) dose ever, a greater decrease of CS at 3 months, and a lower CS dose at one year and at the end of follow up. This study suggests the benefit of IVIg as adjunctive therapy, with an acceptable tolerance profile, and supports its use as a CS-sparing agent, in SScAM.

Existing and Emerging Approaches to Treating Chronic Inflammatory Demyelinating Polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disabling disease with an incompletely understood autoimmune etiology. Differentiating the condition from other neurological diseases can be challenging and appropriate treatment is often delayed. Intravenous immunoglobulin (IVIg), plasmapheresis, corticosteroids and subcutaneous immunoglobulin (SCIg) have all been demonstrated to be beneficial in placebo-controlled, randomized clinical trials. Corticosteroids, including methylprednisolone and dexamethasone are effective and frequently used in CIDP but their long-term use is limited by side effects. One of the most commonly prescribed treatments for CIDP is IVIg which diminishes inflammatory processes and prevents disease progression. Treatment with IVIg has proven effective in randomized, double blind, placebo controlled, clinical trials and the results support its use in CIDP. For some patients, the benefit of IVIg, is limited by the frequency of infusions and systemic side effects such as flu-like symptoms, headache, and nausea. Other effective treatments for CIDP include corticosteroids that are associated with serious side effects in long-term use and plasmapheresis which requires specialized facilities. More recently, SCIg has been demonstrated in double blind, placebo-controlled studies to be effective for maintenance use in CIDP in patients whose disease has been controlled by IVIg. In a large clinical trial, 0.2 g/kg and 0.4 g/kg body weight doses of 20% SCIg equivalent to 1 mL/kg or 2 mL/kg, respectively, administered weekly, demonstrated efficacy in CIDP and were well tolerated. Immunomodulating treatments such as cyclophosphamide, mycophenolate mofetil and rituximab have also shown efficacy in select populations with CIDP.

Immunoglobulin for alloimmune hemolytic disease in neonates.

Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy. Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

Myopathies nécrosantes à anti-HMG-CoA réductase : à propos de 4 observations

IntroductionAnti-3-hydroxy-3-méthylglutaryl-coenzyme A reductase antibody-associated necrotizing autoimmune myopathy has been recently described (2011). This myopathy is distinct from statin toxic myopathy. Our objective is to report on the clinical and para-clinical characteristics of this myopathy and to show the difficulties of therapeutic care. Case reportsWe describe 4 cases of patients followed-up in Brittany, France. All data have been analyzed retrospectively. The mean age of our patients was 59.5 years, with a sex ratio of 1. The clinical presentation was homogeneous, with a subacute painful proximal and symmetrical weakness, without extra-muscular involvement. Other presentations have been described (including pseudo-dystrophic presentation). All patients had a previous statin medication (mean duration of 3.75 years) although this criteria is not a requisite. All patients had high levels of creatine kinase and abnormal electromyographic examination. The pathological pattern on muscular biopsy was a necrotizing myopathy without significant inflammatory cells infiltration. Cardio-respiratory function was normal and no associated neoplasia was found. Over the follow-up, we observed a marked corticosteroid-dependence, not improved by immunosuppressive drugs (azathioprine and methotrexate). The benefit of intravenous immunoglobulin was clear with, sometimes, prolonged responses. ConclusionAn early diagnosis of this myopathy is necessary in order to introduce an immunotherapy associated with a close monitoring. The therapeutic strategy (within which the stead of intravenous immunoglobulin seems increased) remains to be defined and long-term prospective studies are thus needed.

Intravenous Immunoglobulin as an Immunomodulating Agent in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A French Nationwide Study of Ninety-Two Patients.

Intravenous immunoglobulin (IVIG) represents a therapeutic alternative in antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but its efficacy has been evaluated in only 2 small prospective trials. The aim of this study was to evaluate the efficacy and safety of IVIG in patients with AAV. We conducted a nationwide retrospective study of patients who received IVIG as immunomodulatory therapy for AAV. A total of 92 patients (mean age 51 years) presenting with either granulomatosis with polyangiitis (Wegener's) (68%), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (22%), or microscopic polyangiitis (10%) received at least 1 course of IVIG. Antineutrophil cytoplasmic antibodies were present in 72% during the flare that required IVIG, as determined by immunofluorescence assay. IVIG was initiated because of relapsing disease in 83% of cases. IVIG was given for a median of 6 months (range 1-156 months) and in combination with corticosteroids in 21% of the patients or with other immunosuppressive agents in 77%. Efficacy of IVIG was assessed in the entire population and in a subset of 34 patients with unmodified background therapy. Remission rates at 6 months were 56% in the entire population and 58% in the unmodified background therapy group. Refractory disease and treatment failure at 6 months were observed in 7% and 18% in the whole population and 3% and 21% in the unmodified background therapy group, respectively. Adverse events (AEs) occurred in 33%, including serious AEs in 12% and AEs leading to discontinuation of IVIG in 7%. This large study shows the clinical benefit of IVIG as adjunctive therapy, with an acceptable tolerance profile, and thus supports its use in AAV patients with refractory or relapsing disease.

Use of intravenous immunoglobulin in severe Clostridium difficile-associated diarrhea

Objective. Clostridium difficile infection is an increasingly common cause of healthcare-acquired diarrhea. There remains substantial morbidity and mortality, even with current modalities of treatment. The aim of our study was to investigate the role of intravenous immunoglobulin (IVIG) on mortality in patients with severe Clostridium difficile-associated diarrhea (CDAD). Methods. A retrospective chart review of 21 patients with severe CDAD treated with IVIG in our affiliated hospitals from January 2000 to December 2012 was conducted. As a matching control group, we randomly selected 21 patients meeting the definition of severe CDAD from the same period. Data were compared between these groups using appropriate statistical tests. Results. Patients in the IVIG group were older (69.8 vs 60.9 years, p = 0.05) and had a higher severity score (5.4 vs 3.9, p = 0.02). Mortality was lower among those who received IVIG as compared to the group who did not receive IVIG; however not statistically significant (18.2 vs 22.7%, p = 0.51). Conclusion. Our data demonstrate that although the patients who received IVIG had significantly severe infection, there was no difference in the mortality rate. Prospective controlled studies are needed to assess the true benefit of IVIG in patient with severe Clostridium difficle infection.

Intravenous immunoglobulin and immune response.

Intravenous immunoglobulin and immune response.

Intravenous immunoglobulin exerts reciprocal regulation of Th1/Th17 cells and regulatory T cells in Guillain-Barré syndrome patients.

Guillain-Barré syndrome (GBS) is an acute, autoimmune inflammatory disorder of peripheral nervous system characterized by a severe functional motor weakness. Treatment with intravenous immunoglobulin (IVIg) is one of the approved and preferred therapeutic strategies for GBS. However, the mechanisms underlying the therapeutic benefit with IVIg in GBS are not completely understood. In the present study, we observed that GBS patients have increased frequencies of Th1 and Th17 cells, but reduced number of Foxp3(+) regulatory T cells (Treg cells) with defective functions. We show that IVIg treatment in GBS patients results in a marked reduction in the frequency of Th1 and Th17 cells with a concomitant expansion of Treg cells. Importantly, IVIg-expanded Treg cells exhibited an increased T cell suppressive function. Together our results demonstrate that therapeutic benefit of IVIg in GBS patients implicates the reciprocal regulation of Th1/Th17 and Treg cells.

Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since been updated, most recently in 2013. To review systematically the evidence from randomised controlled trials (RCTs) concerning the efficacy and safety of IVIg in CIDP. On 4 December 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, issue 11 in the Cochrane Library), MEDLINE and EMBASE to December 2012 and ISI from January 1985 to May 2008. We searched for ongoing trials through two metaRegistries (World Health Organization International Clinical Trials Registry Platform Search Portal and Current Controlled Trials). We selected RCTs testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP. Two authors reviewed literature searches to identify potentially relevant RCTs, scored their quality and extracted data independently. We contacted authors for additional information. We considered eight RCTs, including 332 participants, to be eligible for inclusion in the review. These trials were homogeneous and the overall risk of bias low. Five studies, in a total of 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange, one trial compared IVIg with prednisolone in 32 participants, and one trial, newly included at this update, compared IVIg with intravenous methylprednisolone in 46 participants.A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome 3.03 (95% CI 2.33 to 4.55), high quality evidence). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials, including 84 participants, the disability score could be transformed to the modified Rankin score, on which improvement of one point after IVIg treatment compared to placebo was barely significant (RR 2.40, 95% CI 0.98 to 5.83) (moderate quality evidence). Only one placebo-controlled study included in this review had a long-term follow-up. The results of this study suggest that IVIg improves disability more than placebo over 24 and 48 weeks.The mean disability score revealed no significant difference between IVIg and plasma exchange at six weeks (moderate quality evidence). There was no significant difference in improvement in disability on prednisolone compared with IVIg after two or six weeks, or on methylprednisolone compared to IVIg after two weeks or six months (moderate quality evidence).There were no statistically significant differences in frequencies of side effects between the three types of treatment for which data were available (IVg versus placebo or steroids). (moderate or high quality evidence) Mild and transient adverse events were found in 49% of participants treated with IVIg, while serious adverse events were found in six per cent. The evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of three. During this period it has similar efficacy to plasma exchange, oral prednisolone and intravenous methylprednisolone. In one large trial, the benefit of IVIg persisted for 24 and possibly 48 weeks. Further research is needed to compare the long-term benefits as well as side effects of IVIg with other treatments.

Research in Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN): a network of specialist TEN centres is needed to undertake effective clinical studies and therapeutic trials

ORIGINAL ARTICLE, p 1304 When a case of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) presents, a management plan must be instigated immediately. Along with discontinuation of the culprit drug, institution of optimal supportive care is mandatory. Specialist dermatology nursing, local treatment of skin and mucous membranes, fluid replacement, nutrition and analgesia are all essential to improve the chances of survival and minimize sequelae. However, dermatologists are also prompted to consider prescribing active therapy in an attempt to ‘switch off’ keratinocyte apoptosis and limit the extension of skin involvement. Over the past 15 years, intravenous immunoglobulin (IVIg) has been used to this end, and many papers have been published indicating efficacy. However, in 2012 Huang et al.1 published a systematic review and meta‐analysis of all studies using IVIg in the treatment of SJS/TEN and concluded that the evidence does not support unambiguous therapeutic benefit. In the current issue of the BJD, Lee et al.2 have presented the outcome of 64 patients with SJS/TEN treated with IVIg in one specialist centre. This is a retrospective analysis using SCORTEN (a validated severity‐of‐illness score) at presentation to predict patient mortality. All 64 patients received IVIg in combination with a standardized regimen of supportive care. Twenty of 64 patients (31%) died; the standardized mortality rate was 1·10 (95% confidence interval 0·62–1·58), indicating that, in keeping with the conclusions of Huang et al.,1 IVIg does not appear to confer a survival benefit in TEN and may in fact be harmful. In previous studies authors have argued that the benefit of IVIg is achieved using higher doses; in the study by Lee et al.2 there was no mortality difference between patients when stratified for high dosage (≥ 3 g kg−1) vs. low dosage (< 3 g kg−1). The study's conclusion was that IVIg does not produce a survival benefit in SJS/TEN. Despite the findings from the study of Lee et al., and the conclusions from the meta‐analysis by Huang et al., we suspect that many dermatologists will continue to prescribe IVIg.

Defining the Benefits of Desensitization Therapy

Defining the Benefits of Desensitization Therapy

The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis

Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking. To provide a meta-analysis evidence-based examination of IVIg efficacy against TEN. A systematic review and meta-analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high-dose and low-dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg. Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19.9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1.00 [95% confidence interval (CI) 0.58-1.75; P=0.99]. The pooled OR for mortality in patients treated with high-dose IVIg vs. supportive care was 0.63 (95% CI 0.27-1.44; P=0.27). Adults treated with high-dose IVIg exhibited significantly lower mortality than those treated with low-dose IVIg (18.9% vs. 50%, respectively; P=0.022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0.494; 95% CI 0.106-2.300; P=0.369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21.6%; P=0.001). Although high-dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.

Intravenous immunoglobulins and acquired von Willebrand syndrome

Dear Sir, I read with interest the letter “Are intravenous immunoglobulins really inappropriate in the acquired von Willebrand syndrome?” by Federici et al1. Intravenous immunoglobulin (IVIG) is a fractionated blood product made from pooled human plasma. It was introduced in the late 1970s and rapidly subsumed the use of intramuscular preparations as replacement therapy in primary and secondary immunodeficiencies. It is increasingly important in replacement therapy and as an immunomodulatory agent in autoimmune disease and transplantation. IVIG is the market driver for the plasma industry in the developed world. The literature on this therapeutic agent increases exponentially and the burgeoning interest in therapeutic immunoglobulin is rapidly generating new evidence, both expanding and reducing current therapeutic indications, with varying levels of supportive evidence. In 1998, the effectiveness of IVIG was demonstrated in an open-label crossover study in patients with acquired von Willebrand syndrome associated with monoclonal gammopathy of uncertain significance of the IgG class2. In 2000, an in ternational registry series reported that one-third of the 63 patients treated with high-dose IVIG had a good response1. The currently limited evidence of the probable benefit of IVIG in the very rare bleeding disorder known as autoimmune acquired von Willebrand disease, though mainly coming from case reports and case series and not from large well-designed, prospective, randomised trials, is continuously growing, also thanks to the international registry of the International Society on Thrombosis and Haemostasis. Despite the low level of evidence case reports and case series can provide us with, they are still part of the evidence hierarchy in evidence-based practice and guide an important part of clinical practice. Case series are incorporated in a significant proportion of health technology assessments3. In 2007, the Australian Health Ministers’ Conference issued the “Criteria for the clinical use of intravenous immunoglobulin in Australia” and suggested that the management of autoimmune acquired von Willebrand syndrome includes the treatment of the underlying medical condition and should be undertaken only by or in consultation with haemophilia treatment centres keeping in mind that IVIG constitutes only part of the management of these complex patients4, who also require additional haemostatic support. This very rare and severe bleeding disorder is one of the conditions for which IVIG use is suggested in exceptional circumstances only. These circumstances include the management of bleeding and prior to invasive procedures, except cases associated with IgM paraprotein in which response is unlikely. The use of IVIG is also indicated in cases of failure to respond to chemotherapy/immunosuppressants or when there is insufficient time for chemotherapy/immunosuppressants to be given. In 2011, the guidelines of the United Kingdom Department of Health also recommended that IVIG treatment in this severe bleeding disorder be only undertaken in a comprehensive care centre for haemophilia. In addition, “IVIG is only recommended for patients with acquired von Willebrand syndrome with life- or limb-threatening haemorrhage who have not responded to other treatments, or prior to invasive procedures (grade B recommendation, level IIa evidence)” 5. For the above reasons, although more research is needed, undoubtedly autoimmune acquired von Willebrand syndrome deserves to be included in the rapidly growing list of non-recognised conditions in which IVIG has been utilised with some benefit, as suggested by Federici et al1.

113. Therapeutic benefit of intravenous immunoglobulin found in patient with POEMS syndrome

113. Therapeutic benefit of intravenous immunoglobulin found in patient with POEMS syndrome